Method for treating noninvasive cancer of urinary bladder

FIELD: medicine, oncourology.

SUBSTANCE: the present innovation deals with treating locally spread tumor diseases of urinary bladder due to applying either chemo- and/or radiation therapy. Moreover, one should intravenously once inject by drops autologous mesenchymal stem cells (AMSC) at the quantity of 1 mln cells/kg patient's body weight. Moreover, in case of chemotherapy AMSC should be injected during the period before the 20-th d after the last injection of chemopreparation, in case of radiation therapy - 12-15 d against the day of irradiation. In case of chemoradiation therapy AMSC should be injected after chemotherapy before the course of radiation therapy. This method enables to carry out chemoradiation therapy in patients with severe accompanying diseases that prevent such a therapy, and prevent the development of general toxic complications of chemoradiation therapy and medicinal and radiation-caused cystitis.

EFFECT: higher efficiency of therapy.

3 ex, 2 tbl

 

The invention relates to medicine, more specifically to oncourology, and may find application in the treatment of locally advanced tumours.

Bladder cancer (RMP) is currently one of the most common urologic diseases. Every year in the world there are more than 150 thousand new cases. In Europe RMP takes 5th place in men and 11 women in frequency among all malignant neoplasms. Frequency RMP is constantly growing. From 1991 to 1998, the increase in the number of newly diagnosed patients RMP men was 13.4%in women of 12.3%. Among patients with RMP within one year from the time of diagnosis die from the underlying disease to 20-25% of patients.

Currently, the treatment of RMP are leading operational methods. Radical cystectomy is the most effective method of treatment of primary tumors of the bladder. However, this intervention perform a small proportion of patients RMP - operation is highly traumatic, significantly impairs the quality of life of patients, and postoperative mortality reaches of 3.6%-26,9%.

Given that tumor field for RMP is the entire mucosa, the main condition for the treatment of patients is not only the surgical impact on the tumor, but the whole shell through the use of chemotherapy and/or radiation therapy day is.

When chemotherapeutic treatment of patients RMP mainly used drugs platinum, adriblastin, vinblastine, cyclophosphamide and methotrexate. When combined, these drugs more than half of patients who achieve an objective response. The effectiveness of systemic chemotherapy (XT) depends on the dose of the drugs used. The main limiting factor preventing the use of high doses XT is the toxicity of the drugs. All chemotherapeutic agents hematologic toxicity, platinum and adriablastin, in addition, highly toxic against infarction. Therefore, the holding of high-dose XT is associated with the risk of severe, sometimes fatal, complications.

When radiation therapy (RT) for the local treatment of the tumor is necessary to summarize the bladder of high doses of the order 64-70 Gy. These doses exceed the tolerance of normal tissues of the bladder and rectum, inevitably fall into the zone of intense radiation exposure. Therefore, the main limiting factor LT is radiation damage to the bladder and rectum. In addition, intensive LT in 20-25% of patients accompanied General and haematological reactions. The occurrence of local and systemic radiation damage determines the need is ü interrupt LT or reduce the total focal dose. This, in turn, dramatically reduces the effectiveness of irradiation. So, when announcing to the tumor dose of 40-50 Gy, the frequency of the local treatment does not exceed 5-12%, and at doses 64-68 Gr reaches 35-48%.

Closest to the proposed method is a method of treatment of invasive RMP by systemic chemotherapy and/or radiation therapy (monograph “Radiation therapy in gynecology and oncourology” //Ameno, Volvieron. - SPb - 2002. - P.222-232).

The method consists in carrying out systemic polychemotherapy (PCT) under the scheme of M-VAC. Methotrexate is administered at a dose of 30 mg/m2in the 1st, 15th and 22nd days; vinblastine 3 mg/m2in the 1st, 15th and 22nd days; doxorubicin 30 mg/m2in the 2nd day and cisplatin at a dose of 70 mg/m2in the 2nd day. All drugs administered as intravenous infusion, cisplatin - on the background of pre - and posthydration. On average, during the course of the patient is administered a chemotherapeutic agent in the following dosages: methotrexate -300 mg, vinblastine 30 mg, cisplatin 200 mg doxorubicin - 100 mg Treatment carried out through two courses of chemotherapy with an interval of 4 weeks.

Distance LT is used as an independent method or combination with chemotherapy. Given the radioresistance RMP requires summing high total focal dose (SOD) 70 Gr.

Progress LTL and active when RMP chemotherapeutic drugs allow PR is the combination of LT and XT with organoboranes operational intervention to achieve 5-year survival, comparable with radical cystectomy. However, in connection with preservation of the bladder and its function, the quality of life of these patients is higher.

However, LT is often accompanied by radiation reactions and tissue damage of the bladder and surrounding healthy tissues, it is critical organs. The most pronounced radiation complications of the urinary bladder manifested picture of acute radiation cystitis, frequency, and severity of which increased with increasing SOD. When this essential initial state of the bladder and lower urinary tract. Similarly, the presence of comorbidity on the part of the intestine, and in particular the rectum, is the reason that increase the risk of developing severe radiation complications.

Chemotherapy is very toxic, hard tolerated, leads to a significant decrease in hematological parameters, especially the number of leukocytes and platelets, has expressed the present, many patients causes a pronounced drug cystitis.

To prevent side effects used drugs or stimulants of bone marrow hematopoiesis. Prevention of damage to the tissue of the heart is specific cardioprotection. However, the effectiveness of these drugs is limited, and the cost is very the highest. In addition, these drugs themselves can cause serious, especially allergic adverse reactions.

To prevent local radiation damage when holding LT used topical application of dimethyl sulfoxide, microclysters with therapeutic compounds, vitamins, remedies aimed at the regulation of bowel function, rosatti, antibiotics. Protection of normal tissues by irradiation under hypoxic conditions, since the radiosensitivity of cells is reduced by decreasing the degree of oxygenation. However, despite preventive measures, radiation response of normal tissues continue to develop in almost all patients RMP in the irradiation process, and severe radiation damage are formed in 5-15% of patients. All this makes the quality of life of patients during and after treatment is unsatisfactory.

The technical result of the present invention is to reduce toxic action on the organism of patients and improve their quality of life through the use in the treatment of autologous mesenchymal stem cells (AMSC).

This result is achieved by the fact that in the treatment of RMP by systemic chemotherapy and/or radiation therapy, according to the invention once the patient intravenously injected isolated from biopsies his bone m the ZGA ASK in the amount of 1 million cells per 1 kg of body weight of the patient.

It is advisable when carrying out chemotherapy treatment to enter ASK after the 2nd course of chemotherapy, in the exercise of radiation therapy in 12-15 days after it started, when combined chemoradiation therapy after chemotherapy before radiotherapy.

Methods of cell therapy in the treatment of cancer patients started to use in recent years with the aim of accelerated tissue repair - first blood. However, these methods have significant drawbacks.

In the method of bone marrow transplantation is receiving from the bone marrow of the recipient (the patient or donor) cell mass, which are available with poly potent properties of stem cells. It should be noted that only a small fraction of cells obtained by puncture, refer to the stem - not more than 1-3%, whereas in fact the main component is punctate peripheral blood. Therefore, the traditional methods of transplantation is focused on obtaining a significant volume of bone marrow - up to 1500-2500 ml To obtain such a quantity of bone marrow is required prior 150-200 punctures bones. This procedure is performed under General anaesthesia unsafe for health and associated with a high risk of significant, especially infectious complications. Essential have the t and cellularity get punctate - recipients over the age of 60 volumes of exfuze can be even greater. In these circumstances, side effects are common and local associated with exusia bone marrow is almost inevitable.

Allogeneic bone marrow transplantation requires sophisticated selection of donors, which severely limits its availability (“hematopoietic stem cell Transplantation” //Alexander Rumyantsev, Man. Medical information Agency, M, - 2003, - 912 S.).

AMSC in recent years have begun to use when treating patients with cardiac pathology (Handbook of Cardiovascular Cell Transplantation. - Ed. N.M.Kipstidze et al. in 2004 - 425 p.).

The ability to influence AMSC tumor process being questioned in connection with practical applications in Oncology practice these cells to date not found.

ASK is the fraction of highly purified autologous stem cells. To obtain AMSC you want to take 20-35 ml bone marrow (the procedure is performed under local short-term intravenous anesthesia and lasts 10-15 min). In a further fraction of AMSC stands out from the bone marrow, thepirouette and grown in a special medium. After 10-12 days from the start of culturing, the number of AMSC reaches 80-100 million, which is ten times higher than the content in the bone marrow. Back introduction AMSC is safe (own cells, eliminates the option of allergic reactions), the number of input cells allows to receive the expressed clinical effect.

To use ASK in the treatment RMP us prompted the observation of patients admitted to the clinic in cnerry with common RMP. The patient was danano in the surgical treatment due to the large number of comorbidities cardiac character (ischemic heart disease, circulatory insufficiency of II degree, cardiomyopathy mixed Genesis). From the urogenital system also had concomitant pathology: cystitis, pyelonephritis. Since the chemotherapeutic treatment is associated with a high risk of cardiac and hematological complications, the patient was denied and in the conduct of XT, and he was sent to cnerry for possible radiation treatment. Due to the risk of serious complications from cardiovascular system when conducting the necessary stage of the disease high doses, it was decided to prevent them to enter the patient ASK. To do this, before starting treatment, the patient was taken 25 ml of bone marrow and grown culture of mesenchymal cells, which have entered the patient 12 days after the beginning of the LT in the amount of 1 million cells per 1 kg of patient's body weight (50 ml of culture suspension containing 72 million cells). This introduction patient underwent without p the shares and complications because native cells exclude the possibility of adverse reactions. Then LT went on to SOD 68 Gr. In this case the patient satisfactorily underwent a course of treatment without interruption, deterioration of cardiac activity was not observed, the blood counts were not significantly decreased, there have been also weakness and fatigue, usually occurring at the end of the course LT. Despite conducting patient intensive LT amid existed prior to the treatment of inflammatory changes in the bladder, symptoms of radiation cystitis was not observed.

This satisfactory condition of the patient, with a history of a great bouquet of serious concomitant diseases, including inflammatory side of the urinary tract, allowed us to use ASK and when conducting chemotherapeutic treatment for the patients, which such treatment is contraindicated. It turned out that in this case the positive effect was so unexpected that it allowed us to repeatedly apply biotransplant AMSC heavy contingent of cancer patients with concomitant diseases that impede the exercise of chemotherapy and/or radiation treatment.

The essence of the method is illustrated by examples.

Example 1. Patient K., aged 63, case history No. 517, received 16.02.2004 in the Department of new technologysociety therapy clinic cnerry RF Ministry of health complaints at periodic nagging pain in the lower abdomen, single makrogematuriya 10.02.2004.

Considers himself ill since 2003, when first appeared dragging pain in the lower abdomen. Has addressed to the urologist at the place of residence. Ultrasonography (US) revealed the formation in the bladder, but when cystoscopy was not found. In the fall of 2003, the patient was again performed ultrasound and again revealed a tumor in the bladder. 25.11.2003, performed computer tomography: the size of the detected education 13,6×12,1×14,4 mm 29.01.04 was performed transurethral resection of bladder tumors. Histological examination: transitional cell cancer of the bladder.

The survey showed that ultrasound 24.02.2004, - bladder of sufficient capacity, contents homogeneous, back unevenly thickened up to 11 mm for 31 mm, of the bladder wall inlaid, indicating a concomitant inflammation. Intravenous urography 20.02.2004,: Cavitary system of the kidneys and ureters are slightly expanded, the bladder is reduced in size. Biochemical analysis of blood 18.02.2004,: glucose 4,6 mmol/l, urea at 8.36 mmol/l, creatinine 134,8 mmol/l, alkaline phosphatase 154 u/l, lactate dehydrogenase 439 u/l, bilirubin total of 10.2 mmol/l, potassium of 4.38 mmol/l, iron at 14.5 µmol/l, total protein, 67 g/l Triglycerides 18.02.2004,: prothrombin 60%, fibrinogen 4.9 g/l, thrombin is the first time 24 sec. The clinical analysis of blood 18.02.2004,: leukocytes 5,93×109/l, stab 1%, segmented 69%, eosinophils 2%, monocytes 3%, lymphocytes 25%, erythrocytes br4.61×1012/l, hemoglobin 136 g/l, platelets 262×109/l, Erythrocyte sedimentation rate, 33 mm/h Total urine 19.02.2004, share 1017, pH 5.0, leukocytes, erythrocytes - cover all fields of view, mucus +cocci +.

In the examination diagnosed with perekhodnocletocny bladder cancer T2NOMO. Among opportunistic diseases - ischemic heart disease, myocardial infarction in 1999, circulatory insufficiency 2 degrees, cardiomyopathy mixed Genesis, hypothyroidism, hay fever with the annual spring exacerbations since 1989. In connection with severe concomitant diseases the patient refused surgical treatment. The limited nature of the process (stage II) and severe cardiac pathology were contraindications for XT. So LT was the only treatment option for this patient. However, the confidence that the patient has undergone LT without interruption and in full was not, so he was offered biotransplant own bone marrow.

To do this, prior to treatment the patient was made fence 25 ml of own bone marrow and grown culture was ASK. 12.03.2004 72 million was ASK (1 million cells per kg of body weight) were introduced ill the mu intravenously in 50 ml of culture suspension. Introduction the patient underwent without reactions and complications. 12 million was AMSC were placed in a cryo-Depositary for possible future use.

With 26.02.2004, started a course of radiation therapy apparatus SL 75-5: with two opposite opposite fields 0 and 180 degrees - irradiation of regional lymph nodes and bladder, field h cm, single focal dose (GENUS) - 2 Gr. After summing up the dose of 18 Gy, 12.03.2004, that the patient has made a re-introduction of AMSC, and radiation therapy was continued for up to 46 Gy. It was further held local irradiation of the bladder with three fields 0 - field 10×10 cm, 120 - box 9×10 cm, 240 - field 9×10 cm, GENUS=3 Gy, to SOD - 68 Gr.

Table 1

Dynamics of indicators of clinical blood analysis of the patient K.
DateIndicators
leukocytes, ×109erythrocytes, ×1012hemoglobin, g/lplatelets, ×109ESR, mm/hour
18.02.04to 5.93br4.6113626233
02.03.04to 4.62to 4.6212723523
11.03.044,674,53141 16515
19.03.043,684,51421689
29.03.044,284,8114017512
15.04.043,174,751512197

Cytological analysis of urine from 08.04.04: - structureless mass. Tumor items are not installed. Single distribuzione epithelial cells.

Ultrasound from 08.05.04: - wall of urinary bladder smooth, signs of tumor growth is not available.

Cystoscopy from 31.05.04: - wall of the bladder is covered unchanged mucosa, with no signs of tumor.

Thus, the patient K. the irradiation process is not observed radiation reactions on the part of the bladder and rectum, as well as manifestations of General and Hematology (table 1) toxicity. The deterioration of cardiac activity during the observation period is not marked. After completion of treatment health remained satisfactory, weakness and fatigue, typical for patients undergoing intensive radiation, was not observed. The patient was discharged in satisfactory condition.

One month after completing the treatment of the signs of the tumor on rezultata ultrasound and cytological studies the study was not determined. Two months later, she is in remission. Symptoms of radiation cystitis with control cystoscopy revealed no signs of ranjita also not mentioned.

This clinical observation has allowed us to conclude that the application of ASK patients RMP undergoing intensive LT, is able to prevent the development of radiation (Hematology, cardiology and other) complications.

Example 2. Patient B., 51 year history No. 422, 09.02.04 was admitted to the Department of new technologies clinic cnerry health Ministry with complaints of intermittent pain during urination and episodes macrohematuria.

Considers herself a patient 09.12.2003, when in the urine appeared bright red blood, addressed to the urologist at the place of residence. Was performed ultrasound: education in the bladder on the right side wall of 1.9×1.3 cm, protrude into the cavity of the bladder. Was sent to the regional Oncology center, where 20.01.04 performed a transurethral resection of bladder tumors.

During the examination in the clinic cnerry were identified: ultrasound 13.02.2004 - Kidney: usually located in the sizes have not changed, the structure of the parenchymal layer saved, cavitary system is not extended. The bladder of sufficient capacity, contents homogeneous, defined irregular thickening of the posterior wall to 6.5 mm Angioprotective 12.02.04: angiopathy - flow for Ellen on both sides. On renogram - excretory function of the kidney will be reduced somewhat. Biochemical analysis of blood 09.02.2004 g: glucose 5.2 mmol/l, urea of 5.15 mmol/l, creatinine 64,2 mmol/l, lactate dehydrogenase 533 u/l, bilirubin total of 6.2 mmol/l, potassium of 4.75 mmol/l, iron 22,4 µmol/l, total protein 82 g/l Triglycerides 09.02.2004,: prothrombin 88%, fibrinogen 2.8 g/l, thrombin time 14 sec. The clinical analysis of blood 09.02.2004,: leukocytes 4,45×109/l, stab 4%, segmented 59%, monocytes 3%, lymphocytes 34%, erythrocytes 4,79×1012/l, hemoglobin 140 g/l, platelets 256×109/l, erythrocyte sedimentation rate 5 mm/h BGCI urine analysis 10.02.2004, share 1005, pH 6.0, leukocytes 25-27-30 in the field of view, erythrocytes cover all fields of view.

In the examination diagnosed with bladder cancer, T3NOMO, histological form - perekhodnocletocny cancer. Among comorbidities - hypothyroidism. Due to the prevalence of the tumor process, the patient refused surgical treatment. So intense XT was the main method of treatment of advanced cancers of the bladder. However, the XT was associated with a high risk hematological and cardiotoxic complications, the peak of which usually accounts for 7-20 days after the last injection of chemotherapeutic drugs. Considering we found a positive effect of ASK the body, the patient was offered biotransplant bone marrow.

To do this, prior to treatment, the patient was made fence 30 ml of own bone marrow and grown culture was ASK. Cell culture was placed in a cryo-Depositary on the 12th day from the beginning of cultivation on the achievement in the culture of the 90 million ASK. With 18.02.2004) underwent two courses of polychemotherapy according to the scheme M-VAC. A total dose of methotrexate 300 mg; vinblastine - 30 mg; cisplatin 200 mg; doxorubicin - 100 mg.

08.04.2004 year, 2 days after the last drug administration, the culture of OMSK was thawed and 70 million AMSC (1 million cells per kg of body weight) were introduced patient B. vnutrepenialnye in 50 ml of culture suspension. 20 million AMSC placed in a cryo-Depositary for possible future use. Introduction patient underwent without reactions and complications.

2,60
Table 2

Dynamics of hematological indicators of patient B.
DateIndicators
leukocytes, ×109erythrocytes, ×1012hemoglobin, g/lplatelets, ×109ESR, mm/hour
01.04.041,063,661097930
12.04.043,3610111921
08.05.044,353,8011117717
25.05.044,203,8512220110

Cytological analysis of urine from 08.04.04: - structureless mass. Tumor items are not installed. Single distribuzione epithelial cells.

Ultrasound from 08.05.04: - wall of urinary bladder smooth, signs of tumor growth is not available.

Cystoscopy from 31.05.04: - wall of the bladder is covered with unmodified pink mucosa, with no signs of tumor.

Thus, the patient B. by the end of treatment, the level of leukocytes was nearly critical, but expect a further reduction has not occurred (table 2). The deterioration of cardiac activity during the observation period is not marked. After completion of treatment health remained satisfactory, weakness and fatigue, typical for patients undergoing intensive chemotherapy, was not observed. Signs of drug cystitis, characteristic for the circuit M-VAC, when the control cystoscopy is not revealed. The patient was discharged in good condition.

One month after completing the treatment of the signs of the tumor according to the ZI and cytological study was not determined, two months later she is in remission.

This clinical observation has allowed us to conclude that the application of ASK patients RMP undergoing intensive XT, can prevent the development of hematological, cardiac and other complications.

Example 3. Patient N., 58 years old, medical history, No. 588, received 14.03.2004 in the Department of new technologies in radiotherapy clinic cnerry health Ministry with complaints makrogematuriya March 2004

Considers himself ill with 02.2004, when he first came blood in the urine. Has addressed to the urologist at the place of residence, when an ultrasound revealed the formation in the bladder sizes 8×9×7 see 20.02.04 was performed transurethral resection of bladder tumors. Histological examination: transitional cell cancer of the bladder.

The survey established: ultrasound 15.03.2004, the Capacity of the bladder is limited, the lumen is a massive crimson swelling, bleeding in the study. Intravenous urography 17.03.2004,: Cavitary system of the kidneys and ureters are dilated, more to the left, the bladder is reduced in size, its walls with irregular contours, on the left wall is exophytic education. Biochemical analysis of blood 16.03.2004,: glucose of 5.6 mmol/l, urea of 9.6 mmol/l, creatinine 156,2 mmol/l, alkaline phosphatase 159 u/l, lactatemia enasa 444 u/l, bilirubin total of 11.4 µmol/l, potassium 4.8 mmol/l, the iron of 13.6 µmol/l, total protein 62 g/l Triglycerides 16.03.2004,: prothrombin 66%, fibrinogen 4,6 g/l), thrombin time 26 sec. The clinical analysis of blood 16.03.2004,: leukocytes 8,8×109/l, stab 9%, segmented 61%, eosinophils 6%, monocytes 5%, lymphocytes 19%, erythrocytes 3,6×1012/l, hemoglobin 90 g/l, platelets 2787×109/l, ESR 46 mm/h Total urine 15.03.2004, share 1011, pH 5.6, leukocytes, erythrocytes - densely cover all fields of view, mucus +++, cocci ++.

In the examination diagnosed with perekhodnocletocny bladder cancer T3NXMO. Among opportunistic diseases - coronary heart disease, angina, circulatory insufficiency 1 degree. Due to the prevalence of the tumor and the presence of comorbidities the patient refused surgical treatment. Locally advanced nature of the process, reduction of bladder capacity, macrohematuria were indications for chemotherapy treatment. To prevent complications in the implementation of chemotherapy the patient was offered biotransplant bone marrow.

To do this, prior to treatment the patient was made fence 30 ml of own bone marrow and grown culture was ASK.

With 23.03.2004, patients received ku is with polychemotherapy according to the scheme M-VAC. A total dose of methotrexate 150 mg; vinblastine - 15 mg; cisplatin 100 mg; doxorubicin - 50 mg By the end of the chemotherapy in hematological indicators worsened: the number of leukocytes decreased to 1.8×109/l, platelet - up 101×1012/L. This prevented the continuation of XT, while the patient continued to determine the tumor in the bladder size 55×40×27 mm (ultrasound from 23.03.04), cytological examination of urine (22.03.04) remained malozemelnye tumor cells.

Considering the need to continue treatment, 22.04.2004, on the second day after completion of chemotherapy 78 million AMSC (1 million cells per 1 kg of body weight) were introduced to the patient intravenously in 50 ml of culture suspension. Back introduction the patient underwent without reactions and complications. About 10 million of OMSK were placed in a cryo-Depositary for possible future use.

With 26.04.2004, started a course of radiation therapy apparatus SL 75-5: with two opposite opposite fields 0 and 180 degrees - irradiation of regional lymph nodes and bladder, field 15×18 cm, single focal dose of 2 Gy, the total focal dose of 46 Gy. We then conducted local irradiation of the bladder with three fields 0 - field 10×10 cm, 120 - field 8×10 cm, 240 - field 8×10 cm, GENUS=3 Gr. To SOD=64 Gr.

During irradiation hematological parameters of the patient pozvolyaet treatment without interruption. The maximum reduction in the number of cells is 1.7×109/l, platelet - up to 98×1012/HP

Within one month after completion of chemoradiation therapy a significant reduction in hematological parameters were observed, the condition and health of the patient H. it was quite satisfactory. Cytological analysis of urine from 18.06.04: - tumor elements not found. Ultrasound from 18.06.04: - wall of urinary bladder smooth, signs of the tumor is not available. Cystoscopy from 21.06.04: - wall of the bladder is covered unchanged mucosa.

Thus, the patient H. introduction ASK during chemoradiation treatment resulted in a low hematological indicators continue specific treatment (radiation therapy). After completion of treatment health remained satisfactory, weakness and fatigue, typical for patients undergoing intensive chemotherapy and radiation, was not observed. One month after the end of chemoradiation treatment of the signs of the tumor was not determined. Signs of radiation and/or drug cystitis in control cystoscopy revealed no signs of ranjita also not mentioned.

To date, the proposed method were treated 8 patients RMP with severe comorbidity. In 3 patients - radiotherapy, 4 - chemotherapy, one chemo treatment. All patients received a positive result.

The proposed method is compared with existing has a number of advantages.

Introduction ASK improves the tolerability of chemotherapy and/or radiation therapy patients RMP with severe comorbidity.

The method developed in the Department of new radiotherapy technologies, cnerry health Ministry and was clinically tested in 8 patients with a positive result.

A method for the treatment of invasive bladder cancer by chemotherapy and/or radiation therapy, characterized in that it further once intravenously injected autologous mesenchymal stem cells (AMSC) in the amount of 1 million cells per 1 kg of patient weight, and chemotherapy was AMSC administered during the period up to 20 days after the last injection of chemotherapy drugs, radiation therapy in 12-15 days from the beginning of the exposure, and when chemoradiation therapy was AMSC administered after chemotherapy before radiotherapy.



 

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3 cl

FIELD: medicine, oncology, chemical-pharmaceutical industry and technology, pharmacy.

SUBSTANCE: tablet with antitumor effect contains acceptable carrier on which the following mixture of aqueous-alcoholic tinctures is applied: bloody geranium, penny-cress, common cocklebur and European wild ginger. Tablets by mass 1 g including slipping substance contains the following amounts of indicated tinctures as measure for dry matters, g: bloody geranium, 0.015-0.020; penny-cress, 0.011-0.015; common cocklebur, 0.011-0.017, and European wild ginger, 0.024-0.036. Method for preparing tablet involves applying on carrier the mixture of aqueous-alcoholic tinctures of above indicated plants, the following drying the prepared mass, its granulating and tableting. Method for prophylaxis and treatment of oncological patients involves prescription 0.5-2 tablets with oncological designation, tree times per a day and the treatment course is determined individually based on objective data of treatment. Tablet made by claimed methods shows complex properties: it delays tumor growth and metastazing and can be recommended for treatment and prophylaxis of oncological pathology both independently and in combination with chemo-radiation therapy. Invention can be used in technology for making medicinal formulations of preparations with oncological designation and for treatment of patients with oncological pathology of different organs and body systems.

EFFECT: improved for making tablet, valuable medicinal properties of tablet.

7 cl, 4 ex

FIELD: medicine, oncology, chemical-pharmaceutical technology, pharmacology, pharmacy.

SUBSTANCE: tablet eliciting the antitumor effect comprises active dose of aconite alkaloids in the amount 0.0125-0.0375 mg. Invention relates to a method for making tablet with antitumor effect. Method involves treatment suitable carrier taken in the amount corresponding to the content of alkaloids in tablet 0.0125-0.0375 mg with aconite tincture wherein amount of the total content of alkaloids is determined preliminary. Then carrier treated by such manner is dried at temperature 30-35°C, not above, granulated, granules are powdered and tableted. Also, invention relates to a method for treatment of oncological patients that involves prescription to patient 0.5-2 tablets with oncological designation being this treatment is determined individually. Invention can be used in manufacturing medicinal formulations of preparations used for treatment of patients with oncological pathology.

EFFECT: improved method for treatment and making, valuable medicinal properties of tablet.

8 cl, 2 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to new compounds - pluraflavines of the formula (I): wherein R1 represents sugar group of the formula: ; R2 represents -COOH or -CH2-O-(R7)m wherein R7 represents sugar group of the formula: ; R3 is taken among the groups: and , and to all its stereochemical forms and mixtures of indicated forms in any ratio, and to their physiologically acceptable salts; R5 means hydrogen atom; R4 and R6 represent in common group -X2 with a double bond wherein X2 means oxygen atom (O); R8 and R10 represent in common group -X2 with a double bond wherein X2 means oxygen atom (O), and m = n = 1, and to all its stereochemical forms and mixtures of indicated forms in any ratio and to its physiologically acceptable salts. Invention relates to a method for preparing these compounds from culture of microorganism actinomycetes HAG 003959, DSM 12931 by fermentation, to the strain Actinomycetales HAG 003959, DSM 12931 used for preparing compounds of the formula (I) and to pharmaceutical composition inhibiting transcriptase activity and eliciting cytotoxic effect based on above said compounds. Compounds of the formula (I) are used as medicinal agents, for example, as antitumor agents.

EFFECT: improved method for preparing, valuable medicinal properties of compounds and composition.

19 cl, 3 tbl, 12 ex

FIELD: medicine, surgery.

SUBSTANCE: method involves every day covering a wound with an agent comprising of pig spleen homogenate and oxygenated with perfluorane taken in the following amounts: 100 g of pig spleen homogenate and 10 ml of oxygenated perfluorane. Invention promotes to accelerating sanitation of suppurative wounds due to activation of topical immunity and activation of regenerating processes. Invention can be used in treatment of suppurative wounds.

EFFECT: improved treatment method of wounds.

2 ex

FIELD: medicine.

SUBSTANCE: method involves introducing autologic mesenchyma trunk cells as a single intravenous drop dose or in the amount of 1 mln cells per 1 kg of patient body weight.

EFFECT: provided stable clinical remission.

FIELD: medicine.

SUBSTANCE: method involves using mononuclear autologic marrow fraction containing 6-9x104 mesenchyma cells per 1 ml or autologic mesenchyma trunk cells. The cells are separated from brain bioptate in the amount of 106 cells/kg of patient body mass. The preparations are intracoronarily introduced in fractions at a rate of 3-5 ml/min into the right coronary artery. The introduction is also carried out in intra-arterial mode in jets or in drops.

EFFECT: higher survival rate and life quality of cardiologic patients.

1 dwg

FIELD: medicine, surgery, transplantology.

SUBSTANCE: embryonic spleen should be sampled, washed in nutritive medium № 199 to be placed into fresh medium № 199 to obtain homogenate in teflon homogenizer followed by centrifuging; then one should isolate the upper, medium and inferior layers, suck off medium layer and the upper part of inferior layer; the cell mixture obtained should be diluted in nutritive medium № 199 to be then introduced by injections into mesentery of small intestine or rectus muscle of abdomen. The present innovation favors the activation of immune system in patients undergone splenectomic operation and in those in case of surgical immunodefficient state due to high functional and regenerating activity of transferred embryonic splenic cells.

EFFECT: higher efficiency of prophylaxis.

6 dwg, 2 tbl

The invention relates to medicine, namely to psychiatry and pharmacotherapy of borderline mental disorders
The invention relates to the technology of obtaining biologically active compounds to increase the resistance of the organism of animals

The invention relates to medicine, namely to methods of producing biologically active preparations from bone marrow of animals

The invention relates to medicine, namely to Oncology, and can be used for the treatment of patients with malignant tumors of the organs of the oral cavity and pharynx
The invention relates to medicine, and is intended for the treatment of peritonitis

FIELD: medicine, surgery, transplantology.

SUBSTANCE: embryonic spleen should be sampled, washed in nutritive medium № 199 to be placed into fresh medium № 199 to obtain homogenate in teflon homogenizer followed by centrifuging; then one should isolate the upper, medium and inferior layers, suck off medium layer and the upper part of inferior layer; the cell mixture obtained should be diluted in nutritive medium № 199 to be then introduced by injections into mesentery of small intestine or rectus muscle of abdomen. The present innovation favors the activation of immune system in patients undergone splenectomic operation and in those in case of surgical immunodefficient state due to high functional and regenerating activity of transferred embryonic splenic cells.

EFFECT: higher efficiency of prophylaxis.

6 dwg, 2 tbl

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