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Introduction. It has been reported that overexpression and altered compartmentalization of γtubulin may contribute to tumorigenesis and tumor aggressiveness in a variety of human malignancies. We have shown that γ-tubulin expression and cellular distribution pattern is also altered in non-small cell lung cancer (NSCLC) (Histol. Histopathol. 2012; 27: 1183- 1194). In the present study we examined the relationship between γ-tubulin expression and patient overall survival (OS). Material and methods. Immunohistochemistry was performed, with well-characterized anti-γ-tubulin antibodies, on 109 formalin-fixed, paraffin-embedded NSCLC specimens (p-TNM stage IIII). γ-Tubulin labeling indexes (LIs) were determined, and the association of γ-tubulin expression with clinicopathological parameters was evaluated. To analyze OS rates according to γ-tubulin LIs, patients were categorized into three groups: those with low (0- 30%), intermediate (31-69%) or high (70-100%) γtubulin LI. Association of clinicopathological parameters and γ-tubulin with survival were examined using univariate and multivariate Cox regression analysis. Results. No statistically significant association was seen between γ-tubulin overexpression and histological type, tumor differentiation, p-TNM stage and adenocarcinoma subtyping. Longer survival was observed in the high γtubulin LI group of patients with p-TNM stages II+III when compared to intermediate or low γ-tubulin LI groups, but the difference was not statistically significant (p=0.066). On the other hand, when combined low and intermediate γ-tubulin LI groups (p-TNM stages II+III) where compared to high γ-tubulin LI group, statistically significant longer survival was observed in high γtubulin group (p=0.021). Conclusion. Our findings suggest that level of γ-tubulin expression may have an impact on patient survival at more advanced NSCLC stages.

In this study, we examined the effect of in vivo treatment of acutely SIV infected Mamu-A*01+ rhesus macaques with interleukin 15 (IL-15). IL-15 treatment during acute infection increased viral set point by 3 logs and accelerated the development of simian AIDS in 2 out of 6 animals with one developing early minimal lesion SIV meningoencephalitis. Although IL-15 induced 2–3 fold increase in SIV-specific CD8+ T cell and NK cell numbers at peak viremia and reduced lymph node (LN) SIV-infected cells this had no impact on peak viremia and did not lower viral set point. At viral set point however activated SIV-specific CD8+ T cells and NK cells were reduced in the blood of IL-15 treated animals and LN SIV-infected cells were increased. Week 30 LN from IL-15 treated animals had significantly increased Gag-specific CD8+ T cell numbers, whereas total cell, lymphocyte, and CD4+ T cell numbers were reduced. IL-15 treatment significantly reduced anti-SIV antibody concentrations at week 3 and viral set point. IL-15 increased Ki-67+CD4+ T cells at week 1 of treatment and reduced blood CCR5+ and CD45RA-CD62L− CD4+ T cells. The frequency of day 7 Ki-67+CD4+ T cells strongly correlated with viral set point. These findings suggest that CD4+ T cell activation during acute infection determines subsequent viral set-point and IL-15 treatment by increasing such activation elevates viral set-point. Finally, IL-15 treated acutely SIV infected primates may serve as a useful model to investigate the poorly understood mechanisms that control viral set point and disease progression in HIV infection.

Retinoids are effective growth modulators of human ovarian carcinoma cell lines. Their effects are mediated by nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which are transcriptional factors and members of the steroid/thyroid receptor superfamily. To our knowledge, until now, the cellular distribution of RAR proteins in human ovarian tumor specimens is unknown. This study provides new data on the differential cellular localization of RAR alpha protein in 16 serous adenocarcinomas originating from the ovaries, fallopian tubes, and the peritoneum. Using an affinity-purified antiserum specific for RAR alpha and a monoclonal antibody recognizing the full-length estrogen receptor molecule (clone 6F11), we performed immunohistochemistry on frozen tissue sections and examined the relationship between RAR alpha and estrogen receptor protein expression by comparing the percentage of immunostained tumor cells for either receptor. Our findings indicate a strong linear relationship between the percentages of RAR alpha- and estrogen receptor-labeled tumor cells as determined by linear regression analysis (P0.005, r = 0.825). A modest inverse relationship was found between the percentage of RAR alpha-positive tumor cells and histological grade, attesting to a differentiation-dependent trend (P0.04). No significant relationship was found between RAR alpha-labeled cells and clinical stage (P = 0.139), site of tumor origin (ovaries versus fallopian tubes versus peritoneum) (P = 0.170), and primary versus metastatic lesion (P = 0.561). Thus, serous adenocarcinomas are capable of expressing RAR alpha and estrogen receptor despite high histological grade and advanced stage of neoplastic disease. Compared with the heterogeneous localization of RAR alpha in cancer cells, there was widespread RAR alpha immunoreactivity in tumor-infiltrating lymphocytes, vascular endothelial cells, and stromal fibroblasts, underscoring the value of immunohistochemistry in the accurate determination of RAR/(RXR) content in tumor specimens.