Phosphodiesterase (PDE) gene family is a large family having at least 21 genes and multiple versions (isoforms) of the phosphodiesterase enzymes. These enzymes catalyze the inactivation of intracellular mediators of signal transduction such as cAMP and cGMP and therefore, play a pivotal role in various cellular functions. PDE inhibitors (PDEI) are drugs that block one or more of the five subtypes of the PDE family and thereby prevent inactivation of the intracellular cAMP and cGMP by the respective PDE-subtypes.
View Article and Find Full Text PDFThere are around 20 Cyclin-dependent kinases (CDKs) known till date, and various research groups have reported their role in different types of cancer. The X-ray structures of some CDKs especially CDK2 was exploited in the past few years, and several inhibitors have been found, e.g.
View Article and Find Full Text PDFHuman antigen (Hu) R is an RNA-binding protein whose overexpression in human cancer correlates with aggressive disease, drug resistance, and poor prognosis. HuR inhibition has profound anticancer activity. Pharmacologic inhibitors can overcome the limitations of genetic inhibition.
View Article and Find Full Text PDFHER2 amplification/overexpression accounts for aggressive clinical features of HER2 positive breast cancer. Epigenetic changes including DNA methylation, histone modifications and ncRNAs/miRNAs are associated with regulation of DNA chromatin and specifically, gene transcription. Hence, these produce eminent effects upon proto-oncogenes, tumor-suppressors and key cancer-regulatory signaling pathways.
View Article and Find Full Text PDFHER2 positive breast cancer is characterized by the low survival rate in the metastatic patients. Development of resistance and disease-relapse are the major problems associated with the currently available therapies for HER2 positive breast cancer. There are two major targeted therapies for HER2 positive breast cancer viz.
View Article and Find Full Text PDFSelective downregulation of the human antigen R (HuR) protein by siRNA may provide a powerful approach for treating lung cancer. To this end, we investigated the efficacy of transferrin receptor-targeted liposomal nanoparticle-based HuR siRNA (HuR-TfNP) therapy and compared with control siRNA (C)-TfNP therapy both, and using lung cancer models. studies showed HuR-TfNP, but not C-TfNP, efficiently downregulated HuR and HuR-regulated proteins in A549, and HCC827 lung cancer cells, resulting in reduced cell viability, inhibition of cell migration and invasion, and induction of G cell-cycle arrest culminating in apoptosis.
View Article and Find Full Text PDFStructure-based design and synthesis of pyrimidine containing reversible epidermal growth factor receptor (EGFR) inhibitors 1a-d are reported. The compounds (1a-d) inhibited the EGFR kinase activity in vitro with IC range 740 nm to 3 μm. mRNA expression of EGFR downstream target genes, that is twist, c-fos and aurora were found to be altered upon treatment with compounds 1a-d.
View Article and Find Full Text PDFDrug Dev Ind Pharm
September 2017
RNA interference (RNAi) is emerging as a powerful approach in cancer treatment. siRNA is an important RNAi tool that can be designed to specifically silence the expression of genes involved in drug resistance and chemotherapeutic inactivity. Combining siRNA and other therapeutic agents can overcome the multidrug resistance (MDR) phenomenon by simultaneously silencing genes and enhancing chemotherapeutic activity.
View Article and Find Full Text PDFVolumetric modulated arc therapy (VMAT) is modern rotational intensity modulated therapy used for treatment of several sites. The study aimed to analyze partial tangential arc VMAT treatment planning and delivery, including analyzing the cardiac and contralateral breast doses resulting from this technique. A total of 153 consecutively treated breast cancer (conservation as well as mastectomy) patients were taken for this dosimetric study.
View Article and Find Full Text PDFBackground: Time and accuracy are commonly used metrics to assess laparoscopic skills in a simulated environment. However, they do not provide trainees with meaningful information about how to improve their skills. The objective of this study was to provide preliminary validity evidence for the creation a formative feedback tool (FFT) for advanced laparoscopic suturing skills.
View Article and Find Full Text PDFThe utility of novel FeO@Au nanoparticles as magnetically separable and recyclable heterogeneous catalysts for the A-coupling reaction of aldehydes, amines and terminal alkynes to yield the corresponding propargylamines is demonstrated. Herein we present a comprehensive analysis of the experimentally observed trends in the conversions with computational analysis using LUMO density on molecular isosurfaces and the electrostatic potential (ESP) effects estimated using DFT calculations.
View Article and Find Full Text PDFIn recent years, researchers have focused on targeted gene therapy for lung cancer, using nanoparticle carriers to overcome the limitations of conventional treatment methods. The main goal of targeted gene therapy is to develop more efficient therapeutic strategies by improving the bioavailability, stability, and target specificity of gene therapeutics and to reduce off-target effects. Polymer-based nanoparticles, an alternative to lipid and inorganic nanoparticles, efficiently carry nucleic acid therapeutics and are stable in vivo.
View Article and Find Full Text PDFOverexpression of BMI1 in human cancer cells, a member of the polycomb group of repressive complexes, correlates with advanced stage of disease, aggressive clinico-pathological behavior, poor prognosis, and resistance to radiation and chemotherapy. Studies have shown that experimental reduction of BMI1 protein level in tumor cells results in inhibition of cell proliferation, induction of apoptosis and/or senescence, and increased susceptibility to cytotoxic agents and radiation therapy. Although a role for BMI1 in cancer progression and its importance as a molecular target for cancer therapy has been established, information on the impact of silencing BMI1 in triple-negative breast cancer (TNBC) and its consequence on radiotherapy have not been well studied.
View Article and Find Full Text PDFIEEE Trans Nanobioscience
December 2016
Gene silencing through RNA interference (RNAi) has emerged as a potential strategy in manipulating cancer causing genes by complementary base-pairing mechanism. Small interfering RNA (siRNA) is an important RNAi tool that has found significant application in cancer therapy. However due to lack of stability, poor cellular uptake and high probability of loss-of-function due to degradation, siRNA therapeutic strategies seek safe and efficient delivery vehicles for in vivo applications.
View Article and Find Full Text PDFPurpose: Obtain baseline data of cell-phone usage in the medical (MO), surgical (SO) and radiation (RO) oncology community practicing in India.
Materials And Methods: Indigenously prepared cell-phone usage related questionnaire was used in the present study after approval by the Institutional Ethics/Scientific Committees. The questionnaire had 41 items and was made to assess the cell-phone usage parameters, utility in clinical practice, awareness, and to compare parameters between oncology specialties.
Background: Breast cancer is the most frequently diagnosed life-threatening malignancy among women, across the globe. HER2 positive is a distinct breast cancer subtype, on account of its unique biology and physiological behavior.
Results: Amplification of HER2 oncogene/polysomy 17 leads to HER2 overexpression that is a significant causal implication in HER2 positive breast cancer.
Successful chemotherapeutic intervention for management of lung cancer requires an efficient drug delivery system. Gold nanoparticles (GNPs) can incorporate various therapeutics; however, GNPs have limitations as drug carriers. Nano-sized cellular vesicles like exosomes (Exo) can ferry GNP-therapeutic complexes without causing any particle aggregation or immune response.
View Article and Find Full Text PDFThe performance of GaAs nanowire (NW) devices depends critically on the presence of crystallographic defects in the NWs such as twinning planes and stacking faults, and considerable effort has been devoted to understanding and preventing the occurrence of these. For self-catalysed GaAs NWs grown by molecular beam epitaxy (MBE) in particular, there are in addition other types of defects that may be just as important for NW-based optoelectronic devices. These are the point defects such as the As vacancy and the Ga antisite occurring due to the inherently Ga-rich conditions of the self-catalysed growth.
View Article and Find Full Text PDFA mini-review with 79 references. In this review, the most recent trends in 3D-printed microfluidic devices are discussed. In addition, a focus is given to the fabrication aspects of these devices, with the supplemental information containing detailed instructions for designing a variety of structures including: a microfluidic channel, threads to accommodate commercial fluidic fittings, a flow splitter; a well plate, a mold for PDMS channel casting; and how to combine multiple designs into a single device.
View Article and Find Full Text PDFInterleukin (IL)-24, a novel tumor suppressor/cytokine exhibits antitumor activity against a broad-spectrum of human cancer cells. In a recent study, we showed that IL-24 inhibited AKT in lung cancer cells. However, the molecular mechanism of AKT inhibition by IL-24 remains elusive.
View Article and Find Full Text PDFHuR is an mRNA-binding protein whose overexpression in cancer cells has been associated with poor prognosis and resistance to therapy. While reports on HuR overexpression contributing to chemoresistance exist, limited information is available on HuR and radioresistance especially in triple-negative breast cancer (TNBC).In this study we investigated the role of HuR in radiation resistance in three TNBC (MDA-MB-231, MDA-MB-468 and Hs578t) cell lines.
View Article and Find Full Text PDFDue to bandgap tunability, GaAsSb nanowires (NWs) have received a great deal of attention for a variety of optoelectronic device applications. However, electrical and optical properties of GaAsSb are strongly affected by Sb-related defects and scattering from surface states and/or defects, which can limit the performance of GaAsSb NW devices. Thus, in order to utilize the GaAsSb NWs for high performance electronic and optoelectronic devices, it is required to study the material and interface properties (e.
View Article and Find Full Text PDFRadiotherapy (RT) is a powerful tool for the palliation of the symptoms of advanced cancer, although access to it is limited or absent in many low- and middle-income countries (LMICs). There are multiple factors contributing to this, including assumptions about the economic feasibility of RT in LMICs, the logical challenges of building capacity to deliver it in those regions, and the lack of political support to drive change of this kind. It is encouraging that the problem of RT access has begun to be included in the global discourse on cancer control and that palliative care and RT have been incorporated into national cancer control plans in some LMICs.
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