Prostate Cancer: Countdown to Choice between Stitch in Time and Eleventh Hour Begins

Androgen ablation therapy presumed to be an effective treatment for advanced prostate cancer (PCa) is relentlessly challenged. Remissions are impermanent and patients almost inescapably progress to become castration-resistant prostate cancer (CRPC). CRPC is almost invincible and is the major stumbling block in the treatment. It is a dramatic shift of androgen receptor (AR) from normal activities to the oncogenesis. AR signaling is remarkably increased under an androgen-depleted environment. It utilizes a miscellany of mechanisms and pathways to compensate for the decreasing levels of androgens. These range from mutations in the receptor more like a business tactic to attract more clients, to the illegitimate crosstalks which promote the signaling. The review will encompass various mechanistic insights of the AR manipulations. Moreover efficacy of therapeutic interventions recently designed keeping in view the molecular hierarchy will be evaluated

Parkinson disease: identifying different players sharing a common principle

Parkinson disease is a multifactorial molecular disorder. Miscellaneous regulators have been characterized to date and their implication in disease progression is well documented. Compromised neuromuscular activity is a serious threat posed by malfunctioning of various regulators. The integrity and maintenance of neural architecture underpins neural activities. Despite the fact that various breakthroughs have been made, yet many proteins are unidentified while some unaddressed. Furthermore, miRNA pathway impairment results in subversion of core biological system and draws attention towards novel miRNA-based therapeutic strategies. Thus proteins and mitrons work in collaboration with various cellular organelles to ensure normal dynamics of neural circuitry. In this review we will emphasize the derailed activities of proteins at molecular level that might help in getting a step closer to personalized medicine

Methylation and loss of Imprinting: Unending rivalries unleashed between “kneaded erasers†and “fate writersâ€Â

Genome is a complex barcode that is interpreted at molecular level. There are various proteins which are modulating the expression or repression of the genes. Miscellaneous proteins work in collaboration to stimulate or repress the gene expression. Chromatin remodeling factors are the artists which chisel, carve and mould the sculpture of genome. In this review we will emphasize on exemptions and extensions which trigger genomic instability in broad range of molecular anomalies. Doubtlessly therapeutic interventions have shown tremendous promise in cancer therapy, but the selectivity profiles of these compounds have largely relied on serendipity or 'off-target' activities rather than rational drug design. Purposefully designed compounds with activity against methyltransferase, demethylase and HDAC will bring us a step closer to personalized medicine

Critical Molecular and Genetic Markers in Primary Brain Tumors with Their Clinical Importance

Classification of primary brain tumors is based mainly on histopathological characteristics. Due to the peculiarity of the central nervous system (CNS), the location of the tumor is also used in the naming of the CNS tumors. These features, histopathology, and location determine the main prognostic factors in these tumors. Updated molecular and genetic findings in the last two decades accumulated vast amount of knowledge about the biological behavior, response to the treatment, and consequently the prognosis of CNS tumors. After the clinical use of these data, a recent classification is proposed by the International Society of Neuropathology named as “integrated diagnosis.

Pollination of Grewia asiatica (Malvaceae) by Megachile cephalotes (Hymenoptera: Megachilidae): Male vs. Female Pollination

Phalsa, Grewia asiatica is a multi-purpose crop while cross-pollination can significantly improve its reproductive success. Megachile bees (Megachilidae) are the most important group of pollinators of G. asiatica. In this study we observed the foraging behavior of Megachile cephalotes and its ultimate impact on reproductive success of phalsa at Bahawalpur (Punjab), Pakistan. Although visitation rate and stay time were statistically similar in both the sexes but visitation frequency (2.06±0.14 individuals/120 seconds) and pollen deposition (39.35±3.17 pollen grains /stigma/visit) of females were significantly higher than that of males (0.44±0.06 individuals/120 seconds and 12.05±1.19 pollen grains/stigma/visit, respectively). The environmental factors (i.e. ambient temperature, relative humidity, sunlight intensity and wind speed) greatly influenced -either positively or negatively- both the sexes (Pearson’s correlation). Female pollinated fruits were significantly greater in weight (0.41±0.017 g) followed by open (0.31±0.012 g) and male (0.27±0.011 g) pollinated fruits. Percent weight loss remained significantly lower in female pollinated fruits than open and male pollinated fruits until12 hours after harvest. Fruit wrinkling significantly increased with the increase in post-harvest intervals in open, female and male pollinated fruits while fruit color changed only in female pollinated fruits. The results of present study suggest female M. cephalotes as the efficient pollinators of G. asiatica in terms of it reproductive success and post-harvest parameters. Future studies should focus biology and ecology of M. cephalotes with special focus on its artificial nesting

Minimally Invasive Surgery in Gynecology

The first laparoscopic procedure was performed by 1901 by Georg Kelling in dogs while the first laparoscopic procedure in humans was performed by Hans Chrisitan Jacobaeus in 1910. Minimally invasive surgery offers multiple advantages over conventional laparotomy and is associated with reduced estimated blood loss, a lower incidence of complications and a shorter hospital stay and recovery. Over a century later, the vast majority of surgical procedures in gynecology are performed via minimal invasive technique. These include laparoscopy, minilaparoscopy, robotic surgery, laparoendoscopic single site surgery (LESS) and natural orifices transluminal endoscopic surgery. In this chapter we review these surgical techniques, analyze the main differences among these techniques and comment on their advantages and disadvantages

Nanomedicine for the delivery of RNA in cancer

The complexity, and the diversity of the different types of cancers allied to the tendency to form metastasis make treatment efficiency so tricky and often impossible due to the advanced stage of the disease in the diagnosis. In recent years, due to tremendous scientific breakthroughs, we have witnessed exponential growth in the elucidation of mechanisms that underlie carcinogenesis and metastasis. The development of more selective therapies made it possible to improve cancer treatment. Although interdisciplinary research leads to encouraging results, scientists still have a long exploration journey. RNA technology represents a promise as a therapeutic intervention for targeted gene silencing in cancer, and there are already some RNA-based formulations in clinical trials. However, the use of RNA as a therapeutic tool presents severe limitations, mainly related to its low stability and poor cellular uptake. Thus, the use of nanomedicine employing nanoparticles to encapsulate RNA may represent a suitable platform to address the major challenges hampering its therapeutic application. In this review, we have revisited the potential of RNA and RNA-associated therapies to fight cancer, also providing, as support, a general overview of nanoplatforms for RNA delivery.This work received financial support from PT national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through project UIDB/50006/2020

Role of Nanotechnology and Gene Delivery Systems in TRAIL-Based Therapies

Since its identification as a member of the tumour necrosis factor (TNF) family, TRAIL (TNF-related apoptosis-inducing ligand) has emerged as a new avenue in apoptosis-inducing cancer therapies. Its ability to circumvent the chemoresistance of conventional therapeutics and to interact with cancer stem cells (CSCs) self-renewal pathways, amplified its potential as a cancer apoptotic agent. Many recombinant preparations of this death ligand and monoclonal antibodies targeting its death receptors have been tested in monotherapy and combinational clinical trials. Gene therapy is a new approach for cancer treatment which implies viral or non-viral functional transgene induction of apoptosis in cancer cells or repair of the underlying genetic abnormality on a molecular level. The role of this approach in overcoming the traditional barriers of radiation and chemotherapeutics systemic toxicity, risk of recurrence, and metastasis made it a promising platform for cancer treatment. The recent first Food Drug Administration (FDA) approved oncolytic herpes virus for melanoma treatment brings forth the potency of the cancer gene therapy approach in the future. Many gene delivery systems have been studied for intratumoural TRAIL gene delivery alone or in combination with chemotherapeutic agents to produce synergistic cancer cytotoxicity. However, there still remain many obstacles to be conquered for this different gene delivery systems. Nanomedicine on the other hand offers a new frontier for clinical trials and biomedical research. The FDA approved nanodrugs motivates horizon exploration for other nanoscale designed particles\u27 implications in gene delivery. In this review we aim to highlight the molecular role of TRAIL in apoptosis and interaction with cancer stem cells (CSCs) self-renewal pathways. Finally, we also aim to discuss the different roles of gene delivery systems, mesenchymal cells, and nanotechnology designs in TRAIL gene delivery

Overview of the oncogenic signaling pathways in colorectal cancer: Mechanistic insights.

Colorectal cancer is a multifaceted disease which is therapeutically challenging. Based on insights gleaned from almost a quarter century of research, it is obvious that deregulation of spatio-temporally controlled signaling pathways play instrumental role in development and progression of colorectal cancer. High-throughput technologies have helped to develop a sharper and broader understanding of the wide ranging signal transduction cascades which also contribute to development of drug resistance, loss of apoptosis and, ultimately, of metastasis. In this review, we have set the spotlight on role of JAK/STAT, TGF/SMAD, Notch, WNT/β-Catenin, SHH/GLI and p53 pathways in the development and progression of colorectal cancer. We have also highlighted recent reports on TRAIL-mediated pathways and molecularly distinct voltage-gated sodium channels in colorectal cancer

Oleuropein and Cancer Chemoprevention: the Link is Hot

Cancer comprises a collection of related diseases characterized by the existence of altered cellular pathways resulting in an abnormal tendency for uncontrolled growth. A broad spectrum, coordinated, and personalized approach focused on targeting diverse oncogenic pathways with low toxicity and economic natural compounds can provide a real benefit as a chemopreventive and/or treatment of this complex disease. Oleuropein, a bioactive phenolic compound mainly present in olive oil and other natural sources, has been reported to modulate several oncogenic signalling pathways. This review presents and critically discusses the available literature about the anticancer and onco-suppressive activity of oleuropein and the underlying molecular mechanisms implicated in the anticarcinogenic and therapeutic effects. The existence of limitations and the promising perspectives of research on this phenolic compound are also critically analyzed and discussed.This article is the outcome of an in-house financially non-supported study. A. Sureda was partially supported by the Spanish Ministry of Health, Social Services and Equality (CIBEROBN-B12/03/30038). A. Mocan acknowledges funding from UEFISCDI, Romania, project no. PNII-RU-TE-2014-4-1247.info:eu-repo/semantics/publishedVersio