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1
Rusin, Matthew, Nardine Ghobrial, Endre Takacs, Jeffrey S. Willey, and Delphine Dean. "Changes in ionizing radiation dose rate affect cell cycle progression in adipose derived stem cells." PLOS ONE 16, no. 4 (April 27, 2021): e0250160. http://dx.doi.org/10.1371/journal.pone.0250160.
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Biomedical use of radiation is utilized in effective diagnostic and treatment tools, yet can introduce risks to healthy tissues. High energy photons used for diagnostic purposes have high penetration depth and can discriminate multiple tissues based on attenuation properties of different materials. Likewise, the ability to deposit energy at various targets within tumors make the use of photons effective treatment for cancer. Radiation focused on a tumor will deposit energy when it interacts with a biological structure (e.g. DNA), which will result in cell kill should repair capacity of the tissue be overwhelmed. Likewise, damage to normal, non-cancerous tissues is a consequence of radiation that can lead to acute or late, chronic toxicity profiles. Adipose derived stem cells (ADSCs) are mesenchymal stem cells that have been proven to have similar characteristics to bone marrow derived stem cells, except that they are much easier to obtain. Within the body, ADSCs act as immunomodulators and assist with the maintenance and repair of tissues. They have been shown to have excellent differentiation capability, making them an extremely viable option for stem cell therapies and regenerative medicine applications. Due to the tissue ADSCs are derived from, they are highly likely to be affected by radiation therapy, especially when treating tumors localized to structures with relatively high ADSC content (eg., breast cancer). For this reason, the purpose behind this research is to better understand how ADSCs are affected by doses of radiation comparable to a single fraction of radiation therapy. We also measured the response of ADSCs to exposure at different dose rates to determine if there is a significant difference in the response of ADSCs to radiation therapy relevant doses of ionizing radiation. Our findings indicate that ADSCs exposed to Cesium (Cs 137)-gamma rays at a moderate dose of 2Gy and either a low dose rate (1.40Gy/min) or a high dose rate (7.31Gy/min) slow proliferation rate, and with cell cycle arrest in some populations. These responses ADSCs were not as marked as previously measured in other stem cell types. In addition, our results indicate that differences in dose rate in the Gy/min range typically utilized in small animal or cell irradiation platforms have a minimal effect on the function of ADSCs. The potential ADSCs have in the space of regenerative medicine makes them an ideal candidate for study with ionizing radiation, as they are one of the main cell types to promote tissue healing.
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Chavali, Laxmi B., Adana A. M. Llanos, Jing-Ping Yun, Stephanie M. Hill, Xiang-Lin Tan, and Lanjing Zhang. "Radiotherapy for Patients With Resected Tumor Deposit–Positive Colorectal Cancer: A Surveillance, Epidemiology, and End Results–Based Population Study." Archives of Pathology & Laboratory Medicine 142, no. 6 (October 19, 2017): 721–29. http://dx.doi.org/10.5858/arpa.2017-0099-oa.
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Context.— According to the American Joint Committee on Cancer's Cancer Staging Manual, 7th edition, TNM classification, tumor deposit (TD)–positive colorectal cancers (CRCs) are classified as N1c. The effects of radiotherapy and the effects of the updated American Joint Committee on Cancer 7th edition TNM N1c classification for patients with TD-positive CRC are unclear. Objective.— To investigate outcomes of radiotherapy in patients with resected TD-positive CRC. Design.— Resected TD-positive CRCs diagnosed from 2010 to 2014 were identified in the Surveillance, Epidemiology, and End Results 18 database. Factors associated with overall survival (OS) and cancer-specific survival (CSS) were investigated using Kaplan-Meier and Cox proportional hazards models. Results.— We included 2712 qualified CRC patients, who either underwent adjuvant radiotherapy (n = 187; 6.9%) or received no radiotherapy (n = 2525; 93.1%). Univariate Cox proportional models showed improved CSS among all CRC patients who underwent adjuvant radiotherapy (CSS hazard ratio, 0.73; 95% CI, 0.57–0.95) and among rectal cancer patients when separated by location (hazard ratio, 0.57; 95% CI, 0.40–0.83), although these associations were attenuated in multivariable-adjusted models. There was improved OS among rectal cancer patients (hazard ratio, 0.77; 95% CI, 0.59–0.99). In subgroup analyses, radiotherapy was not associated with OS or CSS in either metastatic or nonmetastatic CRC patients. Instead, N1c category (versus N0) was associated with a worse OS (hazard ratio, 1.43; 95% CI, 1.31–1.57) but was not associated with CSS. Conclusions.— Radiotherapy did not independently improve OS among TD-positive CRC patients. In this study, classifying TD positivity as N1c was associated with worse OS than classifying TD positivity as N0. The findings seem to challenge the benefits of radiotherapy and the new N1c classification of TD for TD-positive CRC patients.
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Win, Aung Zaw, and Carina Mari Aparici. "Omental Nodular Deposits of Recurrent Chromophobe Renal Cell Carcinoma Seen on FDG-PET/CT." Journal of Clinical Imaging Science 4 (September 23, 2014): 51. http://dx.doi.org/10.4103/2156-7514.141560.
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We present the case of a 69-year-old male with chromophobe renal cell carcinoma (RCC). Chromophobe RCC accounts for only 4% of renal cancers and it is the least aggressive type. Omental nodular deposits due to RCC metastasis are very rare and it is reported only in more aggressive forms of RCC. This is the first report that shows FluoroDeoxyGlucose – Positron Emission Tomography/Computed Tomgraphy (FDG-PET/CT) images of omental nodular deposits from chromophobe RCC. FDG-PET/CT is becoming very useful in restaging RCC with distant metastases.
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Kozlovskaya, L. V., V. V. Rameev, I. N. Kogarko, N. B. Gordovskaya, N. V. Chebotareva, T. V. Androsova, S. V. Roshchupkina, et al. "Renal lesions associated with monoclonal gammopathies of undetermined significance: clinical forms, mechanisms of development, approaches to treatment." Clinical Medicine (Russian Journal) 94, no. 12 (February 19, 2017): 892–901. http://dx.doi.org/10.18821/0023-2149-2016-94-12-892-901.
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The term «monoclonal gammopathies of undetermined significance» (MGUS) was introduced by R. Kyle in 1978 to designate the condition characterized by the presence ofsmall amounts ofM-protein in the serum. In some patients, such condition remains benign for a long time but predetermines for the development of multiple myeloma and other B-lymphocytic tumours. Also, it can provoke non-cancerous diseases due to the toxic action of monoclonal proteins (immunoglobulins and free light chains) on various organs, especially kidneys. MGUS-associated renal lesions include glomerulopathies with organized deposits, such as AL-amyloidosis (amyloid light chain of immunoglobulin), cryoglobulinic and immunotactoid glomerulonephritis, and with unorganized deposits (light chain deposition and proliferative forms of idiopathic glomerulonephritis. The available experimental data throw light on the possible mechanisms of renal lesions. We summarized the literature data and original observations to describe methods for differential diagnostics of MGUS-associated renal lesions including the highly sensitive test for free light chine identification (Freelite method) and principles of pathogenetic treatment by the impact on the pathological B-cell clone.
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Malik, Akshat, and Sudhir Nair. "Reply to Letter to the Editor regarding “Soft tissue deposits in oral cancers”." Head & Neck 42, no. 11 (August 13, 2020): 3467–68. http://dx.doi.org/10.1002/hed.26412.
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Meesat, Ridthee, Hakim Belmouaddine, Jean-François Allard, Catherine Tanguay-Renaud, Rosalie Lemay, Tiberius Brastaviceanu, Luc Tremblay, et al. "Cancer radiotherapy based on femtosecond IR laser-beam filamentation yielding ultra-high dose rates and zero entrance dose." Proceedings of the National Academy of Sciences 109, no. 38 (August 27, 2012): E2508—E2513. http://dx.doi.org/10.1073/pnas.1116286109.
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Since the invention of cancer radiotherapy, its primary goal has been to maximize lethal radiation doses to the tumor volume while keeping the dose to surrounding healthy tissues at zero. Sadly, conventional radiation sources (γ or X rays, electrons) used for decades, including multiple or modulated beams, inevitably deposit the majority of their dose in front or behind the tumor, thus damaging healthy tissue and causing secondary cancers years after treatment. Even the most recent pioneering advances in costly proton or carbon ion therapies can not completely avoid dose buildup in front of the tumor volume. Here we show that this ultimate goal of radiotherapy is yet within our reach: Using intense ultra-short infrared laser pulses we can now deposit a very large energy dose at unprecedented microscopic dose rates (up to 1011 Gy/s) deep inside an adjustable, well-controlled macroscopic volume, without any dose deposit in front or behind the target volume. Our infrared laser pulses produce high density avalanches of low energy electrons via laser filamentation, a phenomenon that results in a spatial energy density and temporal dose rate that both exceed by orders of magnitude any values previously reported even for the most intense clinical radiotherapy systems. Moreover, we show that (i) the type of final damage and its mechanisms in aqueous media, at the molecular and biomolecular level, is comparable to that of conventional ionizing radiation, and (ii) at the tumor tissue level in an animal cancer model, the laser irradiation method shows clear therapeutic benefits.
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Udugama, Maheshi, Elaine Sanij, Hsiao P. J. Voon, Jinbae Son, Linda Hii, Jeremy D. Henson, F. Lyn Chan, et al. "Ribosomal DNA copy loss and repeat instability in ATRX-mutated cancers." Proceedings of the National Academy of Sciences 115, no. 18 (April 18, 2018): 4737–42. http://dx.doi.org/10.1073/pnas.1720391115.
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ATRX (alpha thalassemia/mental retardation X-linked) complexes with DAXX to deposit histone variant H3.3 into repetitive heterochromatin. Recent genome sequencing studies in cancers have revealed mutations in ATRX and their association with ALT (alternative lengthening of telomeres) activation. Here we report depletion of ATRX in mouse ES cells leads to selective loss in ribosomal RNA gene (rDNA) copy number. Supporting this, ATRX-mutated human ALT-positive tumors also show a substantially lower rDNA copy than ALT-negative tumors. Further investigation shows that the rDNA copy loss and repeat instability are caused by a disruption in H3.3 deposition and thus a failure in heterochromatin formation at rDNA repeats in the absence of ATRX. We also find that ATRX-depleted cells are reduced in ribosomal RNA transcription output and show increased sensitivity to RNA polymerase I (Pol I) transcription inhibitor CX5461. In addition, human ALT-positive cancer cell lines are also more sensitive to CX5461 treatment. Our study provides insights into the contribution of ATRX loss of function to tumorigenesis through the loss of rDNA stability and suggests the therapeutic potential of targeting Pol I transcription in ALT cancers.
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Nambiar, Sudheer, and Asha Karippot. "Multiple Cutaneous Metastases as Initial Presentation in Advanced Colon Cancer." Case Reports in Gastrointestinal Medicine 2018 (2018): 1–3. http://dx.doi.org/10.1155/2018/8032905.
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Skin metastases from advanced colorectal cancer are relatively rare and occur most often when the cancer is advanced, following the spread to other organs. Cutaneous metastases occur in about 3% of advanced colorectal cancers. We present an extremely rare case of a 68-year-old woman with advanced ascending colon adenocarcinoma that presented with multiple rapidly progressing painless cutaneous metastatic lesions with no other distant metastases. Of all the tumors, breast cancer most commonly spreads as cutaneous metastasis is followed by lung, colorectal, renal, ovarian, and bladder cancers. Cutaneous metastases can present in a variety of clinical manifestations, such as a rapidly growing painless dermal or subcutaneous nodule with intact overlying epidermis or as ulcers. In cases where the cutaneous deposit is isolated, as in visceral metastasis, there is a role for radical management such as wide local excision and reconstruction. In our patient, since she had multiple cutaneous metastases she began treatment with palliative systemic combination chemotherapy.
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Raldow, Ann, James Lamb, and Theodore Hong. "Proton beam therapy for tumors of the upper abdomen." British Journal of Radiology 93, no. 1107 (March 2020): 20190226. http://dx.doi.org/10.1259/bjr.20190226.
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Proton radiotherapy has clear dosimetric advantages over photon radiotherapy. In contrast to photons, which are absorbed exponentially, protons have a finite range dependent on the initial proton energy. Protons therefore do not deposit dose beyond the tumor, resulting in great conformality, and offers the promise of dose escalation to increase tumor control while minimizing toxicity. In this review, we discuss the rationale for using proton radiotherapy in the treatment of upper abdominal tumors—hepatocellular carcinomas, cholangiocarcinomas and pancreatic cancers. We also review the clinical outcomes and technical challenges of using proton radiotherapy for the treatment of these malignancies. Finally, we discuss the ongoing clinical trials implementing proton radiotherapy for the treatment of primary liver and pancreatic tumors.
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Al-Bahlani, Shadia, Buthaina Al-Dhahli, Kawther Al-Adawi, Abdurahman Al-Nabhani, and Mohamed Al-Kindi. "Platinum-Based Drugs Differentially Affect the Ultrastructure of Breast Cancer Cell Types." BioMed Research International 2017 (2017): 1–13. http://dx.doi.org/10.1155/2017/3178794.
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Breast cancer (BC) is the most common cause of cancer-related death worldwide. Although platinum-based drugs (PBDs) are effective anticancer agents, responsive patients eventually become resistant. While resistance of some cancers to PBDs has been explored, the cellular responses of BC cells are not studied yet. Therefore, we aim to assess the differential effects of PBDs on BC ultrastructure. Three representative cells were treated with different concentrations and timing of Cisplatin, Carboplatin, and Oxaliplatin. Changes on cell surface and ultrastructure were detected by scanning (SEM) and transmission electron microscope (TEM). In SEM, control cells were semiflattened containing microvilli with extending lamellipodia while treated ones were round with irregular surface and several pores, indicating drug entry. Prolonged treatment resembled distinct apoptotic features such as shrinkage, membrane blebs, and narrowing of lamellipodia with blunt microvilli. TEM detected PBDs’ deposits that scattered among cellular organelles inducing structural distortion, lumen swelling, chromatin condensation, and nuclear fragmentation. Deposits were attracted to fat droplets, explained by drug hydrophobic properties, while later they were located close to cell membrane, suggesting drug efflux. Phagosomes with destructed organelles and deposits were detected as defending mechanism. Understanding BC cells response to PBDs might provide new insight for an effective treatment.
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Eljabu, W., G. Finch, J. Nottingham, and N. Vaingankar. "Metastatic Deposits of Breast Lobular Carcinoma to Small Bowel and Rectum." International Journal of Breast Cancer 2011 (2011): 1–4. http://dx.doi.org/10.4061/2011/413949.
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Breast cancer is the most frequent malignancy in women accounting for approximately 32% of all cancers, with a lifetime risk of 1 in 10. It causes considerable morbidity and mortality. Recently, the survival rate has dramatically increased due to early detection of the disease and improvement in the treatment measures. However, more than 30% of the patients develop metastatic diseases following surgical treatment, radiotherapy, hormonal therapy, or chemotherapy. Distant spread is usually found in bones, lungs, liver, brain and skin. Rarely, it spreads to bowel, spleen, gallbladder, pancreas, urinary bladder, and eyes. Breast cancer is the second commonest primary tumour responsible for gastrointestinal metastases after malignant melanoma. We report a case of a Caucasian female who developed an intestinal obstruction secondary to metastatic deposits to the small bowel and later to the rectum from breast lobular carcinoma 2 years after mastectomy, axillary clearance, radiotherapy, hormonal therapy, and transverse rectus abdominis myocutaneous (TRAM) flap for reconstruction.
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Romero, Ignacio, and Robert C. Bast. "Minireview: Human Ovarian Cancer: Biology, Current Management, and Paths to Personalizing Therapy." Endocrinology 153, no. 4 (March 13, 2012): 1593–602. http://dx.doi.org/10.1210/en.2011-2123.
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More than 90% of ovarian cancers have been thought to arise from epithelial cells that cover the ovarian surface or, more frequently, line subserosal cysts. Recent studies suggest that histologically similar cancers can arise from the fimbriae of Fallopian tubes and from deposits of endometriosis. Different histotypes are observed that resemble epithelial cells from the normal Fallopian tube (serous), endometrium (endometrioid), cervical glands (mucinous), and vaginal rests (clear cell) and that share expression of relevant HOX genes which drive normal gynecological differentiation. Two groups of epithelial ovarian cancers have been distinguished: type I low-grade cancers that present in early stage, grow slowly, and resist conventional chemotherapy but may respond to hormonal manipulation; and type II high-grade cancers that are generally diagnosed in advanced stage and grow aggressively but respond to chemotherapy. Type I cancers have wild-type p53 and BRCA1/2, but have frequent mutations of Ras and Raf as well as expression of IGFR and activation of the phosphatidylinositol-3-kinase (PI3K) pathway. Virtually all type II cancers have mutations of p53, and almost half have mutation or dysfunction of BRCA1/2, but other mutations are rare, and oncogenesis appears to be driven by amplification of several growth-regulatory genes that activate the Ras/MAPK and PI3K pathways. Cytoreductive surgery and combination chemotherapy with platinum compounds and taxanes have improved 5-yr survival, but less than 40% of all stages can be cured. Novel therapies are being developed that target high-grade serous cancer cells with PI3Kness or BRCAness as well as the tumor vasculature. Both in silico and animal models are needed that more closely resemble type I and type II cancers to facilitate the identification of novel targets and to predict response to combinations of new agents.
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Adams, Reid B., and Bernard Langer. "Resection Margins for Colorectal Metastases to The Liver: Do They Make A Difference?" HPB Surgery 9, no. 2 (January 1, 1996): 115–17. http://dx.doi.org/10.1155/1996/95180.
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Objective: The authors determined an appropriate surgical treatment for liver metastases from colorectal cancers. Clinicopathologic featuresof metastatic lesions of colorectal cancers were studied.Summary Background Data: Major hepatic resection is the usual procedure for treatment of hepatic metastases from colorectal cancers.Methods: Forty consecutive patients who underwent hepatic resections were prospectively studied, for a total of 89 metastatic liver tumors.Results: Metastatic tumor often extended along Glisson’s capsule, including invasion to the portal vein (9 cases), the hepatic vein (3 cases), the bile duct (16 cases), and the nerve (6 cases). The main tumor had small satellite nodules in only one patient, and there were no microscopic deposits in the parenchyma, even within 10 mm from the metastatic tumors. Fibrous pseudocapsule formation was observed in 28 patients.Discussion: The rarity of intrahepatic metastasis from metastatic tumor supports nonanatomic limited hepatic resection as the procedure of choice for metastatic colorectal cancer in the liver. The spread via Glisson's capsule should be taken into consideration for complete tumor clearance.
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Belt, E. J. Th, M. F. M. van Stijn, H. Bril, E. S. M. de Lange-de Klerk, G. A. Meijer, S. Meijer, and H. B. A. C. Stockmann. "Lymph Node Negative Colorectal Cancers with Isolated Tumor Deposits Should Be Classified and Treated As Stage III." Annals of Surgical Oncology 17, no. 12 (July 13, 2010): 3203–11. http://dx.doi.org/10.1245/s10434-010-1152-7.
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Doki, Y. "Cytokeratin Deposits in Lymph Nodes Show Distinct Clinical Significance from Lymph Node Micrometastasis in Human Esophageal Cancers." Journal of Surgical Research 107, no. 1 (September 2002): 75–81. http://dx.doi.org/10.1016/s0022-4804(02)96506-6.
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Doki, Yuichiro, Osamu Ishikawa, Masayuki Mano, Masahiro Hiratsuka, Yo Sasaki, Masao Kameyama, Hiroaki Ohigashi, et al. "Cytokeratin Deposits in Lymph Nodes Show Distinct Clinical Significance from Lymph Node Micrometastasis in Human Esophageal Cancers." Journal of Surgical Research 107, no. 1 (September 2002): 75–81. http://dx.doi.org/10.1006/jsre.2002.6506.
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Rezo, A., K. Rodins, A. J. Davis, B. Shadbolt, Y. Zhang, F. Huynh, and J. Dahlstrom. "Assessment of tumour size and its relationship to nodal involvement in multifocal and multicentric breast cancer." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 10602. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.10602.
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10602 Background: The AJCC/UICC staging system categorises tumour size in multifocal and multicentric breast cancer (MMBC) using the largest dimension of the largest focus of tumour. This under-estimates the total tumour burden and therefore may under-estimate the potential of these tumours to metastasise. This study tests the hypothesis that an aggregate measurement of tumour size in MMBC is more closely related to nodal status than the size of the largest focus. Methods: This prospective cohort study involved women with ipsilateral invasive breast cancer with known nodal status using data from the ACT & SENSW BCTG database from July 1997 to June 2004. Pathology reports were reviewed to obtain tumour size in the unifocal group and nodal status in all women. The histopathology of MMBC cases were reviewed measuring all tumour foci that were recorded as: (1) the diameter of the largest deposit (LD), (2) the aggregate diameter (AD) of all deposits, and (3) a calculation of the aggregate volume (AV) using the largest dimension of each focus. The MMBC dimensions were compared with unifocal cancers and against nodal status using a multivariate logistic regression analysis and compared against each other using a stepwise method to determine which method is most predictive of nodal involvement. Results: 795 women met the criteria for study entry: 139 (17.5%) had MMBC and 656 (82.5%) had unifocal disease. When adjusting for tumour size method of measurement in MMBC, there was strong agreement between the AD MMBC and unifocal groups in terms of nodal status (p=0.7). Conversely, there were statistically significant differences in nodal status using LD (p=0.008) and AV (p=0.02) measurements in MMBC when compared to the unifocal group. Within the MMBC group the aggregated diameter measure was most significantly related to nodal status (p=0.001). Conclusions: The results of this study confirm that the current tumour staging system in MMBC under-estimates the potential for nodal spread and that aggregate diameter is more clinically useful. Nodal status is used in this study as a surrogate for tumour behaviour. Further studies are underway to assess relationship of aggregate size of MMBC to relapse and survival. No significant financial relationships to disclose.
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Brown, Charles, Farzad Sekhavati, Ruben Cardenes, Claudia Windmueller, Karma Dacosta, Jaime Rodriguez-Canales, and Keith E. Steele. "CTLA-4 Immunohistochemistry and Quantitative Image Analysis for Profiling of Human Cancers." Journal of Histochemistry & Cytochemistry 67, no. 12 (October 14, 2019): 901–18. http://dx.doi.org/10.1369/0022155419882292.
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There is an important need in immuno-oncology to develop reliable immunohistochemistry (IHC) to assess the expression of CTLA-4+ tumor-infiltrating lymphocytes in human cancers and quantify them with image analysis (IA). We used commercial polyclonal and monoclonal antibodies and characterized three chromogenic cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) assays with suitable specificity and sensitivity for use in formalin-fixed, paraffin-embedded (FFPE) tissues. We found variable numbers of CTLA-4+ lymphocytes in multiple types of cancer and secondary lymphoid organs (SLOs) and other normal human tissues. Combining CTLA-4 with CD3, CD4, or CD8 by immunofluorescence showed that CTLA-4+ lymphocytes in SLOs and tumors were typically CD3+ and CD4+, but not CD8+. Individual lymphocytes expressed CTLA-4 either as primarily granular cytoplasmic staining or as excentric globular deposits. The CTLA-4/FoxP3 (forkhead box P3 protein) duplex IHC demonstrated that CTLA-4+/FoxP3− lymphocytes predominated in the germinal centers of SLOs and tumor tertiary lymphoid structures (TLSs), whereas CTLA-4+/FoxP3+ lymphocytes populated the T-cell zone of SLOs and TLSs, plus tumor stroma. IA scoring was highly comparable with pathologist scoring for CTLA-4 and CTLA-4/FoxP3 assays and a FoxP3 single IHC. Our findings show that CTLA-4 IHC can be used to reliably label lymphocytes in FFPE human tissues, making it possible to investigate the role of CTLA-4 in the tumor microenvironment.
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Tinganelli, Walter, and Marco Durante. "Tumor Hypoxia and Circulating Tumor Cells." International Journal of Molecular Sciences 21, no. 24 (December 16, 2020): 9592. http://dx.doi.org/10.3390/ijms21249592.
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Circulating tumor cells (CTCs) are a rare tumor cell subpopulation induced and selected by the tumor microenvironment’s extreme conditions. Under hypoxia and starvation, these aggressive and invasive cells are able to invade the lymphatic and circulatory systems. Escaping from the primary tumor, CTCs enter into the bloodstream to form metastatic deposits or re-establish themselves in cancer’s primary site. Although radiotherapy is widely used to cure solid malignancies, it can promote metastasis. Radiation can disrupt the primary tumor vasculature, increasing the dissemination of CTCs. Radiation also induces epithelial–mesenchymal transition (EMT) and eliminates suppressive signaling, causing the proliferation of existent, but previously dormant, disseminated tumor cells (DTCs). In this review, we collect the results and evidence underlying the molecular mechanisms of CTCs and DTCs and the effects of radiation and hypoxia in developing these cells.
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Schumacher, Udo, and Elizabeth Adam. "Immunohistochemical Detection of the MUC1 Gene Product in Human Cancers Grown in scid Mice." Journal of Histochemistry & Cytochemistry 46, no. 1 (January 1998): 127–34. http://dx.doi.org/10.1177/002215549804600116.
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Alterations in mucin expression have been detected in many clinically relevant cancers and, in particular, the polymorphic epithelial mucin, encoded by the MUC1 gene, has attracted considerable attention. We investigated its expression in human breast, colon, ovarian, lung, and skin cancer cells and their metastases grown in severe combined immunodeficient ( scid) mice using three different monoclonal antibodies (HMFG-1, HMFG-2, and SM3). Four of five breast cancer cell lines, three of five colon cancer cell lines, two of three small-cell carcinoma of the lung cell lines, and A 431 cells all expressed the MUC1 gene product. Neuraminidase predigestion often enhanced HMFG-1 immunoreactivity, which was more widespread and stronger than SM3 immunoreactivity. A considerable heterogeneity of MUC1 gene product expression was observed in the same tumors grown in different mice. The binding pattern between single-cell/small-cell clusters (up to 10 cells) and larger cell number aggregates varied. The results indicate that the MUC1 gene expression both in primary tumors and metastases is not tightly controlled within a particular tumor cell line. Because of this heterogeneous antigen expression in vivo, it appears impossible to target all metastatic deposits by a single monoclonal antibody directed against the MUC1 gene product.
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Lucassen, E., A. C. Andres, E. Reichmann, A. Entwistle, and M. Noble. "The effects of the neuN and neuT genes on differentiation and transformation of mammary epithelial cells." Journal of Cell Science 107, no. 10 (October 1, 1994): 2919–29. http://dx.doi.org/10.1242/jcs.107.10.2919.
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Overexpression of the proto-oncogene product, p185neuN, in a non-tumorigenic mammary epithelial line (31E) facilitates aspects of lactogenic differentiation. Formation of branching cords and induction of beta-casein synthesis by 31E cells normally require co-culture of these cells with fibroblasts, or the presence of collagen or fibronectin. In contrast, 31E cells expressing p185neuN spontaneously form branching cords when grown on tissue culture plastic and can synthesize beta-casein in the absence of exogenous substrates or feeder layers. Under these conditions, the cells deposit laminin and fibronectin, indicating a possible role for p185neuN in the deposition of extracellular matrix proteins. Overexpression of the corresponding oncogene product, p185neuT, has markedly different effects. Expression of p185neuT does not facilitate the formation of branching cords or the synthesis of beta-casein when grown on tissue culture plastic, although these cells do deposit laminin and fibronectin. Confocal microscopy indicates a significant difference in the distribution of laminin and fibronectin in 31E cells expressing p185neuT compared to those expressing p185neuN. The effects of p185neuN and p185neuT expression on cell transformation depend on cell type. Expression of both p185neuN and p185neuT increases anchorage-independent growth of 31E cells, but only p185neuT induces anchorage-independent growth of NIH 3T3 fibroblasts. This lineage specificity in the action of p185neuN may be related to observations that overexpression of p185c-erbB-2 (the human homologue of p185neuN) is only associated with the development of human epithelial cancers. The effects of p185neuN on laminin deposition by 31E cells may be relevant to the transforming ability of p185neuN, since laminin can induce anchorage-independent growth of mouse mammary cells. These results suggest that p185neuN and p185neuT could exert their effects on differentiation and transformation of mammary epithelial cells in part by promoting the deposition of extracellular matrix proteins.
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Gupta, Amit, ROHIK ANJUM, Rishit Mani, Navin Kumar, Anoushika Mehan, Sweety Gupta, Nilotpal Chowdhury, and Utkarsh Kumar. "Small cell carcinoma of gall bladder: An uncommon histologic entity." Polish Journal of Surgery 92, no. 5 (July 16, 2020): 1–5. http://dx.doi.org/10.5604/01.3001.0014.3177.
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Gall bladder small cell carcinoma (scc) comprises of 0.5% of all GB cancers. It carries a poor prognosis in view of its aggressive nature. We here report a case of small cell carcinoma GB 55-year old lady presented with features of obstructive jaundice with significant weight loss. Examination revealed hard lump in right upper abdomen with multiple scratch marks all over the body. Clinically she had jaundice. Blood investigations revealed hyperbilirubinemia. Tumour markers showed raised CA 19-9. Staging CECT thorax and Abdomen reported polypoidal enhancing wall thickening of gall bladder with multiple metastatic deposits close to pancreatic head encasing main portal vein and common bile duct. Histopathology was suggestive of small cell carcinoma. Patient was referred to Oncology department and is receiving palliative cisplatin-etoposide chemotherapy
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Davar, Sandra, and Dominique Hanna. "Sister Mary Joseph's Nodule." Journal of Cutaneous Medicine and Surgery 16, no. 3 (May 2012): 201–4. http://dx.doi.org/10.1177/120347541201600313.
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Background: Sister Mary Joseph's nodule (SMJN) represents an unusual clinical feature of metastatic deposit at the umbilicus originating from an intra-abdominal malignancy. Objective: To outline the paucity of such a condition, review the associated pathologies, and demonstrate the importance of clinical and histopathologic correlation. Methods: Case report of a 75-year-old man with vesical and prostatic cancers treated 2 years prior to presenting with an umbilical lesion. Histopathologic and radiologic examinations were performed to confirm the clinical diagnosis. Results: Histopathology of the umbilical biopsy revealed a carcinoma of urothelial origin, but immunohistochemistry suggested a squamous cell carcinoma. Clinically, the lesion did not support a diagnosis of primary squamous cell carcinoma; in addition, the positron emission tomographic scan revealed a captation at the ureterovesical junction that was compatible with vesical cancer relapse. Conclusion: SMJN is a rare but typical cutaneous metastasis of internal malignancy, and its recognition is of great importance because it may be the first presenting sign in a patient with an unknown malignant disease.
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Takatsuna, Masafumi, Manabu Takeuchi, Hiroyuki Usuda, and Shuji Terai. "Case of early-stage gastric cancer identified in the gastric mucosa with lanthanum phosphate deposition." Endoscopy International Open 07, no. 07 (July 2019): E893—E895. http://dx.doi.org/10.1055/a-0918-5804.
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Abstract Background and study aims A 78-year-old man with Helicobacter pylori infection had been undergoing hemodialysis for chronic renal failure and receiving lanthanum carbonate preparations for 3 years. Endoscopy revealed fine white granular discoloration throughout the stomach, a moderately reddish depression on the lesser curvature of the gastric angle, and white granular discoloration in the surrounding area. A magnified image using narrow-band imaging showed that the depressed part had irregular vascular and pit structures. We established a diagnosis of intramucosal gastric cancer and performed endoscopic submucosal dissection. Histopathological examination revealed a well-differentiated adenocarcinoma that was confined to the mucosa of the depressed area. Moreover, using an electron probe microanalyzer-equipped electron microscope, we found that the degree of lanthanum deposition was lower in the tumor region than in the non-tumor region. Thus, the current case can help in understanding the relationship between lanthanum deposition and early-stage gastric cancer. Because gastric cancers can occur in lanthanum deposit-containing mucosa, esophagogastroduodenoscopy should be used carefully after understanding the characteristics of early- stage gastric cancer in such cases.
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Brun, Romana, Juliane Hutmacher, Daniel Fink, and Patrick Imesch. "Erroneously Suspected Ovarian Cancer in a 38-Year-Old Woman with Pelvic Inflammatory Disease and Chlamydia." Case Reports in Obstetrics and Gynecology 2017 (2017): 1–3. http://dx.doi.org/10.1155/2017/2514613.
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Chlamydia trachomatis is the most common bacterial cause of sexually transmitted disease and can cause pelvic inflammatory disease (PID), leading to severe outcomes such as ectopic pregnancy, infertility, or pelvic pain. We report a case of a 38-year-old patient with abdominal pain and dyspareunia. Clinical examination revealed diffuse abdominal tenderness. Vaginal and abdominal sonography showed substantial ascites and CA-125 level was elevated. Therefore, the attendant physician performed an abdominal CT scan for further diagnosis. Radiographically diffuse peritoneal enhancement, consistent with peritoneal carcinomatosis, 4-quadrant ascites, and slightly enlarged ovaries with solid and cystic structures were diagnosed, leading to the suspicion of ovarian cancer. In addition, the results of the cervical smear PCR for chlamydia were positive. Due to the positive chlamydia result, the suspicious CT scan, and the young age, we decided to perform a diagnostic laparoscopy as a first step. Intraoperatively, the ovaries were of normal aspect without any cancerous lesions. However, the ascites and the yellow-reddish jelly-like deposits were consistent with acute PID. Thus, chlamydia infection may simulate the presentation of ovarian cancer. Therefore, especially in young patients, we recommend careful scrutiny of every diagnosis of ovarian cancer even if its presentation seems to be typical.
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Bullock, Martin J., Jonathan J. Beitler, Diane L. Carlson, Isabel Fonseca, Jennifer L. Hunt, Nora Katabi, Philip Sloan, S. Mark Taylor, Michelle D. Williams, and Lester D. R. Thompson. "Data Set for the Reporting of Nodal Excisions and Neck Dissection Specimens for Head and Neck Tumors: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting." Archives of Pathology & Laboratory Medicine 143, no. 4 (November 30, 2018): 452–62. http://dx.doi.org/10.5858/arpa.2018-0421-sa.
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Standardized, synoptic pathologic reporting for tumors greatly improves communication among clinicians, patients, and researchers, supporting prognostication and comparison about patient outcomes across institutions and countries. The International Collaboration on Cancer Reporting is a nonprofit organization whose mission is to develop evidence-based, universally available surgical pathology reporting data sets. Within the head and neck region, lymph node excisions and neck dissections are frequently performed as part of the management of head and neck cancers arising from the mucosal sites (sinonasal tract, nasopharynx, oropharynx, hypopharynx, oral cavity, and larynx) along with bone tumors, skin cancers, melanomas, and other tumor categories. The type of specimen, exact location (lymph node level), laterality, and orientation (by suture or diagram) are essential to accurate classification. There are significant staging differences for each anatomic site within the head and neck when lymph node sampling is considered, most importantly related to human papillomavirus–associated oropharyngeal carcinomas and mucosal melanomas. Number, size, and site of affected lymph nodes, including guidelines on determining the size of tumor deposits and the presence of extranodal extension and soft tissue metastasis, are presented in the context of prognostication. This review elaborates on each of the elements included in the data set for Nodal Excisions and Neck Dissection Specimens for Head & Neck Tumours.
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Gupta, Amit, Rohik Anjum, Rishit Mani, Navin Kumar, Anoushika Mehan, Sweety Gupta, Nilotpal Chowdhury, and Utkarsh Kumar. "Small cell carcinoma of gall bladder: An uncommon histologic entity." Polish Journal of Surgery 93, no. 1 (July 17, 2020): 1–5. http://dx.doi.org/10.5604/01.3001.0014.4878.
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<b>Introduction:</b> Gall bladder (GB) small cell carcinoma (SCC) comprises 0.5% of all gall bladder cancers. It carries a poor prognosis in view of its aggressive nature. <br><b>Case report:</b> We here report a case of small cell carcinoma of GB in a female who presented with obstructive jaundice. Examination revealed a hard lump in the right upper abdomen. Tumour markers showed raised CA 19-9. Staging CECT of the thorax and abdomen reported polypoidal enhancing wall thickening of the gall bladder with multiple metastatic deposits close to the pancreatic head encasing the main portal vein and common bile duct. Histopathology report was suggestive of small cell carcinoma, which was confirmed by immunohistochemistry. Patient was referred to the Oncology Department for palliative chemotherapy.
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Domoto, Hideharu, Akiko Watanabe, Michio Sakata, Akihiko Shimada, and Kiyoshi Mukai. "Invasive Solid Papillary Carcinoma of the Nipple With Pagetoid Extension and Nodal Metastasis." International Journal of Surgical Pathology 26, no. 6 (March 27, 2018): 573–77. http://dx.doi.org/10.1177/1066896918766237.
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We report a case of invasive solid papillary carcinoma (SPC) of the nipple with Pagetoid extension to the skin and lymph node metastasis. SPC is an uncommon primary breast cancer accounting for less than 1% of all breast cancers. Only 2 cases occurring in the nipple have been reported. However, both cases were without Pagetoid extension or lymph node metastasis. The presently reported tumor consisted of irregularly shaped solid cell nests with delicate fibrovascular cores. The tumor cells had round nuclei with low-grade atypia and eosinophilic cytoplasm. Neuroendocrine differentiation was confirmed by immunohistochemical positivity for CD56, synaptophysin, and chromogranin A. Immunohistochemistry also confirmed the absence of myoepithelial cells around the tumor cell nests. Therefore, a diagnosis of invasive SPC was made. Additionally, tumor cell deposits in the intramammary and axillary lymph nodes were identified, and these deposits had the same histological characteristics as the invasive SPC of the nipple. The invasiveness of SPC can be difficult to determine. However, the tumor cell nests in the current case exhibited a retraction artifact, which is known to be associated with invasive carcinoma and a poor prognosis, as well as morphological patterns that have been previously identified as characteristic of invasive SPC. Although SPC is widely recognized as having a favorable outcome, the existence of exceptionally aggressive cases occurring in the nipple must be recognized. Additional cases of invasive SPC of the nipple are needed to analyze the clinicopathological correlation.
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Chajon, Enrique, Marc Pracht, Yan Rolland, Thierry De Baere, France Nguyen, Jean-Pierre Bronowicki, Veronique Vendrely, et al. "First-in-class hafnium oxide nanoparticles NBTXR3 in the treatment of liver cancers." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e15642-e15642. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e15642.
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e15642 Background: Hafnium oxide nanoparticles, NBTXR3, increase the effect of radiotherapy (RT) by enhancing local energy dose deposit within tumor cells, resulting in increased cell death compared to the same dose of RT alone. NBTXR3 efficacy was demonstrated in a phase II/III study in soft tissue sarcoma (NCT02379845) and is currently evaluated in other solid tumors including liver cancers. The use of this radio enhancer is particularly relevant in liver cancer management, a difficult to treat heterogenous population, due to the presence of underlying liver dysfunction. Methods: Phase I/II study of NBTXR3 activated by RT in patients (pts) with HCC (with/without portal vein tumor thrombus) or liver metastasis (mets) [NCT02721056]. The dose escalation part followed a 3+3 design with tested dose levels equivalent to 10%, 15%, 22% and 33% of baseline tumor volume. Patients were treated with a single intralesional injection (ILI) of NBTXR3 followed by Stereotaxic Body RT (SBRT: 45 Gy/3 fractions/5 to 7 days). Determination of recommended dose(s) and early dose limiting toxicities (DLT) were primary endpoints. Secondary endpoints include assessment of global safety profile, liver function evaluated by Child-Pugh score (CPS), AST to Platelet Ratio Index (APRI), and response rate (mRECIST/RECIST 1.1). Results: The 4 levels of ILI dose escalation were finalized (n = 17): 6 pts at 10% (2 SBRT doses tested due to organs constraints), 4 pts at 15% and 22% (due to fiducial displacement and ILI shift) and 3 pts at 33% were included. ILIs were successful and SBRT was delivered as planned with no observed DLT or NBTXR3-related SAE at all levels. Only one grade 1 AE (fatigue) related to NBTXR3 was reported at dose level 33%. No relevant change of CPS or APRI was observed over time. Among 7 evaluable HCC pts the best target lesion responses by mRECIST were: 3 CR and 4 PR and among 5 evaluable mets pts: 2 PR, 1 SD and 2 PD. Conclusions: This study demonstrated the feasibility and good tolerance of the first in class NBTXR3 ILI. These results have supported a protocol amendment adding a higher dose of NBTXR3 (42% of the tumor volume). This innovative approach might constitute a valuable solution for patients with unresectable liver tumors and liver dysfunction. Clinical trial information: NCT02721056.
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Dai, Yuan-Chang, Chuan-Yin Fang, Hsin-Yi Yang, Yi-Jun Jian, Shou-Chieh Wang, and Yi-Wen Liu. "The correlation of epithelial-mesenchymal transition-related gene expression and the clinicopathologic features of colorectal cancer patients in Taiwan." PLOS ONE 16, no. 7 (July 2, 2021): e0254000. http://dx.doi.org/10.1371/journal.pone.0254000.
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Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths in the world. It has been the most prevalent malignancy in Taiwan for consecutive thirteen years. Despite the diversity of its etiologic and pathophysiologic factors, a biological process named as epithelial-mesenchymal transition (EMT) is indispensable in the progression of epithelial cancer. Our aim is to investigate the correlation between the expression of 8 EMT-related proteins (E-cadherin, β-catenin, claudin-1, CD44, N-cadherin, fibronectin, vimentin, S100A4) and the clinicopathologic features of CRC in Taiwan, along with the DNA CpG epigenetic status of CD44 gene. In immunohistochemical assessment, decreased expression of E-cadherin is statistically associated with the progression of cancer stage, while decreased expression of claudin-1 as well as increased β-catenin nuclear translocation and N-cadherin expression is statistically associated with the progression of histopathologic grade. E-cadherin, nuclear β-catenin and claudin-1 are also associated with other important prognostic factors, including nodal metastasis, tumor deposits, and elevated serum CA 19–9 levels. In addition, the left-sided colon and rectal cancers show increased nuclear translocation of β-catenin compared to the right-sided colon cancers, while the rectal cancers show increased fibronectin expression compared to the right-sided and left-sided colon cancers. Moreover, vimentin is aberrantly expressed in one case of signet-ring cell carcinoma. The DNA methylation levels of CD44 gene promoter between the tumoral and non-tumorous tissues by NGS comparison showed statistical difference on six CpG sites. However, such difference may not be sufficient because these DNA methylation proportions are too low to inactivate CD44 gene. Our results demonstrate the expression of E-cadherin, claudin-1, and nuclear β-catenin is closely related to the clinicopathologic prognostic determinants of CRC in Taiwan. The DNA methylation level of CD44 gene and its protein expression, however, show no correlation with the clinicopathologic features in CRC.
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Fukumoto, M., Y. Kuwahara, Y. Ohkubo, and L. Wang. "Analysis of carcinogenic mechanisms of liver cancers induced by chronic exposure to alpha-particles from internally deposited Thorotrast." Radiation Measurements 41, no. 9-10 (October 2006): 1186–90. http://dx.doi.org/10.1016/j.radmeas.2006.01.004.
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Grudzińska, M., Katarzyna Jakubowska, M. Koda, L. Koda, W. Kisielewski, N. Smereczański, N. Rogoz-Jezierska, and W. Famulski. "Systemic inflammation markers in blood samples of colorectal cancer patients." Progress in Health Sciences 10, no. 1 (June 11, 2020): 92–101. http://dx.doi.org/10.5604/01.3001.0014.1917.
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Introduction: Colorectal cancer (CRC) is one of the most common cancers in Poland. The aim of this study was to investigate the clinical significance of absolute monocyte count, neutrophil-to-monocyte ratio (NMR) and monocytetolymphocyte ratio (MLR) in pre- and postoperative blood samples of patients with CRC. Materials and Methods: We retrospectively reviewed medical records of 160 patients diagnosed with CRC who underwent surgery. Blood samples were obtained within 3 days before and after the surgical treatment. Venous blood samples were also obtained from 42 healthy controls. Results: Pre- and postoperative NMR were significantly higher than healthy controls (p<0.0001; p<0.0001). Moreover, MLR in pre-and postoperative blood samples were higher than voluntaries (p<0.001; p<0.001). The area under the ROC curve for pre and postNMR showed that the parameter exhibits strong diagnostic power (1.000). Pre- and postMLR had moderate diagnostic power amount 0.751 and 0.746. There is also correlation between monocyte count in samples obtained before and after surgery and, lymph node metastasis and size of lymph node metastasis in both cases. PreNMR value was significantly associated with venous and lymphatic invasion and the presence of cancer deposits. PostNMR was found to correlate with presence of distant metastasis and cancer cell deposits (R=0.633, p<0.001; R=0.158, p=0.040). Moreover, preMLR value was correlated with only perineural invasion. Conclusions: Analyzed hematologic markers may be useful as simply obtained parameters, next to histopathological examination, that determine a systemic immune response
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Chajon, Enrique, Marc Pracht, Thierry De Baere, France Nguyen, Jean-Pierre Bronowicki, Veronique Vendrely, Anne-Sophie Baumann, Valérie Croisé-Laurent, and Eric Deutsch. "A phase I/II trial of NBTXR3 nanoparticles activated by SBRT in the treatment of liver cancers." Journal of Clinical Oncology 36, no. 4_suppl (February 1, 2018): TPS551. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.tps551.
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TPS551 Background: A new class of material with high electron density, hafnium oxide, was designed at the nanoscale (NBTXR3) to efficiently enhance the energy dose deposit from within the tumor cells and increase lethality of tumors, when exposed to radiotherapy (RT). The physical mode of action of NBTXR3 may represent a breakthrough approach for the local treatment of liver cancers, as it does not engage liver and renal functions, i.e. nanoparticles are not metabolized and not excreted by kidney. A phase I/II trial has been implemented for the treatment of hepatocellular carcinoma and liver metastasis [NCT02721056]. The study is currently recruiting patients. Methods: Patients (pts) receive a single intralesional (IL) injection of NBTXR3 (53.3g/L) at Volume levels equivalent to 10%, 15%, 22% and 33% of the baseline tumor volume, followed by RT (SBRT, 45Gy / 3 fractions / 5 to 7 days). For the Phase I part, primary endpoints include determination of the Recommended Dose and Dose Limiting Toxicities (DLT). The Phase II part will test three different groups of patients, HCC with portal vein thrombus, HCC without portal vein thrombus and a third cohort with liver metastases. Primary endpoints are complete response rate and safety. Results: Enrollment was completed for Volume levels 10% (6 pts) and 15% (4 pts) and is currently recruiting patients at 22% level. The NBTXR3 injections were successful in all cases. Radiotherapy has been delivered as planned without any DLT occurrence. No serious adverse event (SAE) related to NBTXR3 or the treatment procedure occurred. Three adverse events related to the injection were reported and no adverse event related to NBTXR3. Importantly, NBTXR3 nanoparticles did not have any impact on the reliability of image-guided radiation therapy (IGRT). Conclusion: The injection of NBTXR3 was safe and well tolerated at these levels. Patients received the planned RT. No DLT occurred. Enrollment is now opened at the 22% level. NBTXR3 shows promising results in terms of safety and antitumor activity and is also currently evaluated in other six clinical studies. Clinical trial information: NCT02721056.
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Lim, Aaron, Benjamin Grant, John Avramovic, Yik-Hong Ho, and Corrine Wallace. "Synchronous Primary Anorectal Melanoma and Sigmoid Adenocarcinoma: A Case Report." International Surgery 100, no. 5 (May 1, 2015): 814–17. http://dx.doi.org/10.9738/intsurg-d-14-00243.
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Synchronous primary anorectal melanoma and colorectal adenocarcinoma is extremely rare, with only 5 cases reported in the literature. Here, a case is reported and the currently available literature is summarized. A 72-year-old white male presented with changes in his bowel habits and unintentional weight loss. Colonoscopy revealed a polypoid mass in the distal rectum extending to the anal verge anteriorly and a circumferential polypoid mass in the distal sigmoid colon. Biopsies were taken, which revealed poorly differentiated melanoma of the anorectal mass and moderately differentiated adenocarcinoma of the sigmoid mass with nodal involvement. Computed tomography of the abdomen showed liver metastasis. An extended abdominoperineal resection was undertaken for palliation, relief of symptoms, and definitive histology to guide further management. Consequently, a resection of the hepatic metastasis was attempted; however, macroscopic deposits were discovered on 7 of 8 liver segments perioperatively. He was subsequently referred to medical oncology for palliative chemotherapy. Synchronous primary anorectal melanoma and colorectal adenocarcinoma is rare, this being the sixth report found in the literature. In summary of the available cases, all synchronous cancers were located in the rectosigmoid and had very similar presentations. Most presented relatively late and were generally treated with abdominoperineal resection, which appears to be the best treatment option. Overall, prognosis appears to be dismal. General and colorectal surgeons should always be aware of the possibilities of simultaneous primary cancers because this can affect treatment modalities and prognosis for the patient.
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Stanojevic, Zorica, Biljana Djordjevic, and Danijela Zivanovic. "Influence of the primary malignant tumor site on the incidence and features of metastatic ovarian tumors." Vojnosanitetski pregled 64, no. 10 (2007): 691–96. http://dx.doi.org/10.2298/vsp0710691s.
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Background/Aim. Ovary is the organ of the female reproductive system most commonly affected by metastases. The aim of the study was to determine the frequency and features of metastatic ovarian tumors (MOT) depending on the site of the primary malignant tumor. Methods. The study group consisted of 488 patients with histopathologically confirmed ovarian cancers treated at the Clinic of Oncology, Clinical Center Nis, in the period from 1 January 1998 to 31 December 2005. MOT were found in 41 patients. Regarding the site of the primary malignant tumor, those with secondary ovarian tumor were divided into two groups: group A - primary malignant tumor involving the genital organs (n = 30) and group B - primary malignant tumor of extragenital origin (n = 11). Results. MOT were confirmed in 8.40% (41/488) of the patients. Secondary ovarian malignancies were the consequence of endometrial carcinoma spreading in 73.17%, breast carcinoma in 19.51%, stomach carcinoma in 4.88% and colon carcinoma in 2.44% of the cases. No significant differences were found between the group A and group B by the factors of age, body mass index, parity and menopausal status. Contrary to the group A, metastatic tumors in the group B patients were more commonly asymptomatic (p < 0.001), bilateral (p < 0.05), with larger ovarian diameter (p < 0.05), associated with ascites (p < 0.001) and abdominal metastases (p < 0.01), all of statistical significance. Conclusions. Metastatic tumors made up 8.40% of ovarian neoplasmas. With non-genital primary tumors, secondary ovarian deposits were frequently asymptomatic, bilateral, associated with larger ovarian diameter, ascites and abdominal metastatic deposits, compared to malignant tumors of genital origin.
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Gajanin, Radoslav, Aleksandar Guzijan, Vesna Gajanin, Igor Sladojevic, and Zelimir Eric. "Jejunal tumor made of primary gastrointestinal stromal tumor and metastatic breast carcinoma - an extremely rare case." Srpski arhiv za celokupno lekarstvo 145, no. 9-10 (2017): 516–21. http://dx.doi.org/10.2298/sarh161107089g.
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Introduction. The occurrence of synchronous or metachronous malignant epithelial and mesenchymal tumors is rare. Infiltrating ductal breast cancer rarely produces metastasis in the gastrointestinal tract, and when it does, it represents a significant differential diagnostic problem. Morphologically, they can mimic primary cancers localized in the gastrointestinal tract or peritoneum. Case outline. In this paper, we present a female patient with primary, synchronous bilateral breast cancer, which after five years of follow-up had given metastases to the lungs, bones, peritoneum and mesentery, and in a node localized in the small intestine. The node was composed of two malignant components ? a mesenchymal one and an epithelial one. The mesenchymal component had histologic and immunophenotypic characteristics of a gastrointestinal stromal tumor and the epithelial component was morphologically and immunohistochemically identical to the diagnosed primary breast cancer. Because of all this, the nodal tumor mass was interpreted as a primary gastrointestinal stromal tumor of the small intestine, in which the deposit of metastatic ductal breast carcinoma was observed. Conclusion. Metastases of breast cancer in organs of the gastrointestinal tract are encountered rarely, mainly in the terminal stage of the disease. In available literature, a case of metastasis of breast cancer (metastasis of malignant epithelial tumors) in gastrointestinal stromal tumor has not been found.
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Shenoy, Ashok M., A. Nanjundappa, Pradeep Kumar, Rekha V. Kumar, B. K. M. Reddy, V. Kannan, and N. Anantha. "Interjugular neck dissection and post-operative irradiation for neck control in advanced glottic cancers – are we justified?" Journal of Laryngology & Otology 108, no. 1 (January 1994): 26–29. http://dx.doi.org/10.1017/s0022215100125745.
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AbstractAt the Kidwai Memorial Institute of Oncology, advanced laryngeal cancers are subjected routinely to primary surgery and/or post-operative radiotherapy (RT). The surgery consists of wide field laryngectomy which entails total laryngectomy, ipsilateral/bilateral thyroid lobectomy, bilateral paratracheal clearance, and bilateral clearance of levels 2, 3 and 4 lymphatics. Post-operative RT is indicated in event of the following histopathological (HPE) situations to consolidate local-regional control: (1) T4 primary; (2) significant subglottic extension; and (3) jugular/paratracheal metastatic deposits. This prospective study highlights the therapeutic efficacy of this protocol at our centre in 45 consecutive T4/T3 glottic cancers and specifically evaluates the role of interjugular dissection and/or post-operative RT in prevention of regional recurrence. Fifty-two per cent of primary lesions needed a post-surgical upstaging as against 14 per cent of the neck lesions. Accordingly 91 per cent of the cases (41/45) qualified for post-operative RT and 82 per cent (37/41) complied with the prescribedschedule. Recurrent disease in the lateral neck was noted in 2/37 who received the prescribed schedule and 1/4 non-compliant cases; while a recurrent central neck disease was noted in 1/37 and 1/4 of these cases respectively. All cases were followed-up for a period of two years and 66 per cent of the evaluable cases for a period of five years. This study confirms conclusively that our treatment schedule yields extremely gratifying two-year local-regional control rates of 89 per cent which translates into a two and five-year actuarial survival rate of 92 and 70 per cent respectively.
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De Baere, Thierry, Marc Pracht, Yann Rolland, Jerome Durand-Labrunie, Nicolas Jaksic, France Nguyen, Jean-Pierre Bronowicki, et al. "Results from the phase I dose-escalation study of the radiation enhancer NBTXR3 for the treatment of HCC and liver metastases." Journal of Clinical Oncology 39, no. 3_suppl (January 20, 2021): 319. http://dx.doi.org/10.1200/jco.2021.39.3_suppl.319.
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319 Background: NBTXR3, a first-in-class radioenhancer composed of functionalized hafnium oxide nanoparticles, is administered by one time intratumoral injection (ITI) and activated by radiotherapy (RT), such as stereotactic body RT (SBRT). NBTXR3 increases RT energy deposit inside tumor cells and subsequently increases tumor cell death compared to RT alone, while sparing healthy tissues. SBRT is well-tolerated in hepatocellular carcinoma (HCC) or liver metastases (mets) and a valuable alternative for patients not eligible for surgery or radiofrequency ablation. However, energy dose deposit to tumor cells is limited due to potential toxicity to surrounding healthy tissues. Patients with unresectable liver cancers including patients with liver or renal dysfunction might benefit from NBTXR3. A Phase 1 clinical trial was conducted to evaluate the safety and Recommended Phase 2 Dose (RP2D) of NBTXR3 activated by SBRT [NCT02721056] in these patients, here we report the results. Methods: A 3+3 dose escalation scheme tested 5 NBTXR3 levels: 10, 15, 22, 33, and 42% of baseline tumor volume. NBTXR3 ITI was followed by SBRT (45 Gy / 3 fractions / 5-7 days or 50 Gy / 5 fractions / up to 15 days) in patients with HCC or liver mets. Primary endpoints included RP2D determination and early DLT incidence. Secondary endpoints include safety profile, liver disease scores evolution, and early efficacy by response rate (mRECIST for HCC/RECIST 1.1 for liver mets). Results: 23 patients were treated: 6 patients at 10% (2 SBRT doses tested due to organ constraints), 4 patients each at 15% and 22% (due to fiducial displacement and ITI shift), 3 patients at 33% and 6 patients at 42%. No early DLT was observed at any dose level. 1 SAE (grade 3 late onset bile duct stenosis) related to NBTXR3 and RT occurred at 22%. There were 11 AEs related to NBTXR3 and/or ITI, of which grade 3 AEs were: 2 abdominal pain (ITI related; 15%) and 1 late onset bile duct stenosis (22%), lesion close to the bile duct. No NBTXR3 or ITI related grade 4-5 AEs were observed. RT related AEs were as expected with SBRT. No clinically meaningful changes in Child-Pugh score or APRI were observed post-treatment. CT-scan showed NBTXR3 present within the tumor without leakage to surrounding healthy tissues. Best observed responses (MRI) in injected target lesions from HCC patients (n = 15) were 5 CRs (33.3%), 5 PRs(33.3%), 1 SD (6.7%), 2 NE (13.3%), 2 patients did not have post baseline MRI and for liver mets (n = 8) were 5 PRs (62.5%), 2 SD (25.0%) and 1 NE (12.5%). Conclusions: No early DLTs were observed and NBTXR3 demonstrated a good safety and tolerability profile. The RP2D was determined to be 42% of tumor volume. Initial efficacy is promising and highlights the potential for NBTXR3 to address an unmet medical need in patients with unresectable primary or metastatic liver cancers. Clinical trial information: NCT02721056.
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Jiang, Jiazhong, Thomas M. Ulbright, Cheryl Younger, Katya Sanchez, David G. Bostwick, Michael O. Koch, John N. Eble, and Liang Cheng. "Cytokeratin 7 and Cytokeratin 20 in Primary Urinary Bladder Carcinoma and Matched Lymph Node Metastasis." Archives of Pathology & Laboratory Medicine 125, no. 7 (July 1, 2001): 921–23. http://dx.doi.org/10.5858/2001-125-0921-cacipu.
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Abstract Background.—Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) are 2 types of intermediate filament protein. Expression of CK7 is seen in the majority of primary urinary bladder carcinomas. CK20 is restricted to superficial and occasional intermediate cells of the normal urothelium of the bladder. Aberrant CK20 expression has been documented in urothelial carcinoma and has proved useful as an ancillary diagnostic aid for urinary bladder tumor. Our hypothesis is that the pattern of CK7 and CK20 expression in metastatic urothelial carcinoma duplicates the expression of the same markers in the primary tumors. Therefore, immunohistochemical staining of metastatic tumors for these 2 markers may be helpful for differential diagnosis in ambiguous metastatic tumor deposits. Objective.—To determine the concordance of CK7 and CK20 expression in primary bladder urothelial carcinoma and the matched lymph node metastasis. Design.—We studied 26 patients with lymph node metastases who underwent radical cystectomy and bilateral lymphadenectomy for bladder carcinoma. Immunohistochemical staining for CK7 and CK20 was performed on formalin-fixed paraffin-embedded tissues containing primary cancers and lymph node metastases. Results.—In all cases, there was a concordant expression of CK20 in the primary cancer and its matched lymph node metastasis. Twelve cases (46%) showed positive CK20 immunoreactivity in the primary tumor and its matched lymph node metastases, whereas 14 cases (54%) were negative for CK20 in both the primary tumor and lymph node metastasis. All cases showed positive CK7 immunoreactivity in the primary cancers and matched lymph node metastases. Conclusions.—CK20 immunoreactivity is reliably observed in metastases from bladder cancer when the primary tumor expresses CK20.
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Guo, Yuxin, and Adrian Jit Hin Koh. "Needle Tract Seeding of Thyroid Follicular Carcinoma after Fine-Needle Aspiration." Case Reports in Otolaryngology 2020 (February 22, 2020): 1–4. http://dx.doi.org/10.1155/2020/7234864.
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Introduction. Fine-needle aspiration (FNA) biopsies are fundamental procedures in the diagnoses of thyroid tumours. Reports of needle tract tumour seeding, however, question its practice regarding patient safety and potentially jeopardizing its widespread usage. Case Report. We describe a case of a 50-year-old lady with known multinodular goitre, and previous fine-needle aspiration (FNA) biopsies of her thyroid nodules in 2010, who developed palpable right neck nodules 8 years after the initial FNA. Imaging and histological biopsies revealed suspicious right sternocleidomastoid (SCM) nodules that are likely needle tract tumour deposits. She underwent a total thyroidectomy with central compartment clearance and excision of the right SCM nodules and received radioactive iodine therapy thereafter. Discussion. Contrary to other forms of malignancies, needle tract seeding is an uncommon occurrence for thyroid cancers. Nevertheless, there is speculation regarding its potential in cutaneous spread of malignancy with studies investigating its optimal techniques and application. Conclusion. While FNA remains an indisputable tool in the management of thyroid tumours, precautions must be taken to safeguard patient safety and improve patient outcomes.
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Kleinstreuer, C., and Z. Zhang. "Targeted Drug Aeroso Deposition Analysis for a Four-Generation Lung Airway Model With Hemispherical Tumors." Journal of Biomechanical Engineering 125, no. 2 (April 1, 2003): 197–206. http://dx.doi.org/10.1115/1.1543548.
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One important research area of broad interest is the development of highly efficient drug delivery systems for desired site deposition and uptake. For example, controlled drug aerosol release and targeting to specific regions of the lung is a novel way to combat lung diseases, diabetes, virus infections, cancers, etc. Determination of feasible air-particle streams is a prerequisite for the development of such delivery devices, say, smart inhalers. The concept of “controlled particle release and targeting” is introduced and results are discussed for a representative model of bronchial lung airways afflicted with hemispherical tumors of different sizes and locations. It is shown that under normal particle inlet conditions a particle mass fraction of only up to 11% may deposit on the surface of a specific tumor with critical radius r/R≈1.25, while a controlled particle release achieves deposition fractions of 35 to 92% for a realistic combination of inlet Stokes and Reynolds numbers, depending mainly on tumor size. Furthermore, with the controlled release and targeting approach nearby healthy tissue is hardly impacted by the typically aggressive drug aerosols. Assuming laminar, quasi-steady, three-dimensional air flow and spherical non-interacting micron-particles in sequentially bifurcating rigid airways, the results were obtained using a validated commercial finite-volume code with user-enhanced programs on a high-end engineering workstation. The new concept is generic and hence should be applicable to other regions of the respiratory system as well.
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Tansi, Felista L., Filipp Fröbel, Wisdom O. Maduabuchi, Frank Steiniger, Martin Westermann, Rainer Quaas, Ulf K. Teichgräber, and Ingrid Hilger. "Effect of Matrix-Modulating Enzymes on the Cellular Uptake of Magnetic Nanoparticles and on Magnetic Hyperthermia Treatment of Pancreatic Cancer Models In Vivo." Nanomaterials 11, no. 2 (February 9, 2021): 438. http://dx.doi.org/10.3390/nano11020438.
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Magnetic hyperthermia can cause localized thermal eradication of several solid cancers. However, a localized and homogenous deposition of high concentrations of magnetic nanomaterials into the tumor stroma and tumor cells is mostly required. Poorly responsive cancers such as the pancreatic adenocarcinomas are hallmarked by a rigid stroma and poor perfusion to therapeutics and nanomaterials. Hence, approaches that enhance the infiltration of magnetic nanofluids into the tumor stroma convey potentials to improve thermal tumor therapy. We studied the influence of the matrix-modulating enzymes hyaluronidase and collagenase on the uptake of magnetic nanoparticles by pancreatic cancer cells and 3D spheroids thereof, and the overall impact on magnetic heating and cell death. Furthermore, we validated the effect of hyaluronidase on magnetic hyperthermia treatment of heterotopic pancreatic cancer models in mice. Treatment of cultured cells with the enzymes caused higher uptake of magnetic nanoparticles (MNP) as compared to nontreated cells. For example, hyaluronidase caused a 28% increase in iron deposits per cell. Consequently, the thermal doses (cumulative equivalent minutes at 43 °C, CEM43) increased by 15–23% as compared to heat dose achieved for cells treated with magnetic hyperthermia without using enzymes. Likewise, heat-induced cell death increased. In in vivo studies, hyaluronidase-enhanced infiltration and distribution of the nanoparticles in the tumors resulted in moderate heating levels (CEM43 of 128 min as compared to 479 min) and a slower, but persistent decrease in tumor volumes over time after treatment, as compared to comparable treatment without hyaluronidase. The results indicate that hyaluronidase, in particular, improves the infiltration of magnetic nanoparticles into pancreatic cancer models, impacts their thermal treatment and cell depletion, and hence, will contribute immensely in the fight against pancreatic and many other adenocarcinomas.
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Shen, Colette, Jessica Frakes, Jiaxin Niu, Jared Weiss, Jimmy Caudell, Katherine Jameson, Patricia Said, and Tanguy Seiwert. "410 Phase I study of intratumoral NBTXR3 in combination with anti-PD-1 in patients with advanced cancers." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (November 2020): A435. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0410.
Full textAbstract:
BackgroundCancer immunotherapies have shown promising clinical outcomes; however, the majority of patients are non-responders or will develop resistance during the course of treatment. One of the current challenges is to increase the response rate to immune checkpoint inhibitors (ICIs). Combining immunotherapy with radiation therapy (RT) is emerging as a valuable strategy to prime the immune response. However, RT dose and ultimate efficacy are limited by toxicity related to exposure of healthy tissues. First-in-class radioenhancer NBTXR3, administered by one-time direct intratumoral injection, is designed at the nanoscale to increase RT dose deposit with subsequent increase in tumor cell killing, without increasing toxicity to normal tissue. Preclinical and early clinical data suggest NBTXR3/RT can prime the immune system and act as an in situ vaccine leading to an anti-tumor immune response, producing both local and systemic (abscopal) effects. We hypothesize NBTXR3/RT in combination with anti-PD-1 (NBTXR3/RT/PD-1), will act synergistically to increase the proportion of ICI responders or convert ICI non-responders to responders.MethodsA multicenter, open-label, phase I trial [NCT03589339] evaluating safety and tolerability of NBTXR3/RT/PD-1 in three cohorts: (1; H&N) Locoregional recurrent or recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) amenable to re-irradiation of the HN field, (2; lung) lung or (3; liver) liver metastases from any primary cancer eligible for approved anti-PD-1 treatment. NBTXR3 injected volume is based on a percentage of baseline tumor volume. Stereotactic body RT (SBRT) is delivered as per standard practice. The primary objective is to determine NBTXR3/RT/PD-1 recommended phase II dose in each cohort. Secondary objectives are to evaluate anti-tumor response (objective response rate), safety and feasibility of NBTXR3 injection, and NBTXR3 body kinetic profile.ResultsTo date 6 patients have been treated: 3 in H&N (2 anti-PD-1 naïve) and 3 in lung (all anti-PD-1 non-responders. No DLT or SAE has been observed. Grade 2 nausea related to NBTXR3 or injection procedure was observed in H&N. 2 H&N patients and 3 lung patients have completed RT and initiated anti-PD-1 treatment. RT-related safety profile was as expected. Tumor shrinkage was observed in 1 anti-PD-1 naive and 2 anti-PD-1 non-responders and additional preliminary efficacy and updated safety results will be presented.ConclusionsTo date, NBTXR3 administration activated by SBRT in combination with anti-PD-1 treatment has been safe and well tolerated in patients with advanced cancers. Promising early signs of efficacy in anti-PD-1 naïve, as well as in patients having progressed on previous anti-PD-1 therapy will be presented.Trial RegistrationNCT03589339Ethics ApprovalThis study was approved by local institution’s review board
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Chen, Su, Minglei Yang, Nanzhe Zhong, Qian Ziliang, Jian Jiao, Yasong Xiao, Dongjie Jiang, et al. "Elevated plasma cell-free DNA copy number variations to predict survival for cancer patient with spinal metastasis." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e14522-e14522. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e14522.
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e14522 Background: Approximately 70% of patients with cancer have evidence of spinal metastatic disease at the time of their deaths. The spinal column is the most common location among osseous sites for metastatic deposits. Expected overall survival is the major determinant of treatments for those ones suffering from intractable pain, neurologic deficits, and even paralysis. We sought to evaluate copy number variations (CNV) in spinal metastatic cancer via cfDNA and determine if CNV is associated with prognosis and treatment decision. Methods: In this study, 314 patients with pathologically confirmed spinal metastatic cancers were recruited since November 2015. 314 plasma samples were sent to low-coverage genome-wide sequencing of cfDNA from plasma followed by a customized bioinformatics workflow UCAD. Tokuhashi score was also evaluated for each patient before surgery. Statistical correlation with clinical index like prognosis was estimated. Results: 280 evaluable data were collected (34 samples failed Quality Control). The median follow-up time is 276 days. 114 (40.7%) patients died during follow up till December the 25th, 2018. Elevated CNVs was found in 109 (38.9%) patients, including 9(69.2%) head&neck, 15(46.9%) liver and gallbladder, 27(44.3%) lung, 7(38.9%) breast, 2(28.6%) prostate, 5(19.2%) thyroid cancer, 4 (10.5%) kidney and 20(40.0%) cancer with unknown primary site. Further analyses showed that patients with elevated CNVs were found with worse survival. The median overall survival (OS) was 298 (95% CI: 258-422) days, as compared with those low-CNVs status with median OS 657 (95% CI:433-NA) days (Hazard ratio = 3.73 [95% CI: 2.22-6.27], P < 0.01). Especially for patients with low Tokuhashi score (≤8) who have the predictive survival less than 6 months, CNVs score distinguish those well-prognosis patients with median OS 433 (95% CI: 308-NA) days from the worse survival group with median OS 285(95% CI:243-348) days (Hazard ratio = 2.42 [95% CI:1.38-4.25], P = 0.013). Conclusions: We present the largest cfDNA genomic characterization of spinal metastatic cancers. Specific CNVs features are enriched in spinal metastasis cancers with different primary sites. Elevated CNVs in plasma cfDNA is significantly associated with worse survival in a large spinal metastatic cancer cohort. This demonstrates that cfDNA CNVs could be a useful marker in estimating the survival time of spinal metastasis cancer patients for whom the outcome is mainly dependent on the selection of proper treatment.
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Shen, Colette, Jessica M. Frakes, Jiaxin Niu, Ari Rosenberg, Jared Weiss, Jimmy J. Caudell, Katherine LaRoque Jameson, Patricia Said, and Tanguy Y. Seiwert. "A phase I trial evaluating NBTXR3 activated by radiotherapy in combination with nivolumab or pembrolizumab in patients with advanced cancers." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 2590. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.2590.
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2590 Background: Immune checkpoint inhibitors (ICIs) targeting PD-1 are an effective treatment for a variety of cancers. However, the majority of patients (pts) exhibit resistance to ICIs. Overcoming this resistance represents a major challenge in immuno-oncology. Emerging evidence suggests radiation therapy (RT) produces an immunomodulatory effect that may act synergistically with ICIs. However, RT dose and ultimate efficacy are limited by toxicity to surrounding healthy tissues. NBTXR3, a novel radioenhancer administered by direct intratumoral injection (ITI), is designed at the nanoscale to increase RT dose deposit within tumor cells and subsequent tumor cell killing, without increasing toxicity to surrounding healthy tissue. Preclinical data suggest NBTXR3/RT can trigger a local and systemic anti-tumor immune response and overcome anti-PD-1 resistance. NBTXR3/RT combined with anti-PD-1 may prime the immune system to increase the proportion of ICI responders, or convert ICI non-responders to responders. Methods: This is a multicenter, open-label, phase I trial [NCT03589339] to evaluate NBTXR3/RT/anti-PD-1 in 3 cohorts: (1) Locoregional recurrent or recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) amenable to HN re-irradiation, and metastases from any primary cancer eligible for anti-PD-1 (nivolumab or pembrolizumab) treatment specifically localized in the lung (2) or liver (3), respectively. Stereotactic body RT (SBRT) is delivered at tumor-site selective doses per standard practice. The primary objective is NBTXR3/RT/anti-PD-1 recommended phase 2 dose in each cohort. Secondary objectives are anti-tumor response (objective response rate), safety and feasibility of NBTXR3 injection. Results: Nine pts have been treated: 3 HNSCC, 4 lung, 2 liver. 7/9 pts were anti-PD-1 non-responders. Overall tumor regression was observed in 8/9 pts. NBTXR3/RT/anti-PD-1 resulted in tumor regression in 6/7 pts who had progressed on prior anti-PD-1. A complete response in the injected lymph node lasting over 1 year was observed in 1 anti-PD-1 naïve pt. 2 SAEs related to anti-PD-1 and possibly related to NBTXR3 (G5 pneumonitis, G4 hyperglycemia) were observed in 1 anti-PD-1 naïve HNSCC pt and considered DLTs. This pt also experienced 2 other SAEs related to anti-PD-1 (G4 diabetic ketoacidosis, G4 acute kidney injury). SBRT-related safety profile was as expected. Updated results will be presented. Conclusions: Data from this first-in-human phase I trial evaluating NBTXR3/RT/anti-PD-1 in pts with advanced cancers, show NBTXR3 ITI is feasible and well-tolerated. NBTXR3/RT/anti-PD-1 demonstrated promising signs of efficacy. Of particular interest, NBTXR3/RT can overcome ICI resistance in pts having progressed on prior anti-PD-1, supporting further development of NBTXR3 in combination with anti-PD-1 as well as other ICIs. Clinical trial information: NCT03589339.
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Puppa, Giacomo, Angelica Sonzogni, Romano Colombari, and Giuseppe Pelosi. "TNM Staging System of Colorectal Carcinoma: A Critical Appraisal of Challenging Issues." Archives of Pathology & Laboratory Medicine 134, no. 6 (June 1, 2010): 837–52. http://dx.doi.org/10.5858/134.6.837.
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Abstract Context.—Colorectal cancer is the leading cause of morbidity and death among gastrointestinal tumors and ranks fourth after lung, breast, and ovarian cancers. Despite a continuous refinement of the T (tumor), N (node), and M (metastasis) staging system to express disease extent and define prognosis, and eventually to guide treatment, the outcome of patients with colorectal cancer may vary considerably even within the same tumor stage. Therefore, the need for new factors, either morphologic or molecular, that could more precisely stratify patients into different risk categories is clearly warranted. Objectives.—To present the state of the art with regard to the colorectal cancer staging system and to discuss confusing and/or challenging issues, including the assessment of peritoneal membrane involvement, vascular invasion, tumor deposits, and pathologic tumor response to neoadjuvant chemoradiotherapy. Data Sources.—Literature review of relevant articles indexed in PubMed (US National Library of Medicine) and primary material from the authors' institutions. Conclusions.—Two emerging needs exist for the TNM system, namely, further stratification of patients with the same tumor stage and incorporation of nonanatomic factors, the latter including molecular and treatment factors. The identification and classification of morphologic features encountered in the pathologic examination of colorectal cancer specimens may be difficult and a source of subjective variability. Enhanced pathologic analysis, agreed-upon standard protocols, and standardization should improve the completeness and accuracy of pathology reports.
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Merrouche, Y., S. Negrier, C. Bain, V. Combaret, A. Mercatello, B. Coronel, J. F. Moskovtchenko, P. Tolstoshev, R. Moen, and T. Philip. "Clinical application of retroviral gene transfer in oncology: results of a French study with tumor-infiltrating lymphocytes transduced with the gene of resistance to neomycin." Journal of Clinical Oncology 13, no. 2 (February 1995): 410–18. http://dx.doi.org/10.1200/jco.1995.13.2.410.
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PURPOSE Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and interleukin-2 (IL-2) has been reported to mediate tumor regression in some human cancers. To define better the biologic characteristics of TIL, especially survival and distribution in vivo, we performed a gene-marker study in patients with advanced malignancies. PATIENTS AND METHODS We treated five patients with metastatic melanoma or renal cell carcinoma with adoptive immunotherapy. TIL were genetically modified, before their infusion, using a recombinant retroviral vector that contained the marker gene coding for resistance to neomycin (NeoR). RESULTS All of the patients tolerated the treatment well and none of the theoretic safety hazards due to the retroviral gene transduction was observed. The presence of the NeoR gene in TIL was detected by Southern blot analysis, with an efficiency of transduction that ranged from 1% to 26%. With polymerase chain reaction (PCR) analysis, we demonstrated that gene-modified TIL can survive for several months after reinjection, since positive blood samples were observed up to day 260 following reinjection. Eight malignant biopsy specimens were obtained from three patients after cell infusion. TIL were detected in only four of these eight tumor deposits on days 7 and 260. CONCLUSION These results confirm the feasibility and safety of using in vitro retroviral gene transduction in human lymphocytes to analyze their in vivo distribution for further therapeutic applications. However, a selective and prolonged retention of TIL at the tumor site was not found in this study.
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Wadhawan, Vinita, Yogesh A. Kolhe, Nikhil Sangith, Amit Kumar Singh Gautam, and Prasanna Venkatraman. "From prediction to experimental validation: desmoglein 2 is a functionally relevant substrate of matriptase in epithelial cells and their reciprocal relationship is important for cell adhesion." Biochemical Journal 447, no. 1 (September 12, 2012): 61–70. http://dx.doi.org/10.1042/bj20111432.
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Accurate identification of substrates of a protease is critical in defining its physiological functions. We previously predicted that Dsg-2 (desmoglein-2), a desmosomal protein, is a candidate substrate of the transmembrane serine protease matriptase. The present study is an experimental validation of this prediction. As demanded by our published method PNSAS [Prediction of Natural Substrates from Artificial Substrate of Proteases; Venkatraman, Balakrishnan, Rao, Hooda and Pol (2009) PLoS ONE 4, e5700], this enzyme–substrate pair shares a common subcellular distribution and the predicted cleavage site is accessible to the protease. Matriptase knock-down cells showed enhanced immunoreactive Dsg-2 at the cell surface and formed larger cell clusters. When matriptase was mobilized from intracellular storage deposits to the cell surface there was a decrease in the band intensity of Dsg-2 in the plasma membrane fractions with a concomitant accumulation of a cleaved product in the conditioned medium. The exogenous addition of pure active recombinant matriptase decreased the surface levels of immunoreactive Dsg-2, whereas the levels of CD44 and E-cadherin were unaltered. Dsg-2 with a mutation at the predicted cleavage site is resistant to cleavage by matriptase. Thus Dsg-2 seems to be a functionally relevant physiological substrate of matriptase. Since breakdown of cell–cell contact is the first major event in invasion, this reciprocal relationship is likely to have a profound role in cancers of epithelial origin. Our algorithm has the potential to become an integral tool for discovering new protease–substrate pairs.
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Benesch, Matthew G. K., Yi M. Ko, Xiaoyun Tang, Jay Dewald, Ana Lopez-Campistrous, Yuan Y. Zhao, Raymond Lai, Jonathan M. Curtis, David N. Brindley, and Todd P. W. McMullen. "Autotaxin is an inflammatory mediator and therapeutic target in thyroid cancer." Endocrine-Related Cancer 22, no. 4 (June 2, 2015): 593–607. http://dx.doi.org/10.1530/erc-15-0045.
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Autotaxin is a secreted enzyme that converts extracellular lysophosphatidylcholine to lysophosphatidate (LPA). In cancers, LPA increases tumour growth, metastasis and chemoresistance by activating six G-protein coupled receptors. We examined >200 human thyroid biopsies. Autotaxin expression in metastatic deposits and primary carcinomas was four- to tenfold higher than in benign neoplasms or normal thyroid tissue. Autotaxin immunohistochemical staining was also increased in benign neoplasms with leukocytic infiltrations. Malignant tumours were distinguished from benign tumours by high tumour autotaxin, LPA levels and inflammatory mediators including IL1β, IL6, IL8, GMCSF, TNFα, CCL2, CXCL10 and platelet-derived growth factor (PDGF)-AA. We determined the mechanistic explanation for these results and revealed a vicious regulatory cycle in which LPA increased the secretion of 16 inflammatory modulators in papillary thyroid cancer cultures. Conversely, treating cancer cells with ten inflammatory cytokines and chemokines or PDGF-AA and PDGF-BB increased autotaxin secretion. We confirmed that this autotaxin/inflammatory cycle occurs in two SCID mouse models of papillary thyroid cancer by blocking LPA signalling using the autotaxin inhibitor ONO-8430506. This decreased the levels of 16 inflammatory mediators in the tumours and was accompanied by a 50–60% decrease in tumour volume. This resulted from a decreased mitotic index for the cancer cells and decreased levels of vascular endothelial growth factor and angiogenesis in the tumours. Our results demonstrate that the autotaxin/inflammatory cycle is a focal point for driving malignant thyroid tumour progression and possibly treatment resistance. Inhibiting autotaxin activity provides an effective and novel strategy for decreasing the inflammatory phenotype in thyroid carcinomas, which should complement other treatment modalities.
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Pullaiah, Nagaraja, Dorai Venkatasekhar, Padarthi Venkatramana, and Balaraj Sudhakar. "Detection of Breast Cancer on Magnetic Resonance Imaging Using Hybrid Feature Extraction and Deep Neural Network Techniques." International Journal of Intelligent Engineering and Systems 13, no. 6 (December 31, 2020): 229–40. http://dx.doi.org/10.22266/ijies2020.1231.21.
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Breast cancer is one of the most occurring cancers in women due to the uncontrolled growth of abnormal cells in the lobules or milk ducts. The treatment for the breast cancer at an early stage is important using Magnetic Resonance Imaging (MRI) which effectively measures the size of the cancer and also checks tumors in the opposite breast. The deposition of calcium components on the breast tissue is known as micro-calcifications. The calcium salts deposited in the breast are involved with the cancer and were not diagnosed accurately due to the low effectiveness of existing imaging technique namely Haralick feature extraction technique. The MRI breast cancer diagnosis creates problems during classification of breast image and leads to misclassifications, such as unidentified calcium deposits in the existing K-Nearest Neighbour (KNN) classifier. The misclassification issues are overcome by an accurate classification and identification of calcium salts and checks whether deposited salt on breast tissue is involved with cancer or not. Initially, Contrast-Limited Adaptive Histogram Equalization (CLAHE) is used to remove the unwanted noise in the MRI and Morphological, Multilevel Otsu’s Thresholding and region growing techniques perform segmentation to mask unwanted breast tissues. The proposed Hybrid LOOP Haralick feature extraction technique is developed by combining the both Local Optimal Oriented Pattern (LOOP) and Haralick texture feature and the hybrid parameters are applied to the Stacked Auto Encoder based (SAE) to classify the breast MRI image as a Malignant or Benign. The performance of the proposed hybrid LOOP Haralick feature extraction shows significant accuracy improvement of 3.83% when compared to the Haralick feature extraction technique.