[Are the properties of peripheral blood lymphocytes of patients with prostate cancer connected with the efficiency of radiation therapy?].

The genome damage (frequency of cells with micronuclei and chromosome aberrations), concentration of reactive oxygen forms (ROS), markers of lymphocytes activation, expression of proliferation (CD69, Ki67) and proapoptotic antigen (CD95), as well as the ability to adaptive response have been investigated in blood lymphocytes of healthy donors and patients with prostate gland cancer. The influence of hormone-therapy on lymphocytes properties and connection between the parameters studied with the effectiveness of treatment, which was estimated by the level of prostate specific antigen (PSA), have been investigated. It was discovered that the genome damage to the patients with prostate gland cancer lymphocytes does not differ from control. The increase of the ROS level and decrease of radiosensitivity (irradiation of isolated lymphocytes in vitro at a dose of 1 Gy) are observed but they are insignificant. The content of the cells expressing CD69 and CD95 markers doesn't change but the expression of proliferative activity marker Ki67 in cells decreases. Radiosensitivity of lymphocytes in patients with prostate gland cancer correlates with the CD95 markers expression--a higher radio sensitivity points to their predisposition to apoptotic death. The expression of the markers studied depends on the oxidative status--a high ROS level suppresses their expression. The hormone therapy applied before radiotherapy leads to the increase in radiosensitivity and decrease in ROS. As the MN test shows, the ability to adaptive response of the lymphocytes in patients with prostate gland cancer is increased as compared with lymphocytes of healthy donors but it is insignificant; moreover, hormones do not influence the ability to the adaptive response. The high oxidative status further the formation of the adaptive response. We suppose that the discovered correlation between the initial, before treatment, frequency of lymphocytes with micronuclei and treatment effectiveness, namely, the decreased number of damaged cells associated with the treatment efficiency, is very important for the treatment prognosis. The results obtained can be very important for the experimental justification and understanding a possible use of blood lymphocytes for the additional diagnostics of prostate gland cancer and prognosis for its successful treatment.

[Some molecular-genetic markers, defining the pathogenesis of superficial and invasive bladder cancer].

We have investigated deletions of 3p14, 9p21, 9q34, 17p13 (TP53) loci, activating FGFR3 mutations in exon 9 and aberrant methylation of RASSF1, RARbeta, P16, P14, CDH1 genes with the aim of the molecular pathogenesis pathways analysis of bladder cancer. FGFR3 activating mutations and 9p21 deletions were observed significantly more frequent in the group of non-invasive bladder cancer pTa than in minimally-invasive cancers pT1 (p = 0.004 and 0.006 respectively). It was shown that groups of superficial and invasive bladder cancer are significantly differing in the frequency of 17p13 (p = 0.006) and 9q34 (p = 0.04) deletions and in aberrant methylation of the gene P16 (p = 0.02). We have revealed some differing molecular-genetic alterations in groups of superficial and invasive bladder cancers. Therefore we suppose that these two types of bladder cancer might have different pathways of development.

[Inactivation of the VHL gene in sporadic clear cell renal cancer].

Renal cell carcinoma is the most common variant of the kidney cancer, which accounts approximately 75% patients with this disease. The majority of those tumors are characterized by inactivation of the VHL gene suppressor as a result of mutations, allelic deletions and/or methylation. We have conducted the complex molecular-genetic analysis of 64 samples obtained from patients with the clear cell renal cancer. VHL mutations were detected by single strand conformation polymorphism and subsequent sequencing, loss of heterozygosity was analyzed using two STR-markers, methylation was tested by methylsensitive polymerase chain reaction. All revealed variations were statistically analyzed in respect to the parameters of primary tumors in various groups of patients. Seventeen VHL somatic mutations were detected, 12 from which were described for the first time. Allelic deletions of VHL were found in 31.6%, and methylation--in 7.8% samples of the renal cancer. As a whole, VHL inactivating events were presented in 46.9% cases of disease, in 51.7% -among renal cancer patients with first stage. We have not observed any association of mutations, loss of heterozygosity and methylation with clinical-pathological parameters of disease. Results of this investigation specify for expediency of further studies of molecular genetics aberrations in the VHL gene. Perhaps, it would promote renal cancer molecular markers evaluation, for example, a determination of suppressor genes methylated in renal cancer.

[Use of novel radiation fractionation regimens in organ-sparing therapy of bladder cancer].

The findings of evaluation of complex organ-sparing therapy of 153 patients with invasive bladder cancer are discussed. Transurethral resection of the exophytic end of tumor was followed by two courses of polychemotherapy plus combined treatment. Radiotherapy was carried out by conventional fractionation (group I), hyperfractionation (group II) and accelerated hyperfractionation (group III) (total focal dose--up to 60-66 Gy). Overall and corrected 5-year survival rates were: 47.3 +/- 7.5% and 51.7 +/- 7.5% (group I), 65.6 +/- 1% and 70.4 +/- 8.4% (group II), 53.9% +/- 6.8% and 61.9% +/- 6.8% (group III), respectively. Our tentative results suggest that further efforts be made to improve the efficiency of radiotherapy by introduction of novel techniques.

[Changes in prostate-specific antigen in casodex (bicalutamide) monotherapy in a dose 150 mg/day given to patients with locally advanced and/or advanced prostatic cancer]. / Dinamika prostatspetsificheskogo antigena pri monoterapii kasodeksom (bikalutamidom) v doze 150 mg v den' u bol'nykh mestno-rasprostranennym i (ili) rasprostranennym rakom predstatel'noi zhelezy.

Three-month treatment with casodex (150 mg/day) of untreated patients with locally advanced and/or advanced cancer of the prostate is well tolerated. The only side effect encountered in 9(60%) patients was temporary breast painfulness and swelling. Subjective effects consisted of higher activity (in 40% of patients), pain relief (in 33.3%), improved urination (in 80%). Objective effects comprise: reduction of prostate-specific antigen in 14(93.3%) patients by 150.4 ng/ml at the average; a rise in testosterone concentration in 12(80%) patients; regression of the tumor by more than 50% in 5(33.3%) patients; stabilization and partial regression of regional metastases (1 case); stabilization of distant metastases (3 of 4 cases). One patient showed progression of bone metastasizing in partial local regression of the tumor.

[The diagnosis and treatment of bladder cancer metastases]. / Diagnostika i lechenie metastazov raka mochevogo puzyria.

The study included 27 patients with regional and distant metastases of bladder cancer. Regional and distant metastases were detected in 12 (44.4%) and 15 (55.6%) patients, respectively. Basic treatment consisted in chemotherapy (MVAC scheme) which combined with reaferon immunotherapy. Chemoimmunotherapy in combination with radiotherapy was used in 8 patients to relieve pain caused by the metastases. The response was seen in 37% of patients with regional metastases and 22% of patients with distant ones. The former and the latter were followed up for 15.9 and 9.3 months, respectively.

[The intravesical administration of BCG vaccine in treating recurrent superficial bladder cancer]. / Vnutripuzyrnoe vvedenie vaktsiny BTsZh pri lechenii retsidiva poverkhnostnogo raka mochevogo puzyria.

The authors consider general immunological effects of intravesical BCG vaccine as an independent method of immunotherapy of superficial cancer of the bladder (CB). 27 patients (15 males and 12 females, mean age 57 years) with a recurrence of superficial CB (T1-2N0M0) were treated. The patients had undergone transurethral or transvesical bladder resection and combined therapy. Intravesical immunotherapy of CB recurrence with BCG vaccine induced persistent changes in the immune system: stimulate lymphocyte activity and phagocytic activity of neutrophils, T-cell function, normalizes function of endogenic suppressors, increases the amount of IgM and CIC. Repeat courses of the vaccine maintain the above immunological effects for a long time.

[The combined treatment of locally disseminated bladder cancer]. / Kombinirovannoe lechenie mestnorasprostranennogo raka mochevogo puzyria.

39 untreated patients with local cancer of the bladder without distal metastases were included in the trial to assess efficacy of combined drug plus radiation treatment, its toxicity and chances to preserve the bladder. The examination comprised tumor biopsy, ultrasonography, computed tomography, excretory urography and routine laboratory tests. The patients received one or two courses of intraarterial chemotherapy, radiation (50 Gy) and two doses of cysplatinum in a dose 70 mg/m2 before and after radiation. A complete response was achieved in 66.6%, partial in 12.8%, stabilization in 10.3% and progression in 10.3% of patients. One-year survival was reported in 89.7%, recurrence-free survival with functioning bladder being 66.7%. Side effects were mild and did not demand the treatment discontinuation.

[The immunomodulating action of bestatin in the combined therapy of bladder cancer patients]. / Immunomoduliruiushchee deistvie bestatina pri kompleksnoi terapii bol'nykh rakom mochevogo puzyria.

A beneficial effect of bestatin used as adjuvant in the course of chemo- and radiotherapy of local cancer of the bladder manifested itself as a reduction of postradiation immunosuppression: increased count of T mu-helper/inductors and T gamma-suppressors/killers, enhancement of neutrophil phagocytic activity. Bestatin recovers radiation-impaired immune system by inhibition of T gamma-suppressor killers and their precursors generation, of endogenic regulators suppressive activity, normalization of T-lymphocyte and natural killer activity, stimulation of B-lymphocyte recovery.

[The combined treatment of bladder cancer]. / Kompleksnoe lechenie raka mochevogo puzyria.

The paper presented the results of the combined multistage treatment of 60 patients with advanced carcinoma of the urinary bladder: intra-arterial chemotherapy, immunotherapy, radiation therapy and surgery. Intra-arterial chemotherapy was performed in total dosages of the following drugs: 5-fluorouracil, 3-4 g/m2, adriamycin, 100-120 mg/m2, methotrexate, 20-40 mg/m2, platidiam, 30-50 mg/m2. Immunotherapy was exercised through endolymphatic administration of BCG vaccine in a dose of 0.08-0.12 mg. The majority of the patients were exposed to a remote gamma-therapy in a total focal dosage of 50-54 gram-roentgen. The treatment resulted in a complete regression of the tumor in 26.7, partial regression in 43.3 per cent of the patients. 3-6 mos after the radiation therapy, 46.6 per cent of the patients were operated on, mainly with the use of organ-sparing techniques. A three-year survival rate reached 100 per cent in the patients with stage T2 disease, 85.2 in those with T3a and 58.6 per cent in those with stages T3b--T4. The analysis of the survival revealed higher mortality rates in patients with low-differentiated tumors.

[Ultrasonic scanning in determining the local spread of bladder cancer]. / Ul'trazvukovoe skanirovanie v opredelenii mestnogo rasprostraneniia raka mochevogo puzyria.

The results of ultrasound investigation were analysed in 48 patients with urinary bladder cancer. Potentialities of longitudinal intracavitary echography in the determination of the local dissemination of malignant urinary bladder tumors were studied. This method proved to be most informative for tumors sited in the cervix, basis and anterior wall of the bladder whereas transabdominal echography provided reliable diagnostic information for tumors of the lateral and posterior walls. In choosing methods for the determination of the local dissemination of urinary bladder cancer preference should be given to combined echography in view of its high accuracy, noninvasive and safe nature.