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Background: Tumor infiltrating lymphocytes (TILs) are a promising inexpensive prognostic and predictive biomarker in breast cancer. High levels of TILs are associated with improved survival and higher probability to achieve pathological complete response in triple-negative breast cancer (TNBC)., Objective: To assess the level of TILs in TNBC samples and analyze the association between the level of TILs and the main pathological parameters, to identify their impact on long-term results., Material and Methods: The study included information on 140 patients with I-III stage TNBC and estrogen receptors <10%. Tumor tissue samples at baseline biopsies were evaluated the histological type, HER2 expression, estrogen expression levels, Ki-67 and TILs. The pathological response was evaluated according to the ypTNM, Miller-Payne, and RCB classifications., Results: The average level of TILs in biopsy specimens before NACT was 29.3±23.1%. Low levels of TILs (<10%) were defined in 21% of cases, intermediate levels (≥10% to ≤40%) in 55% of cases, and high levels (>40%) in 24% of cases. Using the two-tiered system, low TILs (≤40%) were defined in 76% and high TILs (>40%) in 24% of cases. The level of TILs was correlated with histological grade (R=0.187; p =0.027) and estrogen receptor expression level (R=0.211; p =0.012). There were no significant differences depending on the level of TILs and other pathological parameters. Three-year event-free survival (EFS) in patients with high TILs levels was 95% versus 65% in the low TILs group ( p =0.037)., Conclusion: Stromal TILs are an important prognostic biomarker in TNBC. Using a cutoff of 40%, high TILs are significantly associated with longer EFS.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common (30%-35%) type of B-cell lymphoma. Only about 60% of all newly diagnosed advanced-stage DLBCL can be completely treated with x6 R-CHOP. High-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation in the first remission (upfront auto-HSCT) can serve as an option to improve a prognosis in these patients., Aims: This trial aimed to improve prognosis in DLBCL by upfront auto-HSCT., Methods and Results: A group of 105 patients: DLBCL NOS, age 18-65, stage IV, IPI ≥2, CR/PR after x6 R-CHOP/DA-EPOCH-R from 2010 to 2019 at NMRC of Oncology named after N.N.Petrov of MoH of Russia was retrospectively analyzed. The HSCT group included patients with upfront HDCT followed by auto-HSCT (n = 35). The control group included patients with non-invasive follow-up after induction (n = 70). Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), response rate and relapse rate. The 3-year OS (p = .013) and 3-year PFS (p = .033) were significantly higher in the HSCT group. The 3-year OS was decreased by the occurrence of relapse (p ≤ .001) and weight loss (B-symptom) (p = .04). DEL was the negative prognostic factor for 3-year PFS in all patients (p = .001) and control group (p = .001). DA-EPOCH-R significantly increased the 3-year PFS (p = .041)., Conclusion: Upfront HDCT followed by auto-HSCT can increase 3-year OS and PFS and improve prognosis in DLBCL NOS, age 18-65, stage IV, IPI ≥2 patients., (© 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Eyelid tumors are the most common neoplasms in everyday ophthalmic practice and cover a wide range of benign and malignant lesions. Surgical methods, cryodestruction, laser therapy and radiation therapy are used in the treatment of malignant eyelid tumors. Chemotherapy does not occupy a prominent place in the treatment of malignant eyelid tumors, its use is limited to sensitive tumors., Objective: To assess the antitumor activity of the Russian-developed chemical compound 2-[3-(2-chloroethyl)-3-nitrosoureido]-1.3-propandiol (chlonisol) on the models of transplantable tumors of various histogenesis implanted into the lower eyelid., Material and Methods: The study was carried out on 67 mice of lines 129/SN, BALB/c and C57BL/6 that had Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and B16 melanoma transplanted into the eyelid. Tumor transplantation was done by injecting 0.05 ml of sterile sodium chloride solution containing 10 6 cells of Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1, or 10% suspension of tumor tissue of B16 melanoma. The injection was performed into the right lower eyelid in the direction from the outer towards the inner corner of the eye using a thin needle (29G). Chlonisol was administered at the maximum tolerated dose of 20 mg/kg or at the lower dose of 15 mg/kg intraperitoneally 24 hours after tumor transplantation., Results: In mice with Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and melanoma B16 transplanted under the skin of the lower eyelid, a single intraperitoneal injection of chlonisol at the dose of 20 or 15 mg/kg caused significant inhibition of tumor growth reaching 100%. Chlonisol significantly increased overall survival in animals with Ehrlich carcinoma (log rank test, p =0.0464), sarcoma 37 (log rank test, p <0.0001), lymphosarcoma LIO-1 (log rank test, p =0.0122) and B16 melanoma (log rank test, p <0.0001); the proportion of animals that were fully healed was 25, 78, 67 and 25%, respectively., Conclusion: Chlonisol has a pronounced antitumor effect in mice with Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and B16 melanoma transplanted into the eyelid.

Modern approaches to the organization of diagnosis and treatment of elderly and senile patients with malignant tumors allow to maintain the necessary level of health, improve the quality of life and increase life expectancy. Assessment of geriatric status in Oncology allows: to predict complications during the complex treatment, including drug treatment; to modify treatment to reduce the risk factors of adverse outcomes; to select patients for specialized treatment using standard schemes. So, timely assessment of geriatric syndromes and their correction can expand the indications for specialized treatment of elderly and senile patients.

HER2-positive breast tumors are found in 25-30% of patients with breast cancer and are characterized by aggressive course and reduced sensitivity to both chemotherapy and hormone therapy. The aim of the work was to study the possibilities of enhancing the therapeutic effect of anti-estrogen drug toremifene by combining it with biguanide, metformin, on the HER2-positive breast cancer model in FVB/N HER-2/neu transgenic mouse. Male FBV/N mice with intramuscularly transplanted HER2-positive mammary gland tumor from a female mouse of the same strain have been given toremifene (30 mg/kg, orally daily) or metformin (100 mg/kg, orally daily) that had a moderate antitumor effect (decrease the area under the kinetic curve of tumor growth by 1.6 and 1.5 times, respectively, when compared with intact control). Co-administration of these drugs in the same doses had a more pronounced effect (the area under the kinetic curve of tumor growth decreased by 3.1 times compared to intact control; p<0.05). After 10 days, in group receiving toremifene all 10 mice developed inguinal-scrotal hernias, and in group that received toremifene plus metformin - only 5 of 10 (p=0.0325). By the 15 th day after the start of treatment, the hernias was also determined in all mice treated with the combination of toremifene and metformin, but the size of the hernial sac was significantly smaller than in those receiving only toremifene - 537 ± 96 mm 3 and 1309 ± 120 mm 3 , respectively (p=0.0001). A possible explanation is the manifestation of collagen-degrading effect of toremifene., Competing Interests: The authors declare that there is no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Using of radiochemotherapy improves short-term and long-term results of treatment in patients with primary Hodgkin’s lymphoma (HL) comparing with treatment by chemotherapy alone. The rates of 5-year, 10-year OS and DFS are 88%, 83% and 90%, 86% in case of radiochemotherapy, versus 73%, 66% and 72%, 68% using chemotherapy alone. The 5-year and 10-year OS, DFS estimates in treatment with ABVD are 84% and 83%, 75% and 74%; BEACOPP-baseline - 83% and 82%, 82% and 81% (p<0.05). At the same time ABVD chemotherapy develops less toxicity (p<0.001). The treatment with 6 cycles of ABVD is considered as the most appropriate in primary Hodgkin’s lymphoma patients with extranodal lesions. Comparison of complications rate during chemotherapy with MOPP, ABVD, BEACOPP-baseline, BEACOPP-escalated reveals major hematologic toxicity and infectious complications rate in BEACOPP-escalated program (p<0,05). The age ≥45 years, hemoglobin <105g/l, B symptoms, fibrinogen >5g/l, involvement of 3 and more areas of lymph nodes, liver involvement, inguinal lymph nodes are defined by the multiple-factor analysis as adverse prognostic factors of patients with primary Hodgkin’s lymphoma (HL) with extranodal lesions (p<0.05). Allocation of group of high risk is proved by correlation between survival and the Prognostic Score (PS). The 5-year and 10-year DFS, OS for patients with PS-0-2 estimates are 88% and 86%, 89% and 83%, for patients with PS-3-4 - 78% and 69%, 80% and 77%, for patients with PS-5-6 - 43% and 42%, 60% and 38% respectively (p<0.001).

Gemcitabine is known to exert a therapeutic effect on brain tumors despite the limited permeability of the blood-brain barrier (BBB). In our experimental research single intraperitoneal (i.p.) injection of gemcitabine 25 mg/kg provided increase in median survival of mice with intracranially transplanted Ehrlich carcinoma by 41-89% (p < 0.001). In this experimental model i.p. administration of gemcitabine (permeability of the BBB of less than 10%), carmustine (good permeability of the BBB), cyclophosphamide (poor permeability of the BBB) and cisplatin (doesn't penetrate through the BBB) increased median survival of mice by 88% (p < 0.001), 59% (p = 0.001), 35% (p = 0.005) and 18% (p = 0.302) respectively. Considering strong correlation between antitumor activity of the drugs (carmustine, cyclophosphamide and cisplatin) and their permeability of the BBB, efficacy of gemcitabine in intracranial tumors could be due to its wide range of therapeutic doses.

Using of radiochemotherapy improves short-term and long-term results of treatment in patients with primary Hodgkin's lymphoma (HL) comparing with treatment by chemotherapy alone. The rates of 5-year, 10-year OS and DFS are 88%, 83% and 90%, 86% in case of radiochemotherapy, versus 73%, 66% and 72%, 68% using chemotherapy alone. The 5-year and 10-year OS, DFS estimates in treatment with ABVD are 84% and 83%, 75% and 74%; BEACOPP-baseline--83% and 82%, 82% and 81% (p < 0.05). At the same time ABVD chemotherapy develops less toxicity (p < 0.001). The treatment with 6 cycles of ABVD is considered as the most appropriate in primary Hodgkin's lymphoma patients with extranodal lesions. Using more than 6 cycles doesn't seem to improve OS and DFS (the 5-year and 10-year DFS, OS estimates are 79% and 72%, 80% and 77% versus 88% and 87%, 90% and 89% (p < 0.05). Comparison of complications rate during chemotherapy with MOPP (919 cycles), ABVD (1300 cycles), BEACOPP-baseline (584 cycles), BEACOPP-escalated (140 cycles) reveals major hematologic toxicity and infectious complications rate in BEACOPP-escalated program (p < 0.05).

Michael Lazarevich Gershanovich was born 90 years ago. He has made a significant contribution to foundation and development of chemotherapy for malignant tumors. Doctor of Medical Sciences, Professor, Laureate of the State Prize of the Russian Federation, Honored Scientist of the Russian Federation, Academician of the Russian Academy of Natural Sciences, a member of the Editorial Board of the Journal "Problems in Oncology" ("Voprosy Onkologii), member of the World Club of Petersburgians, a retired lieutenant-colonel Michael Lazarevich, until his last day (16.12.2013), was the head of the Department of Medical Oncology of the N.N.Petrov Research Institute of Oncology, St. Petersburg.

In order to identify immunohistochemical markers associated with primary refractory Hodgkin's lymphoma, 20 patients with primary refractory form at stage IIAB in complete remission underwent histological examination and immunohistochemical determination of Bcl-6, Bcl-2, c-kit (CD117), CD15, CD30, P-53, Ki-67. In the group with primary refractory Hodgkin's lymphoma at stage IIAB Bcl-6 expression was found in 2 patients (10%), Bcl-2 in 14 patients (70%), c-kit (CD117) in 16 patients (80%), CD15 in 9 patients (45%). The expression of CD30 and P-53 was observed in all patients in this group (100%). The expression of Ki-67 ranged from 20% to 100%, 80-100% in 16 patients (80%). As a result, multivariate analysis revealed no immunohistochemical markers of primary refractory Hodgkin's lymphoma. In univariate and multivariate analyzes in a group of primary refractory Hodgkin's lymphoma a high level P-53 expression (80-100%) was significantly associated with decreased overall survival. A 5-year overall survival in patients with Hodgkin's lymphoma with the expression level of P-53 < 80% was 78%, with the expression level of P-53 80-100%-22%. A 5-year overall survival of Hodgkin's lymphoma primary patients in complete remission significantly exceeded the rates of patients with primary refractory Hodgkin's lymphoma--100% vs. 52%.

In a retrospective study during the primary mode MOPP to primary patients LH II/IVAB stages with a poor prognosis rate of CR, 5--and 10-year DFS, OS was 69%, 71% and 68%, 74% and 64%, ABVD--76%, 78%, 83% and 68%, BEACOPP-baseline--73%, 97%, 85% and 82%, respectively. When the program ran BEACOPP-baseline it was revealed higher rates of DFS compared with ABVD and MOPP. Higher OS rates were observed in the primary patients treated with BEACOPP-baseline compared with MOPP (p = 0.04). In terms of DFS and OS MOPP regimen did not differ from ABVD. Program ABVD and BEACOPP-baseline had no differences in terms of OS. The frequency of primary refractory forms of LH did not depend on the conducted regimens of PCT. Significantly less recurrences occurred during the regimen of BEACOPP-baseline compared to MOPP and ABVD. BEACOPP-baseline was accompanied by a more pronounced reversible hematologic toxicity. Against the background of the program BEACOPP-baseline, neutropenia of III-IV degree was detected in 32%, ABVD--16%, MOPP--13%.

The absolute sensitivity signs of breast cancer to the drug have not yet been developed. Data from clinical trials on the study of experimental laboratory predictive markers of chemosensitivity: TOP2alpha (topoisomerase 2-alpha), beta-tubulin (subunit of dimeric protein tubulin), and BRCA1 (breast cancer 1) are contradictory and not numerous. Analysis of the results by the end of the clinical trial will allow examining the correlation between the effectiveness of preoperative taxane-chemotherapy and the level of experimental and standard molecular markets that is important for development of algorithm of treatment tactics for patients with locally advanced breast cancer.

The retrospective study revealed the 15% relapse rate in patients with stage II-IV unfavorable prognosis Hodgkin lymphoma, 5-year OS in relapsed patients was 84%. Karnofsky score less than 80 (p=0,0001), more than 1 extranodal lesion (p=0,0004), extensive (equal to stage III-IV) involvement on relapse (p=0,001), b-symptoms on relapse (p=0,023), more than 5 lymph nodal lesions (p=0,027), albumin level less than 40 g per liter (p=0,037), detection of new nodal lesions (p=0,041) were shown by discriminative analysis as the therapy effect predictors in patients with Hodgkin lymphoma relapse. In patients with second-line therapy failure the actuarial survival rate was lower by 55% in comparison to patients with chemosensitive relapses (40% and 95%). The secondary therapy resistance was shown to be an unfavorable prognosis predictive factor (p=0,0001). The multifactorial overall survival analysis revealed the following adverse prognostic factors: failure of second-line treatment (p=0,0001), first early relapse (p=0,01), albumin level on relapse less than 40 g per liter (p=0,02), use of standard chemotherapy instead of irradiation (p=0,02). The relapse patients with 1 or less risk factors had 95% 5-year OS, the patients with 3 or more adverse risk factors had 70% OS (p=0,0002). The lowest 10-year OS was observed in patients with 2 or more adverse risk factors, 48% and 28% accordingly. Adverse risk factors must be considered while choosing the optimal treatment strategy aimed at better survival rate.

Retrospective analysis defined risk factors of primary-refractory course of Hodgkin's lymphoma as well as adverse prognostic factors, efficacy of I and II therapy lines in patients with primary-refractory forms of Hodgkin's lymphoma. By means of discriminant analysis risk factors were as follows: massive tumor lesion, chemotherapy as compared to chemoradiotherapy in the I line, intoxication symptoms, IPS > or = 3, LDH level more than 1,5xULN, late beginning of specialized treatment (over 12 months from initial symptoms of disease), damage of 5 and more areas of lymph nodes, age more than 45 years, increase of ESR higher than 30 mm/h in Stage B and 50 MM/H in Stage A, Stage IV of disease, leukocyte rate higher than 15 x 10(9)/l, presence of more than one extranodal lesion. As a result there were revealed 4 prognostic factors unfavorably influencing on survival rates in primary-refractory forms of Hodgkin's lymphoma with originally Stages II/IV with poor prognosis. The worst 5-year survival rates were found in the presence of 3 and 4 adverse prognostic factors. These circumstances should be taken into consideration choosing optimal treatment and predicting of success of the proposed treatment.

SHR mice with intracranial transplanted lymphosarcoma LIO-1 received a single intraperitoneal gemcitabine injection in maximal tolerated dose of 25 mg/kg or single maximal tolerated oral dose of lomustine, 50 mg/kg. Compared to control group gemcitabine injection increased the mice lifespan 1.4-fold (p < 0,01) and oral lomustine 1.6-fold (p < 0,01). The median lifespan of the mice receiving both gemcitabine and lomustine in maximal dose underwent a significant 3.3-fold increase (p < 0,01) compared to controls (2.4-fold compared to gemcitabine and 2.1-fold compared to lomustine group). Combined therapy didn't cause an increase of toxicity.

In this retrospective clinical study 100 patients with primary unfavorable prognosis stage II Hodgkin lymphoma (HL) (n = 50) or stage IV HL (n = 50). The ABVD chemotherapy allowed to achieve remission in 90% of cases with 5-year relapse-free survival (RFS) and overall survival (OS) of 64% and 92%, the basic BEACOPP regimen lead to the same 90% remission rate with 74% DFS and 94% OS. These results for ABVD and basic BEACOPP regimens are characterized by similar statistic values (p = 1.0; p = 0.6; p = 0.9), although the use basic BEACOPP lead to statically valid decrease of grade III-IV toxicity (p = 0.005). The occurrence of primary refractory HL was slightly higher in basic BEACOPP group (18% versus 10% in ABVD group), although this difference had no statistical value (p = 0.3) and was probably due to higher number of patients with > 1 extranodal localizations. The occurrence of primary refractory HL correlated to disease stage: 6% in stage II and 22% in stage IV (p = 0.04). HL relapse frequency in ABVD and BEACOPP groups was similar (12% and 8%), there was no statistically valid difference (p = 0.5). In ABVD and basic BEACOPP recipients with stage II/IV HL the primary refractory disease rate was 15%, relapse rate was 10%. Five-year OS in primary refractory and relapsed patients was lower, than in general patient population (64% and 70% compared to 80%), although the difference had no statistical significance (p = 0.6, p = 0.7).

Antitumor activity of a new cytostatic drug combination of gemcitabine and dioxadet have been studied in 86 female SHR mice transplanted with 5 x 10(6) of ascitic Ehrlich's tumor cells each. All mice received a single injection of gemcitabine, dioxadet on combination 48 hams after tumor cells introduction. In first series, experimental animals received maximal tolerable dose of gemcitabine (25 mg/kg) and one half of dioxadet maximal tolerable dose (2.5 mg/kg). In the second series of experiments, the animals received 5 mg/kg of dioxadet along with the same gemcitabine dose. Effect of drugs was compared using the time to ascites detection, body weight increase, and survival time. Gemcitabine and dioxadet administered separately and in combination inhibited the growth of ascitic Ehrlich's tumor in the mice. In both series of experiments antineoplastic activity of gemcitabine and dioxadet combination was significantly higher in comparison to the control groups receiving these drugs separately. The highest antineoplastic activity of the gemcitabine and dioxadet combination was observed when the maximal tolerable doses of both drugs was applied. However, the tumor cells growth was also significantly inhibited in mice receiving half of dioxadet dose. Synergism of antitumor activity of gemcitabine and dioxadet was not accompanied by appreciable increase in toxicity.

Efficiency of gemcitabine plus lomustine treatment of transplantable lymphosarcoma LIO-1 in mice was significantly higher than that of monotherapy. According to the area under the kinetic curve for tumor growth, antitumor action, for single maximum tolerable dose of gemcitabine 25 mg/kg body, rose 4.6 times (p < or = 0.001), for lomustine 50 mg/kg body,--2.9 times (p < or = 0.01). The combination involved moderately increased toxicity. Lethality rate for gemcitabine+lomustine, 50 mg/kg body each, was as low as one and a half times as compared with gemcitabine therapy alone, 50 mg/kg body, (30 and 20%, respectively). The antitumor action of the combination (50 mg/kg body), was 32 times that of gemcitabine 50 mg/kg body (p < or = 0.001) and lomustine 50 mg/kg body--30 times (p < or = 0.001).

Late complications in type 2 diabetic patients are commonly associated with accelerated development of atherosclerosis. In type 2 diabetes mellitus, non-enzymatic glycosylation of apo-B that is a function of hyperglycaemia is an efficient biochemical way of low-density lipoprotein atherogenic modification. So, proper metabolic control is needed to prevent late complications of diabetes. The study was performed to estimate the effects of time-released garlic powder tablet Allicor on the parameters of metabolic control and plasma lipids in type 2 diabetes mellitus. The metabolic action of Allicor was investigated in the 4-week double-blinded placebo-controlled study in 60 type 2 diabetic patients. Fasting blood glucose was measured daily, and serum fructosamine as well as cholesterol and triglyceride levels were determined at the baseline, after 1, 2, 3 and 4 weeks. It has been demonstrated that treatment with Allicor resulted in better metabolic control due to the lowering of fasting blood glucose, serum fructosamine and serum triglyceride levels. The results of this study may allow recommending garlic powder tablets Allicor for the treatment of type 2 diabetes mellitus along with dietary treatment and/or sulfonylurea derivatives to achieve better metabolic control. The benefits from garlic preparations may lead to the reduction of cardiovascular risk in diabetic patients.

Retrospective investigation was carried out of clinical course and effectiveness of therapy in 31 patients with primary hepatic involvement in Hodgkin's disease and 63 cases of hepatic lesions relating to dissemination of relapsing tumor. Clinical diagnosis of hepatic involvement ought to be made using at least two procedures, preferably liver scanning and computed tomography of the abdominal cavity. Special attention should be given to most likely cases of specific lesions of liver who had previously presented with intoxication symptoms and spleen and/or subphrenic lymph node involvement. Dissemination-related hepatic lesions were among the most frequent (78%) in patients with primary tumor while focal and diffuse liver involvement was limited to 71% of cases of dissemination of relapsing tumor. MOPP, ABVD and BEACOPP regimes should be given preference in dealing with primary Hodgkin's disease. The latter procedure should predominate in cases of initial extended involvement or as second-line chemotherapy designed to defeat drug resistance and improve end results.

Spinal cord compression was diagnosed in 33 patients with Hodgkin's disease. Specific involvement of the brain was identified in 17 cases of dissemination relapse. Timely use of cytostatic and/or radiotherapy resulted in sustained and complete recovery of the spinal cord. The results in cases of sustained spinal disorders were worse. Tumor-induced specific changes in the brain and spinal cord compression had worse prognosis and median of survival from time of tumor detection was approx. 12 months. In patients with spinal cord compression or cerebral involvement and with concomitant neurologic symptoms, sustained response after chemotherapy with derivatives of nitrosourea (nitrosomethylurea, lomustine and carmustine) (CCNU-OPP, NVPP/NOPP, DVCPP) was (59%) and (64%), respectively. Adequate polychemotherapy with nitrosourea and radiotherapy derivatives and surgery, if required, can improve the efficacy of treatment of Hodgkin's disease patients with spinal cord compression.

Clinical trials were carried out of the protective action of dicarbamin in 33 patients with Hodgkin's disease (13 males and 20 females, average age--31 years). They received standard chemotherapy ABVD (doxorubicin--25 mg/m2, bleomycin--10 mg/m2, vinblastine--6 mg/m2, dacarbazine--375 mg/m2, intravenously, on days 1 and 15 of each cycle, every 4 weeks. Patients suffering neutropenia after the first injection of the cytostatic drugs were given dicarbamin 100 mg/day on day 5 before a second administration. Treatment with dicarbamin continued for 15 days. Its protective effect was reported in 27 patients (81.8%). Leukocyte and granulocyte count before dicarbamin was 3.74 +/- 0.25 x 10(9)/l and 1.42 +/- 0.17 x 10(9)/l, respectively. On completion of the polychemotherapeutic cycle, the indices rose to 5.0 +/- 0.28 x 10(9)/13 and 2.49 +/- 0.25 x 10(9)/l, respectively. The beneficial effect of dicarbamin was also demonstrated by a quick recovery of leukocyte levels than in controls (p > 0.5). After the next cycle of polychemotherapy (ABVD) plus dicarbamin was given for Hodgkin's disease and grade III-IV leuko- and granulocytopenia, leukocyte and granulocyte concentrations returned back to normal which indicated the protective action of dicarbamin.

The mechanism of acetate assimilation by the purple nonsulfur bacterium Rhodobacter sphaeroides, which lacks the glyoxylate shortcut, has been studied. In a previous work, proceeding from data on acetate assimilation by Rba. sphaeroides cell suspensions, a suggestion was made regarding the operation, in this bacterium, of the citramalate cycle. This cycle was earlier found in Rhodospirillum rubrum in the form of an anaplerotic reaction sequence that operates during growth on acetate instead of the glyoxylate shortcut, which is not present in the latter bacterium. The present work considers the enzymes responsible for acetate assimilation in Rba. sphaeroides. It is shown that this bacterium possesses the key enzymes of the citramalate cycle: citramalate synthase, which catalyzes condensation of acetyl-CoA and pyruvate and, as a result, forms citramalate, and 3-methylmalyl-CoA lyase, which catalyzes the cleavage of 3-methylmalyl-CoA to glyoxylate and propionyl-CoA. The regeneration of pyruvate, which is the acetyl-CoA acceptor in the citramalate cycle, involves propionyl-CoA and occurs via the following reaction sequence: propionyl-CoA (+ CO2) --> methylmalonyl-CoA --> succinyl-CoA --> succinate --> fumarate --> malate --> oxalacetate (- CO2) --> phosphoenolpyruvate --> pyruvate. The independence of the cell growth and the acetate assimilation of CO2 is due to the accumulation of CO2/HCO3- (released during acetate assimilation) in cells to a level sufficient for the effective operation of propionyl-CoA carboxylase.

The mechanism of acetate assimilation in the purple nonsulfur bacterium Rhodobacter sphaeroides, which lacks the glyoxylate pathway, is studied. It is found that the growth of this bacterium in batch and continuous cultures and the assimilation of acetate in cell suspensions are not stimulated by bicarbonate. The consumption of acetate is accompanied by the excretion of glyoxylate and pyruvate into the medium, stimulated by glyoxylate and pyruvate, and inhibited by citramalate. The respiration of cells in the presence of acetate is stimulated by glyoxylate, pyruvate, citramalate, and mesaconate. These data suggest that the citramalate cycle may function in Rba. sphaeroides in the form of an anaplerotic pathway instead of the glyoxylate pathway. At the same time, the low ratio of fixation rates for bicarbonate and acetate exhibited by the Rba. sphaeroides cells (approximately 0.1), as well as the absence of the stimulatory effect of acetate on the fixation of bicarbonate in the presence of the Calvin cycle inhibitor iodoacetate, suggests that pyruvate synthase is not involved in acetate assimilation in the bacterium Rba. sphaeroides.

The efficacy and tolerability of therapy with gemcitabine plus cisplatin were evaluated in 49 patients with disseminated breast cancer refractory to anthracyclines, docetaxel and capecitabine. Gemcitabine 600-750 mg/m2 and cisplatin 30 mg/m2 were injected intravenously, dropwise, on days 1 and 8 of a 3-week course. Overall response rate was 27%; median response duration - 8.0 months, median mediation time until tumor progression--3.2 months, and median survival time--10.3 months. Untoward side-effects were moderate, reversible and, therefore, did not require dosage to be corrected or cut down.

We have found the ATP production in the Rhodobacter sphaeroides chromatophores illuminated by single short light flash, that is under conditions when the proton gradient formed as a result of electron transport after the second flash, is absent. The ATP synthesis was accompanied by the H2O2 formation. Simultaneous formation of H2O2 is indicative of the oxidative activation of phosphate during the ATP synthesis, as in the model systems with isolated chlorophyll. These data provide a theoretical background to the fitting of illumination parameters in both laboratory and industrial photobioreactors with photosynthetic bacteria used in biotechnological processes.

Itaconate is known as a potent inhibitor of isocitrate lyase. Unexpectedly, itaconate was a strong inhibitor of acetate and propionate assimilation in isocitrate lyase-negative purple non-sulfur bacterium Rhodospirillum rubrum. It was shown that in cell extracts of R. rubrum itaconate inhibited propionyl-CoA carboxylase (PCC) activity. The participation of PCC in propionate assimilation in R. rubrum is well-documented, but the inhibition of acetate assimilation suggests that PCC is also involved in acetate metabolism. PCC is one of the enzymes of the citramalate cycle, the anaplerotic pathway proposed for R. rubrum as a substitute for the glyoxylate cycle. These results provide further support for the hypothesis of the occurrence of the citramalate cycle in R. rubrum. PCC from other isocitrate lyase-negative phototrophs, Rhodobacter sphaeroides and Phaeospirillum fulvum, was not inhibited by itaconate.

The formation of ATP during photophosphorylation in chromatophores from purple nonsulfur bacterium Rhodobacter sphaeroides in the presence of phenazine methosulfate and without exogenous electron carriers under constant illumination and by the action of single light flashes was studied. It was shown that the photoinduced transport of electrons to the exogenous electron acceptor depends on phosphate. It was assumed that phosphate ions are electron donors in the reaction center P870; by the action of light, P870 converts the phosphate ion HPO4(2-) into anion radical HPO4-.. In the difference EPR spectra "light minus darkness" at 77 K, an asymmetrical doublet signal with a weak low-field line was observed. The signal had a g-tensor of about 2.014 and a hyperfine coupling constant of about 2.5 mT and belongs probably to the phosphate anion radical.