The method of determining individual sensitivity to chemotherapy of patients with ascitic form of ovarian cancer stage iii-iv
(57) Abstract:The invention relates to medicine, in particular to gynecology, and can be used to treat patients with ovarian cancer stage III - IV. The method provides the choice of an appropriate regimen without the use of expensive reagents and equipment. Ascitic fluid of a patient is incubated with various drugs and their combinations for 30 min at 37othen estimate the number of live and dead cells and opt for chemotherapy combination of himiopreparatov, causing the greatest loss of cells in ascitic fluid. The method is carried out for 1.5 h, does not require expensive reagents and equipment and allows to achieve a good clinical effect. The method of determining individual sensitivity to chemotherapy of patients with ascitic form of ovarian cancer III-IV stages.The invention relates to medicine, namely to gynecology, and can be used to treat patients with common form of ovarian cancer (stage III-IV).There is a method of determining the sensitivity of tumor cells to cytotoxic agents using podkupolnogo test, the OS is VA N. With. Prediction of individual response of malignant human tumors to radiation and drug therapy (experimental study). The dissertation on competition of a scientific degree of doctor B. N., M., 1991, 344 C.). However, along with the many advantages this method has the following limitations: not all tumors of the person have a sufficient rate of growth in animals; it is expensive (requires a large number of animals and the cost of human labor), as well as long - 6-7 days.There is a method of predicting hemiculterella ovarian carcinomas using microtitration test (see Kullak O. A. Micrometrology test in predicting hemiculterella ovarian carcinomas person. The dissertation on competition of a scientific degree K. B. N., M., 1993, 166 C.). The method is based on the ability of a number of mitochondrial dehydrogenases, which activity is highest in tumor cell carcinomas of most types, to restore salt of tetrazole. However, this method requires the use of nonpublic equipment and reagents. The tests will take 4 days.There is a method of determining the sensitivity to the treatment of patients with ovarian cancer III-IV stages changed the., Dolmatova O. K. , Arkhangelsk A. Century of authorship 1718650 from 16.06.92), taken as a prototype. The method allows for 3 hours to determine the sensitivity of tumor cells to various chemotherapeutic agents and their combinations. However, the method requires the use of reagent kits Bio-Lachema test, Prague, Czechoslovakia, which limits the possibility of its wide use at the present time.The aim of the invention is the selection of an appropriate regimen without the use of expensive reagents and equipment.This objective is achieved in that in the ascitic fluid after incubation with chemotherapy to determine the number of living and dead cells and selected for further chemotherapy drugs, which 20% or more dead cells.The invention is new, because it is not known from the level of medicine in determining individual sensitivity to chemotherapy of patients with ascitic form of ovarian cancer by exploring the viability of cells in ascitic fluid.Known in the medical literature ways of assessing the sensitivity of tumor cells to cytotoxic agents associated with p. the properties of these cells with the use of expensive reagents and equipment (for example, immunofluorescent antinucleons test), or the ability of tumor cells to growth (count of clonogenic and podkapsulnaya tests) that is limited to the slow growth of many human cells in unusual conditions, and requires the use of a large number of animals and labour costs.The novelty of the invention lies in the fact that the sensitivity to cytotoxic drugs is judged by the percentage of cell death ascitic fluid by incubation with the appropriate drugs. It does not involve expensive equipment and reagents.The invention involves an inventive step, as for a specialist oncologist is not obvious from the level of development of medicine in the treatment of cancer patients.The invention is industrially applicable as it can be used in medical institutions of various types (research Institute of Oncology, oncological dispensaries) in the treatment of cancers of various localizations, accompanied by the accumulation of ascitic fluid. Its application does not require expensive equipment and highly skilled employees, may be implemented in any clinical laboratory.The way is as follows.Ascitic fluid is centrifuged at about 1.5 thousand./min for 15 minutes the precipitate washed twice with saline and bring them to the final concentration of tumor and mesothelial cells 2 1061 ml of suspension. In tubes for incubation, add 2 ml of medium 199, 0.2 ml of a suspension of washed cells of ascitic fluid and 0.3 ml diluted in physiological solution of various chemotherapeutic agents and combinations thereof at a concentration of 50 μg/ml of cyclophosphamide and 5 µg/ml for other drugs (metotrexat, thiotepa, vinblastine, doxorubicin, prospidin, 5-fluorouracil, platinum). Test tubes with samples incubated for 30 min at a temperature of 37oC. After incubation, the sample rate the number of live and dead cells by staining with 0.05% solution nitrazine. Calculation and estimation of the proportion of viable cells is carried out in the Goryayev camera under a light microscope. Control cells are ascitic fluid of patients incubated with 0.3 ml of saline. For further therapy is preferred by those chemotherapy drugs and combinations thereof, incubation with which gives the highest percentage of dead cells.Examples of specific implementation method.Example 1. Patient S., 58, I. B. N 12426/d, the settlement of the metastases in the liver, CL group 2. The first step in the comprehensive therapy performed cytoreductive surgery in the amount of bilateral adnexectomy. Postoperative Geest. analysis N 467351-354: moderately differentiated papillary cystadenocarcinoma. During the operation was collected ascitic fluid and made her study of the proposed method. In the sample, incubated without the addition of drugs, all cells were alive. In samples containing cyclophosphamide, identified 6% of dead cells, methotrexate - 8%, platinol - 0%, thiotepa - 1%, prospidin - 10%, i.e. cells of ascitic fluid was almost insensitive to all tested drugs. Patients received three courses of intraperitoneal chemotherapy (WBHT) scheme CPV (cyclophosphamide, platinol, vinblastine). However, chemotherapy is ineffective, stated the generalization process.Example 2. Patient P., 73, I. B. N 5178/W, was admitted to the gynecological Department of RNII in may 1998 with a diagnosis of ovarian cancer, ascitic form, stage III, class a group 2. Made laparotomies evacuated to 5 liters straw yellow ascitic fluid. CIT. analysis N 25021-22 - adenocarcinoma. Exploration of ascitic fluid by the proposed method. the l; the thiotepa + platinol; cyclophosphamide + methotrexate + 5-fluorouracil; thiotepa + methotrexate + 5-fluorouracil, all cells in ascitic fluid was alive. A course of neoadjuvant WBHT scheme CMF (cyclophosphamide, methotrexate, 5 - fluorouracil). The cumulative dose of cyclophosphamide 4 g, methotrexate 50 mg, 5-fluorouracil - 3 g without significant clinical effect. Conducted explorative laparotomy revealed a generalization of ovarian cancer in the peritoneum, the germination of the great seal in the transverse colon, a single tumor infiltration in the pelvic cavity. Geest. analysis N 506900-06 - poorly-differentiated papillary cystadenocarcinoma.Example 3. Patient C. , 50 years, and. b. N 778/e, was admitted to the gynecological Department of RNII in February 1997 with a diagnosis of ovarian cancer, ascitic form, stage III, class a group 2. Made cytoreductive surgery full volume - supracervical amputation of the uterus with appendages, omentectomy. The size of residual tumor was less than 2 see Geest. analysis N 121456-458 - moderately differentiated cystadenocarcinoma. The study ascitic fluid by the proposed method. In the sample, incubated without drugs detected 3% of dead cells in the sample with cyclophosphan Olney was chosen regimen CPV. Conducted 6 cycles WBHT on the selected scheme. Cumulative dose was 30 mg of vinblastine, 4.8 g of platinum, 950 mg platinol. Over 18 months the patient is in complete clinical remission.Example 4. Patient F., 51, I. B. N 10864/d, was admitted to the gynecological Department of RNII in October 1996 with a diagnosis of ovarian cancer, ascitic form, IV stage, metastasis to the umbilicus, CL group 2. The first step in the comprehensive therapy produced laparotomy with excision of umbilicus, supracervical amputation of the uterus with appendages, omentectomy. The size of residual tumor greater than 2, see Postoperative Geest. analysis N 463170-73 - serous cystadenocarcinoma; N 461374-376 - metastases in the omentum, the navel. The study ascitic fluid by the proposed method. In the sample, incubated without drugs, all cells were alive, in the sample with cyclophosphamide identified 28% of dead cells, prospidinom - 11%, with thiotepa - 12%, with methotrexate - 22% and Platinium - 57%. After the operation performed 5 cycles WBHT schema: CF. Cumulative dose: 6 g of cyclophosphamide, 900 mg platydema. More than 20 months the patient is in complete clinical remission.Technical and economic effect of the method of determining individual chuvstvitel complete clinical remission, preventing side effects of drugs, avoiding unnecessary use of clearly ineffective drugs.The determination of individual sensitivity of patients to drugs proposed method can be implemented in practical health care, as it eliminates the use of expensive reagents, equipment and highly qualified specialists. The method of determining individual sensitivity to chemotherapy of patients with ascitic form of ovarian cancer stage III - IV, including the incubation of ascitic fluid with chemotherapy, characterized in that in the ascitic fluid determine the number of live and dead cells by staining with 0.05% solution nitrazine and choose for further chemotherapy drugs, which 20% or more dead cells.
FIELD: organic chemistry, microbiology, pharmacy.
SUBSTANCE: invention relates to new biologically active compounds. Invention describes a compound of the formula (1):
wherein R1 means carbon chain with 2-30 carbon atoms that can be linear, branched, saturated and can be substituted once or twice with the following groups: -OH, =O, -(C1-C6)-alkyl or the group:
; R2 means (C1-C6)-alkyl; E means phosphorus atom (P); each X1, X2 and X3 means independently of one another -O- in its all stereochemical forms and mixtures of these forms taken in any ratio, and its physiologically acceptable salts also. Also, invention describes a method for preparing cyclipostins and the strain Streptomyces HAG 004107, DSM 13381 as a producer of cyclipostins. Invention provides preparing new compounds possessing valuable biological properties.
EFFECT: improved preparing method, valuable properties of substances.
12 cl, 9 tbl, 21 ex
FIELD: biology, medicine, organic chemistry.
SUBSTANCE: invention proposes compound of the general formula (I): wherein A means effector group; L means a linker link; B represents Skulachev-ion Sk or charged hydrophobic peptide. Compound can be used in preparing a pharmaceutical composition for target (directed) delivery of active substances in mitochondria carried out by electrochemical potential of hydrogen ions into mitochondria. Also, invention can be useful in treatment of diseases and states associated with disturbance of normal function of mitochondria, in particular, diseases associated with increased formation of free radicals and active forms of oxygen. The claimed invention owing to directed accumulation of biologically active substance in mitochondria provides enhancing the effectiveness of substance, to decrease total dose, probability and strength of adverse effects.
EFFECT: improved and valuable properties of method and pharmaceutical composition.
26 cl, 14 dwg, 16 ex
FIELD: medicine, oncology, pharmacy.
SUBSTANCE: invention relates to drugs and concerns docetaxel as a drug used in accessory therapy for treatment of metastatic cancer breast in combination with doxorubicin and cyclophosphamide. Proposed combination of drugs provides the enhanced viability coefficient in patients with superexpressed glands ER, PR and/or HER2.
EFFECT: enhanced effectiveness of treatment.
6 cl, 36 ex
FIELD: medicine; pharmacology.
SUBSTANCE: application of Sodium citratum dihydrate or potassium Citras dihydrate, or Sodium hydrogenum or bicarbonate of potassium, carbonate of sodium, arginine or their admixture as the antibiotic stabiliser fosfo-mitsina tromethamole, and their pharmaceutical structures for granulating is proposed. The invention allows for lowering destruction reaction of tromethamole fosfomicin in granulate by 35-70% (which provides stability of structure ready to use), and also in the presence of a gastric juice.
EFFECT: possess improved efficiencyof the structures.
8 cl, 3 ex
FIELD: medicine; pharmacology.
SUBSTANCE: subjects of invention are also pharmaceutical drugs or agents for prophylaxis and treatment of neuropathy, increase of production and treatment of the neurotrophic factor, for pain relief, for nerve protection, for prophylaxis and treatment of the neuropathic pain containing compound of the formula or of the formula . In the compounds of the formulas (I) and (II) symbols and radicals have the meanings mentioned in the invention formula. The specified agents have an excellent effect and low toxicity. There are also proposed ways of treatment and prophylaxis of the abovementioned conditions by means of the compounds of the formula (I) or (II) and application of these compounds for production of the abovementioned agents. Besides, one has proposed methods for production of the specified compounds and intermediate pyrazol compounds.
EFFECT: compound has an effect increasing production and secretion of the neurotrophic factor.
46 cl, 1 tbl, 233 ex
SUBSTANCE: invention relates to novel flavonoid compounds of formula 1 where R1-R5 assume values given in the description. The invention also relates to a pharmaceutical composition based on said compounds and a treatment and prevention method. Such compounds and corresponding pharmaceutically acceptable derivatives and/or salts are used in pharmaceutical, veterinary and nutraceutical fields.
EFFECT: compounds and compositions have antioxidant properties and are especially effective in treating ischemic and reperfusion injury.
39 cl, 19 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to new compounds of general formula 1 or their stereoisomers or pharmaceutically acceptable salts possessing the properties of inhibitors of RNA polymerase HCV NS5B, and to methods for producing them. In general formula 1 R1 represents C1-C4alkyl; R2 and R3 represents fluorine, or R2 represents fluorine, while R3 represents methyl; one of R4 and R5 represents hydrogen, and the other of R4 and R5 represents C1-C6acyl optionally substituted by α-aminoacyl specified in a group containing (dimethylamino)acetyl, 1-tert-butoxycarbonylamino-2-methyl-propylcarbonyl, 1-methylpyrrolidine-2-carbonyl, 1-methylpiperidine-3-carbonyl and 1-methylpiperidine-4-carbonyl, R6 represents hydrogen, methyl, methoxy and halogen.
EFFECT: compounds can be used for treating and preventing viral infections, including hepatitis C, optionally with additional agents specified in an inhibitor of inosin-5-monophosphate dehydrogenase, eg Ribamidine, an inhibitor of hepatitis C protease C NS3, eg Asunaprevir (BMS-650032), an inhibitor of hepatitis C protease C NS3/4A, eg Sofosbuvir (TMC435), an inhibitor of RNA-polymerase NS5A, eg Daclatasvir (BMS-790052) or Ledipasvir (GS-5885).
18 cl, 1 tbl, 14 ex