Georgi Pirtskhalaishvili

Endothelium-derived factors as paracrine mediators of prostate cancer progression

Vascular endothelium represents a complex network of cells producing a large number of active substrates affecting physiologic, metabolic, and immunologic properties of the whole organism, as well as particular organs or tissues. The potential influence of endothelium‐derived paracrine factors on prostate cancer progression has only begun to be examined.

Transduction of Dendritic Cells with Bcl-xL Increases Their Resistance to Prostate Cancer-Induced Apoptosis and Antitumor Effect in Mice

We have shown that prostate cancer (PCa) causes apoptosis of dendritic cells (DC), which might block the development of specific antitumor immune responses. Analysis of murine prostatic carcinoma tissues revealed the significant decrease in intratumoral DC number during tumor progression. We demonstrated that the cytokine-mediated increase in DC survival was accompanied by an elevated expression of the anti-apoptotic protein Bcl-xL. Next, we evaluated the resistance to tumor-induced apoptosis and the antitumor efficiency of genetically engineered DC overexpressing Bcl-xL. DC were transduced with an adenoviral vector encoding the murine Bcl-xL gene and injected intratumorally. Data analysis revealed that treatment of PCa-bearing mice with Bcl-xL-transduced DC resulted in significant inhibition of tumor growth compared with the administration of nontransduced DC. Thus, our data suggest that the protection of DC from PCa-induced apoptosis might significantly increase the efficacy of DC-based therapies in cancer even in the absence of available tumor-specific Ags.

Human prostate cancer regulates generation and maturation of monocyte-derived dendritic cells

The progression of prostate cancer is accompanied by a marked suppression of the immune system, including the apoptotic death of dendritic cells (DC) responsible for the induction of antitumor immunity. In this study, we evaluated whether prostate cancer might inhibit DC generation and maturation in vitro.

Detection of tumorigenesis in rat bladders with optical coherence tomography

Optical coherence tomography (OCT) is a novel technique that enables noninvasive cross-sectional imaging of biological tissues. Because of its high resolution (approximately 10 microm), superior dynamic range (140 dB in our case) and up to 2-3 mm penetration depth, OCT is potentially useful for noninvasive screening of superficial lesions. Bladder cancer arises within the transitional epithelium. Despite the ability to visualize the epithelium via cystoscopy, it is often difficult to detect early epithelial cancers and to determine their penetration to the underlying layers. To investigate the potential of OCT to enhance imaging of bladder cancers and other epithelial lesions, we applied OCT to normal and diseased bladder epithelium, and correlated the results with histological findings. OCT images of porcine bladder (a close homolog of human bladder) confirm the ability of this method to image human tissues. To determine whether OCT can track the course of bladder cancer, a standard rat model of bladder cancer in which Fisher rats are exposed to methyl-nitroso-urea (MNU), was followed both with OCT and histological studies. Our results show that the micro morphology of porcine bladder such as the urothelium, submucosa and muscles is identified by OCT and well correlated with the histological evaluations. OCT detected edema, inflammatory infiltrates, and submucosal blood congestion as well as the abnormal growth of urothelium (e.g., papillary hyperplasia and carcinomas). By contrast, surface imaging, which resembles cystoscopy, provided far less sensitivity and resolution than OCT. This is the first OCT study of any tumor documented in a systematic fashion, and the results suggest the potential of OCT for the noninvasive diagnosis of both bladder inflammatory lesions and early urothelial abnormalities, which conventional cystoscopy often misses, by imaging characterization of the increases in urothelial thickening and backscattering. However, because of the depth limitation, OCT may have limited applications in staging the invasion of higher-state urothelial cancers, especially for papillary carcinomas.

The Endothelin Receptor

Endothelin-1 (ET-1), a potent vasoconstrictor, was discovered in 1988. Its role in cardiovascular and pulmonary diseases has been widely investigated. Recent investigations of the pleiotropic actions of the endothelins, such as mitogenesis and inhibition of apoptosis, provide evidence for their potential role in cancer. Available data suggest that ET-1 plays a significant role in the growth and progression of such neoplasms as prostate and ovarian cancer, melanoma, bone malignancies, and other tumors. Development of endothelin receptor antagonists has allowed a better understanding of the role of ET-1 in cancer pathogenesis, and provided the possibility of therapeutic intervention. ET-1 exerts its action via the endothelin receptors A (ETA) and B (ETB); however, it appears that most of the mitogenic activity of ET-1 is mediated through the ETa receptor. Preliminary data from clinical trials investigating the ETa receptor antagonist, atrasentan, in patients with prostate cancer, were encouraging. The role of the endothelin axis in other malignancies is discussed as well.