Recent advances with cyclin-dependent kinase inhibitors: therapeutic agents for breast cancer and their role in immuno-oncology

Introduction: Collaborative interactions between several diverse biological processes govern the onset and progression of breast cancer. These processes include alterations in cellular metabolism, anti-tumor immune responses, DNA damage repair, proliferation, anti-apoptotic signals, autophagy, epithelial-mesenchymal transition, components of the non-coding genome or onco-mIRs, cancer stem cells and cellular invasiveness. The last two decades have revealed that each of these processes are also directly regulated by a component of the cell cycle apparatus, cyclin D1.

Area covered: The current review is provided to update recent developments in the clinical application of cyclin/CDK inhibitors to breast cancer with a focus on the anti-tumor immune response.

Expert opinion: The cyclin D1 gene encodes the regulatory subunit of a proline-directed serine-threonine kinase that phosphorylates several substrates. CDKs possess phosphorylation site selectivity, with the phosphate-acceptor residue preceding a proline. Several important proteins are substrates including all three retinoblastoma proteins, NRF1, GCN5, and FOXM1. Over 280 cyclin D3/CDK6 substrates have b\een identified. Given the diversity of substrates for cyclin/CDKs, and the altered thresholds for substrate phosphorylation that occurs during the cell cycle, it is exciting that small molecular inhibitors targeting cyclin D/CDK activity have encouraging results in specific tumors.     

Is Involvement a Good Thing? The Undesirable Consequences of Topical and Conversational Involvement in the Context of Alcohol Consumption

Whereas there is evidence that interpersonal communication, or conversation, influences predictors of alcohol consumption, the role of involvement in conversation effects remains unclear. This study explored how three aspects of involvement (topical relevance, or how relevant the topic of alcohol is; conversational relevance, or how relevant a conversation about alcohol is; and conversational effort, or how much effort people put into such a conversation), influence conversation effects. After assessing topical relevance, 46 same-sex dyads were requested to talk about the negative consequences of heavy drinking. Within each dyad, one participant was asked to take on an active talking role and the other participant a passive listening role. Next, conversational relevance, effort, and predictors of heavy drinking were measured. Results showed that participants who drank more alcohol found the topic of heavy drinking more relevant. This topical relevance increased conversational relevance and conversational effort. Conversational effort further increased when a talking role was assigned. Furthermore, participants who put more effort in the conversation and found it more relevant had more positive norms, identified more strongly with alcohol, and had higher intentions to drink. These findings suggest that more involvement in an alcohol-related conversation does not always lead to desirable outcomes.     

HPLC-MS Method for Simultaneous Quantitative Determination of an Innovative Russian Gestagen and its Metabolites in Rat and Rabbit Blood Sera

Pharmaceutical Chemistry Journal - An HPLC-MS method for simultaneous quantitative determination of a novel gestagenic pharmaceutical and two of its metabolites in rat and rabbit blood sera was...     

Atypical Abnormal Pulmonary Vein Drainage with Atrial Septal Defect: Surgical Treatment

Sinus venosus atrial septal defect (SV‐ASD) usually coexists with partial anomalous pulmonary vein connection (PAPVC). It is a difficult diagnosis in transthoracic echocardiography (TTE) due to eccentric position of defects. We present a rare case of atypical anatomical variation in PAPVC, which was never described before. Two right pulmonary veins drained into superior vena cava, which overrode SV‐ASD and interatrial septum, a third pulmonary vein into the right atrium. Complete diagnosis could not be set after TTE, nor transesophageal echocardiography, whereas angio‐CT was finally conclusive. This diagnostic approach allowed the surgical planning.     

Assessment of the Antimetastatic Activity of Extracts of Filipedula ulmaria Depending on Extractant

Pharmaceutical Chemistry Journal - Three extracts were produced from the above-ground part of the meadowsweet Filipendula ulmaria (L.) Maxim. using water, 40% ethanol, and 70% ethanol. Comparative...     

In vivo epigenetic effects induced by engineered nanomaterials: A case study of copper oxide and laser printer-emitted engineered nanoparticles

Evidence continues to grow on potential environmental health hazards associated with engineered nanomaterials (ENMs). While the geno- and cytotoxic effects of ENMs have been investigated, their potential to target the epigenome remains largely unknown. The aim of this study is two-fold: 1) determining whether or not industry relevant ENMs can affect the epigenome in vivo and 2) validating a recently developed in vitro epigenetic screening platform for inhaled ENMs. Laser printer-emitted engineered nanoparticles (PEPs) released from nano-enabled toners during consumer use and copper oxide (CuO) were chosen since these particles induced significant epigenetic changes in a recent in vitro companion study. In this study, the epigenetic alterations in lung tissue, alveolar macrophages and peripheral blood from intratracheally instilled mice were evaluated. The methylation of global DNA and transposable elements (TEs), the expression of the DNA methylation machinery and TEs, in addition to general toxicological effects in the lung were assessed. CuO exhibited higher cell-damaging potential to the lung, while PEPs showed a greater ability to target the epigenome. Alterations in the methylation status of global DNA and TEs, and expression of TEs and DNA machinery in mouse lung were observed after exposure to CuO and PEPs. Additionally, epigenetic changes were detected in the peripheral blood after PEPs exposure. Altogether, CuO and PEPs can induce epigenetic alterations in a mouse experimental model, which in turn confirms that the recently developed in vitro epigenetic platform using macrophage and epithelial cell lines can be successfully utilized in the epigenetic screening of ENMs.