Journal articles on the topic 'Veterinary cancer care'

Despite the emergence some years ago of oncology as a veterinary specialty, there has been very little in the way of ethical debate on the use of chemotherapy in dogs. The purpose of this article is to undertake an ethical analysis to critically examine the use of chemotherapy to prolong the life of dogs suffering from cancer. If dogs have no concept of the future and are likely to suffer at least some adverse effects with such treatments, consideration should be given as to whether it is ethical and in the animal’s best interests to use chemotherapy. Chemotherapeutic drugs are mutagenic, carcinogenic, teratogenic and may be irritant. Furthermore, chemotherapy may involve multiple trips to the veterinarian, multiple procedures and periods in isolation. Cancer-associated pain has been shown to be under-diagnosed and pet owners overestimate the effects of chemotherapy on treatment survival time. Of additional concern is the public health risks associated with chemotherapeutic drugs. As chemotherapy is not generally considered curative, it is in effect palliative care. However, palliative care may not be in the best interests of a terminally ill animal. As the specialty of veterinary oncology continues to grow and as the use of chemotherapy becomes more commonplace in the treatment of animals with cancer, it is imperative that there is an ongoing ethical debate on the use of chemotherapy in animals.

Dogs are second only to humans in medical surveillance and preventative health care, leading to a recent perception of increased cancer incidence. Scientific priorities in veterinary oncology have thus shifted, with a demand for cancer genetic screens, better diagnostics, and more effective therapies. Most dog breeds came into existence within the last 300 years, and many are derived from small numbers of founders. Each has undergone strong artificial selection, in which dog fanciers selected for many traits, including body size, fur type, color, skull shape, and behavior, to create novel breeds. The adoption of the breed barrier rule—no dog may become a registered member of a breed unless both its dam and its sire are registered members—ensures a relatively closed genetic pool within each breed. As a result, there is strong phenotypic homogeneity within breeds but extraordinary phenotypic variation between breeds. One consequence of this is the high level of breed-associated genetic disease. We and others have taken advantage of this to identify genes for a large number of canine maladies for which mouse models do not exist, particularly with regard to cancer.

AbstractTransitional cell carcinoma (TCC), is the most common form of urinary bladder cancer in dogs and represents 2% of all reported canine cancers. Canine TCC is usually a high-grade invasive cancer and problems associated with TCC include urinary tract obstruction and distant metastases in more than 50% of affected dogs. TCC is most commonly located in the trigone region of the bladder precluding complete surgical resection. Current treatment options for TCC in dogs include medical therapy, surgery or radiation. Mycobacterium Cell Wall Fraction (MCWF) is a biological immunomodulator derived from non-pathogenic Mycobacterium phlei. MCWF possesses a potential in multiple veterinary areas such as anticancer therapy, palliative care and treatment of infectious diseases in both small and large animals. MCWF is considered a bifunctional anti-cancer agent that induces apoptosis of cancer cells and stimulates cytokine and chemokines synthesis by cells of the immune system. Here we report the results from in vitro and in vivo studies that could suggest use of MCWF as an additional treatment option for TCC in dogs. Particularly, we demonstrated that MCWF induces a concentration dependent inhibition of proliferation of K9TCC cells which was associated with the induction of apoptosis as measured by the proteolytic activation of caspase-3 and the degradation of PARP. Furthermore, we demonstrated the safety and potential for in vivo MCWF treatment efficacy in dogs bearing stage T2 TCC by reducing clinical signs, and improving the quality of life in dogs with TCC.

Naturally occurring cancers in non-laboratory species have great potential in helping to decipher the often complex causes of neoplasia. Wild animal models could add substantially to our understanding of carcinogenesis, particularly of genetic and environmental interactions, but they are currently underutilized. Studying neoplasia in wild animals is difficult and especially challenging in marine mammals owing to their inaccessibility, lack of exposure history, and ethical, logistical and legal limits on experimentation. Despite this, California sea lions ( Zalophus californianus ) offer an opportunity to investigate risk factors for neoplasia development that have implications for terrestrial mammals and humans who share much of their environment and diet. A relatively accessible California sea lion population on the west coast of the USA has a high prevalence of urogenital carcinoma and is regularly sampled during veterinary care in wildlife rehabilitation centres. Collaborative studies have revealed that genotype, persistent organic pollutants and a herpesvirus are all associated with this cancer. This paper reviews research to date on the epidemiology and pathogenesis of urogenital carcinoma in this species, and presents the California sea lion as an important and currently underexploited wild animal model of carcinogenesis.

ABSTRACT The osteosarcoma (OSA) is the most diagnosed primary bone cancer in canine patients. This work reports a case of a canine, six years old, mongrel, female, intact, with an OSA in the hard palate. Physical examination detected a firm mass in the palate. Thoracic radiographs, hematological and biochemical exams, histopathological exams and computed tomography were requested. A chondroblastic OSA was diagnosed and the tumor was characterized by immunohistochemistry. There was never evidence of metastasis in this case. The treatment consisted of the combination of conventional chemotherapy, metronomic chemotherapy, and palliative care, aiming at greater survival and well-being of the patient since surgical excision was not possible due to the location and extension of the tumor. Osteogenic sarcomas of the hard palate are rarely seen and described in the literature. In this article we present a characterization of the osteosarcoma with uncommon localization in the hard palate.

Background: Clients who seek veterinary care for pets with cancer are often concerned about the potential negative impact of chemotherapeutic treatments on their animals’ quality of life. A consensus currently exists in veterinary oncology regarding the quantification and rating of adverse treatment effects in dogs and cats in response to chemotherapy agents. This grading system is referred to as Veterinary Cooperative Oncology Group - Common Terminology Criteria for Adverse Events. The purpose of this retrospective case series was to investigate the delayed acute effects of chemotherapy drugs in cats receiving cancer treatment.Materials, Methods & Results: Medical records were reviewed to determine the chemotherapy agent used and delayed adverse effects. Side effects were classified according to Veterinary Co-operative Oncology Group grading. All cats were evaluated after the first chemotherapy administration, after a single dose. The reported effects included hematologic effects (e.g., neutropenia, thrombocytopenia, increases in liver enzymes, and azotemia), gastrointestinal effects (e.g., vomiting, diarrhea, and inappetence), and sepsis. All of the cats in this study received ondansetron and omeprazol in the first five days following chemotherapy administration. If vomiting occurred with oral medication, maropitant was administered subcutaneously for three consecutive days. If diarrhea (> grade II) occurred, probiotics were administered for seven days. Hematologic examination was performed 3-14 days after chemotherapy. If neutropenia (> grade III) occurred, Human granulocyte colony stimulating factor was administered subcutaneously for three consecutive days together with prophylactic antibiotics. Lomustine, carboplatin, vincristine, doxorubicin, cyclophosphamide, mitoxantrone, and vinblastine were administered in 33%, 19%, 16%, 5%, 16%, 10% and 2% of the cases examined, respectively. The most common adverse events were vomiting, inappetence, neutropenia, and thrombocytopenia. Vomiting occurred in 6% cases, most of them associated with cyclophosphamide. Inappetence/anorexia affected 12% of the cases, mostly those involving cyclophosphamide or doxorubicin. Neutropenia was observed in 22% of the cases, with cyclophosphamide, followed by carboplatin and lomustine. According to the current grading system of adverse effects induced by chemotherapy, grade I toxicity was observed in 83% of the cases, whiles grade II-IV were observed in 7%, 8%, and 2% of the cases examined, respectively.Discussion: In general, the chemotherapy regimens in the cases examined were well tolerated. The toxicity experienced was infrequent and mostly mild, thereby resulting in satisfactory tolerability of the chemotherapy regimens. According to the current grading system for the adverse effects of chemotherapy, 83% of the cases examined included grade I, indicating that most of the cats experienced asymptomatic, or mild symptoms, and medical intervention was not needed. In previous studies of dogs and cats, a severe adverse event following chemotherapy was reported for fewer than 1 in 4 animals, and approximately 3-5% experienced a serious adverse event that led to hospitalization. In the present study, 2% of the cats experienced serious or life threatening adverse events. The only chemotherapeutic agent that was associated with inappetence, vomiting, and neutropenia was cyclophosphamide. Based on the data examined, we would recommend that cyclophosphamide should be used with caution for the treatment of cancer in cats, with adequate antiemetic and nutritional support available if needed. In addition, febrile neutropenia/sepsis may be avoided by using a fractionated schedule.

ABSTRACT All companion animal practices will be presented with oncology cases on a regular basis, making diagnosis and treatment of cancer an essential part of comprehensive primary care. Because each oncology case is medically unique, these guidelines recommend a patient-specific approach consisting of the following components: diagnosis, staging, therapeutic intervention, provisions for patient and personnel safety in handling chemotherapy agents, referral to an oncology specialty practice when appropriate, and a strong emphasis on client support. Determination of tumor type by histologic examination of a biopsy sample should be the basis for all subsequent steps in oncology case management. Diagnostic staging determines the extent of local disease and presence or absence of regional or distant metastasis. The choice of therapeutic modalities is based on tumor type, histologic grade, and stage, and may include surgery, radiation therapy, chemotherapy, immunotherapy, and adjunctive therapies, such as nutritional support and pain management. These guidelines discuss the strict safety precautions that should be observed in handling chemotherapy agents, which are now commonly used in veterinary oncology. Because cancer is often a disease of older pets, the time of life when the pet–owner relationship is usually strongest, a satisfying outcome for all parties involved is highly dependent on good communication between the entire healthcare team and the client, particularly when death or euthanasia of the patient is being considered. These guidelines include comprehensive tables of common canine and feline cancers as a resource for case management and a sample case history.

The Golden Retriever Lifetime Study (GRLS) is the first prospective longitudinal study attempted in veterinary medicine to identify the major dietary, genetic and environmental risk factors for cancer and other important diseases in dogs. The GRLS is an observational study that will follow a cohort of 3000 purebred Golden Retrievers throughout their lives via annual online questionnaires from the dog owner and annual physical examinations and collection of biological samples by the primary care veterinarian. The field of comparative medicine investigating naturally occurring disorders in pets is specifically relevant to the many diseases that have a genetic basis for disease in both animals and humans, including cancer, blindness, metabolic and behavioural disorders and some neurodegenerative disorders. The opportunity for the GRLS to provide high-quality data for translational comparative medical initiatives in several disease categories is great. In particular, the opportunity to develop a lifetime dataset of lifestyle and activity, environmental exposure and diet history combined with simultaneous annual biological sample sets and detailed health outcomes will provide disease incidence data for this cohort of geographically dispersed dogs and associations with a wide variety of potential risk factors. The GRLS will provide a lifetime historical context, repeated biological sample sets and outcomes necessary to interrogate complex associations between genes and environmental influences and cancer.

It is well documented that diet restriction (DR) increases life expectancy, slows aging, and decreases the incidence of a variety of age-associated diseases including cancer and chemical-induced carcinogenesis. With regard to chemical toxicity, very few studies have attempted to investigate the effects of DR on noncancer toxicity outcomes. This review summarizes the findings of how DR influences acute toxicity outcomes and mechanisms. DR-induced protection in ozone lung inflammation, acute toxicity of isoproterenol, ganciclovir-, aspirin-and acidified ethanol-induced gastric injury are discussed. Because similar physiologic mechanisms exist in humans, DR, if practiced as a fife-style option, may improve quality of life in addition to accruing savings in burgeoning health care costs. Finally, these studies may be of value in boosting research in the area of pharmacology and therapeutics in developing potential therapeutic and safety assessment tools in human and veterinary medicine.

Background: Since 2006 there have been increased reports of severe agranulocytosis and vasculitis associated with levamisole use. Historically, levamisole was an immunomodulatory agent used in various cancer treatments in the United States. Currently the drug is used as an antihelminthic veterinary medication, but it is also used as an additive in freebase cocaine. There are multiple reports of levamisole-induced vasculitis in the head and neck but limited reported cases in the lower extremities. This article describes a 60-year-old woman who presented to the emergency department with multiple painful lower-extremity ulcerations. Results: Radiographs, laboratory studies, and punch biopsy were performed. Physical examination findings and laboratory results were negative for signs of infection. Treatment included local wound care and education on cocaine cessation, and the patient was transferred to a skilled nursing facility. Her continued use of cocaine, however, prevented her ulcers from healing. Conclusions: Local wound care and cocaine cessation is the optimal treatment for levamisole-induced lesions. With the increase in the number of patients with levamisole-induced vasculitis, podiatric physicians and surgeons would benefit from the immediate identification of these ulcerations, as their appearance alone can be distinct and pathognomonic. Early identification of levamisole-induced ulcers is important for favorable treatment outcomes. A complete medical and social history is necessary for physicians to treat these lesions with local wound care and provide therapy for patients with addictions.

GRID directs alternating regions of high- and low-dose radiation at tumors. A large animal model mimicking the geometries of human treatments is needed to complement existing rodent systems (eg, microbeam) and clarify the physical and biological attributes of GRID. A pilot study was undertaken in pet dogs with spontaneous soft tissue sarcomas to characterize responses to GRID. Subjects were treated with either 20 Gy (3 dogs) or 25 Gy (3 dogs), delivered using 6 MV X-rays and a commercial GRID collimator. Acute toxicity and tumor responses were assessed 2, 4, and 6 weeks later. Acute Radiation Therapy Oncology Group grade I skin toxicity was observed in 3 of the 6 dogs; none experienced a measurable response, per Response Evaluation Criteria in Solid Tumors. Serum vascular endothelial growth factor, tumor necrosis factor α, and secretory sphingomyelinase were assayed at baseline, 1, 4, 24, and 48 hours after treatment. There was a trend toward platelet-corrected serum vascular endothelial growth factor concentration being lower 1 and 48 hours after GRID than at baseline. There was a significant decrease in secretory sphingomyelinase activity 48 hours after 25 Gy GRID ( P = .03). Serum tumor necrosis factor α was quantified measurable at baseline in 4 of the 6 dogs and decreased in each of those subjects at all post-GRID time points. The new information generated by this study includes the observation that high-dose, single fraction application of GRID does not induce measurable reduction in volume of canine soft tissue sarcomas. In contrast to previously published data, these data suggest that GRID may be associated with at least short-term reduction in serum concentration of vascular endothelial growth factor and serum activity of secretory sphingomyelinase. Because GRID can be applied safely, and these tumors can be subsequently surgically resected as part of routine veterinary care, pet dogs with sarcomas are an appealing model for studying the radiobiologic responses to spatially fractionated radiotherapy.

Selective breeding for desirable traits in strictly controlled populations has generated an extraordinary diversity in canine morphology and behaviour, but has also led to loss of genetic variation and random entrapment of disease alleles. As a consequence, specific diseases are now prevalent in certain breeds, but whether the recent breeding practice led to an overall increase in genetic load remains unclear. Here we generate whole genome sequencing (WGS) data from 20 dogs per breed from eight breeds and document a ~10% rise in the number of derived alleles per genome at evolutionarily conserved sites in the heavily bottlenecked cavalier King Charles spaniel breed (cKCs) relative to in most breeds studied here. Our finding represents the first clear indication of a relative increase in levels of deleterious genetic variation in a specific breed, arguing that recent breeding practices probably were associated with an accumulation of genetic load in dogs. We then use the WGS data to identify candidate risk alleles for the most common cause for veterinary care in cKCs–the heart disease myxomatous mitral valve disease (MMVD). We verify a potential link to MMVD for candidate variants near the heart specific NEBL gene in a dachshund population and show that two of the NEBL candidate variants have regulatory potential in heart-derived cell lines and are associated with reduced NEBL isoform nebulette expression in papillary muscle (but not in mitral valve, nor in left ventricular wall). Alleles linked to reduced nebulette expression may hence predispose cKCs and other breeds to MMVD via loss of papillary muscle integrity.

Background: The companion animal market has changed over the years. The number of people living in small apartments has increased; as a result, the demand for small pets such as exotics, fish, and small rodents has also increased due to their smaller space requirements and ease of handling and care. Pets help relieve anxiety and stress in people suffering from social issues. Small rodents are usually bred in specific cages with cellulose or wood shaving bedding, and fed with commercially available diets. Small rodent clinics struggle due to the lack of scientific reports on some diseases and therapies. To date, the oncology literature is too limited to develop better diagnosis and treatment methods. Here, we report three cases of squamous cell carcinoma in the mandibular region of Chinese hamsters (Cricetulus griseus).Case: Three adult male hamsters averaging 1.5 years old, from different pet stores, bred under home conditions by different owners in Sergipe, Brazil, were brought to the Dr. Vicente Borelli Hospital at Pio X University for exotic veterinary care. Each animal had been bred alone in a specific breeding cage. Each had a history of apathy, loss of appetite, andrapid deformity of the facial region. Radiographs showed areas of bone involvement and extensive injury, with partial resorption of the left ramus and angle of the mandibular region. Due to the location of the tumor mass, the clinical status, and limitations in systemic treatment, euthanasia was recommended for each animal. After anamnesis, the animals weresubjected to clinical assessment. A firm and well-circumscribed mass was identified on palpation. In case A, it compromised the left mandible from the angle to the body and extended to the maxillary soft tissues and left superior lips. In case B, it extended from the ramus to the symphysis on the left side and to the maxillary region, similar to case A. In case C,it extended on both sides of the mandible symphysis, with no alterations in the maxillary soft tissues. Following clinical examination, each animal underwent laterolateral and dorsoventral radiographic examination; no images were suggestive of pulmonary metastasis. However, an expansive mandibular lesion with partial resorption, suggestive of bone neoplasia,was detected. The animals were dehydrated and in clinical distress, and euthanasia was recommended. Histopathological examination of samples from the tumor sites revealed moderate cellular and nuclear pleomorphism and proliferation of neoplastic keratinocytes, suggestive of squamous cell carcinoma, a malignant tumor of epidermal keratinocytes with a highly invasive and aggressive nature.Discussion: The number of reports in the literature of cancer in small rodent companion animals has lead us to believe that neoplasms in these animals are misdiagnosed and/or that their prevalence is underreported. The literature describes that the tumor incidence in hamsters is 3-40%, and that the incidence is higher in male rodents. This incidence range increases the analysis of cancer in these animals from rare to middle-frequent what do not contribute to the animals’ clinics and to small rodent therapeutics. Differential diagnosis of squamous cell carcinoma and other tumor types should be addressed, especially osteosarcomas. Histopathological examination is essential to clarify the etiopathogenesis.Keywords: rodents, neoplasm, keratinocytes.

<p>This paper aimed to evaluate the use of thermography as an aid method for the early diagnosis of breast cancer in female dogs assisted at the Veterinary Hospital of IFPB Campus Sousa. Five female dogs diagnosed clinically with mammary neoplasia were selected for this study. The protocol was listed in the chronological order of medical care: anamnesis, physical examination of the tumours, thermography, surgery and collection of material for histopathological examination. Patients underwent thermographic examination with the Flir® Thermovisor equipment, model T420. The examination took place in an acclimatized room and upon permission of the animal’s tutor. 60% were pure breed female dogs. Tumours were observed in three non-castrated female dogs and two castrated ones. The masses exhibited three macroscopic presentation patterns. The majority of them were nodular, followed by pendular and flat. Masses in animal 1 showed no increase in volume and there was no difference in temperature between the breast affected by neoplasia and healthy one, whereas for animals 2, 3, 4 and 5 there was an increase in temperature of 0.6ºC, 1.0°C, 1.2°C and 2.3°C, respectively. Three different types of carcinoma were found according to histopathological examination: complex carcinoma, tubular and tubulo-papillary carcinoma. In 100% of the animals the lesions were malignant, reporting high frequency of malignant epithelial tumours in the canine species. Based on these results, it was concluded that no direct relationship was found between the thermographic imaging pattern among the types of malignant mammary tumours in female dogs. Therefore, the conception of new studies on the matter is necessary due to the small number of animals on this research, where it was not possible to affirm the capacity of the thermography in the early differentiation of the malignancy of the masses. Future researches in oncology will promote a better understanding of the pathological aspects related to mammary tumours.</p>

Prostate cancer is the most common prostate disease diagnosed in castrated dogs. However, prostate cancer is considered to be quite rare in dog population. The presence of prostate tumours can lead to urethral obstruction. Other clinical signs include asymmetric, painful, hard growths on rectal examination, neurological deficit or lameness of the pelvic limbs and general symptoms such as anorexia, weight loss or difficult urination. The neoplastic process may spread to the neighbouring organs and give metastases to the lymph nodes, lungs and skeletal system. Patient with histopathologically confirmed prostate cancer should be examined for metastases. The prognosis is usually unfavourable because of late diagnosis and the presence of metastases. Therapeutic options include surgery, chemotherapy and radiotherapy. Complete prostatectomy carries with it many complications and often requires osteotomy of pelvic fusions. For that reason, total prostatectomy is not commonly performed in companion animals; however, it should be considered in cases of early detection with the absence of metastases. This report presents the procedure of a complete prostatectomy in a dog with a pre-pubic anastomosis of the urethra, without osteotomy of the pelvic septum. The anastomosis of the urinary tract was placed outside the abdominal cavity, caudally from the laparotomy wound. The presented technique seems to be appropriate for the treatment of malignant tumours of the prostate gland in dogs.

Veterinary staff could be in frequent exposure to a variety of physical, chemical and biological hazards. Epidemiologic studies have showed that veterinarians are at increased risk of many occupational illnesses such as dermatoses, respiratory tract illnesses, zoonotic infections, acute pesticide-associated toxicity, fetal loss and site-specific cancers. Most biological hazards are distributed in the form of aerosols in the workplaces. This study intended to investigate the potential occupational hazards faced by veterinarians in small-animal practices through field sampling for microbial pathogens in their working environment. Sampling of bacterial and fungal bioaerosols was carried out using an SKCⓇstandard biostage impactor at an air-flow rate of 28.3[Formula: see text]L[Formula: see text]min[Formula: see text] by a vacuum pump through 400 (0.25-mm) holes for 30[Formula: see text]s. Identification of microbial organisms was carried out by DNA extraction and sequencing for 16S and 18S ribosomal DNA of bacteria and fungi. The results showed the bacteria that occurred most frequently in the sampled hospitals were Micrococcus spp. and Staphylococcus spp., and the fungi were Coriolopsis spp. and Microporus spp. Although some of these microbiota were zoonotic, there were no virulent pathogens identified. Our results revealed the possible biological risks for the veterinary workers in small animal hospitals in Taiwan. Proper disinfection and sterilization procedures in workplaces with health education to the animal care workers shall protect them from the occupational injuries.

BackgroundCancer immunotherapies are dependent on endogenous biomarker expression and other biological factors that often result in varying response rates across tumor types and benefit only a subset of patients. Conversely, conventional cytotoxics, the first-line treatment against solid tumors, are effective in a large patient population, but lack specificity, and often result in dose-limiting systemic toxicity. Here, we present SQ3370, a modular approach that activates doxorubicin (Dox) directly at the tumor site with reduced toxicity and potentially activates an immune response against tumor. The technology is independent of biomarkers, enzymatic activity, pH or oxygen levels and is hence expected to be effective in a wider group of patients. SQ3370 consists of a local intratumoral injection of a prodrug-capturing biomaterial (SQL70) followed by 5 daily infusions of SQP33, an attenuated prodrug of Dox. Complementary click chemistry groups in both components allow active Dox release at the tumor site (figure 1). SQP33 prodrug is ~82-fold less cytotoxic than Dox in vitro. We safely administered SQ3370 in dogs at 8.95-times the veterinary clinical dose of Dox, thus widening the therapeutic window, and showed minimal side effects including cardiotoxicity and immunosuppression. We hypothesize that releasing Dox at a local site with SQ3370 may also promote immune activation against the tumor. We evaluated this in a dual-tumor model of syngeneic MC38 tumors.MethodsImmunocompetent mice were inoculated with MC38 tumor cells in two subcutaneous flanks. One tumor was intratumorally injected with the biomaterial, SQL70. SQP33 prodrug, control Dox, or saline was administered intravenously as per treatment schedule (figure 2A). Tumors harvested from a subset of mice at 2 weeks were assessed for immune biomarkers.ResultsIn mice bearing two tumors, SQ3370 significantly increased overall survival and the anti-tumor response against injected tumors (figure 2B,C). Surprisingly, SQ3370 also induced regression of the non-injected tumors (figure 2D). Assessment of tumor-Infiltrating immune cells showed an increase in CD3+, CD4+, and CD8+ T cells and a decrease in regulatory T cells in both injected and non-injected lesions (figure 3). The T-cell response correlated with the anti-tumor efficacy data, supporting the immune activation hypothesis.Abstract 82 Figure 1SQ3370 Components and administrationSQ3370 consists of a local intratumoral injection of a prodrug-capturing biomaterial (named SQL70; shown in step 1) followed by 5 daily systemic infusions of SQP33, an attenuated prodrug of doxorubicin (step 2). Complementary chemical groups in the two components allow the local capture of the prodrug (step 3) and trigger release of active doxorubicin at the tumor site (step 4).Abstract 82 Figure 2Systemic anti-tumor response and improved survivalImmunocompetent C57BL/6 mice were inoculated with mouse MC38 tumors. Tumors were implanted on Day 0. Treatments started on Day 7 with local injection of SQL70 biomaterial at ‘injected’ tumor, followed by systemic administration of saline, Dox, or SQP33 prodrug (A). Median overall survival (B) was significantly higher with SQ3370 as compared to Dox, as determined by Logrank test. Injected tumor response (C) was also significantly better with SQ3370, as assessed by corrected t tests, and non-injected tumors (D) showed a favorable response only with SQ3370. Injected-tumor growth curves show mean ± SEM, and growth curves for non-injected tumors show the percent change in tumor size from initial measurement. Curves stopped when a mouse died, or its tumor volume reached 2000 mm3.Abstract 82 Figure 3Tumor-infiltrating immune cells in both tumorsTumor samples were stained with antibodies and analyzed by multicolor flow cytometry. Dead cells were excluded from analysis. Results show mean ± SEM (n = 3–5 per group) as a percentage of total or marker-gated (CD4 or CD8) cells obtained from the tumor sample. Statistical significance was assessed using a corrected t test.ConclusionsSQ3370 is a proof of concept example for a novel modular approach that addresses limitations of current immuno- and cytotoxic therapies for patients with solid tumors. Local release of Dox with SQ3370 expands the therapeutic window of Dox, minimizes toxicities and leads to a robust anti-tumor response that potentially also causes immune activation against the tumors.AcknowledgementsThe authors would like to thank the National Institutes of Health (NIH), the National Science Foundation (NSF), and Y Combinator.Ethics ApprovalThis study, project number: SQI-FFS-ON-20181119_04_v4, was approved by the Institutional Animal Care and Use Committee (IACUC) of the vendor, following the guidance of Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC), accreditation number 001516.

The British mycologist, I.B. Pole-Evans, was appointed as the first South African government mycologist in 1905 following the Anglo-Boer War (1899-1902). The Onderstepoort Veterinary Research Institute was founded in 1908 with the Swiss veterinarian, Arnold Theiler, as the first director. Thus, the stage was set for the commencement of mycotoxicological research when the Union of South Africa came into being in 1910. The first accounts of this pioneering research appeared in the 'Seventh and eight reports of the Director of Veterinary Research, Union of South Africa. 1918' in which D.T. Mitchell reported on the experimental reproduction of the neurotoxic syndrome, diplodiosis, in cattle with pure cultures of Stenocarpella maydis (= Diplodia zea) isolated by P.A. Van der Bijl and grown on sterile maize kernels. This is the first report of the experimental reproduction of a veterinary mycotoxicosis with a pure culture of a fungus in South Africa and possibly in the world. This seminal research was followed by a great deal of multidisciplinary research on veterinary mycotoxicoses as well as human syndromes in which fungal toxins are suspected to be involved, taxonomy of mycotoxigenic fungi and chemistry of mycotoxins in South Africa. The mycotoxicoses studied in South Africa include the following (more or less in chronological order): diplodiosis, Paspalum staggers, aflatoxicosis, human hepatocellular carcinoma, ochratoxicosis, lupinosis, facial eczema, tremorgenic mycotoxicosis, hyperoestrogenism, stachybotryotoxicosis, ergotism, leukoencephalomalacia and human oesophageal cancer. A major breakthrough in mycotoxicological research was made in South Africa in 1988 with the isolation and chemical characterisation of the carcinogenic fumonisins produced by Fusarium verticillioides in maize. Current research at the PROMEC Unit of the South African Medical Research Council on the risk assessment of fumonisins and intervention methods to reduce fumonisin intake by rural populations on a maize staple diet is highlighted. This paper concludes with a selected list of mycotoxicological publications by South African mycologists/plant pathologists, veterinarians and chemists/biochemists.

BackgroundCancer immunotherapies have been very successful in recent times; however, they benefit only a subset of patients and have varying response rates across tumor types. Conversely, conventional chemotherapies are effective in a large group of patients, but have limited dosing capabilities, lack specificity, and often result in systemic adverse events. Here, we present SQ3370, a novel approach that activates doxorubicin (Dox) at the tumor site while avoiding systemic toxicities commonly associated with the therapy, and also potentially activates an immune response against tumors. SQ3370 is based on a local intratumoral injection of a prodrug-capturing biomaterial (SQL70) followed by 5 daily systemic infusions of an attenuated form of Dox (SQP33). Mutually-reactive click chemistry groups in the 2 components allow the capture and release of active Dox at the tumor site. While conventional Dox is known to induce immune activation1 and enhance tumor responsiveness to checkpoint inhibitors,2 its benefit is limited by cumulative dose cardiotoxicity. We safely administered SQ3370 in dogs at 8.95-times the veterinary clinical dose of Dox with minimal side effects including cardiotoxicity and immunosuppression. In syngeneic mouse models, SQ3370 improved overall survival and induced a robust anti-tumor response against the biomaterial-injected lesion compared to conventional Dox. Surprisingly, SQ3370 also induced regression of the non-injected tumor and enhanced T-cell infiltration in both injected and noninjected tumors. We hypothesize that activating Dox at a local site with SQ3370 promotes activation of the native immune system against the tumor. Thus, SQ3370 represents a new therapeutic modality to treat solid tumors by using a drug with known efficacy, Dox, and expanding its therapeutic window. SQ3370 could potentially also benefit patients with widely disseminated or micro-metastatic lesions.MethodsSQ3370-001 (NCT04106492), the first-in-human Phase 1 study, is currently open in the United States and Australia to treat patients with advanced solid tumors. SQ3370-001 is enrolling patients ≥ 18 years of age with an injectable local or metastatic lesion, for which published data indicates responsiveness to anthracyclines. Patients must be relapsed or refractory following standard of care therapy and must not have received more than 225 mg/m2 of Dox (or equivalent anthracycline). Each cycle will be for 21 days with no limit on total cycles. Primary objectives include determining the safety, tolerability, and recommended Phase 2 dose. Additional objectives include assessment of the pharmacokinetic profile, preliminary efficacy per RECIST 1.1, and immune response.ResultsN/AConclusionsN/AAcknowledgementsThe authors would like to thank the National Institutes of Health (NIH), the National Science Foundation (NSF), and Y Combinator.Ethics ApprovalThis study was approved by:1. The Institutional Review Board (IRB) of Stanford University; eProtocol Number: 54928.2. The IRB of The University of Texas MD Anderson Cancer Center; IRB ID Number: 2020-0185_MOD001.3. Western IRB, on behalf of The Angeles Clinic and Research Institute and Henry Ford Health System IRB Office; IRB Tracking Number: 20200758.4. Bellberry Limited Human Research Ethics Committee, on behalf of Royal North Shore Hospital and Chris O’Brien Lifehouse; Application Number: 2019-10-848.ReferencesMattarollo SR, Loi S, Duret H, Ma Y, Zitvogel L, Smyth MJ. Pivotal role of innate and adaptive immunity in anthracycline chemotherapy of established tumors. Cancer Res 2011;71:4809–4820.Zitvogel L, Galluzzi L, Smyth MJ, Kroemer G. Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. Immunity 2013;39:74–88.

Malignant neoplasms arising from epithelial cells are called carcinomas. Such cancers are diagnosed in about one in three humans in ‘developed’ countries, with the most common sites affected being lung, breast, prostate, colon, ovary and pancreas. By contrast, carcinomas are said to be rare in captive chimpanzees, which share more than 99% protein sequence homology with humans (and possibly in other related ‘great apes’—bonobos, gorillas and orangutans). Simple ascertainment bias is an unlikely explanation, as these nonhuman hominids are recipients of excellent veterinary care in research facilities and zoos, and are typically subjected to necropsies when they die. In keeping with this notion, benign tumours and cancers that are less common in humans are well documented in this population. In this brief overview, we discuss other possible explanations for the reported rarity of carcinomas in our closest evolutionary cousins, including inadequacy of numbers surveyed, differences in life expectancy, diet, genetic susceptibility, immune responses or their microbiomes, and other potential environmental factors. We conclude that while relative carcinoma risk is a likely difference between humans and chimpanzees (and possibly other ‘great apes’), a more systematic survey of available data is required for validation of this claim.

Visceral hemangiosarcoma (HSA) is one of the more frequent cancers in dogs and has a high metastatic rate and poor prognosis, as clinical signs only become apparent in advanced stages of tumor development. In order to improve early and differential diagnostic capabilities and hence, prognosis for dogs with HSA, two types of biomarker are needed: a point-of-care diagnostic biomarker and a prognostic biomarker—preferentially based on samples obtained with minimally invasive methods. In this study, we applied a lectin magnetic bead array-coupled tandem mass spectrometry (LeMBA-MS/MS) workflow through discovery and validation phases to discover serum glycoprotein biomarker candidates for canine HSA. By this approach, we found that Datura stramonium (DSA), wheat germ agglutinin (WGA), Sambucus nigra (SNA), and Pisum sativum (PSA) lectins captured the highest number of validated candidate glycoproteins. Secondly, we independently validated serum LeMBA-MS/MS results by demonstrating the in situ relationship of lectin-binding with tumor cells. Using lectin-histochemistry and immunohistochemistry (IHC) for key proteins on tissues with HSA and semi-quantitation of the signals, we demonstrate that a combination of DSA histochemistry and IHC for complement C7 greatly increases the prospect of a more specific diagnosis of canine HSA.

Epidemiological research of canine cancers could inform comparative studies of environmental determinants for a number of human cancers. However, such an approach is currently limited because canine cancer data sources are still few in number and often incomplete. Incompleteness is typically due to under-ascertainment of canine cancers. A main reason for this is because dog owners commonly do not seek veterinary care for this diagnosis. Deeper knowledge on under-ascertainment is critical for modelling canine cancer incidence, as an indication of zero incidence might originate from the sole absence of diagnostic examinations within a given sample unit. In the present case study, we investigated effects of such structural zeros on models of canine cancer incidence. In doing so, we contrasted two scenarios for modelling incidence data retrieved from the Swiss Canine Cancer Registry. The first scenario was based on the complete enumeration of incidence data for all Swiss municipal units. The second scenario was based on a filtered sample that systematically discarded structural zeros in those municipal units where no diagnostic examination had been performed. By means of cross-validation, we assessed and contrasted statistical performance and predictive power of the two modelling scenarios. This analytical step allowed us to demonstrate that structural zeros impact on the generalisability of the model of canine cancer incidence, thus challenging future comparative studies of canine and human cancers. The results of this case study show that increased awareness about the effects of structural zeros is critical to epidemiological research.

ABSTRACT: Pain in the cancer patient is an important clinical manifestation that results in low life expectancy and poor prognosis. Pain may be related to tumor type, invasion of adjacent tissues, metastasis, and diagnostic and therapeutic procedures with variable response to analgesic therapy. Many studies have called attention due to their potential therapeutic effect in the modulation of pain and inflammation. Cannabinoid derivatives are chemical compounds obtained from Cannabis that act on specific receptors.Several commercial products have already been approved in Europe and the USA for use in human patients. The present study aimed to review articles on the use of cannabinoids in the control of pain contributing to the well-being and quality of life in cancer patients undergoing palliative care. Although, there are few reports in the veterinary medical literature on the use of cannabinoids in the control of pain in dogs, it is believed that such patients can benefit from this therapeutic modality.

Background: Mammary neoplasms in dogs are commonly observed in veterinary clinical routine, most of which being malignant. Hormonal stimulation, endogenous or exogenous, may possibly influence its development. In addition to clinical evaluation, ultrasound analysis can provide information about the characteristics of breast lumps. The association between clinical-epidemiological and pathological data is important for diagnosis. Therefore, given the importance of this pathology for the health of affected dogs, we aimed to evaluate the clinical and ultrasound alterations, along with the factors associated with the development of benign and malignant mammary neoplasms in female dogs. Materials, Methods & Results: We examined 47 samples from the mammary tumors of 35 female dogs at the Small Animal Clinic of the Veterinary Hospital (HV) of the Santa Cruz State University (UESC). The dogs underwent a complete clinical examination, with clinical staging, via TNM classification, followed by hematological, biochemical, radiological and ultrasound, abdominal, and breast exams. Breast ultrasound examination was used to evaluate the shape parameters such as, limits, margins or contour, ecotexture, echogenicity, hyperechoic halo, posterior acoustic shading, surrounding changes, and nodule components. These criteria were associated with the histopathological classification of neoplasms. Epidemiological data was studied through an adapted questionnaire containing information on risk factors associated with breast cancer. The same questionnaire was applied to tutors of 19, age-matched, female dogs with no history of breast cancer. The results revealed that most female dogs with neoplasia were over eight years of age, with no specific breed and were not castrated, and 31.4% of them had already been administered with contraceptives during the reproductive period. Ovariohysterectomy acted as a protective factor (OR 0.06) to the development of breast tumors, while contraceptive use was considered as a risk factor (OR 6.99). The average time reported between tumor perception and clinical care was 13.2 months. The caudal and inguinal abdominal breasts were the most affected. Among the samples evaluated, 76.6% were malignant, with mixed tumor carcinoma being the most frequent type and 69.4% graded in grade I. Nodules classified as malignant showed the largest diameter (P < 0.05). Breast ultrasound results revealed that tumors with heterogeneous echotextures and mixed components were associated with malignancy (P < 0.05). Discussion: The fact that the average age of female dogs with breast cancer was over eight years of age corroborates the literature. Considering that a greater age would mean a longer exposure to the carcinogenic initiators responsible for mutations, and to promoters, such as hormonal changes. Contraceptives increase the risk of breast lumps, while reduce that of ovariohysterectomy, in female dogs, even when performed after the second heat. The size of the nodules and ultrasound criteria related to echotexture and the type of component of the neoplasia may be used as prognostic parameters of female breast nodules. Additionally, most nodules evaluated in this study were malignant (mixed tumor carcinoma was the most common subtype), possibly due to the owners' delay in seeking veterinary care after tumor observation. Although malignant, most nodules presented with a low histopathological grading.Background: Mammary neoplasms in dogs are commonly observed in veterinary clinicalroutine, most of which being malignant. Hormonal stimulation, endogenous or exogenous,may possibly influence its development. In addition to clinical evaluation, ultrasound analysiscan provide information about the characteristics of breast lumps. The association betweenclinical-epidemiological and pathological data is important for diagnosis. Therefore, given theimportance of this pathology for the health of affected dogs, we aimed to evaluate the clinicaland ultrasound alterations, along with the factors associated with the development of benignand malignant mammary neoplasms in female dogs.Materials, Methods &amp; Results: We examined 47

Mammary adenocarcinomas with metastases are more common in dogs than in cats. Their incidence is 1 in every 4,000 cats. In routine veterinary practice, laboratory exams for diagnosis of these neoplasms are nonspecific and scarcely used. Even though invasive procedure, biopsy, and histopathological findings are the gold standards that define the clinical approach, the clinical evaluation, and image assessment lead the way to the proper treatment, especially when surgical intervention is a possibility. This study describes the clinical signs, histopathological aspects, radiological and scintigraphic findings of a cat with mammary adenocarcinoma and metastases evaluated one hour after intravenous administration of 99mTc-thymine. Our focus was not to discuss the pathological aspects of the disease but the Nuclear Medicine role in metastases detection. Metastases, when lesser than 4mm, could go unnoticed by radiological exams, whereas scintigraphy may detect them. Using 99mTc-thymine scintigraphy, we successfully detected unsuspected metastases in the lungs, liver, and right kidney. Early diagnosis is the key to a better rate of survival due to the given treatment and prognostic. Hence, we strongly recommend the use of 99mTc-thymine scintigraphy as a complementary tool for breast cancer diagnosis in veterinary care.

Recent reports have highlighted a lower-than-expected prevalence of neoplasia in elephants and suggested mechanisms for cancer resistance. But despite infrequent reports in the literature, uterine neoplasia is common in managed Asian elephants ( Elephas maximus). This study is an archival review of reproductive tract neoplasia in 80 adult female Asian elephant mortalities in managed care facilities in the United States from 1988 to 2019. Neoplasms occurred in 64/80 (80%) of cases. Most were in the uterus (63/64; 98%) with only a single case of ovarian neoplasia. Myometrial leiomyomas were present in 57/63 (90%) cases with uterine neoplasia. Uterine adenocarcinoma was present in 8/63 (13%) cases. Remaining cases included endometrial adenoma (2), focal carcinoma in situ in endometrial polyps (1), anaplastic carcinoma (1), endometrial hemangioma (1), primitive neuroectodermal tumor (PNET; 1), and angiosarcoma (1). One case with uterine adenocarcinoma had a separate pelvic mass histologically characterized as an anaplastic sarcoma. Distant metastases were documented in 5/8 (63%) cases of uterine adenocarcinoma, and in the uterine anaplastic carcinoma, PNET, and angiosarcoma. Four uterine adenocarcinomas and one carcinoma in situ were examined immunohistochemically for pan-cytokeratin, vimentin, and estrogen receptor. In all, neoplastic cells were pan-cytokeratin positive and vimentin negative, and in 2 cases were immunoreactive for estrogen receptor. Results show that female reproductive tract neoplasia, particularly of the uterus, is common in Asian elephants and is not limited to leiomyomas. Importantly, uterine neoplasms have the potential to impact fecundity and may represent obstacles to conservation in managed care.

Abstract Background Listeria monocytogenes is a promising therapeutic vaccine vector for cancer immunotherapy. Although highly attenuated, three cases of systemic listeriosis have been reported in people following treatment with Listeria-based therapeutic vaccines. This complication has thus far not been reported in canine patients. Case presentation A dog previously diagnosed with osteoblastic osteosarcoma was presented for care following administration of three doses of the Canine Osteosarcoma Vaccine-Live Listeria Vector. On routine staging chest radiographs, mild sternal lymphadenopathy and a right caudoventral thoracic mass effect were noted. Further evaluation of the mass effect with computed tomography and ultrasound revealed a cavitated mass associated with the 7th right rib. Aspirates of the mass cultured positive for Listeria monocytogenes. The mass and associated ribs were surgically removed. Histopathology was consistent with metastatic osteoblastic osteosarcoma. Treatment was continued with doxorubicin chemotherapy and at the time of publication, the dog was alive over 1 year following diagnosis with no evidence of further disease progression. Genotyping of the abscess-derived L. monocytogenes was consistent with the vaccine strain. Conclusions This case represents the first veterinary case to describe development of a Listeria abscess following administration of a Listeria-based therapeutic vaccine.

Pulsed Electromagnetic Field (PEMF) therapy is a non-invasive and non-thermal treatment widely used nowadays to treat various types of disorders and traumas, both in humans and animals. Initially applied only for wound healing, today it finds many applications in medicine for the treatment of bone fractures, arthritis, inflammation, edema, and pain. Although their mechanisms of action are still being studied today, and mainly related to the calcium signaling pathway, they are effective in the adjuvant treatment of many human diseases in different medical specialties. This work aims to report the main evidence and research in the medical field with particular reference to the application of PEMF to some medical specialties as regenerative medicine (wound care), sports medicine, orthopedics, and physiotherapy. Finally, this work also wanted to deepen one of the most recent applications of PEMF in the field of complex diseases, i.e. in the adjuvant treatment of cancer. Pulsed electromagnetic field therapy may play an important role in medicine as a complementary treatment for various human diseases and, by deepening the studies in the future, it will be possible not only to understand the exact mechanisms of action but also to extend its application to other pathologies both in the medical and veterinary fields.

Background: Prostatic cancer is a rare condition in cats but should be included as a differential diagnosis whenever middle-aged cats present lower urinary tract signs, such as dysuria and hematuria. Abdominal ultrasound can indicate the disease, but fine-needle aspiration cytology and histopathology are necessary to establish the neoplastic origin and the therapeutic plan. Because of the limited data, no standard-of-care treatment or prognostic information exists in cats with prostate carcinoma. This report describes the clinical signs, diagnosis and surgical approach in a case of prostatic carcinoma in a cat. Case: A 6-year-old, intact male, domestic short-haired cat was presented with a 3-day history of dysuria, hematuria, inappetence, constipation, lethargy and prostration. On physical examination, the cat was in a very poor general condition and abdominal palpation revealed firm mass located caudally to the urinary bladder. The urinary bladder presented high repletion degree, while the large bowel was distended and presented soft faecal content. Blood count, serum biochemistry and urinalysis showed neutrophilic leukocytosis, hypoalbuminemia and high serum creatinine level, and severe hematuria, respectively. Abdominal ultrasound showed a mass located in the prostatic area with hypoechogenic and slightly heterogeneous parenchyma, measuring 3.3 x 3.0 cm. Echo-guided trans-abdominal fine-needle aspiration of the prostate was performed. Microscopically, the cells were round with basophilic cytoplasm, and had round to ovoid nuclei, dense chromatin and prominent nucleoli. Some cells were binucleated and mild anisocytosis and marked anisokaryosis were documented. These findings were compatible with malignant prostatic neoplasia. After initial clinical stabilization, the patient underwent an exploratory laparotomy for tumor resection. Cystotomy followed by pubic osteotomy was performed to access the tumor. Urethral anastomosis was necessary due to adherence of the neoplasm to adjacent structures. However, the patient died during the immediate postoperative period. No complications related to surgery were observed at necropsy. Tissue specimens were collected and stained by hematoxylin and eosin. Prostatic carcinoma was confirmed by immunohistochemistry tests using streptavidin-biotin-peroxidase complex method, and primary antibodies against vimentin, cytokeratin AE1/AE3 and 7. Discussion: Prostatic neoplams are rare in cats and clinical signs are suggestive of lower urinary tract disease, such as dysuria and/or hematuria, associated with tenesmus. Abdominal or rectal palpation seems to be essential to detect the prostatic enlargement. Ultrasound imaging was more sensitive than radiography, since it brings more information about structure, size, form and prostatic internal architecture. The patient’s serum creatinine value above the normal range for cats indicated partial urethral obstruction, due to neoplastic concentric growth. Echo-guided trans-abdominal fine needle aspiration cytology was an effective method to confirm neoplastic etiology. The advanced stage of the disease and poor clinical condition probably contributed to death at the immediate postoperative period, even though the surgical technique seemed to be appropriate as demonstrated at necropsy. Also, the immunohistochemistry tests allowed to confirm the diagnosis and excluded the main differential diagnoses, such as urothelial carcinoma and prostatic sarcomatoid carcinoma.

Animals, from the pomace fly to the mouse, are widely utilized in research project. They are crucial for allowing scientists to find out more about human biology and health, and for developing new medicines. The use of animals in research project has long been the topic of heated debate. On the one hand it's considered morally wrong to use animals during this way solely for human benefit. On the other hand, our understanding of health and disease would impede after removing animals completely from the lab, and consequently affect the event of latest and vital treatments [1]. No responsible scientist wants to use animals or cause them unnecessary suffering if it are often avoided, and thus scientists accept controls on the utilization of animals in research [2]. Are animal models useful? Animal models are wont to address a spread of scientific questions, from basic science to the event and assessment of novel vaccines, or therapies. The use of animals is not only supported the vast commonalities within the biology of most mammals, but also on the very fact that human diseases often affect other animal species. It is particularly the case for many infectious diseases but also for quite common conditions like Type I diabetes, hypertension, allergies, cancer, epilepsy, myopathies then on. Not only are these diseases shared but the mechanisms are often also so similar that 90% of the veterinary drugs wont to treat animals are identical or very similar to those used to treat humans. Due to observations and testing on animal models, a number of major breakthroughs in basic science and medical research are possible. Most vaccines, which save many human and animal lives per annum, are successfully developed using animal models. However the results obtained on animals aren't necessarily confirmed in further human studies [3]. No animal model is ever perfect and there are still many differences between model organisms and humans [1]. To help minimise the harm animals may experience while being studied within the laboratory, researchers are required to follow a group of principles, the ‘three Rs’. These three Rs Reduction, Refinement, Replacement was proposed by Russel and Birch in 1959 [4]. Replace: Replacing an animal experiment to the best possible extent, as long as adequate alternatives are available. Reduce: The reduction of animal experiments and therefore the number of laboratory animals to the best possible extent. In so doing, it's important to use as many animals as are needed to get a statistically significant outcome. An adequate number of animals are required for the results to be sufficiently significant. Refine: The methods and treatment of the animals during the experiments, and with reference to the way they're kept, should make sure that the distress caused to them is minimized to the best possible extent which their well-being is taken under consideration as far as possible [5]. The inspection and licensing of animal premises, the training and competence of all personal designing projects, performing animal procedures and taking care of animals are the regulatory provisions with which research on animals is conducted and therefore the mandatory authorization of each project by a competent authority upon ethical evaluation by an Animal ethics panel. The criteria for evaluation are supported the 3Rs rules and a cost-benefit analysis to guage if the potential harm to the animals, which must be reduced to the lowest possible level, is outweighed by significant progress in terms of data on human or animal health. Modern medical research facing the greatest challenges that concern complex, multifactorial, diseases such as cancer, infectious diseases, cardiovascular diseases, neurodegenerative disorders, pathological consequences of aging among others, for which all experimental approaches are indispensable. Research on animal models will remain for an extended time a crucial step for fundamental discoveries, for testing hypotheses at the organism level and for the validation of human data. Likewise, animal protection requires permanent consideration. These two objectives, far away from being antagonistic, must be anchored in high-quality science [3].

Introduction: Our current obsession with the lives of others “Biography—that is to say, our creative and non-fictional output devoted to recording and interpreting real lives—has enjoyed an extraordinary renaissance in recent years,” writes Nigel Hamilton in Biography: A Brief History (1). Ian Donaldson agrees that biography is back in fashion: “Once neglected within the academy and relegated to the dustier recesses of public bookstores, biography has made a notable return over recent years, emerging, somewhat surprisingly, as a new cultural phenomenon, and a new academic adventure” (23). For over a decade now, commentators having been making similar observations about our obsession with the intimacies of individual people’s lives. In a lecture in 1994, Justin Kaplan asserted the West was “a culture of biography” (qtd. in Salwak 1) and more recent research findings by John Feather and Hazel Woodbridge affirm that “the undiminished human curiosity about other peoples lives is clearly reflected in the popularity of autobiographies and biographies” (218). At least in relation to television, this assertion seems valid. In Australia, as in the USA and the UK, reality and other biographically based television shows have taken over from drama in both the numbers of shows produced and the viewers these shows attract, and these forms are also popular in Canada (see, for instance, Morreale on The Osbournes). In 2007, the program Biography celebrated its twentieth anniversary season to become one of the longest running documentary series on American television; so successful that in 1999 it was spun off into its own eponymous channel (Rak; Dempsey). Premiered in May 1996, Australian Story—which aims to utilise a “personal approach” to biographical storytelling—has won a significant viewership, critical acclaim and professional recognition (ABC). It can also be posited that the real home movies viewers submit to such programs as Australia’s Favourite Home Videos, and “chat” or “confessional” television are further reflections of a general mania for biographical detail (see Douglas), no matter how fragmented, sensationalized, or even inane and cruel. A recent example of the latter, the USA-produced The Moment of Truth, has contestants answering personal questions under polygraph examination and then again in front of an audience including close relatives and friends—the more “truthful” their answers (and often, the more humiliated and/or distressed contestants are willing to be), the more money they can win. Away from television, but offering further evidence of this interest are the growing readerships for personally oriented weblogs and networking sites such as MySpace and Facebook (Grossman), individual profiles and interviews in periodical publications, and the recently widely revived newspaper obituary column (Starck). Adult and community education organisations run short courses on researching and writing auto/biographical forms and, across Western countries, the family history/genealogy sections of many local, state, and national libraries have been upgraded to meet the increasing demand for these services. Academically, journals and e-mail discussion lists have been established on the topics of biography and autobiography, and North American, British, and Australian universities offer undergraduate and postgraduate courses in life writing. The commonly aired wisdom is that published life writing in its many text-based forms (biography, autobiography, memoir, diaries, and collections of personal letters) is enjoying unprecedented popularity. It is our purpose to examine this proposition. Methodological problems There are a number of problems involved in investigating genre popularity, growth, and decline in publishing. Firstly, it is not easy to gain access to detailed statistics, which are usually only available within the industry. Secondly, it is difficult to ascertain how publishing statistics are gathered and what they report (Eliot). There is the question of whether bestselling booklists reflect actual book sales or are manipulated marketing tools (Miller), although the move from surveys of booksellers to electronic reporting at point of sale in new publishing lists such as BookScan will hopefully obviate this problem. Thirdly, some publishing lists categorise by subject and form, some by subject only, and some do not categorise at all. This means that in any analysis of these statistics, a decision has to be made whether to use the publishing list’s system or impose a different mode. If the publishing list is taken at face value, the question arises of whether to use categorisation by form or by subject. Fourthly, there is the bedeviling issue of terminology. Traditionally, there reigned a simple dualism in the terminology applied to forms of telling the true story of an actual life: biography and autobiography. Publishing lists that categorise their books, such as BookScan, have retained it. But with postmodern recognition of the presence of the biographer in a biography and of the presence of other subjects in an autobiography, the dichotomy proves false. There is the further problem of how to categorise memoirs, diaries, and letters. In the academic arena, the term “life writing” has emerged to describe the field as a whole. Within the genre of life writing, there are, however, still recognised sub-genres. Academic definitions vary, but generally a biography is understood to be a scholarly study of a subject who is not the writer; an autobiography is the story of a entire life written by its subject; while a memoir is a segment or particular focus of that life told, again, by its own subject. These terms are, however, often used interchangeably even by significant institutions such the USA Library of Congress, which utilises the term “biography” for all. Different commentators also use differing definitions. Hamilton uses the term “biography” to include all forms of life writing. Donaldson discusses how the term has been co-opted to include biographies of place such as Peter Ackroyd’s London: The Biography (2000) and of things such as Lizzie Collingham’s Curry: A Biography (2005). This reflects, of course, a writing/publishing world in which non-fiction stories of places, creatures, and even foodstuffs are called biographies, presumably in the belief that this will make them more saleable. The situation is further complicated by the emergence of hybrid publishing forms such as, for instance, the “memoir-with-recipes” or “food memoir” (Brien, Rutherford and Williamson). Are such books to be classified as autobiography or put in the “cookery/food & drink” category? We mention in passing the further confusion caused by novels with a subtitle of The Biography such as Virginia Woolf’s Orlando. The fifth methodological problem that needs to be mentioned is the increasing globalisation of the publishing industry, which raises questions about the validity of the majority of studies available (including those cited herein) which are nationally based. Whether book sales reflect what is actually read (and by whom), raises of course another set of questions altogether. Methodology In our exploration, we were fundamentally concerned with two questions. Is life writing as popular as claimed? And, if it is, is this a new phenomenon? To answer these questions, we examined a range of available sources. We began with the non-fiction bestseller lists in Publishers Weekly (a respected American trade magazine aimed at publishers, librarians, booksellers, and literary agents that claims to be international in scope) from their inception in 1912 to the present time. We hoped that this data could provide a longitudinal perspective. The term bestseller was coined by Publishers Weekly when it began publishing its lists in 1912; although the first list of popular American books actually appeared in The Bookman (New York) in 1895, based itself on lists appearing in London’s The Bookman since 1891 (Bassett and Walter 206). The Publishers Weekly lists are the best source of longitudinal information as the currently widely cited New York Times listings did not appear till 1942, with the Wall Street Journal a late entry into the field in 1994. We then examined a number of sources of more recent statistics. We looked at the bestseller lists from the USA-based Amazon.com online bookseller; recent research on bestsellers in Britain; and lists from Nielsen BookScan Australia, which claims to tally some 85% or more of books sold in Australia, wherever they are published. In addition to the reservations expressed above, caveats must be aired in relation to these sources. While Publishers Weekly claims to be an international publication, it largely reflects the North American publishing scene and especially that of the USA. Although available internationally, Amazon.com also has its own national sites—such as Amazon.co.uk—not considered here. It also caters to a “specific computer-literate, credit-able clientele” (Gutjahr: 219) and has an unashamedly commercial focus, within which all the information generated must be considered. In our analysis of the material studied, we will use “life writing” as a genre term. When it comes to analysis of the lists, we have broken down the genre of life writing into biography and autobiography, incorporating memoir, letters, and diaries under autobiography. This is consistent with the use of the terminology in BookScan. Although we have broken down the genre in this way, it is the overall picture with regard to life writing that is our concern. It is beyond the scope of this paper to offer a detailed analysis of whether, within life writing, further distinctions should be drawn. Publishers Weekly: 1912 to 2006 1912 saw the first list of the 10 bestselling non-fiction titles in Publishers Weekly. It featured two life writing texts, being headed by an autobiography, The Promised Land by Russian Jewish immigrant Mary Antin, and concluding with Albert Bigelow Paine’s six-volume biography, Mark Twain. The Publishers Weekly lists do not categorise non-fiction titles by either form or subject, so the classifications below are our own with memoir classified as autobiography. In a decade-by-decade tally of these listings, there were 3 biographies and 20 autobiographies in the lists between 1912 and 1919; 24 biographies and 21 autobiographies in the 1920s; 13 biographies and 40 autobiographies in the 1930s; 8 biographies and 46 biographies in the 1940s; 4 biographies and 14 autobiographies in the 1950s; 11 biographies and 13 autobiographies in the 1960s; 6 biographies and 11 autobiographies in the 1970s; 3 biographies and 19 autobiographies in the 1980s; 5 biographies and 17 autobiographies in the 1990s; and 2 biographies and 7 autobiographies from 2000 up until the end of 2006. See Appendix 1 for the relevant titles and authors. Breaking down the most recent figures for 1990–2006, we find a not radically different range of figures and trends across years in the contemporary environment. The validity of looking only at the top ten books sold in any year is, of course, questionable, as are all the issues regarding sources discussed above. But one thing is certain in terms of our inquiry. There is no upwards curve obvious here. If anything, the decade break-down suggests that sales are trending downwards. This is in keeping with the findings of Michael Korda, in his history of twentieth-century bestsellers. He suggests a consistent longitudinal picture across all genres: In every decade, from 1900 to the end of the twentieth century, people have been reliably attracted to the same kind of books […] Certain kinds of popular fiction always do well, as do diet books […] self-help books, celebrity memoirs, sensationalist scientific or religious speculation, stories about pets, medical advice (particularly on the subjects of sex, longevity, and child rearing), folksy wisdom and/or humour, and the American Civil War (xvii). Amazon.com since 2000 The USA-based Amazon.com online bookselling site provides listings of its own top 50 bestsellers since 2000, although only the top 14 bestsellers are recorded for 2001. As fiction and non-fiction are not separated out on these lists and no genre categories are specified, we have again made our own decisions about what books fall into the category of life writing. Generally, we erred on the side of inclusion. (See Appendix 2.) However, when it came to books dealing with political events, we excluded books dealing with specific aspects of political practice/policy. This meant excluding books on, for instance, George Bush’s so-called ‘war on terror,’ of which there were a number of bestsellers listed. In summary, these listings reveal that of the top 364 books sold by Amazon from 2000 to 2007, 46 (or some 12.6%) were, according to our judgment, either biographical or autobiographical texts. This is not far from the 10% of the 1912 Publishers Weekly listing, although, as above, the proportion of bestsellers that can be classified as life writing varied dramatically from year to year, with no discernible pattern of peaks and troughs. This proportion tallied to 4% auto/biographies in 2000, 14% in 2001, 10% in 2002, 18% in 2003 and 2004, 4% in 2005, 14% in 2006 and 20% in 2007. This could suggest a rising trend, although it does not offer any consistent trend data to suggest sales figures may either continue to grow, or fall again, in 2008 or afterwards. Looking at the particular texts in these lists (see Appendix 2) also suggests that there is no general trend in the popularity of life writing in relation to other genres. For instance, in these listings in Amazon.com, life writing texts only rarely figure in the top 10 books sold in any year. So rarely indeed, that from 2001 there were only five in this category. In 2001, John Adams by David McCullough was the best selling book of the year; in 2003, Hillary Clinton’s autobiographical Living History was 7th; in 2004, My Life by Bill Clinton reached number 1; in 2006, Nora Ephron’s I Feel Bad About My Neck: and Other Thoughts on Being a Woman was 9th; and in 2007, Ishmael Beah’s discredited A Long Way Gone: Memoirs of a Boy Soldier came in at 8th. Apart from McCulloch’s biography of Adams, all the above are autobiographical texts, while the focus on leading political figures is notable. Britain: Feather and Woodbridge With regard to the British situation, we did not have actual lists and relied on recent analysis. John Feather and Hazel Woodbridge find considerably higher levels for life writing in Britain than above with, from 1998 to 2005, 28% of British published non-fiction comprising autobiography, while 8% of hardback and 5% of paperback non-fiction was biography (2007). Furthermore, although Feather and Woodbridge agree with commentators that life writing is currently popular, they do not agree that this is a growth state, finding the popularity of life writing “essentially unchanged” since their previous study, which covered 1979 to the early 1990s (Feather and Reid). Australia: Nielsen BookScan 2006 and 2007 In the Australian publishing industry, where producing books remains an ‘expensive, risky endeavour which is increasingly market driven’ (Galligan 36) and ‘an inherently complex activity’ (Carter and Galligan 4), the most recent Australian Bureau of Statistics figures reveal that the total numbers of books sold in Australia has remained relatively static over the past decade (130.6 million in the financial year 1995–96 and 128.8 million in 2003–04) (ABS). During this time, however, sales volumes of non-fiction publications have grown markedly, with a trend towards “non-fiction, mass market and predictable” books (Corporall 41) resulting in general non-fiction sales in 2003–2004 outselling general fiction by factors as high as ten depending on the format—hard- or paperback, and trade or mass market paperback (ABS 2005). However, while non-fiction has increased in popularity in Australia, the same does not seem to hold true for life writing. Here, in utilising data for the top 5,000 selling non-fiction books in both 2006 and 2007, we are relying on Nielsen BookScan’s categorisation of texts as either biography or autobiography. In 2006, no works of life writing made the top 10 books sold in Australia. In looking at the top 100 books sold for 2006, in some cases the subjects of these works vary markedly from those extracted from the Amazon.com listings. In Australia in 2006, life writing makes its first appearance at number 14 with convicted drug smuggler Schapelle Corby’s My Story. This is followed by another My Story at 25, this time by retired Australian army chief, Peter Cosgrove. Jonestown: The Power and Myth of Alan Jones comes in at 34 for the Australian broadcaster’s biographer Chris Masters; the biography, The Innocent Man by John Grisham at 38 and Li Cunxin’s autobiographical Mao’s Last Dancer at 45. Australian Susan Duncan’s memoir of coping with personal loss, Salvation Creek: An Unexpected Life makes 50; bestselling USA travel writer Bill Bryson’s autobiographical memoir of his childhood The Life and Times of the Thunderbolt Kid 69; Mandela: The Authorised Portrait by Rosalind Coward, 79; and Joanne Lees’s memoir of dealing with her kidnapping, the murder of her partner and the justice system in Australia’s Northern Territory, No Turning Back, 89. These books reveal a market preference for autobiographical writing, and an almost even split between Australian and overseas subjects in 2006. 2007 similarly saw no life writing in the top 10. The books in the top 100 sales reveal a downward trend, with fewer titles making this band overall. In 2007, Terri Irwin’s memoir of life with her famous husband, wildlife warrior Steve Irwin, My Steve, came in at number 26; musician Andrew Johns’s memoir of mental illness, The Two of Me, at 37; Ayaan Hirst Ali’s autobiography Infidel at 39; John Grogan’s biography/memoir, Marley and Me: Life and Love with the World’s Worst Dog, at 42; Sally Collings’s biography of the inspirational young survivor Sophie Delezio, Sophie’s Journey, at 51; and Elizabeth Gilbert’s hybrid food, self-help and travel memoir, Eat, Pray, Love: One Woman’s Search for Everything at 82. Mao’s Last Dancer, published the year before, remained in the top 100 in 2007 at 87. When moving to a consideration of the top 5,000 books sold in Australia in 2006, BookScan reveals only 62 books categorised as life writing in the top 1,000, and only 222 in the top 5,000 (with 34 titles between 1,000 and 1,999, 45 between 2,000 and 2,999, 48 between 3,000 and 3,999, and 33 between 4,000 and 5,000). 2007 shows a similar total of 235 life writing texts in the top 5,000 bestselling books (75 titles in the first 1,000, 27 between 1,000 and 1,999, 51 between 2,000 and 2,999, 39 between 3,000 and 3,999, and 43 between 4,000 and 5,000). In both years, 2006 and 2007, life writing thus not only constituted only some 4% of the bestselling 5,000 titles in Australia, it also showed only minimal change between these years and, therefore, no significant growth. Conclusions Our investigation using various instruments that claim to reflect levels of book sales reveals that Western readers’ willingness to purchase published life writing has not changed significantly over the past century. We find no evidence of either a short, or longer, term growth or boom in sales in such books. Instead, it appears that what has been widely heralded as a new golden age of life writing may well be more the result of an expanded understanding of what is included in the genre than an increased interest in it by either book readers or publishers. What recent years do appear to have seen, however, is a significantly increased interest by public commentators, critics, and academics in this genre of writing. We have also discovered that the issue of our current obsession with the lives of others tends to be discussed in academic as well as popular fora as if what applies to one sub-genre or production form applies to another: if biography is popular, then autobiography will also be, and vice versa. If reality television programming is attracting viewers, then readers will be flocking to life writing as well. Our investigation reveals that such propositions are questionable, and that there is significant research to be completed in mapping such audiences against each other. This work has also highlighted the difficulty of separating out the categories of written texts in publishing studies, firstly in terms of determining what falls within the category of life writing as distinct from other forms of non-fiction (the hybrid problem) and, secondly, in terms of separating out the categories within life writing. Although we have continued to use the terms biography and autobiography as sub-genres, we are aware that they are less useful as descriptors than they are often assumed to be. In order to obtain a more complete and accurate picture, publishing categories may need to be agreed upon, redefined and utilised across the publishing industry and within academia. This is of particular importance in the light of the suggestions (from total sales volumes) that the audiences for books are limited, and therefore the rise of one sub-genre may be directly responsible for the fall of another. Bair argues, for example, that in the 1980s and 1990s, the popularity of what she categorises as memoir had direct repercussions on the numbers of birth-to-death biographies that were commissioned, contracted, and published as “sales and marketing staffs conclude[d] that readers don’t want a full-scale life any more” (17). Finally, although we have highlighted the difficulty of using publishing statistics when there is no common understanding as to what such data is reporting, we hope this study shows that the utilisation of such material does add a depth to such enquiries, especially in interrogating the anecdotal evidence that is often quoted as data in publishing and other studies. Appendix 1 Publishers Weekly listings 1990–1999 1990 included two autobiographies, Bo Knows Bo by professional athlete Bo Jackson (with Dick Schaap) and Ronald Reagan’s An America Life: An Autobiography. In 1991, there were further examples of life writing with unimaginative titles, Me: Stories of My Life by Katherine Hepburn, Nancy Reagan: The Unauthorized Biography by Kitty Kelley, and Under Fire: An American Story by Oliver North with William Novak; as indeed there were again in 1992 with It Doesn’t Take a Hero: The Autobiography of Norman Schwarzkopf, Sam Walton: Made in America, the autobiography of the founder of Wal-Mart, Diana: Her True Story by Andrew Morton, Every Living Thing, yet another veterinary outpouring from James Herriot, and Truman by David McCullough. In 1993, radio shock-jock Howard Stern was successful with the autobiographical Private Parts, as was Betty Eadie with her detailed recounting of her alleged near-death experience, Embraced by the Light. Eadie’s book remained on the list in 1994 next to Don’t Stand too Close to a Naked Man, comedian Tim Allen’s autobiography. Flag-waving titles continue in 1995 with Colin Powell’s My American Journey, and Miss America, Howard Stern’s follow-up to Private Parts. 1996 saw two autobiographical works, basketball superstar Dennis Rodman’s Bad as I Wanna Be and figure-skater, Ekaterina Gordeeva’s (with EM Swift) My Sergei: A Love Story. In 1997, Diana: Her True Story returns to the top 10, joining Frank McCourt’s Angela’s Ashes and prolific biographer Kitty Kelly’s The Royals, while in 1998, there is only the part-autobiography, part travel-writing A Pirate Looks at Fifty, by musician Jimmy Buffet. There is no biography or autobiography included in either the 1999 or 2000 top 10 lists in Publishers Weekly, nor in that for 2005. In 2001, David McCullough’s biography John Adams and Jack Welch’s business memoir Jack: Straight from the Gut featured. In 2002, Let’s Roll! Lisa Beamer’s tribute to her husband, one of the heroes of 9/11, written with Ken Abraham, joined Rudolph Giuliani’s autobiography, Leadership. 2003 saw Hillary Clinton’s autobiography Living History and Paul Burrell’s memoir of his time as Princess Diana’s butler, A Royal Duty, on the list. In 2004, it was Bill Clinton’s turn with My Life. In 2006, we find John Grisham’s true crime (arguably a biography), The Innocent Man, at the top, Grogan’s Marley and Me at number three, and the autobiographical The Audacity of Hope by Barack Obama in fourth place. Appendix 2 Amazon.com listings since 2000 In 2000, there were only two auto/biographies in the top Amazon 50 bestsellers with Lance Armstrong’s It’s Not about the Bike: My Journey Back to Life about his battle with cancer at 20, and Dave Eggers’s self-consciously fictionalised memoir, A Heartbreaking Work of Staggering Genius at 32. In 2001, only the top 14 bestsellers were recorded. At number 1 is John Adams by David McCullough and, at 11, Jack: Straight from the Gut by USA golfer Jack Welch. In 2002, Leadership by Rudolph Giuliani was at 12; Master of the Senate: The Years of Lyndon Johnson by Robert Caro at 29; Portrait of a Killer: Jack the Ripper by Patricia Cornwell at 42; Blinded by the Right: The Conscience of an Ex-Conservative by David Brock at 48; and Louis Gerstner’s autobiographical Who Says Elephants Can’t Dance: Inside IBM’s Historic Turnaround at 50. In 2003, Living History by Hillary Clinton was 7th; Benjamin Franklin: An American Life by Walter Isaacson 14th; Dereliction of Duty: The Eyewitness Account of How President Bill Clinton Endangered America’s Long-Term National Security by Robert Patterson 20th; Under the Banner of Heaven: A Story of Violent Faith by Jon Krakauer 32nd; Leap of Faith: Memoirs of an Unexpected Life by Queen Noor of Jordan 33rd; Kate Remembered, Scott Berg’s biography of Katharine Hepburn, 37th; Who’s your Caddy?: Looping for the Great, Near Great and Reprobates of Golf by Rick Reilly 39th; The Teammates: A Portrait of a Friendship about a winning baseball team by David Halberstam 42nd; and Every Second Counts by Lance Armstrong 49th. In 2004, My Life by Bill Clinton was the best selling book of the year; American Soldier by General Tommy Franks was 16th; Kevin Phillips’s American Dynasty: Aristocracy, Fortune and the Politics of Deceit in the House of Bush 18th; Timothy Russert’s Big Russ and Me: Father and Son. Lessons of Life 20th; Tony Hendra’s Father Joe: The Man who Saved my Soul 23rd; Ron Chernow’s Alexander Hamilton 27th; Cokie Roberts’s Founding Mothers: The Women Who Raised our Nation 31st; Kitty Kelley’s The Family: The Real Story of the Bush Dynasty 42nd; and Chronicles, Volume 1 by Bob Dylan was 43rd. In 2005, auto/biographical texts were well down the list with only The Year of Magical Thinking by Joan Didion at 45 and The Glass Castle: A Memoir by Jeanette Walls at 49. In 2006, there was a resurgence of life writing with Nora Ephron’s I Feel Bad About My Neck: and Other Thoughts on Being a Woman at 9; Grisham’s The Innocent Man at 12; Bill Buford’s food memoir Heat: an Amateur’s Adventures as Kitchen Slave, Line Cook, Pasta-Maker, and Apprentice to a Dante-Quoting Butcher in Tuscany at 23; more food writing with Julia Child’s My Life in France at 29; Immaculée Ilibagiza’s Left to Tell: Discovering God amidst the Rwandan Holocaust at 30; CNN anchor Anderson Cooper’s Dispatches from the Edge: A Memoir of War, Disasters and Survival at 43; and Isabella Hatkoff’s Owen & Mzee: The True Story of a Remarkable Friendship (between a baby hippo and a giant tortoise) at 44. In 2007, Ishmael Beah’s discredited A Long Way Gone: Memoirs of a Boy Soldier came in at 8; Walter Isaacson’s Einstein: His Life and Universe 13; Ayaan Hirst Ali’s autobiography of her life in Muslim society, Infidel, 18; The Reagan Diaries 25; Jesus of Nazareth by Pope Benedict XVI 29; Mother Teresa: Come be my Light 36; Clapton: The Autobiography 40; Tina Brown’s The Diana Chronicles 45; Tony Dungy’s Quiet Strength: The Principles, Practices & Priorities of a Winning Life 47; and Daniel Tammet’s Born on a Blue Day: Inside the Extraordinary Mind of an Autistic Savant at 49. Acknowledgements A sincere thank you to Michael Webster at RMIT for assistance with access to Nielsen BookScan statistics, and to the reviewers of this article for their insightful comments. Any errors are, of course, our own. References Australian Broadcasting Commission (ABC). “About Us.” Australian Story 2008. 1 June 2008. ‹http://www.abc.net.au/austory/aboutus.htm>. 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