[Down-regulation of RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1 and HYAL2 genes in non-small cell lung cancer].

Chromosomal and genome abnormalities of 3p are frequent events in many epithelial tumours, including lung cancer. Several critical regions with high frequency of hemi--and homozygous deletions in tumours were detected on 3p and more then 20 different cancer-related genes were identified in 3p21.3 locus. Real-time PCR was used to measure mRNA level of tumour-suppressor genes and candidates in 3p21.3 (RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1 and HYAL2 in basic types of non-small cell lung cancer (NSCLC)--squamous cell lung cancer (SCC) and lung adenocarcinoma (AC). Significant (from 2 to 100 times) and frequent (from 44 to 100%) mRNA level decrease was shown in NSCLC. Level and frequency of mRNA decrease for all genes depended on histological type of NSCLC. Down-regulation of RASSF1A and ITGA9 was associated significantly with AC progression, the same tendency was found for genes RBSP3/CTDSPL, NPRL2/G21, HYAL1 and HYAL2. On the contrary, down-regulation of all genes in SCC was not associated with clinical stages, tumor cells differentiation and metastases in lymph nodes. Significant decrease of RBSP3/CTDSPL, NPRL2/G21, ITGA9, HYAL1 and HYAL2 mRNA levels (on average, 5-13 times) with high frequency (83-100%) was already shown at the first stage of SCC. Simultaneous decrease of all six genes mRNA level was found in the same tumor samples and was not depended on their localization on 3p21.3 and functions of the proteins. Spearman's correlation coefficient r(s) was from 0.63 to 0.91, P < 0.001. Co-regulation of gene pairs ITGA9 and HYAL2, HYAL1 and HYAL2, which mediate cell-cell adhesion and cell-matrix interaction, was suggested based on the obtained data. It was shown that genetic and epigenetic mechanisms were important for down-regulation of RBSP3/CTDSPL and ITGA9 genes. These results supported the hypothesis on simultaneous inactivation of cluster cancer-related genes in extended 3p21.3 locus during development and progression of lung cancer and other epithelial tumors. Significant and frequent decrease of mRNA level of six genes in SCC could be important for development of specific biomarker sets for early SCC diagnosis and new therapeutic approaches/strategies for NSCLC.

Pathogenesis of diabetic nephropathy: focus on transforming growth factor-beta and connective tissue growth factor.

Although considerable improvement in the prognosis of diabetic nephropathy has been achieved in recent years due to intensive insulin and angiotensin-converting enzyme inhibitor treatment, these approaches do not provide complete protection against progression of diabetic nephropathy. An urgent need for additional novel therapies to prevent or further slow the progression of diabetic nephropathy motivated us to provide an up-to-date review with particular emphasis on the potential role of two growth factors--transforming growth factor-beta and connective tissue growth factor--in the pathogenesis of diabetic nephropathy. The most intensively studied to date, transforming growth factor-beta appears to play a central role in the pathogenesis of diabetic nephropathy. Recently, attention has focused on connective tissue growth factor, which mimics the biological activity of transforming growth factor-beta in profibrotic tissue formation. Thus, acting as a downstream mediator of the profibrotic activity of transforming growth factor-beta, connective tissue growth factor may constitute a more specific target for future antifibrotic therapies.

[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 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.

Intra-arterial chemotherapy for advanced bladder cancer.

The results of prolonged intra-arterial chemotherapy in 61 patients with locally advanced bladder cancer (T3-T4) are discussed. Regional internal iliac artery infusion of chemotherapeutic agents was done daily for 5 or 7 days at a rate of 1 to 3 ml/h over an 18-20-h period. The total dosages of each course were 60-120 mg/m2 adriamycin, 2.5-3.5 g/m2 5-fluorouracil (5-FU), 20-40 mg/m2 methotrexate or 30-50 mg/m2 cisplatin. At 3 to 4 weeks after the completion of infusional chemotherapy the results were evaluated, based on data from control cystoscopy and sonography. One patient (1.6%) was free of tumor; an objective response of greater than 50% reduction in tumor size occurred in 26 (42.7%) patients; 34 (55.7%) demonstrated objective responses of less than 50%. No further increase in tumor size during the management was detected. Hematuria, dysuria and urine infection were controlled and pain was relieved. The use of cytostatics and prolonged iliac artery catheterization did not incur any serious complications.

[Cyto- and histological comparisons in chemodectomas of the neck]. / Tsito-gistologicheskie sopostavleniia pri khemodektomakh shei.

Cyto-histological correlations in cases of chemodectomas of the neck were made. The patients were divided into 3 groups; with benign (8), malignized (8) and malignant (14 tumors). Decreased vascular component, solidization, marked cellular and nuclear polymorphism taken together are signs of morphological malignizaiton of the tumor. In most patients, however, no relationship between morphological characteristics of chemodectomas and their clinical course was established. Clinico-morphological correlations indicate that cellular and tissue changes are not the only signs of malignancy of a tumor.