Krebswissenschaft und -therapie

Breast cancer is a steroid hormone–dependent tumor. Stratification of patients according to hormone (ER/ PR) receptor status and nodal metastasis is of great therapeutic importance. In this investigation, we could enroll 79 pre and post-menopausal breast cancer patients voluntarily. We classified these cases into four categories of the combinations of ER/PR positive, negative and mixed statuses. Their hormone receptor status as determined by immunohistochemistry correlated with therapy regimens like chemotherapy, hormone therapy and QOL responses. We found that in ER+/PR- and ER-/PR- tumors were more frequent in postmenopausal women than ER+/PR+ tumors. The ER+/PR- tumors were larger than ER+/PR+ tumors. In addition, 21.51% of ER+/PR- and 17.72% of ER-/PR- patients had four or more axillary nodes involved with tumors compared to patients with ER+/PR+ tumors (7.59%). Postmenopausal women with ER+/PR- and ER-/PR- who received adjuvant hormonal therapy or combination of chemo drugs like Cyclophosphamide, Adriamycin, 5-FU (FAC) and Cyclophosphamide, Alurubicin, 5-FU (CAF) showed good response than premenopausal women. Forty patients receiving tamoxifen (hormone therapy) along with other chemo- drugs also showed good response. Tamoxifen induced substantial tumor regression and increased disease free survival. It is concluded that hormone receptor status is important in deciding the choice of treatment for all subgroups and influenced the QOL. Another significant observation was that the frequency of ER+/PR- and ER-/PR- tumors was higher in this study group compared to ER+/PR+ tumors. This is the first report from south Indian population indicating the importance of hormonal status in deciding therapeutic regimens in breast cancer patients affecting their QOL.

Background: We developed a cell culture CO2 incubatorand a mice rack that can continuously irradiate cells ormurine with FIR. Our goal is to make clear the non-thermaleffect of FIR on HepG2 with these instrumentsmorphologically.

Methods: By using them, in vitro , we examined theproliferation of cultured HepG2 cells with hematocytometer,BrdU assay, WST-1 assay, HE staining, Toluidine bluestaining and microarray studies. And in vivo, we measuredthe tumors, observed the sections by IHC, DAPI stainingwith light microscopes and performed microarray studies.

Results: Proliferation of HepG2 cells were suppressed(e.g., cell count declined by 34% after 10 days of FIRirradiation), tumor volumes reduced by 86% after 30 daysof FIR irradiation, mRNA of Vascular Endothelial GrowthFactor (VEGF) decreased by 48%, vascular area in crosssections from the tumors decreased 60% compared withthe control. More frequent properties in apoptosis wereobserved by TUNEL and DAPI staining in FIR-treatedgroups. Body weight of mice increased compared with thecontrol. Oxydation and Reduction (Redox) reactions byH+ (proton and electron)/O2- (a kind of Reactive OxygenSpecies (ROS)) were induced by FIR.

Conclusions: These results clarified that FIR inhibitedthe proliferation of HepG2 at non-thermal circumstances(at 25±0.5, 37±0.5°C). FIR will serve as a tool againstdiseases induced by HepG2.

Summary data from recent epidemiological studies provide overwhelming evidence that areca nut is the main aetiological factor for OSF. Commercially freeze dried products such as pan masala, Guthka and mawa have high concentrates of areca nut per chew and appear to cause OSF more rapidly than by self prepared conventional betel quid that contain smaller amounts of areca nut. It is logical to hypothesize that the increased collagen synthesis or reduced collagen degradation as possible mechanisms in the development of the disease. These chemicals appear to interfere with the molecular processes of deposition and/or degradation of extracellular matrix molecules such as collagen. In vitro studies on human fibroblasts using areca extracts or chemically purified arecoline support the theory of fibroblastic proliferation and increased collagen formation that is also demonstrable histologically in human OSF tissues. The copper content of areca nut is high and the possible role of copper as a mediator of fibrosis is supported by the demonstration of up regulation of lysyl oxidase in OSF biopsies. It has been postulated that areca nut may also induce the development of the disease by increased levels of cytokines in the lamina propria. Current evidence implicates collagen-related genes in the susceptibility and pathogenesis of OSF. The individual mechanisms operating at various stages of the disease– initial, intermediate and advanced–need further study in order to propose appropriate therapeutic interventions.

Introduction Many viruses have been associated with human breast cancers, including Epstein-Barr and Cytomegalovirus. New evidence has revealed the frequent presence of highrisk human papillomavirus (HPV) strains HPV16 and HPV18 in breast carcinoma biopsies. These findings raise the question of whether HPV may infect developing cancers and mediate their growth and development, as was recently observed with oral cancers. The goal of this study is to test the hypothesis that these high-risk HPV strains are sufficient to significantly alter phenotypes of already transformed human breast cancer cell lines. Materials and methods A series of in vitro experiments, including proliferation, adhesion and viability assays, were used to quantify the effects of HPV16 and HPV18 on the human breast cancer cell lines, T-47D and MCF7, following transient transfection with the full length HPV virus. Normal breast and fibroblast cell lines, MCF10A and Hs27, were used as noncancerous controls. Results HPV16 and HPV18 significantly inhibited proliferation and adhesion of T-47D cells, although viability was not affected. Differential effects on proliferation were observed in MCF7 cells; HPV16 inhibited proliferation, while HPV18 stimulated proliferation. No measurable effects in adhesion or viability in MCF7 cells were observed. The phenotypic changes in T-47D and MCF7 cells were associated with changes in mRNA expression of caspase-2,-3 and -8, but not p53 or GAPDH. No measurable changes in proliferation or viability were observed following HPV transfection in the normal human breast cell line, MCF10A, or the normal human fibroblast cell line, Hs27, although adhesion was differentially affected. Conclusions Although HPV is a primary cause of virtually all cervical cancers, it is found as a concomitant infection in many other tumors. While HPV may initiate carcinogenesis in these tumors, recent studies suggest HPV may also modulate the progression or malignancy process in already transformed cancers. Determining what effects HPV has on already transformed breast cancers may therefore become an important step towards understanding the factors that will lead to more effective treatment options for a significant proportion of breast cancer patients.

Elevated Src kinase activity is linked to the progression of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Src regulates HNSCC proliferation and tumor invasion, with the Src-targeted small molecule inhibitor saracatinib displaying potent anti-invasive effects in preclinical studies. However, the pro-invasive cellular mechanism(s) perturbed by saracatinib are unclear. The anti-proliferative and anti-invasive effects of saracatinib on HNSCC cell lines were therefore investigated in preclinical cell and mouse model systems. Saracatinib treatment inhibited growth, cell cycle progression and transwell Matrigel invasion in HNSCC cell lines. Dose-dependent decreases in Src activation and phosphorylation of the invasion-associated substrates focal adhesion kinase, p130 CAS and cortactin were also observed. While saracatinib did not significantly impact HNSCC tumor growth in a mouse orthotopic model of tongue squamous cell carcinoma, impaired perineural invasion and cervical lymph node metastasis was observed. Accordingly, saracatinib treatment displayed a dose-dependent inhibitory effect on invadopodia formation, extracellular matrix degradation and matrix metalloprotease 9 activation. These results suggest that inhibition of Src kinase by saracatinib impairs the pro-invasive activity of HNSCC by inhibiting Src substrate phosphorylation important for invadopodia formation and associated matrix metalloprotease activity.