Cervical cancer is the fourth most common malignancy in women worldwide and a leading cause of cancer-related mortality in developing countries. Important etiological factors in this cancer are high-risk human papillomaviruses (HPV), as roughly 96% of cervical cancer cases are positive for these oncoviruses. On the other hand, it has been recently pointed out that E6/E7 oncoproteins of high-risk HPV can upregulate the programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) axis. Likewise, several recent reports showed that checkpoint blockades targeting PD-1/PD-L1 pathways have achieved efficient clinical responses via suppressing cancer progression and improving survival in several types of human cancers including metastatic cervical cancer. In this review, we summarize recent advances in our understanding of the PD-1/PD-L1 signaling pathway and its interaction with high-risk HPV and their oncoproteins, which could have an important impact on the management of HPV-associated cancers including cervical.

Cardiac remodeling is the process by which the heart adapts to stressful stimuli, such as hypertension and ischemia/reperfusion; it ultimately leads to heart failure upon longterm exposure. Autophagy, a cellular catabolic process that was originally considered as a mechanism of cell death in response to detrimental stimuli, is thought to be one of the main mechanisms that controls cardiac remodeling and induces heart failure. Dysregulation of the adipokines leptin and adiponectin, which plays essential roles in lipid and glucose metabolism, and in the pathophysiology of the neuroendocrine and cardiovascular systems, has been shown to affect the autophagic response in the heart and to contribute to accelerate cardiac remodeling. The obesity-associated protein leptin is a pro-inflammatory, tumor-promoting adipocytokine whose elevated levels in obesity are associated with acute cardiovascular events, and obesity-related hypertension. Adiponectin exerts anti-inflammatory and antitumor effects, and its reduced levels in obesity correlate with the pathogenesis of obesityassociated cardiovascular diseases. Leptin-and adiponectin-induced changes in autophagic flux have been linked to cardiac remodeling and heart failure. In this review, we describe the different molecular mechanisms of hyperleptinemia-and hypoadiponectinemia-mediated pathogenesis of cardiac remodeling and the involvement of autophagy in this process. A better understanding of the roles of leptin, adiponectin, and autophagy in cardiac functions and remodeling, and the exact signal transduction pathways by which they contribute to cardiac diseases may well lead to discovery of new therapeutic agents for the treatment of cardiovascular remodeling.

Objectives The aim of this study was to develop and implement a pharmacy practice research training programme and to determine the effect of the programme on pharmacists' knowledge of, and attitudes towards, research. Methods An intensive 26-h training programme on pharmacy practice research methodology and biostatistics was designed and delivered. Thirty pharmacists from the National Center for Cancer Care and Research and the Heart Hospital in Qatar were recruited. A pre-test-post-test study design was used to subjectively and objectively assess research competencies and attitudes among the trainees. Both descriptive and inferential analyses including Wilcoxon signed-rank, McNemar χ 2 and paired t-tests were performed to assess the utility of the training (P < 0.05 was considered statistically significant). Key findings After completing the training sessions, all subjectively assessed researchrelated skills were significantly improved (P < 0.05). This was also confirmed with an overall significant improvement in the objectively assessed research-related knowledge (P < 0.05). Overall, there was a significant improvement in the mean total knowledge score after the training programme (13.4 ± 6.4 versus 20 ± 6.0; P < 0.001). A modest change was observed when attitude towards research was assessed immediately after the training. Conclusions This study demonstrated that it was feasible to design and implement a pharmacy-tailored research training programme and that such programme could improve pharmacists' knowledge and attitude on short term. This pilot study calls for further research to investigate the long-term outcomes of such programmes.

Breast and cervical cancers comprise 50% of all cancers during pregnancy. In particular, gestational breast cancer is considered one of the most aggressive types of cancers, which is a rare but fatal disease. However, the incidence of this type of cancer is increasing over the years and its prevalence is expected to rise further as more women delay childbearing. Breast cancer occurring after pregnancy is generally triple negative with specific characterizations of a poorer prognosis and outcome. On the other hand, it has been pointed out that this cancer is associated with a specific group of genes which can be used as precise targets to manage this deadly disease. Indeed, combination therapies consisting of gene-based agents with other cancer therapeutics is presently under consideration. We herein review recent progress in understanding the development of breast cancer during pregnancy and their unique subtype of triple negative which is the hallmark of this type of breast cancer.

Proteinuria (albuminuria) plays a crucial role in the etiology of chronic kidney disease (CKD) via alteration of multiple signaling pathways and cellular process in renal cells. The objectives of this study are to investigate the effects of activation of the energy-sensing molecule AMP-activated kinase (AMPK) in renal cells using metformin on endoplasmic reticulum (ER) stress, AKT, mTOR, epithelial-to-mesenchymal transition (EMT), autophagy, and apoptosis that are thought to mediate renal cell injury during proteinuria, and to dissect the AMPK- and non-AMPK mediated effects of metformin using an in vitro model of albumin-induced renal cell injury. Rat renal proximal tubular (NRK-52E) cells were exposed to 10 and 15 mg/ml of albumin for 72 h in the presence of 1 mM Metformin and/or 0.5 µM compound C, and assessed for alterations in the aforementioned pathways. Metformin treatment restored AMPK phosphorylation and augmented autophagy in renal cells exposed to albumin. In addition, metformin treatment attenuated the albumin-induced phosphorylation of AKT and the downstream targets of mTOR, and prevented albumin-mediated inductions of EMT marker (α-SMA), pro-apoptotic ER stress marker CHOP, and apoptotic caspases -12 and -3 in renal cells. Blockade of metformin-induced AMPK activation with compound C blunted the ER defense response and autophagy but had no effect on the markers of EMT and apoptosis in our model. Our studies suggest that metformin protects renal cells against proteinuric cytotoxicity via suppression of AKT and mTOR activation, inhibition of EMT and apoptosis, and augmentation of autophagy and ER defense response through AMPK-independent and AMPK-dependent mechanisms, respectively.