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Topic Review
Chromatin Regulator SPEN/SHARP in Cancer
Enzymes, such as histone methyltransferases and demethylases, histone acetyltransferases and deacetylases, and DNA methyltransferases are known as epigenetic modifiers that are often implicated in tumorigenesis and disease. One of the best-studied chromatin-based mechanism is X chromosome inactivation (XCI), a process that establishes facultative heterochromatin on only one X chromosome in females and establishes the right dosage of gene expression. The specificity factor for this process is the long non-coding RNA Xinactivespecifictranscript (Xist), which is upregulated from one X chromosome in female cells. Subsequently, Xist is bound by the corepressor SHARP/SPEN, recruiting and/or activating histone deacetylases (HDACs), leading to the loss of active chromatin marks such as H3K27ac. In addition, polycomb complexes PRC1 and PRC2 establish wide-spread accumulation of H3K27me3 and H2AK119ub1 chromatin marks. The lack of active marks and establishment of repressive marks set the stage for DNA methyltransferases (DNMTs) to stably silence the X chromosome.
  • 962
  • 25 May 2021
Topic Review
Pediatric-Type Diffuse Low-Grade Glioma
Pediatric-type diffuse low-grade glioma (LGG) are the most common pediatric brain tumor, accounting for approximately one-third of all cases. These tumors are designated as WHO grade 1 or 2 and encompass a wide array of histology and varying molecular backgrounds. Many of these tumors are incidentally found on head imaging with intervention needed when adverse symptoms present or when found to have progressive disease. Pediatric diffuse LGGs are primarily heterogenous in nature and can be molecularly classified into distinct subgroups; diffuse astrocytoma MYB- or MYBL1-altered, angiocentric glioma, polymorphous low-grade neuroepithelial tumors, and diffuse LGG MAPK pathway-altered.
  • 962
  • 25 Jul 2023
Topic Review
Sirtuins in Breast and Prostate Cancer
In mammals, seven sirtuins (SIRT1–7) have been identified, which primarily function as NAD-dependent deacetylases (SIRT1–3 and SIRT5–7) and ADP-ribosyl transferases (SIRT4 and 6). Additionally, sirtuins have been reported to function as demyristoylases (SIRT1–3 and 6), lipoamidases (SIRT4), and desuccinylases/demalonylases/deglutarylases (SIRT5). The forcus herein is the information on the tumor promotion or suppression roles of SIRT1–7 in breast and prostate cancers. Precisely, it is highlighted that sirtuins regulate various proteins implicated in proliferation, apoptosis, autophagy, chemoresistance, invasion, migration, and metastasis of both breast and prostate cancer.
  • 961
  • 03 Nov 2022
Topic Review
IDH Mutations in Chondrosarcoma
Chondrosarcomas are malignant cartilage-producing tumours that frequently harbour isocitrate dehydrogenase 1 and -2 (IDH) gene mutations. Several studies have confirmed that these mutations are key players in the early stages of cartilage tumour development, but their role in later stages remains ambiguous. The prognostic value of the IDH mutation in chondrosarcoma seems controversial and (pre)clinical studies that have focused on the direct and indirect targeting of the IDH mutation have not yielded novel treatment strategies.
  • 961
  • 21 Aug 2023
Topic Review
ADT for castration-resistant prostate cancer
The androgen receptor (AR) is one of the main components in the development and progression of prostate cancer (PCa), and treatment strategies are mostly directed toward manipulation of the AR pathway. In the metastatic setting, androgen deprivation therapy (ADT) is the foundation of treatment in patients with hormone-sensitive prostate cancer (HSPC). However, treatment response is short-lived, and the majority of patients ultimately progress to castration-resistant prostate cancer (CRPC). 
  • 960
  • 08 Apr 2021
Topic Review
Biomarkers of Anastomotic Leakage
Intestinal resection and anastomosis is a commonly performed abdominal procedure used in the treatment of colorectal cancers. Unfortunately, ~7% of all patients will develop an anastomotic leak (AL) following surgery. This situation occurs when the anastomotic site fails to heal correctly leading to contamination of the abdominal cavity with intestinal contents and the development of septic peritonitis. Patients often require revision surgery and intensive care, both of which are associated with significantly longer hospitalisation stays and increased economic costs. Patients also have higher morbidity and mortality rates and poorer oncological prognosis. Predicting which patients are at high-risk of developing an AL or diagnosing an AL early in the post-operative period is essential to optimise patient care and improve outcome. Unfortunately, predicting and diagnosing an AL following surgery for colorectal cancers is extremely difficult. Patients can present with a range of clinical symptoms and have non-specific findings on routine bloodwork. Diagnosis currently relies heavily on abdominal imaging with CT scans and contrast studies. Unfortunately, these techniques suffer from variable sensitivity and specificity and may delay diagnosis. To overcome these issues, pre-clinical and clinical research is continuing to identify diagnostic and predictive AL biomarkers. 
  • 959
  • 17 Jun 2021
Topic Review
5-Aminolevulinic Acid in Gliomas
5-aminolevulinic acid (5-ALA) is a porphyrin precursor in the heme synthesis pathway. When supplied exogenously, certain cancers consume 5-ALA and convert it to the fluorogenic metabolite protoporphyrin IX (PpIX), causing tumor-specific tissue fluorescence. Preoperative administration of 5-ALA is used to aid neurosurgical resection of high-grade gliomas such as glioblastoma, allowing for increased extent of resection and progression free survival for these patients. Targeting the heme synthesis pathway and understanding its dysregulation in malignant tissues could aid the development of adjunct therapies to increase intraoperative fluorescence after 5-ALA treatment
  • 958
  • 14 Apr 2021
Topic Review
Targeting Engineered Nanoparticles for Breast Cancer Therapy
Breast cancer (BC) is the second most common cancer in women globally after lung cancer. Presently, the most important approach for BC treatment consists of surgery, followed by radiotherapy and chemotherapy. Therapeutic drugs or natural bioactive compounds generally incorporate engineered NPs of ideal sizes and shapes to enhance their solubility, circulatory half-life, and biodistribution, while reducing their side effects and immunogenicity. Furthermore, ligands such as peptides, antibodies, and nucleic acids on the surface of NPs precisely target BC cells. Engineered NPs and their ideal methodology can be validated in the next-generation platform for preventive and therapeutic effects against BC.
  • 958
  • 12 Nov 2021
Topic Review
The Gut Microbiome and Colorectal Cancer
Colorectal cancer (CRC) represents a significant global health burden, ranking as the third most common cancer and the second leading cause of cancer-related deaths worldwide. The gut microbiome, composed of trillions of commensal microorganisms, plays a vital role in maintaining homeostasis and overall health. Mounting evidence suggests that alterations in the gut microbiome, referred to as dysbiosis, may contribute to the initiation and progression of CRC by modulating the tumor microenvironment (TME), including the tumor stroma.
  • 958
  • 05 Sep 2023
Topic Review
MITF in Cutaneous and Uveal Melanoma
Microphthalmia-associated transcription factor (MITF) is an important regulator of melanogenesis and melanocyte development. Cutaneous malignant melanomas are heterogeneous in nature, comprising several cell subpopulations with distinct transcriptomic signatures and behaviours. Melanomas carrying different genetic alterations have different clinical features and different relation with sun exposure. MITF-low cutaneous melanoma cells display a higher expression of stem cell markers (OCT4 and NANOG) and are able to produce larger tumours when injected into nude mice. However, both MITF-low and MITF-high cells can give rise to tumours, which then contain both types of cells. Uveal melanomas are malignant tumours that originate in the uveal tract of the eye and have different mutations and behaviour compared to cutaneous melanoma. The role of MITF in uveal melanoma is not clearly defined, but MITF loss is associated with loss of BAP1 expression, which is a marker of poor prognosis, 
  • 958
  • 13 Jun 2022
Topic Review
MicroRNAs in Ovarian Cancer Metastasis
Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer, and the major cause of death is attributed to metastasis. EOC metastasizes mainly through the transcoelomic pathway, in which cells disseminate from the primary EOC tumor by undergoing epithelial-to-mesenchymal transition (EMT), float freely as spheroids in the ascitic fluid, and then attach onto the mesothelium lining or invade deeper into the peritoneal organs. In addition, metastatic EOC cells can transit in the blood or lymph vessels and undergo extravasation to establish new tumors in hematogenous and lymphatic metastasis. MicroRNAs (miRNAs) are a group of small non-coding RNAs that exert important regulatory functions in many biological processes through their effects on regulating gene expression.  Numerous studies have reported that miRNAs can suppress or promote EOC metastasis by regulating the expression of genes involved in various events related to metastasis, such as EMT, cell migration and invasion, as well as tumor angiogenesis and immune suppression. 
  • 957
  • 14 Oct 2020
Topic Review
Microbiome and Resistance to Chemotherapy
Understanding the mechanisms of resistance to therapy in human cancer cells has become a multifaceted limiting factor to achieving optimal cures in cancer patients. Besides genetic and epigenetic alterations, enhanced DNA damage repair activity, deregulation of cell death, overexpression of transmembrane transporters, and complex interactions within the tumor microenvironment, other mechanisms of cancer treatment resistance have been recently proposed. Importantly, preclinical models and clinical studies highlight the critical role of the microbiome in the efficacy of cancer treatment.
  • 957
  • 20 Dec 2022
Topic Review
Microbes Living on the Skin
The human skin represents the largest human organ. It provides an effective barrier between the human organism and the environment. Superficial skin layers are inhabited by different sorts of microorganisms, such as bacteria, viruses, archaea, and fungi. This heterogeneous community of microorganisms are in mutualistic symbiosis. They play an essential role in the protection against invading pathogens and in the breakdown of natural products. Additionally, they contribute to a special form of innate and adaptive immunity, which links antimicrobial functions and tissue repair.
  • 957
  • 21 Mar 2022
Topic Review
Application of mRNA Technology in Cancer Therapeutics
mRNA-based therapeutics pose as promising treatment strategies for cancer immunotherapy. Improvements in materials and technology of delivery systems have helped to overcome major obstacles in generating a sufficient immune response required to fight a specific type of cancer. Several in vivo models and early clinical studies have suggested that various mRNA treatment platforms can induce cancer-specific cytolytic activity, leading to numerous clinical trials to determine the optimal method of combinations and sequencing with already established agents in cancer treatment.
  • 957
  • 02 Sep 2022
Topic Review
Nanoplatform for Delivery of Topotecan in Cancer Milieu
Chemotherapy has been the predominant treatment modality for cancer patients, but its overall performance is still modest. Difficulty in penetration of tumor tissues, a toxic profile in high doses, multidrug resistance in an array of tumor types, and the differential architecture of tumor cells as they grow are some of the bottlenecks associated with the clinical usage of chemotherapeutics. Advances in tumor biology understanding and the emergence of novel targeted drug delivery tools leveraging various nanosystems offer hope for developing effective cancer treatments. Topotecan is a topoisomerase I inhibitor that stabilizes the transient TOPO I-DNA cleavable complex, leading to single-stranded breaks in DNA. Due to its novel mechanism of action, TOPO is reported to be active against various carcinomas, namely small cell lung cancer, cervical cancer, breast cancer, and ovarian cancer. Issues of cross-resistance with numerous drugs, rapid conversion to its inactive form in biological systems, appended adverse effects, and higher water solubility limit its therapeutic efficacy in clinical settings. Topotecan nanoformulations offer several benefits for enhancing the therapeutic action of this significant class of chemotherapeutics. The likelihood that the target cancer cells will be exposed to the chemotherapeutic drug while in the drug-sensitive s-phase is increased due to the slow and sustained release of the chemotherapeutic, which could provide for a sustained duration of exposure of the target cancer cells to the bioavailable drug and result in the desired therapeutic outcome. 
  • 956
  • 11 Jan 2023
Topic Review
Targeting Liver Cancer Stem Cells
       Cancer stem cells (CSCs) are known to be highly resistant to conventional therapeutic approaches, such as chemotherapeutic drugs and radiation. Therefore, selectively targeting CSCs with specific markers or signaling pathways can be an effective therapeutic strategy for treating chemotherapy-resistant liver cancer. However, there is not enough information currently available to make a conclusive statement regarding hepatic CSC-specific signaling pathways and biomarkers. In present study, we provide an overview of the current knowledge on the specific surface markers and critical signaling pathways of hepatic CSC.
  • 955
  • 29 Oct 2020
Topic Review
Metformin in Immunosuppressed Ovarian Cancer
Growing evidence suggests that the immune component of the tumor microenvironment (TME) in high-grade serous ovarian cancer (HGSOC) may play a significant role in the progression of the disease. The poor prognosis of HGSOC necessitates development of novel therapeutic strategies to improve patient outcomes. The type 2 diabetes medication, metformin, has been associated with significant improvement to overall survival in a number of retrospective clinical analyses. Recent data summarized here suggest that metformin may provide such a benefit through modulating the immune TME of HGSOC.
  • 955
  • 10 Feb 2021
Topic Review
Long Non-Coding RNAs in Choriocarcinoma
Choriocarcinoma (CC), a subtype of trophoblastic disease, is a rare and highly aggressive neoplasm. There are two main CC subtypes: gestational and non-gestational, (so called when it develops as a component of a germ cell tumor or is related to a somatic mutation of a poorly differentiated carcinoma), each with very diverse biological activity. Long non-coding (lnc) RNAs are non-coding transcripts that are longer than 200 nucleotides. LncRNAs can act as oncogenes or tumor suppressor genes. Deregulation of their expression has a key role in tumor development, angiogenesis, differentiation, migration, apoptosis, and proliferation. 
  • 955
  • 23 Jul 2021
Topic Review
Mechanisms Governing the Acquisition of Castration-Resistant Prostate Cancer
Despite aggressive treatment and androgen-deprivation therapy, most prostate cancer patients ultimately develop castration-resistant prostate cancer (CRPC), which is associated with high mortality rates. However, the mechanisms governing the development of CRPC are poorly understood, and androgen receptor (AR) signaling has been shown to be important in CRPC through AR gene mutations, gene overexpression, co-regulatory factors, AR shear variants, and androgen resynthesis. A growing number of non-AR pathways have also been shown to influence the CRPC progression, including the Wnt and Hh pathways. Moreover, non-coding RNAs have been identified as important regulators of the CRPC pathogenesis. 
  • 955
  • 19 Sep 2022
Topic Review
Microtubule-Targeting Compounds
The microtubule is the target for chemotherapeutics, such as the microtubule-destabilizing compounds and the microtubule-stabilizing compounds. Both kinds of chemotherapeutics have revolutionized cancer treatment.
  • 955
  • 23 Sep 2022
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