Rodegay8404

The prevalence of breast cancer is remarkably increasing worldwide. Therefore, introduction of new approaches along with improvement of the existing ones in cancer treatment field is of great demand. The present study was designated to investigate the anti-proliferative role of Diallyl trisulfide (DATS) alone or in combination with Doxorubicin (Doxo) in Ehrlich solid carcinoma (ESC)-bearing mice. selleck compound ESC was induced in female albino mice as an experimental model for breast cancer. The anti-tumorigenic effect of DATS was mediated by suppression of Notch signaling proteins (Notch 1, JAG 1 and HES 1), attenuation of tumor inflammation (NFκB, TNF-α, IL-6, IL-1β) and proliferation (cyclin D1, Ki67) and enhancement of apoptosis (caspase 3, p53). DATS and Doxo mono-treatments displayed opposing effect regarding expression of Notch signaling proteins and cyclin D1 gene expression. However, DATS and Doxo co-treatment markedly decreased tumor volume and weight, increased animals' survival rate, and attenuated Doxo-induced tumor inflammation. In parallel, microscopic investigation displayed that ESC tumor tissues from animals treated with DATS and/or DOX showed shrinkage of tumor lesions and wider zones of apoptosis. In conclusion, DATS acts via multiple molecular targets to elicit anti-proliferative activity. Combination of DATS with Doxo -which exhibit different mechanisms of action- might be a potential novel strategy to augment Doxo-antitumor effect.Tumor budding (TB) is a promising prognostic marker in many cancers including oral squamous cell carcinoma. The evaluation of TB in preoperative diagnostic biopsies has been proven be possible; therefore, the association of TB with other morphological features can represent an important aid in the previous treatment decision. This study aims to evaluate TB in oral squamous cell carcinoma (OSCC) biopsies, assessing its association with other morphological characteristics of the sample. A total of 56 cases of OSCC were investigated. In hematoxylin and eosin-stained slides, morphological features including histopathological grading and mode of invasion were evaluated in the deep invasive front. Moreover, immunohistochemistry was performed with anti-multi-cytokeratin antibody helping in the identification of TB, which was graded as low-intensity or no TB and high-intensity TB. Descriptive and bivariate analyses were performed, and the level of significance was set at 5%. The tongue was the most-affected site with 29 (51.7 %) tumors. The predominant mode of invasion (27-48.2 %) was by groups of neoplastic cells without clear boundaries. Of the cases investigated, 37 (66.1 %) were high-intensity TB, which was associated with the mode of invasion of the tumors (p less then 0.05). All cases with the worst mode of invasion showed high-intensity TB. Preliminary results showed the potential of morphological features, such as TB and mode of invasion, evaluated in diagnostic specimens of OSCC, aiding in the treatment decision to select patients who could benefit from more-aggressive treatments.High doses of metformin induces oxidative stress (OS) and transforming growth factor β1 (TGF-β1) in breast cancer cells, which was associated with increased cancer stem cell population, local invasion, liver metastasis and treatment resistance. Considering the impact of TGF- β1 and OS in breast cancer and the interrelation between these two pathways, the objective of this work was to investigate the effects of consecutive metformin treatments, at a non-cytotoxic dosage, in TGF- β1 targets in MCF-7 and MDA-MB-231 cells. Cells were exposed to 6 μM of metformin for seven consecutive passages. Samples were collected to immunocytochemistry (evaluation of p53, Nf-кB, NRF2 and TGF-β1), biochemical (determination of lipoperoxidation, total thiols and nitric oxide/peroxynitrite levels) and molecular biology analyzes (microarray and Real-time quantitative array PCR). Microarray analysis confirmed alterations in genes related to OS and TGF-β1. Treatment interfered in several TGF-β1 target-genes. Metformin upregulated genes involved in OS generation and apoptosis, and downregulated genes associated with metastasis and epithelial mesenchymal transition in MCF-7 cells. In MDA-MB-231 cells, metformin downregulated genes involved with cell invasion, viability and proliferation. The results shows that even a non-cytotoxic dosage of metformin can promote a less aggressive profile of gene expression in breast cancer cells.

In order to find new immune targets for lung cancer with different EGFR mutant status, we describe differential expression profiles of checkpoint molecules of the new discovery B7 family member to find new immune targets for lung cancer with different EGFR statuses.

We performed immunohistochemistry with antibodies of B7-H3, B7-H4, VISTA, B7-H6, HHLA2, IDO-1, PD-L1 and CD8 in lung adenocarcinoma tissues constructed from 372 cases in the discovery cohort and 231 cases in the validation set. The differential expression profiles of these indices in EGFR mutant and wild-type lung adenocarcinoma was described and compared.

In the discovery cohort, the median IHC scores of B7-H4 and HHLA2 for the EGFR mutant group were significantly higher than those in the wild-type group (median score [interquartile range], mutant vs. wild type 3.250 [0-7.000] vs. 5.000 [1.000-7.000], P = 0.045 for B7-H4; 8.000 [6.000-10.500] vs. 7.000 [5.000-8.630] P = 0.003 for HHLA2). Meanwhile, the median IHC scores of IDO-1 and PD-L1 in the wild-type group were significantly higher than those in the mutant group (median score [interquartile range], mutant vs. wild type 1.000 [0-5.000] vs. 3.000 [0-8.500], P = 0.000 for IDO-1; 0 [0-3.500] vs. 3.000 [0-6.000], P = 0.000 for PD-L1). Results above was confirmed in the discovery cohort. The increased CD8 and decreased HHLA2 expression levels were associated with long disease-free survival in lung adenocarcinoma (P = 0.000 for CD8 expression and P = 0.004 for HHLA2 expression).

B7-H4 and HHLA2 are promising immune targets for lung adenocarcinoma, especially for patients with EGFR mutation.

B7-H4 and HHLA2 are promising immune targets for lung adenocarcinoma, especially for patients with EGFR mutation.