Pluripotency inducing Yamanaka factors: role in stemness and chemoresistance of liver cancer.

: Liver cancer is a major cause of mortality and is characterized by the transformation of cells into an uncontrolled mass of tumor cells with many genetic and epigenetic changes, which lead to the development of tumors. A small subpopulation of cell population known as Cancer Stem Cells (CSCs) is responsible for cancer stemness and chemoresistance. Yamanaka factors [octamer-binding transcription factor 4 (OCT4), SRY (sex-determining region Y)-box 2 (SOX2), kruppel-like factor 4 (KLF4), and Myelocytomatosis (MYC); OSKM] are responsible for cancer cell stemness, chemoresistance, and recurrence.

BMI1 polycomb group protein acts as a master switch for growth and death of tumor cells: regulates TCF4-transcriptional factor-induced BCL2 signaling.

For advanced prostate cancer (CaP), the progression of tumors to the state of chemoresistance and paucity of knowledge about the mechanism of chemoresistance are major stumbling blocks in the management of this disease. Here, we provide compelling evidence that BMI1 polycomb group protein and a stem cell factor plays a crucial role in determining the fate of tumors vis-à-vis chemotherapy. We show that progressive increase in the levels of BMI1 occurs during the progression of CaP disease in humans.

BMI1, stem cell factor acting as novel serum-biomarker for Caucasian and African-American prostate cancer.

Background: Lack of reliable predictive biomarkers is a stumbling block in the management of prostate cancer (CaP). Prostate-specific antigen (PSA) widely used in clinics has several caveats as a CaP biomarker. African-American CaP patients have poor prognosis than Caucasians, and notably the serum-PSA does not perform well in this group.

Androgen receptor in human health: a potential therapeutic target.

Androgen is a key for the activation of Androgen Receptor (AR) in most of the disease conditions, however androgen-independent activation of AR is also found in aggressive type human malignancies. An intense search for the inhibitors of AR is underway to cure AR-dependent diseases. In addition to targeting various components of AR signaling pathway, compounds which directly target AR are under preclinical and clinical investigation.

Role of BMI1, a stem cell factor, in cancer recurrence and chemoresistance: preclinical and clinical evidences.

There is increasing evidence that a variety of cancers arise from transformation of normal stem cells to cancer stem cells (CSCs). CSCs are thought to sustain cancer progression, invasion, metastasis, and recurrence after therapy. Reports suggest that CSCs are highly resistant to conventional therapy.

Epicatechin-rich cocoa polyphenol inhibits Kras-activated pancreatic ductal carcinoma cell growth in vitro and in a mouse model.

Activated Kras gene coupled with activation of Akt and nuclear factor-kappa B (NF-κB) triggers the development of pancreatic intraepithelial neoplasia, the precursor lesion for pancreatic ductal adenocarcinoma (PDAC) in humans. Therefore, intervention at premalignant stage of disease is considered as an ideal strategy to delay the tumor development. Pancreatic malignant tumor cell lines are widely used; however, there are not relevant cell-based models representing premalignant stages of PDAC to test intervention agents.

S100A4 calcium-binding protein is key player in tumor progression and metastasis: preclinical and clinical evidence.

The fatality of cancer is mainly bestowed to the property of otherwise benign tumor cells to become malignant and invade surrounding tissues by circumventing normal tissue barriers through a process called metastasis. S100A4 which is a member of the S100 family of calcium-binding proteins has been shown to be able to activate and integrate pathways both intracellular and extracellular to generate a phenotypic response characteristic of cancer metastasis. A large number of studies have shown an increased expression level of S100A4 in various types of cancers.

Lupeol, a novel androgen receptor inhibitor: implications in prostate cancer therapy.

Purpose: Conventional therapies to treat prostate cancer (CaP) of androgen-dependent phenotype (ADPC) and castration-resistant phenotype (CRPC) are deficient in outcome which has necessitated a need to identify those agents that could target AR for both disease types. We provide mechanism-based evidence that lupeol (Lup-20(29)-en-3b-ol) is a potent inhibitor of androgen receptor (AR) in vitro and in vivo.

Experimental Design: Normal prostate epithelial cell (RWPE-1), LAPC4 (wild functional AR/ADPC), LNCaP (mutant functional/AR/ADPC), and C4-2b (mutant functional/AR/CRPC) cells were used to test the anti-AR activity of lupeol.

Beneficial health effects of lupeol triterpene: a review of preclinical studies.

Since ancient times, natural products have been used as remedies to treat human diseases. Lupeol, a phytosterol and triterpene, is widely found in edible fruits, and vegetables. Extensive research over the last three decades has revealed several important pharmacological activities of lupeol.

Induction of hsp70, alterations in oxidative stress markers and apoptosis against dichlorvos exposure in transgenic Drosophila melanogaster: modulation by reactive oxygen species.

We examined a hypothesis that reactive oxygen species (ROS) generated by organophosphate compound dichlorvos modulates Hsp70 expression and anti-oxidant defense enzymes and acts as a signaling molecule for apoptosis in the exposed organism. Dichlorvos (0.015-15.

Synthetic pyrethroid cypermethrin induced cellular damage in reproductive tissues of Drosophila melanogaster: Hsp70 as a marker of cellular damage.

We tested a working hypothesis of whether the synthetic pyrethroid cypermethrin, used worldwide for insecticidal purpose, causes adverse effects on reproduction in Drosophila melanogaster. Freshly eclosed first instar larvae of a transgenic strain of Drosophila melanogaster, Bg9, transgenic for hsp70 (hsp70-lacZ), were transferred to different dietary concentrations of the test chemical (0.002, 0.

Hazardous effect of organophosphate compound, dichlorvos in transgenic Drosophila melanogaster (hsp70-lacZ): induction of hsp70, anti-oxidant enzymes and inhibition of acetylcholinesterase.

We tested a working hypothesis that stress genes and anti-oxidant enzyme machinery are induced by the organophosphate compound dichlorvos in a non-target organism. Third instar larvae of Drosophila melanogaster transgenic for hsp70 were exposed to 0.1 to 100.