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Topic Review
Lysosomes in Maintaining Stem Cell Quiescence
Lysosomes are a critical component of the inner membrane system and are involved in various cellular biological processes, including macromolecular degradation, antigen presentation, intracellular pathogen destruction, plasma membrane repair, exosome release, cell adhesion/migration, and apoptosis. Lysosomes are a critical regulator of cellular metabolism, cancer, metastasis, and resistance to anticancer therapy. Additionally, lysosomal activities play a crucial role in acute myeloid leukemia (AML) development and progression, as well as maintaining the hematopoietic stem cells (HSCs) pool. It has been shown that AML cells undergo metabolic alterations due to chemotherapy or targeted treatment.
  • 579
  • 31 Mar 2022
Topic Review
Mechanisms of Reticulocyte Maturation
Reticulocyte maturation begins after enucleation in the bone marrow. In rats, reticulocytes reside in the bone marrow from 6.5–17 hrs depending on the blood demand. These reticulocytes are termed as R1 and are characterized for their multi-lobular shape and their motility. The final stages of maturation occur during circulation where macrophages residing in the spleen may facilitate the process. These reticulocytes in circulation are termed as R2, are non-motile and have a “deep-dish” shape”. As part of their maturation, reticulocytes need to remove or degrade residual organelles and RNA. In addition, the reticulocyte must reduce its surface area and volume. On average, labelled baboon reticulocytes showed a reduction of 20% of their surface area and 15% of their volume after the first 24 h in circulation; at this point they showed a similar size distribution to that of mature RBC.
  • 626
  • 29 Mar 2022
Topic Review
Autophagy in Osteoarthritis
Autophagy is an intracellular mechanism that maintains cellular homeostasis in different tissues. This process declines in cartilage due to aging, which is correlated with osteoarthritis (OA), a multifactorial and degenerative joint disease. Several studies show that microRNAs regulate different steps of autophagy but only a few of them participate in OA. Therefore, epigenetic modifications could represent a therapeutic opportunity during the development of OA. Besides, polyphenols are bioactive components with great potential to counteract diseases, which could reverse altered epigenetic regulation and modify autophagy in cartilage.
  • 466
  • 29 Mar 2022
Topic Review Video
Crosstalk between Apoptosis and Autophagy
Research in biomedical sciences has changed dramatically over the past fifty years. There is no doubt that the discovery of apoptosis and autophagy as two highly synchronized and regulated mechanisms in cellular homeostasis are among the most important discoveries in these decades. Along with the advancement in molecular biology, identifying the genetic players in apoptosis and autophagy has shed light on our understanding of their function in physiological and pathological conditions. Apoptosis and autophagy play essential roles in human health, and their malfunction leads to many diseases, including cancer, neurodegenerative disease, and autoimmune disorders. These mechanisms are highly regulated, and there is complex crosstalk between them.
  • 410
  • 29 Mar 2022
Topic Review
Tumor-derived exosomes in tumor-induced immune suppression
Exosomes are a class of small membrane-bound extracellular vesicles released by almost all cell types and present in all body fluids. Based on the studies of exosome content and their interactions with recipient cells, exosomes are now thought to mediate “targeted” information transfer. Tumor-derived exosomes (TEX) carry a cargo of molecules different from that of normal cells-derived exosomes. TEX functions to mediate distinct biological effects such as receptor discharge and intercellular cross-talk. The immune system defenses, which may initially restrict tumor progression, are progressively blunted by the broad array of TEX molecules that activate suppressive pathways in different immune cells. Herein, we provide a review of the latest research progress on TEX in the context of tumor-mediated immune suppression, and discuss the potential as well as challenges of TEX as a target of immunotherapy. 
  • 581
  • 29 Mar 2022
Topic Review
Vasculogenic Mimicry in Breast Cancer
In solid tumors, vasculogenic mimicry (VM) is the formation of vascular structures by cancer cells, allowing to generate a channel-network able to transport blood and tumor cells. While angiogenesis is undertaken by endothelial cells, VM is assumed by cancer cells. Besides the participation of VM in tumor neovascularization, the clinical relevance of this process resides in its ability to favor metastasis and to drive resistance to antiangiogenic therapy. VM occurs in many tumor types, including breast cancer, where it has been associated with a more malignant phenotype, such as triple-negative and HER2-positive tumors. The latter may be explained by known drivers of VM, like hypoxia, TGFB, TWIST1, EPHA2, VEGF, matrix metalloproteinases, and other tumor microenvironment-derived factors, which altogether induce the transformation of tumor cells to a mesenchymal phenotype with a high expression rate of stemness markers.
  • 693
  • 29 Mar 2022
Topic Review
IL-6 Cytokines and EMP
Epithelial–mesenchymal plasticity (EMP) plays critical physiological roles during embryonic development, postnatal growth and epithelial homeostasis, but it is also involved in a number of pathological conditions, including wound repair, fibrosis, inflammation and cancer. EMP has been intimately linked with most, if not all, of the steps during cancer development and progression (e.g., migration, invasion, immune escape, drug resistance and metastatic dissemination). Cytokines from the interleukin 6 (IL-6) family play fundamental roles in mediating tumour-promoting inflammation within the tumour microenvironment. In general, IL-6 cytokines activate EMP processes, fostering the acquisition of mesenchymal features in cancer cells. Here, we will summarise all the relevant literature related to all members of the IL-6 family and EMP.
  • 442
  • 29 Mar 2022
Topic Review
Neutrophil in Pancreatic Tumor Microenvironment
Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with a poor prognosis and low survival rates. PDAC is characterized by a fibroinflammatory tumor microenvironment enriched by abundant fibroblasts and a variety of immune cells, contributing to its aggressiveness. Neutrophils are essential infiltrating immune cells in the PDAC microenvironment. Recent studies have identified several cellular mechanisms by which neutrophils are recruited to tumor lesions and promote tumorigenesis. 
  • 691
  • 29 Mar 2022
Topic Review
T Cell-Based Therapies of HCC
The scope of therapeutic options for the treatment of hepatocellular carcinoma (HCC) has recently been expanded by immunotherapeutic regimens. T cell-based therapies, especially in combination with other treatments have achieved far better outcomes compared to conventional treatments alone. However, there is an emerging body of evidence that eliciting T cell responses in immunotherapeutic approaches is insufficient for favorable outcomes.
  • 427
  • 29 Mar 2022
Topic Review
CAF partners with Endometrial Tumor-Cells
A tumor cell carrying characteristic genomic alteration(s) exists within its host’s microenvironment. The tempero-spatial interaction of tumor cells with its microenvironment is the deterministic factor for tumor growth, progression, resistance to therapy, and its outcome in clinics. This manuscript presents a systemic review of the role of CAF in endometrial cancers. Here we present the functional characteristics of CAF in the context of endometrial cancers. We review (1) the characteristics of CAF, (2) their evolution from being anti-tumor to pro-tumor, (3) their involvement in regulating growth and several metastasis-associated phenotypes of tumor cells, (4) their participation in perturbing immune defense and evading immune surveillance, and (5) their role in mediating drug resistance via tumor-CAF cross-talk with particular reference to endometrial cancers. We interrogate the functional characteristics of CAF in the light of its dialogue with tumor cells and other components of TME towards developing a CAF-based strategy for precision therapy to supplement tumor-based therapy. The purpose of the review is to present a new vision and initiate a thought process which recognizes the importance of CAF in a tumor, thereby resulting in a novel approach to the design and management of the disease in endometrial cancers.
  • 441
  • 29 Mar 2022
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