Journal articles on the topic 'Porphyry of Gaza'

The study attempts to determine the economic condition of a small provincial bishopric, namely the church of Gaza (Palestine) during the rule of bishop Porphyry (circa 395–420 AD). All of the information on the subject comes from the Vita Porphyrii by Mark the Deacon – a source whose historical value has often been disputed. Although the information on the wealth of the church in Gaza at the turn of the 4th and 5th centuries is not particularly vast or illuminating, it is nevertheless possible to identify several spheres of economic activity of the Gaza bishopric. These are, among other things, the property owned by the bishopric (real estate), its cash reserves (mostly at the beginning of the 5th century), the endowments of the imperial court (given by emperor Arcadius and his wife, empress Aelia Eudoxia), as well as the charitable activity of the bishopric (especially on the occasion of erecting the Eudoxiane, probably in 407).

γ-Aminobutyric acid (GABA) participates in the regulation of adaptability to abiotic stress in plants. The objectives of this study were to investigate the effects of GABA priming on improving thermotolerance in creeping bentgrass (Agrostis stolonifera) based on analyses of physiology and proteome using iTRAQ technology. GABA-treated plants maintained significantly higher endogenous GABA content, photochemical efficiency, performance index on absorption basis, membrane stability, and osmotic adjustment (OA) than untreated plants during a prolonged period of heat stress (18 days), which indicated beneficial effects of GABA on alleviating heat damage. Protein profiles showed that plants were able to regulate some common metabolic processes including porphyrin and chlorophyll metabolism, glutathione metabolism, pyruvate metabolism, carbon fixation, and amino acid metabolism for heat acclimation. It is noteworthy that the GABA application particularly regulated arachidonic acid metabolism and phenylpropanoid biosynthesis related to better thermotolerance. In response to heat stress, the GABA priming significantly increased the abundances of Cu/ZnSOD and APX4 that were consistent with superoxide dismutase (SOD) and ascorbate peroxidase (APX) activities. The GABA-upregulated proteins in relation to antioxidant defense (Cu/ZnSOD and APX4) for the reactive oxygen species scavenging, heat shock response (HSP90, HSP70, and HSP16.9) for preventing denatured proteins aggregation, stabilizing abnormal proteins, promoting protein maturation and assembly, sugars, and amino acids metabolism (PFK5, ATP-dependent 6-phosphofructokinase 5; FK2, fructokinase 2; BFRUCT, β-fructofuranosidase; RFS2, galactinol-sucrose galactosyltransferase 2; ASN2, asparagine synthetase 2) for OA and energy metabolism, and transcription factor (C2H2 ZNF, C2H2 zinc-finger protein) for the activation of stress-defensive genes could play vital roles in establishing thermotolerance. Current findings provide an illuminating insight into the new function of GABA on enhancing adaptability to heat stress in plants.

Abstract Although the importance of GATA-1 in both primitive and definitive hematopoietic lineages has been shown in vivo, the precise roles played by GATA-1 during definitive hematopoiesis have not yet been clarified. In vitro differentiation of embryonic stem (ES) cells using OP9 stroma cells can generate primitive and definitive hematopoietic cells separately, and we have introduced a method that separates hematopoietic progenitors and differentiated cells produced in this system. Closer examination showed that the expression of erythroid transcription factors in this system is regulated in a differentiation stage-specific manner. Therefore, we examined differentiation of GATA-1 promoter-disrupted (GATA-1.05) ES cells using this system. Because the GATA-1.05 mice die by 12.5 embryonic days due to the lack of primitive hematopoiesis, the in vitro analysis is an important approach to elucidate the roles of GATA-1 in definitive hematopoiesis. Consistent with the in vivo observation, differentiation of GATA-1.05 mutant ES cells along both primitive and definitive lineages was arrested in this ES cell culture system. Although the maturation-arrested primitive lineage cells did not express detectable amounts of ɛy-globin mRNA, the blastlike cells accumulated in the definitive stage showed β-globin mRNA expression at approximately 70% of the wild type. Importantly, the TER119 antigen was expressed and porphyrin was accumulated in the definitive cells, although the levels of both were reduced to approximately 10%, indicating that maturation of definitive erythroid cells is arrested by the lack of GATA-1 with different timing from that of the primitive erythroid cells. We also found that the hematopoietic progenitor fraction of GATA-1.05 cells contains more colony-forming activity, termed CFU-OP9. These results suggest that theGATA-1.05 mutation resulted in proliferation of proerythroblasts in the definitive lineage.

Although the importance of GATA-1 in both primitive and definitive hematopoietic lineages has been shown in vivo, the precise roles played by GATA-1 during definitive hematopoiesis have not yet been clarified. In vitro differentiation of embryonic stem (ES) cells using OP9 stroma cells can generate primitive and definitive hematopoietic cells separately, and we have introduced a method that separates hematopoietic progenitors and differentiated cells produced in this system. Closer examination showed that the expression of erythroid transcription factors in this system is regulated in a differentiation stage-specific manner. Therefore, we examined differentiation of GATA-1 promoter-disrupted (GATA-1.05) ES cells using this system. Because the GATA-1.05 mice die by 12.5 embryonic days due to the lack of primitive hematopoiesis, the in vitro analysis is an important approach to elucidate the roles of GATA-1 in definitive hematopoiesis. Consistent with the in vivo observation, differentiation of GATA-1.05 mutant ES cells along both primitive and definitive lineages was arrested in this ES cell culture system. Although the maturation-arrested primitive lineage cells did not express detectable amounts of ɛy-globin mRNA, the blastlike cells accumulated in the definitive stage showed β-globin mRNA expression at approximately 70% of the wild type. Importantly, the TER119 antigen was expressed and porphyrin was accumulated in the definitive cells, although the levels of both were reduced to approximately 10%, indicating that maturation of definitive erythroid cells is arrested by the lack of GATA-1 with different timing from that of the primitive erythroid cells. We also found that the hematopoietic progenitor fraction of GATA-1.05 cells contains more colony-forming activity, termed CFU-OP9. These results suggest that theGATA-1.05 mutation resulted in proliferation of proerythroblasts in the definitive lineage.

AbstractCongenital erythropoietic porphyria (CEP), an autosomal recessive disorder, is due to mutations of uroporphyrinogen III synthase (UROS). Deficiency of UROS results in excess uroporphyrin I, which causes photosensitization. We evaluated a 3-year-old boy with CEP. A hypochromic, microcytic anemia was present from birth, and platelet counts averaged 70 × 109/L (70 000/μL). Erythrocyte UROS activity was 21% of controls. Red cell morphology and globin chain labeling studies were compatible with β-thalassemia. Hb electrophoresis revealed 36.3% A, 2.4% A2, 59.5% F, and 1.8% of an unidentified peak. No UROS or α- and β-globin mutations were found in the child or the parents. The molecular basis of the phenotype proved to be a mutation of GATA1, an X-linked transcription factor common to globin genes and heme biosynthetic enzymes in erythrocytes. A mutation at codon 216 in the child and on one allele of his mother changed arginine to tryptophan (R216W). This is the first report of a human porphyria due to a mutation in a trans-acting factor and the first association of CEP with thalassemia and thrombocytopenia. The Hb F level of 59.5% suggests a role for GATA-1 in globin switching. A bone marrow allograft corrected both the porphyria and the thalassemia.

Abstract Abstract 3441 Transcription factor GATA1 regulates a set of genes essential for the erythroid and megakaryocytic cell differentiation through the interaction with GATA motifs (consensus sequence: A/TGATAA/T). Two zinc fingers within GATA1 have been identified to be important in the DNA binding of GATA1, which are referred to as C-finger (CF) and N-finger (NF) domains. It has been shown that transactivation activity of GATA1 is completely abolished upon deletion of the CF domain, indicating that the CF domain is a requisite for the DNA binding of GATA1. While conventional reporter transactivation analyses hardly clarified the importance of the NF domain for the DNA binding, substitution mutations on 216th arginine (R216) located in the DNA-interacting surface of the NF domain have been identified to cause familial diseases of thrombocytopenia, thalassemia, and porphyria. As a consequence of the substitution of R216 to glutamine (Q) or tryptophan (W), DNA binding activity of GATA1 to a palindromic configuration of two GATA motifs (palindromic GATA) was largely diminished, while that to a single GATA motif was maintained. In this study we have examined the DNA binding diversity of GATA1 caused by the difference in the configuration of GATA motifs. We performed surface plasmon resonance (SPR) analyses of GATA1 to a single GATA, a palindromic GATA, and a repeating configuration of two GATA motifs (tandem GATA). We found that GATA1 binds to the palindromic GATA motif in a bivalent way, while it binds to the single GATA motif in a monovalent mode. We also found that a double quantity of GATA1 is associated with the tandem GATA motif and GATA1 lacking the NF domain binds to any configurations of GATA motif in a monovalent way. To further investigate contribution of the NF domain to the binding mode of GATA1, we have constructed two types of GATA1 mutants; one type was the substitution mutations on R216 (R216Q and R216W) that were mouse homologues of the human mutations, while the other type was the alanine substitution mutation on three lysine residues (K245, K246 and K312; referred to as 3KA mutant), whereby dimerization potential of GATA1 was reduced to trace level similar to the case for GATA1 lacking the NF domain. Impotantly, R216Q and R216W mutants bind the palindromic GATA motif in a monovalent way, while these mutants bind normally to the other configuration of GATA motifs. In contrast, we found that one molecule of 3KA mutant bound to the tandem GATA motif and this observation seems to explain well the fact that dimerization potential of GATA1 is an important requisite for the full-function of GATA1 in embryos. The binding modes of this 3KA mutant to the other configurations were not influenced. These results thus demonstrate that the both NF and CF domains recognize the multiple configurations of GATA motifs and specify the binding modes of GATA1. Importantly, GATA1-deficient mice rescued with R216Q were lethal during late gestation period due to abnormality in erythroid differentiation, indicating that the contribution of the NF domain to the recognition of the palindromic GATA motif configuration indeed functions in vivo. These results thus support our contention that the NF domain acts to regulate a proper spatio-temporal gene expression of a subset of GATA1 target genes utilizing the variations in the GATA motif configuration. Disclosures: No relevant conflicts of interest to declare.

Abstract Germline mutations in the X-linked hematopoietic transcription factor, GATA-1, have been associated with dyserythropoietic anemia (DEA), macrothrombocytopenia (MTP), and congenital erythropoietic porphyria. Recently, morphological features suggestive of the Gray Platelet Syndrome (GPS) were described in a pedigree with a germline R216Q GATA-1 mutation (Blood106:6a, 2005). The present study has evaluated platelets (Pl) in the electron microscope from members of a previously described pedigree (Blood98:2681–2688, 2001) with GATA-1 G208S, MTP, and dyserythropoiesis without anemia, for whom detailed platelet morphology studies have not been reported. The presence of a hemizygous GATA-1 mutation was confirmed by conventional fluorescent dye chemistry sequencing of DNA from patient peripheral blood mononuclear cells. Their Pl revealed wide variations in size, shape, internal and external structure. Some normal sized and giant Pl contained usual numbers of alpha granules and dense bodies, while most of the large cells were hypogranular. Some contained no membrane systems or organelles. Others were filled with masses of dense tubular system (DTS) channels, and others contained the tubular inclusions found in the Medich Giant Platelets Disorder (Platelets15:345–353, 2004). Many of the hypogranular cells contained small vacuoles that may have been enclosing membranes of alpha granules. Except for the tubular inclusions, all of these structural variations are observed in GPS Pl (Am. J. Pathol.95:445–462, 1979). However, additional striking abnormalities were seen in GATA-1 Pl that are not characteristic of GPS Pl. Many GATA-1 Pl contained unusual, closely associated dense double membranes differing from normal elements of rough endoplasmic reticulum, smooth endoplasmic reticulum, DTS or surface connected open canalicular system (OCS), but resembling channels of the OCS after exposure to EDTA. They were observed previously only in megakaryocytes (Mk) from one family with GATA-1 DEA-MTP (Nat. Genet, 24:266–270, 2000). The dense double membranes were often found in parallel association and, in some examples, isolating areas of cytoplasm. However, the isolated areas were not undergoing autophagic degradation as such areas enclosed by elements of the DTS do in White Platelet Syndrome Pl (Platelets 15:173,2004). Instead, they proved to be another unique feature of GATA-1 platelets, the presence of Pl within Pl. The sequestered cells were usually mature in appearance and often discoid in form with circumferential coils of microtubules. In some GATA-1 Pl there were two Pl within the same cell, and on rare occasions, a Pl within a Pl within a Pl. Pl within Pl have never been observed previously in any human platelet disorder. Another unique feature, related to Pl within Pl, was the frequent Pl to Pl surface attachment of non-activated cells forming large macrothrombocytes with no similarity to aggregates of stimulated normal platelets. Conclusion: The substructural abnormalities of Pl from patients with germline GATA-1 mutations share some overlap with those seen in GPS Pl, but are distinct and unique. The MTP, Pl within Pl and surface Pl to Pl attachments suggest a major defect in the formation and separation of GATA-1 Pl from pro-Pl of the parent Mk, resulting in the MTP characteristic of the disorder.

Mutations in the X-linked hematopoietic transcription factor, GATA-1, have been associated with dyserythropoietic anemia, congenital erythropoietic porphyria and macrothrombocytopenia. Earlier we described the platelet pathology in 3 male members of a previously reported (Mehaffey M.G. et all: Blood. 2001; 98:2681–2688) family with the GATA-1 G208S mutation and serious bleeding problems. All were found to have giant hypogranular platelets with frequent tubular inclusions, parallel associated double membrane sheets connected to channels of the surface connected open canalicular system (OCS), platelets in platelets, and platelets attached to platelets. Their platelets spread normally on formvar grids, but the ability to bind von Willebrand factor (vWF) was half that of normal controls and limited to small multimers rather than the cargo net of large multimers bound by normal platelets. The present study has focused on platelets from four possible female carriers of the GATA-1 mutation in this family. All four of the women have had mild bleeding symptoms, close to normal platelet counts, slight increases in MPV, but no platelet abnormalities on peripheral blood smears. Thin sections of their platelets examined in the electron microscope revealed features consistent with the pathology observed in male family members. Most of their platelets were normal-sized, discoid cells containing the usual complement of alpha and delta storage organelles and channels of the dense tubular system and OCS. However, a significant member of giant platelets containing the usual frequency of alpha and delta granules and hypogranular and agranular giant platelets were observed. The frequency of the macrothrombocytes varied in each of the four women studied, but were present in all. The ability of their platelets to bind multimers of vWF, in contrast to male family members, did not differ from normal controls. Near normal as well as normal platelet counts and the ability of their platelets to bind vWF multimers may protect them from the serious bleeding problems of males with the X-linked GATA-1 G208S mutation. Our findings indicate that obligate female carriers of the GATA-1 gene can be detected by examination of their platelets in the electron microscope.

Geoscientific data interpretation is a highly subjective and complex task because human intuition and biases play a significant role. Based on these interpretations, however, the mining and petroleum industries make decisions with paramount financial and environmental implications. To improve the accuracy and efficacy of these interpretations, it is important to better understand the interpretation process and the impact of different interpretation techniques, including data processing and display methods. As a first step toward this goal, we aim to quantitatively analyze the variability in geophysical data interpretation between and within individuals. We carried out an experiment to analyze how individuals interact with magnetic data during the process of identifying prescribed targets. Participants performed two target spotting exercises where the same magnetic image was presented at different orientations. The task was to identify the magnetic response from porphyry-style intrusive systems. The experiment involved analyzing the data observation pattern during the interpretation process using an eye tracker system that captures the interpreter’s eye gaze motion and the target-spotting performance. The time at which targets were identified was also recorded. Fourteen participants with varying degrees of experience and expertise participated in this study. The results show inconsistencies within and between the interpreters in target-spotting performance. The results show a correlation between a systematic data observation pattern and target-spotting performance. Improved target-spotting performance was obtained when the magnetic image was observed from multiple orientations. These findings will help to identify and quantify the effective interpretation practices, which can provide a roadmap for the training of geoscientific data interpreters and contribute toward the understanding of the uncertainties in the data interpretation process.

Abstract Abstract 3208 The Congenital Erythropoietic Porphyria (CEP) is a rare form of Chronic Porphyria characterized by severe photosensivity. Secondary infections of cutaneous lesions may lead to scarring, deformities and disfigurement of the light-exposed parts of the body such as hands, ears, nose, and eyelids. Erythrodontia, osteodystrophia, combining osteolysis and osteoporosis, hypercellular bone marrow, hemolytic anemia, hypersplenism, splenomegaly and red-coloured urine are present in almost all patients. Generally, CEP is an autosomic recessive disease caused by mutations in homozygosis or compound heterozygosis in UROS gene coding for the fourth enzyme of the heme biosynthesis pathway. At present a new form of CEP with an X-linked inheritance associated with R216W mutation in the GATA 1 gene has been described only in one French-English family by Philips JD et al. GATA1 is a key zinc finger transcription factor that coordinates hematopoietic cell differentiation. We described a Turkish family where a severe CEP phenotype segregates with thalassemia and thrombocytopenia. The propositus is an 4 year old boy who presented photosensitive bullous dermatosis, splenomegaly, short stature and pallor. His mother was chronically anemic (Hb 10.9 g/dL) and thrombocytopenic (96×109/L) known as chronic immune thrombocytopenic purpura, whereas the father and the brother were asymptomatic. At birth, the boy had hypochromic, microcytic anemia, thrombocytopenia and thrombasthenia. Reticulocyte counts slightly increased. At 2 months he was transfused, splenomegaly and heart murmur were detected on physical examination. At this point his Hb level was 6,9 g/dl, WBC 7,400×109/L, platelets 64–106×109/L, MCV 70 flL, RDW 28%. The patient's peripheral-blood smear revealed microcytic, hypochromic red cells, target cells, basophilic stippling, and rare nucleated red cells, findings compatible with thalassemia but DNA analysis for beta and alpha thalassemia was normal. A bone marrow aspirate revealed a hypercellular marrow and erythroid hyperplasia. Dyserythropoiesis was noted with nuclear budding, nuclear bridging, and occasional multinucleation. Megakaryocytes were decreased in number, Hb electrophoresis revealed increased levels of fetal hemoglobin (HbA2 2%; Hb F 68%). At 3 years liver MRI detected iron overload. Ferritin level was 329ng/dL. Because of some skin lesions on his body he was then tested with urine and plasma analysis and the results were consistent with the diagnosis of congenital erythropoietic porphyria. Urine total porphyrins were 5414 nmol/mmol creatinin (N<35) with an excess of isomer I of both Uroporphyrins and Coproporhyrins. Total plasma porhyrins were 312 nmol/L (N<10). We analyzed the UROS gene and we identified a new mutation c.338A>T (D113V) in heterozygosis in the propositus, in his father and in his brother. On the basis of hematological status we decided to analyze also GATA1 gene and the mutation c.646C>T (R216W) has been detected in the child and on one allele of his mother who presents a balanced pattern of X-inactivation. The patient is similar to the case of association of CEP with an hematologic phenotype of beta-thalassemia intermedia. Markedly elevated Hb F levels, and thrombocytopenia result from mutations in the transacting factor GATA-1 presented by Philips JD et al. This patient additionally has a severe liver iron overload. A newborn sibling died at birth because of sepsis and neonatal hepatitis. Liver iron overload was also detected in the sibling's autopsy. All components of family were heterozygous for the H63D mutation in HFE gene but no other HAMP, HJV and SLC40A1 mutations were found. The patient started a regular transfusion program and Deferasirox was given for hemosiderosis after Desferroxamine uncompliance. This is the first report of the association of GATA1 and UROS gene mutations that could explain the very severe hematological phenotype. Disclosures: No relevant conflicts of interest to declare.

Laima Bloznelytė-Plėšnienė1, 2, Daiva sendiulienė1, Jurgita Liutkevičiūtė-Navickienė1, Laimutė Rutkovskienė1, Valerijus Ostapenko1, Narimantas Evaldas Samalavičius1 1 Vilniaus universiteto Onkologijos institutas, Santariškių g. 1, LT-08406 Vilnius2 Klaipėdos universitetas, Herkaus Manto g. 84, LT-92294, KlaipėdaEl. paštas: pdt@mail.lt TikslasNustatyti sensibilizuotų navikų terapijos galimybes gydant išplitusį krūties vėžį. Ligoniai ir metodaiNuo 2001 m. 54 ligonėms išplitusiam krūties vėžiui gydyti taikyta sensibilizuotų navikų terapija (SNT). 53 ligonėms rastos dauginės metastazės. Metastazės smegenyse diagnozuotos 19 ligonių, kauluose – 29, kepenyse – 15, plaučiuose – 12, limfmazgiuose – 16, minkštuosiuose audiniuose – 13 ir odoje – 15 ligonių. Taikydami SNT į veną suleisdavome 2,5 mg/kg hematoporfirino darinio (HpD) ir jis po 24 val. selektyviai susikaupdavo navikiniame audinyje. Praėjus 24 val. po HpD suleidimo jam aktyvinti navikus apšviesdavome raudona 635 nm šviesa – tai vadinamoji fotosensibilizuotų navikų terapija (FDT), ir (arba) taikydavome radiosensibilizuotų navikų terapiją (RST) – praėjus 24, 48 bei 72 val. po HpD suleidimo naviką apšvitindavome 60Co skleidžiamais gama spinduliais 2 Gy doze. Suminė dozė – 6 Gy. RST taikėme visoms 54 ligonėms.FDT taikėme: 16 ligonių vietiškai krūtinės odoje ir poodyje išplitusiam vėžiui gydyti bei 1 ligonei metastazei akies tinklainėje gydyti. Visų odos ir poodžio navikų riboms patikslinti taikėme ir fotodinaminę diagnostiką. Praėjus 24–78 val. po HpD suleidimo, įtartinus odos plotus apšviesdavome violetine 405 nm šviesa. Navikinis audinys švytėdavo avietine spalva. RezultataiPritaikius SNT 54 ligonėms išplitusiam krūties vėžiui gydyti, 33 pacientėms per 7–10 dienų po RST labai pakilo Karnovskio indeksas, šešioms pacientėms visi navikai visiškai regresavo, 14 moterų visi gydyti navikai regresavo daugiau nei 50 %, ligos remisija truko ilgiau nei 6 mėn. Šešiolika ligonių navikų regresija buvo dalinė, 18 ligonių gydymas buvo neveiksmingas. SNT buvo ypač efektyvi krūties vėžio metastazėms smegenyse ir kauluose gydyti. Vienai ligonei po dviejų RST kursų visiškai išnyko visos trys metastazės galvos smegenyse. Šešioms ligonėms visos metastazės smegenyse regresavo daugiau nei 50 %, ligos remisija truko daugiau nei 6 mėnesius. Dauginių krūties vėžio metastazių smegenyse turinčių 19 ligonių vidutinis išgyvenamumas nuo metastazių smegenyse diagnozavimo buvo 12 mėnesių. Pritaikius RST 29 ligonėms dauginėms krūties vėžio metastazėms kauluose gydyti, 7 ligonėms gauta visiška visų dauginių kaulinių metastazių regresija. Ligos remisija (moterys buvo kliniškai sveikos) truko 95; 48; 21; 19; 12; 11 ir 4 mėn. nuo RST. IšvadosSensibilizuotų navikų terapija yra perspektyvus išplitusio krūties vėžio gydymo metodas. Šis metodas ypač veiksmingas gydant krūties vėžio metastazes galvos smegenyse ir kauluose. Tikslinga toliau tyrinėti šį gydymo metodą, siekiant jį modifikuoti pagal ligos išplitimą ir metastazių lokalizaciją. Reikšminiai žodžiai: išplitęs krūties vėžys, sensibilizuotų navikų terapija, hematoporfirino darinys. Sensitized treatment and diagnostics of advanced breast cancer Laima Bloznelytė-Plėšnienė1, 2, Daiva sendiulienė1, Jurgita Liutkevičiūtė-Navickienė1, Laimutė Rutkovskienė1, Valerijus Ostapenko1, Narimantas Evaldas Samalavičius1 1 Vilnius University, Institute of Oncology, Santariškių Str. 1, LT-08406 Vilnius, Lithuania2 Klaipėda University, Herkaus Manto Str. 84, LT-92294, Klaipėda, LithuaniaE-mail: pdt@mail.lt Background / objectiveThe current methodologies used in oncology are of quite limited possibilities. Therefore, there is a constant search for the new perspective treatment methods that could prolong the life of cancer patients and improve its qualitaty. One of such methods is sensitized tumour therapy based on quite selective porphyrin accumulation in tumours. This study presents our primary results in radiosensitized advanced breast cancer therapy using hematoporphyrin derivatives as photo-and radiosensitizers. Patients and methodsIn 2001–2010, a total of 54 female patients with advanced breast cancer underwent radiosensitized treatment (RST). All patients had undergone chemotherapy and / or radiotherapy and surgical treatment before RST. In all cases, any radical method of treatment was impossible. Multiplex metastatic lesions were established in 53 patients. Brain multiplex metastases were diagnosed in 19 patients and multiplex bone metastases in 29 patients. Lung metastatic lesions were found in 12 patients, liver in 15 patients, lymph node metastases in 16 patients. The hematoporphyrin derivative was injected intravenously; 24, 48 and 72 hours after injection of the sensitizer, the tumorus were irradiated with gamma rays from radioactive 60Co, 2 Gy at a time (6 Gy per course). In all cases when it was possible, patients undervent also photodynamic therapy. Tumours were irradiated with red 630 nm laser light. ResultsAs a result of RST, complete regression of all treated tumours was observed in 6 patients after two or more RST courses. A significant response – regression of more than 50% of all brain metastases and remission of the disease for over 6 months – was established in 14 patients. Partial response was observed in 16 patients with malignant brain tumours. For the rest of 18 patients the treatment was ineffective. The Karnofsky performance scale index increased immediately in 33 patients following RST treatment. RST was especially effective in the treatment of brain and bone metastatic lesions. As regards brain metastazes, in one patient all three brain metastatic lesions completely disappeared and there were no evidence of any recurrence in brain for 8 months. In 6 patients, regression of more than 50% of all brain metastases and remission of the disease for over 6 months was established. The median survival of 19 patients with multiplex brain metastases was 12 months from the moment of brain metastases detection. As regards bone metastazes, as a result of RST, all metastatic bone lesions completely disappeared in 7 patients. ConclusionRadiosensitized advanced metastatic breast cancer treatment is a hopeful method, especially when lesions involve the brain and bones. Keywords: advanced breast cancer, radiosensitized treatment, hematoporphyrin derivative.