VHL Expression in Kidney Cancer: Relation to Metastasis Development, Transcription and Growth Factors and Component of Akt/m-TOR Signaling Pathway.

Von Hippel-Lindau protein (VHL) is associated with the development and progression of kidney cancer. An increase in VHL expression was found in patients with the disseminated form of the disease compared to the localized cancer, which was combined with a uniform distribution of decreased (<1.0) and increased (>1.0) VHL mRNA levels in renal cancer patients depending on the dissemination of the process. The increase in VHL expression was accompanied an increase in the level of mRNA for NF-κB p65 and kinases PDK1 and Akt. The revealed data indicate the importance of molecular biological parameters in oncogenesis.

Effect of Target Therapy on the Content of Transcription and Growth Factors, Protein Kinase TOR, and Activity of Intracellular Proteases in Patients with Metastatic Renal Cell Carcinoma.

We analyzed the dynamics of the expression of transcription factors, VEGF and its receptor VEGFR2, serine-threonine protein kinase mTOR and activity of proteasome and calpain in patients with metastatic renal cancer during therapy with tyrosine kinase inhibitor Votrient and mTOR blocker Afinitor. The expression of hypoxic nuclear factor HIF-1α in the tumor tissue decreased during therapy with the target preparations. The decrease of VEGF and its receptor VEGFR2 was observed only in patients treated with mTOR inhibitor. The increase in calpain activity in the tumor tissue was observed in both groups. These findings extend our understanding of the mechanism of action of target anticancer preparations as allow considering the studied markers as predictors in choosing optimal therapy.

Activation of AKT of signaling pathway and the level of mTOR substrates in tumor of patients with kidney cancer, connection with prevalence of malignancy.

Activation of AKT signaling pathway and mTOR substrates of kidney tumor tissue occurs by improving AKT, its phosphorylated form, the serine / threonine proteinkinase m-TOR, the exchange regulator glycogen GSK-3-beta and also the inhibitor of 4E-BP1transcription. Increasing the size of primary tumor is followed by increasing the content of therein c-Raf and decreasing the content of phospho-m-TOR. The development of disseminated forms of the disease was associated with a reduction PTEN and phospho-AKT in tumor.

[Chymotripsin-like activity and subunit composition of proteasomes in human cancers].

Activity of the proteasome, polyfunctional enzymatic complex, is known to undergo changes during cancer development. This phenomenon is, probably, caused by the changes in subunit composition of proteasomes. In present work, we studied chymotrypsin-like activity of proteasomes, subunit composition and their association in breast cancer, head and neck squamous cell carcinoma, endometrial cancer, renal cancer, bladder cancer, stomach cancer and colorectal cancer. The increase of proteasome activity was revealed in most cancer tissues compared with adjacent tissues except for the renal cell carcinoma. Changes in proteasome activity in cancer tissues compared with correspondent normal tissues were accompanied by modification of its subunit composition. High proteasome activity was observed in combination with an increased expression of immune subunits and/or proteasome activator PA28, associated with activity of 20S proteasome. In breast cancer, head and neck squamous cell carcinoma, bladder cancer, stomach cancer and colorectal cancer we additionally found higher expression of Rpt6 subunit of 26S proteasome. Correlations between chymotrypsin like proteasome activity and subunit expressions were found in human cancer tissues. In summary, we suggest that proteasome ac- tivation and changes in its subunit composition plays an important role in cancer pathogenesis.

[Radiologic diagnosis of bone metastases recurrence in patients with prostate cancer treated strontium-89]. / Luchevaia otsenka regressa kostnykh metastazov u patsientov s rakom prostaty pri sistemnoi radioterapii 89SrCl.

Aiming to evaluate efficiency of 89SrCl (Metastron) in patients with metastatic lesion of the skeleton in prostate cancer we have performed a follow-up scintigraphy of the skeleton with 99mTc-methylendiphosphonate (MDP) and MRI with quantitative study of metastatic foci. 12 patients with prostate cancer (on the average 11 +/- 6 bone metastases were examined using scintigraphy of the skeleton with 99mTc-MDP and MRI study in T1, T2 and proton density modes. Investigations were performed before injected as a single dose of 150 MBq (4 mCi). At all the stages there was made a quantitative study of foci of pathological uptake of 99mTc-MDP compromising numbers of foci, focus parameters, intensity of 99mTc-MDP accumulation in the pathological part relatively the contralateral region as well as quantification of MRI signals from metastatic areas in signal intensity units. In 3 month 4 patients with extensive metastatic skeletal lesion (> 12) showed a considerable decrease of number of foci of pathological 99mTc-MDP uptake (on average to 6 +/- 3). In the remained metastatic foci there was noted a decrease of dimensions and 99mTc-MDP uptake intensity at an average by 29.8 +/- 15%, improvement in T1 intensity by 113 +/- 55.6 units. In 2 patients who initially presented a "superscan" pattern on 99mTc-MDP bone scintigraphy the 89SrCl treatment converted this of low intensity had demonstrated their complete regression. Results of radiologic follow-up of bone metastases in prostate cancer using MRI and bone scintigraphy with 99mTc-MDP argue that systemic radiotherapy with 89SrCl induces significant regress of metastatic process that involves all volume of the metastases.