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Topic Review
Radiation Therapy
Tumor radioresistance is associated with a failure to achieve loco-regional disease control following radiotherapy with the highest acceptable doses. Radiobiology research focused on tumor radioresistance has pointed out several mechanisms attenuating the efficacy of tumor irradiation and several treatment answers to overcome such radio-resistance. Personalized medecine allows us to adapt the treatment to diseases according to patient specificities and characteristics. Novel radiotherapy such as heavy ion therapy enable a better balance between high doses to the tumor and low doses to the surrounding healthy tissues.
  • 1.7K
  • 23 Oct 2020
Topic Review
Segmentectomy for Lung Cancer
A lung segmentectomy, a type of sublobar resection, preserves more pulmonary function than is lobectomy. The use of minimally invasive lung segmentectomy for early-stage lung cancer has been increasing. This procedure is associated with technical challenges because (1) it requires a thorough understanding of the complex segmental anatomy that frequently accompanies anomalies, and (2) it is difficult to confirm the location of small tumors during minimally invasive surgery, which makes it difficult to obtain adequate surgical margins. 
  • 1.7K
  • 22 Jul 2021
Topic Review
Natural Blockers of PD-1/PD-L1 Interaction
The limited treatment options for triple-negative breast cancer with brain metastasis (TNBC-BM) have left the door of further drug development for these patients wide open. Although immunotherapy via monoclonal antibodies has shown some promising results in several cancers including TNBC, it cannot be considered the most effective treatment for brain metastasis. This is due to the protective role of the blood–brain barrier (BBB) which limits the entrance of most drugs, especially the bulky ones such as antibodies, to the brain. For a drug to traverse the BBB via passive diffusion, various physicochemical properties should be considered. 
  • 1.7K
  • 11 Jan 2023
Topic Review
Sorcin in cancer drug resistance
The development of drug resistance is one of the main causes of failure in anti-cancer treatments. Tumor cells adopt many strategies to counteract the action of chemotherapeutic agents, e.g., enhanced DNA damage repair, inactivation of apoptotic pathways, alteration of drug targets, drug inactivation, and overexpression of ABC (Adenosine triphosphate-binding cassette, or ATP-binding cassette) transporters. These are broad substrate-specificity ATP-dependent efflux pumps able to export toxins or drugs out of cells; for instance, ABCB1 (MDR1, or P-glycoprotein 1), overexpressed in most cancer cells, confers them multidrug resistance (MDR). The gene coding for sorcin (SOluble Resistance-related Calcium-binding proteIN) is highly conserved among mammals and is located in the same chromosomal locus and amplicon as the ABC transporters ABCB1 and ABCB4, both in human and rodent genomes (two variants of ABCB1, i.e., ABCB1a and ABCB1b, are in rodent amplicon). Sorcin was initially characterized as a soluble protein overexpressed in multidrug (MD) resistant cells and named “resistance-related” because of its co-amplification with ABCB1.
  • 1.7K
  • 21 Dec 2020
Topic Review
Cisplatin
Cisplatin, also referred to as cis-diamminedichloroplatinum (II) (CDDP), is a widely used, Pt-based anti-cancer chemotherapeutic agent. This transition metal coordination complex has a square planar molecular geometry and presents as a solid, yellow powder at room temperature. CDDP is fairly insoluble in most substances; however, it can be dissolved in dimethylformamide, and is somewhat soluble in water, but most preferable in saline sodium. In solid form, CDDP is stable for about two years if stored at room temperature in dry conditions and light protected; however, it is known to convert slowly to its trans-form. The stability of CDDP in sodium chloride solution is dependent on the chloride ion concentration; it is more stable when suspended in normal saline (0.9% sodium chloride). Saline also provides a reno-protective function, increasing hydration and aiding in excretion of CDDP from the kidneys.
  • 1.7K
  • 14 Dec 2022
Topic Review
Antitumor Action of Mango Peel
Today, an improved understanding of cancer cell response to cellular stress has become more necessary. Indeed, targeting the intracellular pro-oxidant/antioxidant balance triggering the tumor commitment to cell demise could represent an advantageous strategy to develop cancer-tailored therapies. Ethanolic extracts from Mangifera indica L. have been proved to possess anti-tumor properties in many cancer systems. However, although most effects have been demonstrated with fruit pulp extract, the underlying molecular mechanisms of mango peel are still unclear. This research was undertaken to explore the effects of mango peel extract (MPE) on colon cancer cell lines. Data obtained demonstrated that MPE can affect the cell viability of three colon cancer cell lines (HT29, Caco-2 and HCT116), inducing an imbalance of cellular redox responses. A consistent decline in thiol group content, which was accompanied by upregulation of MnSOD—a mitochondrial scavenger enzyme that modulates the cellular response against oxidative damage- was observed. Such an effect was the consequence of an early production of mitochondrial superoxide anions that appeared after just 30 min of exposure of colon cancer cells to MPE. The effect was accompanied by mitochondrial injury, consisting of the dissipation of mitochondrial membrane potential and a decrease in the level of proteins localized in the mitochondrial membrane (VDAC1, mitofilin, and some members of Bcl-2 family) —with the mitochondrial release of apoptogenic factors (cytochrome C and AIF). The analysis of the cytotoxic effects exerted by the different constituents of MPE (gallic acid, mangiferin, citric acid, quinic acid, pentagalloyl glucose, and methyl gallate) allowed us to identify those phytochemicals responsible for the observed anticancer effects, sustaining their future employment as chemopreventive or therapeutic agents.
  • 1.7K
  • 04 Aug 2021
Topic Review
Claudins and Gastric Cancer
Despite recent improvements in diagnostic ability and treatment strategies, advanced gastric cancer (GC) has a high frequency of recurrence and metastasis, with poor prognosis. To improve the treatment results of GC, the search for new treatment targets from proteins related to epithelial–mesenchymal transition (EMT) and cell–cell adhesion is currently being conducted. EMT plays an important role in cancer metastasis and is initiated by the loss of cell–cell adhesion, such as tight junctions (TJs), adherens junctions, desmosomes, and gap junctions. Among these, claudins (CLDNs) are highly expressed in some cancers, including GC. Abnormal expression of CLDN1, CLDN2, CLDN3, CLDN4, CLDN6, CLDN7, CLDN10, CLDN11, CLDN14, CLDN17, CLDN18, and CLDN23 have been reported. Among these, CLDN18 is of particular interest. In The Cancer Genome Atlas, GC was classified into four new molecular subtypes, and CLDN18–ARHGAP fusion was observed in the genomically stable type. An anti-CLDN18.2 antibody drug was recently developed as a therapeutic drug for GC, and the results of clinical trials are highly predictable. Thus, CLDNs are highly expressed in GC as TJs and are expected targets for new antibody drugs. 
  • 1.7K
  • 10 Jan 2022
Topic Review
ZEB Family
Molecular signaling pathways involved in cancer have been intensively studied due to their crucial role in cancer cell growth and dissemination. Among them, zinc finger E-box binding homeobox-1 (ZEB1) and -2 (ZEB2) are molecules that play vital roles in signaling pathways to ensure the survival of tumor cells, particularly through enhancing cell proliferation, promoting cell migration and invasion, and triggering drug resistance. Importantly, ZEB proteins are regulated by microRNAs (miRs). In this review, we demonstrate the impact that miRs have on cancer therapy, through their targeting of ZEB proteins. MiRs are able to act as onco-suppressor factors and inhibit the malignancy of tumor cells through ZEB1/2 down-regulation. This can lead to an inhibition of EMT mechanism, therefore reducing metastasis. Also, miRs are able to inhibit ZEB1/2-mediated drug resistance and immunosuppression. Additionally, we explore the upstream modulators of miRs such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), as these regulators can influence the inhibitory effect of miRs on ZEB proteins and cancer progression.
  • 1.7K
  • 19 Jul 2020
Topic Review
Glioblastoma Pathogenesis
Glioblastoma is one of the most common and detrimental forms of solid brain tumor, with over 10,000 new cases reported every year in the United States. Despite aggressive multimodal treatment approaches, the overall survival period is reported to be less than 15 months after diagnosis. A widely used approach for the treatment of glioblastoma is surgical removal of the tumor, followed by radiotherapy and chemotherapy. While there are several drugs available that are approved by the Food and Drug Administration (FDA), significant efforts have been made in recent years to develop new chemotherapeutic agents for the treatment of glioblastoma.
  • 1.7K
  • 28 Dec 2020
Topic Review
Structure and Function of Sorting Nexin 27
SNX27 belongs to the sorting nexin (SNX) family of proteins that play a critical role in protein sorting and trafficking in the endocytosis pathway. This protein family is characterized by the presence of a Phox (PX) domain; however, SNX27 is unique in containing an additional PDZ (post-synaptic density 95/discs large/zonula occludens-1) domain.
  • 1.7K
  • 29 Jan 2023
Topic Review
Immunogenic Cell Death in Cancer
Cell death resistance is a key feature of tumor cells. One of the main anticancer therapies is increasing the susceptibility of cells to death. Cancer cells have developed a capability of tumor immune escape. Hence, restoring the immunogenicity of cancer cells can be suggested as an effective approach against cancer. Accumulating evidence proposes that several anticancer agents provoke the release of danger-associated molecular patterns (DAMPs) that are determinants of immunogenicity and stimulate immunogenic cell death (ICD).
  • 1.7K
  • 25 Dec 2020
Topic Review
Genetic and Molecular Basis of Von Hippel-Lindau Disease
Von Hippel-Lindau disease (VHL disease or VHL syndrome) is a familial multisystem neoplastic disorder, stemming from germline disease-associated variants of the VHL tumor suppressor gene. VHL protein is involved in oxygen sensing and adaptive response to hypoxia through the EPO-VHL-HIF signaling axis. In recent years, numerous HIF-independent pathways of VHL have been identified, expanding the role of VHL throughout several cellular processes. In addition to VHL syndrome-associated tumors, VHL variations have also been associated with the development of eythrocytosis. Research indicated that there is a distinction between erythrocytosis-causing VHL variations and VHL variations causing VHL disease with tumor development. Therefore, elucidating the molecular background of the pathogenic effects of VHL variants could help determine the best approach to VHL disease management.  
  • 1.7K
  • 24 Mar 2022
Topic Review
DNA Polymerases
Recent studies on tumor genomes revealed that mutations in genes of replicative DNA polymerases cause a predisposition for cancer by increasing genome instability. The past 10 years have uncovered exciting details about the structure and function of replicative DNA polymerases and the replication fork organization. The principal idea of participation of different polymerases in specific transactions at the fork proposed by Morrison and coauthors 30 years ago and later named “division of labor,” remains standing, with an amendment of the broader role of polymerase δ in the replication of both the lagging and leading DNA strands. However, cancer-associated mutations predominantly affect the catalytic subunit of polymerase ε that participates in leading strand DNA synthesis. 
  • 1.7K
  • 14 Dec 2020
Topic Review
Aurora Kinases in Lung Cancer
Lung cancer has remained one of the major causes of death worldwide. Thus, a more effective treatment approach is essential such as the inhibition of specific cancer-promoting molecules. Aurora kinases regulate the process of mitosis - a process of cell division that is necessary for normal cell proliferation. However, dysfunction of these kinases can contribute to cancer formation. The aberrant expression of Aurora kinases in lung cancer points to their crucial role in lung carcinogenesis. Therefore, understanding the fundamental functions as well as the cellular localization of Aurora kinases may contribute to evaluate their precise oncogenic function that will may lead to better specific targeting of these cancer-related molecules.  
  • 1.7K
  • 07 Jul 2021
Topic Review
Glycosylation of Cancer Extracellular Vesicles
Glycans are major constituents of extracellular vesicles (EVs). Alterations in the glycosylation pathway are a common feature of cancer cells, which gives rise to de novo or increased synthesis of particular glycans. Therefore, glycans and glycoproteins have been widely used in the clinic as both stratification and prognosis cancer biomarkers. Interestingly, several of the tumor-associated glycans have already been identified in cancer EVs, which constitutes valuable sources of cancer biomarkers. Furthermore, glycans have also shown to play a role in EV protein sorting, uptake and tropism. Altogether, the EV glycan signatures hold tremendous potential to be applied into the clinical setting for both biomarker discovery and as therapeutic delivery systems.
  • 1.7K
  • 25 Jan 2021
Topic Review
T Lymphocyte and CAR-T Cell-Derived Extracellular Vesicles
Extracellular vesicles (EV) are a very diverse group of cell-derived vesicles released by almost all kind of living cells. EV are involved in intercellular exchange, both nearby and systemically, since they induce signals and transmit their cargo (proteins, lipids, miRNAs) to other cells, which subsequently trigger a wide variety of biological responses in the target cells. However, cell surface receptor-induced EV release is limited to cells from the immune system, including T lymphocytes. T cell receptor activation of T lymphocytes induces secretion of EV containing T cell receptors for antigen and several bioactive molecules, including proapoptotic proteins. These EV are specific for antigen-bearing cells, which make them ideal candidates for a cell-free, EV-dependent cancer therapy.
  • 1.7K
  • 29 Mar 2022
Topic Review
Pancreatic Ductal Adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies. The complex mechanism underlying the development and progression of PDAC includes interactions between genomic, epigenomic, and signaling pathway alterations. PDAC remains a devastating disease, despite extensive research efforts focused on the discovery of early diagnostic biomarkers and efficient therapeutic approaches, showing a high resistance to treatment that significantly contributes to poor survival. The success of epi-drugs in hematological malignancies and the robust body of evidence supporting the hypothesis about their ability to synergize with other anti-cancer drugs, sensitizing resistant tumor cells in preclinical models, have encouraged the search for these agents suitable for the future clinical management of PDAC.
  • 1.7K
  • 27 Oct 2020
Topic Review
Cytokines
Cytokines are key molecules within the tumor microenvironment (TME) that can be used as biomarkers to predict the magnitude of anti-tumor immune responses. During immune monitoring, it has been customary to predict outcomes based on the abundance of a single cytokine, in particular IFN-γ or TGF-β, as a readout of ongoing anti-cancer immunity. However, individual cytokines within the TME can exhibit dual opposing roles. For example, both IFN-γ and TGF-β have been associated with pro- and anti-tumor functions. Moreover, cytokines originating from different cellular sources influence the crosstalk between CD4+ and CD8+ T cells, while the array of cytokines expressed by T cells is also instrumental in defining the mechanisms of action and efficacy of treatments. Thus, it becomes increasingly clear that a reliable readout of ongoing immunity within the TME will have to include more than the measurement of a single cytokine.
  • 1.7K
  • 05 Apr 2021
Topic Review
Extracellular matrix in tumor microenvironment
The tumor microenvironment (TME) has become the focus of interest in cancer research and treatment. It includes the extracellular matrix (ECM) and ECM-modifying enzymes that are secreted by cancer and neighboring cells. The ECM serves both to anchor the tumor cells embedded in it and as a means of communication between the various cellular and non-cellular components of the TME. The cells of the TME modify their surrounding cancer-characteristic ECM. This in turn provides feedback to them via cellular receptors, thereby regulating, together with cytokines and exosomes, differentiation processes as well as tumor progression and spread. Matrix remodeling is accomplished by altering the repertoire of ECM components and by biophysical changes in stiffness and tension caused by ECM-crosslinking and ECM-degrading enzymes, in particular matrix metalloproteinases (MMPs). These can degrade ECM barriers or, by partial proteolysis, release soluble ECM fragments called matrikines, which influence cells inside and outside the TME.
  • 1.7K
  • 19 Jan 2021
Topic Review
Targeting Tumor-Associated Macrophages
Immune checkpoint inhibitors (ICIs) represent a promising therapeutic intervention for a variety of advanced/metastatic solid tumors, including melanoma, but in a large number of cases, patients fail to establish a sustained anti-tumor immunity and to achieve a long-lasting clinical benefit. Cells of the tumor micro-environment such as tumor-associated M2 macrophages (M2-TAMs) have been reported to limit the efficacy of immunotherapy, promoting tumor immune evasion and progression. 
  • 1.7K
  • 06 May 2021
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