Skin mediated human papillomavirus infection in breast: A report of four cases

To address the ambiguity of different modes of human papillomavirus (HPV) transmission in breast, the immunohistochemical expression of two oncoproteins E6/E7 of HPV16 was analyzed in primary breast cancer (BC) and adjacent normal skin of 4 samples. The patients were of 35–55 years old having no previous history of cancer. The E6/E7 expressions were evident in both skin and BC. In skin, high/moderate cytoplasmic expressions of E6/E7 proteins were seen in all samples, whereas in BC, high/moderate cytoplasmic expressions of the proteins were observed in 2–3 samples. Thus, it seems that HPV infection in the breast may occur through the skin

Association of Augmented Immune-Staining of G-Quadruplex Tertiary DNA Structure in Chemo-Tolerant TNBC with Downregulation of WNT/Epidermal Growth Factor Receptor Pathway receptor Genes: A Pilot Clinicopathological Study

Purpose: The aim of the study is to understand the involvement of G-Quadruplex (G-Q) structures in altering the expression profile of WNT/epidermal growth factor receptor (EGFR) pathway receptor genes in chemo-tolerant Triple Negative Breast Cancer (TNBC) samples. Materials and Methods: At first, Gene Expression Omnibus datasets were mined where the expression profile of WNT/EGFR pathway genes in TNBC samples and MDA-MB-231, a TNBC cell line, were checked in response to doxorubicin, a chemotherapeutic drug. Next, to unveil the probable mechanism of regulation, the presence of G-Q structure was checked in in silico study and later validated by immunohistochemical analyses in our pool of sample. These observed results were correlated with patient's demography and survival status. Results: Expression of the receptors (FZD7, LRP6, EGFR) of the WNT/EGFR pathway were found to be differentially expressed in TNBC samples; further emphasized in our samples (n = 61). Notably, these G-Q structures were found in the promoter region of the WNT pathway receptor genes (FZD7, LRP6, and EGFR). Validating in our patient sample pool, a significant increase in G-Q immunostaining was observed in samples, after neoadjuvant chemotherapy (NACT) samples (n = 17) than the pretherapeutic samples (n = 44). Similar pattern of G-Q immunostaining was noticed in doxorubicin-treated MDA-MB-231 cell line. Intriguingly, low staining of G-Q among the pretherapeutic samples, but NACT TNBC samples, was found to be significantly correlated with lymph node metastasis. Conclusions: This study showed that the augmented immunostaining of G-Q structure might have an important involvement in regulating the expression pattern of the WNT/EGFR pathway genes in response to doxorubicin treatment of TNBC

Differential activation of NOTCH1 pathway in HNSCC cell lines of different anatomical sites

244-251Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent types of cancers, and the role of NOTCH1 pathway during development of HNSCC is debatable. Here, we have made an attempt to evaluate the NOTCH1 pathway status in HNSCC cell lines from different anatomical subsites. At first, mRNA expression status of NOTCH1 pathway associated genes (NOTCH1/JAG1/JAG2/HES1/HEY1/CD44/FBXW7/HIF1α/VEGF) was analysed in two HNSCC cell lines: FaDu (hypopharyngeal carcinoma) and SCC9 (tongue carcinoma) and was compared with publicly available database. Then, molecular profiling (RNA/protein) of the genes and cell cycle phase distribution analysis were done after DAPT (γ-secretase inhibitor) administration at different concentrations on the cell lines to see the differential effect, if any. High NOTCH1 pathway activation was noted in FaDu cell line than the SCC9. In cytotoxicity assay with DAPT, FaDu showed more sensitivity than SCC9. Therefore, gradual decline of the expression of NOTCH1 pathway associated genes was noted in FaDu with the increasing DAPT concentrations, leading to high S/G2-M arrest of the cell population. Contrastingly, SCC9 showed significant reduced expression of the genes at higher concentration of DAPT with comparatively low S/G2-M arrest of the cell population. The study demonstrates distinct NOTCH1 pathway signature in the HNSCC cell lines of specific sub-sites of head and neck