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Topic Review
Cyclin-Dependent Kinases Pathway Dysregulation in Soft Tissue Sarcoma
Soft tissue sarcomas (STSs) are rare malignant conditions with more than 70 subtypes that are difficult to treat, especially in advanced or metastatic states. Next-generation sequencing technologies have provided comprehensive information and developed personalized medicine for treating cancer in general and STSs in particular. Growing knowledge of diverse gene alterations and biomolecular targets in various subtypes of STSs raises hope for novel treatment approaches and heralds a paradigm shift in the treatment of STSs. Activated cyclin-dependent kinases (CDKs) appear to play a critical role in sarcoma development and represent important targets for sarcoma therapy. 
  • 1.0K
  • 18 Aug 2022
Topic Review
Exosomes Diversity
Cells can communicate through special “messages in the bottle”, which are recorded in the bloodstream inside vesicles, namely exosomes. The exosomes are nanovesicles of 30–100 nm in diameter that carry functionally active biological material, such as proteins, messanger RNA (mRNAs), and micro RNA (miRNAs). Therefore, they are able to transfer specific signals from a parental cell of origin to the surrounding cells in the microenvironment and to distant organs through the circulatory and lymphatic stream. More and more interest is rising for the pathological role of exosomes produced by cancer cells and for their potential use in tumor monitoring and patient follow up. In particular, the exosomes could be an appropriate index of proliferation and cancer cell communication for monitoring the minimal residual disease, which cannot be easily detectable by common diagnostic and monitoring techniques. The lack of unequivocal markers for tumor-derived exosomes calls for new strategies for exosomes profile characterization aimed at the adoption of exosomes as an official tumor biomarker for tumor progression monitoring.
  • 1.0K
  • 21 Nov 2020
Topic Review
PARP Inhibitors in Cancer Immunotherapy
Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) induce cytotoxic effects as single agents in tumors characterized by defective repair of DNA double-strand breaks deriving from BRCA1/2 mutations or other abnormalities in genes associated with homologous recombination. Preclinical studies have shown that PARPi-induced DNA damage may affect the tumor immune microenvironment and immune-mediated anti-tumor response through several mechanisms. In particular, increased DNA damage has been shown to induce the activation of type I interferon pathway and up-regulation of PD-L1 expression in cancer cells, which can both enhance sensitivity to Immune Checkpoint Inhibitors (ICIs).
  • 1.0K
  • 30 Nov 2022
Topic Review
Tumor Microenvironment in Cancer Metastasis
Metastasis, the process by which cancer cells escape primary tumor site and colonize distant organs, is responsible for most cancer-related deaths. The tumor microenvironment (TME), comprises different cell types, including immune cells and cancer-associated fibroblasts, as well as structural elements, such as collagen and hyaluronan that constitute the extracellular matrix (ECM). 
  • 1.0K
  • 08 May 2021
Topic Review
Irreversible Electroporation (IRE)
Electroporation (IRE) is a novel cancer treatment that may improve survival and quality of life in LAPC. 
  • 1.0K
  • 07 May 2021
Topic Review
Angiocrine Factors Control Tumor Progression
A solid tumor mass consists not only of cancer cells, but of numerous other resident and infiltrating cells and the extracellular matrix, which together form the tumor microenvironment (TME). The TME contains three main cell entities: fibroblasts, immune cells and endothelial cells. Endothelial cells control their microenvironment through the expression of membrane-bound and secreted factors. Such angiocrine functions are frequently hijacked by cancer cells, which deregulate the signaling pathways controlling the expression of angiocrine factors.
  • 1.0K
  • 23 Jun 2021
Topic Review
Genetic Aspects of Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are myeloid neoplasms characterized by the presentation of overlapping features from both myelodysplastic syndromes and myeloproliferative neoplasms. Although the classification of MDS/MPN relies largely on clinical features and peripheral blood and bone marrow morphology, studies have demonstrated that a large proportion of patients (~90%) with this disease harbor somatic mutations in a group of genes that are common across myeloid neoplasms. These mutations play a role in the clinical heterogeneity of these diseases and their clinical evolution. 
  • 1.0K
  • 31 May 2021
Topic Review
Neuropeptide Y Peptide Family and Cancer
Peptidergic systems are involved in cancer progression and regulate crucial roles such as cell proliferation, migration, and angiogenesis. Available data on the involvement of neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) and their receptors (YRs) in cancer are updated. The structure and dynamics of YRs and their intracellular signaling pathways are also studied. 
  • 1.0K
  • 14 Jun 2023
Topic Review
Golden Syrian Hamster Models for Cancer Research
The golden Syrian hamster (Mesocricetus auratus) has long been a valuable rodent model of human diseases, especially infectious and metabolic diseases. Hamsters have also been valuable models of several chemically induced cancers such as the DMBA-induced oral cheek pouch cancer model.
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  • 19 Aug 2022
Topic Review
Hemoptysis in Cancer Patients
Hemoptysis in cancer patients is a potentially serious symptom that requires detailed evaluation by oncologists and emergency department physicians. Timely diagnosis and appropriate management are crucial to address both the immediate concern of bleeding and the broader implications for the patient's cancer care. As hemoptysis in cancer patients indicates the presence of complications or progression of the disease, investigating the underlying cause using appropriate diagnostic procedures such as imaging studies (CT scans, bronchoscopy) and laboratory tests is vital, as it can significantly impact treatment choices and potentially alter the patient's overall prognosis. Risk stratification for cancer patients presenting with hemoptysis will support a personalized treatment approach that ensures that each patient receives tailored and effective care and identifies patients who are at a higher risk of deterioration, warranting more aggressive diagnostic and treatment plans and close, continuous monitoring for these patients.
  • 1.0K
  • 12 Oct 2023
Topic Review
Locoregional Therapies in Patients with Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the most commonly diagnosed primary liver malignancy. Its efficient management depends on early detection, the stage of progression of the disease and underlying liver function. Available curative treatments include liver transplantation, resection and ablation. These are in addition to cryoablation, microwave ablation and percutaneous alcohol injection. In cases of the late detection of HCC, many patients with locally advanced disease and are offered locoregional therapies, including transarterial chemoembolization and selective internal radiation therapy, plus external beam radiation.
  • 1.0K
  • 28 Mar 2023
Topic Review
Cancer Photodynamic Therapy
The effectiveness of photodynamic therapy (PDT) is based on the triad effects of photosensitizer (PS), molecular oxygen and visible light on malignant tumors. Such complex induces a multifactorial manner including reactive-oxygen-species-mediated damage and the killing of cells, vasculature damage of the tumor, and activation of the organism immunity. The effectiveness of PDT depends on the properties of photosensitizing drugs, their selectivity, enhanced photoproduction of reactive particles, absorption in the near infrared spectrum, and drug delivery strategies. Photosensitizers of the tetrapyrrole structure (porphyrins) are widely used in PDT because of their unique diagnostic and therapeutic functions.
  • 1.0K
  • 02 Mar 2022
Topic Review
Immunotherapy of Colorectal Cancer
Immunotherapy has become one of the pillars of treatmemt of Colorectal Cancer. This entry explains what Immune Checkpoint Inhibitors are, how they work and which patients are most likely to benefit from them. You will get an overview of the current (2020) scientific evidence on their efficacy in terms of objective tumor response, progression free survival and overall survival, as well as on safety, adverse effects and potential impact on quality of life indicators. Furthermore, ongoing or planned trials are listed.
  • 1.0K
  • 23 Nov 2020
Topic Review
Diffuse Large B-Cell Lymphomas
Diffuse large B-cell lymphoma (DLBCL) is the commonest form of lymphoid malignancy, with a prevalence of about 40% worldwide. The term DLBCL reflects the growth pattern and size of the neoplastic cells, which tend to diffusely efface the normal structure of the involved organ (most frequently the lymph node) and are provided with a diameter at least twice that of normal lymphocytes. Although during the last few years several distinct clinical-pathological categories of DLBCL have been reported in the literature, which are nowadays listed in the Revised 4th Edition of the WHO Classification of the Tumours of Haematopoietic and Lymphoid Tissues, about 80% of DLBCLs do not enter into any of these categories and are therefore termed not otherwise specified (NOS). DLBCL-NOS displays a quite variable morphology and only rarely consists of only one cytotype (centroblastic, immunoblastic or anaplastic). Thus, microscopic examination fails to define the cell of origin, prognostic indicators and novel potential therapeutic targets. The standard of care  is the immuno-chemotherapy R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), which cures up to 65% of patients. The remaining individuals with DLBCL-NOS experience resistant or relapsing disease and eventually die of it. This situation has promoted a huge number of studies focusing on the pathobiology of the tumour and based on high-throughput techniques, including gene expression profiling and next generation sequencing. In addition, attention has been focused on the mcroenvironmental composition, which can influence the behaviour and response to therapy of the tumour in conjunction with the molecular characteristics of neoplastic cells. The aim of the present review is to discuss the most recent acquisitions in the field of DLBCL-NOS based on the extensive application of molecular techniques, which paves the way to a more rational classification of the tumour along with the identification of effective prognostic indicators and novel therapeutic targets for  ad hoc personalised approaches. 
  • 1.0K
  • 23 Jun 2021
Topic Review
Microbiota Alterations in Pancreatic Cancer
The human microbiome is a key factor in many malignancies, having the ability to alter host metabolism and immune responses and participate in tumorigenesis. Gut microbes have an influence on physiological functions of the healthy pancreas and are themselves controlled by pancreatic secretions. An altered oral microbiota may colonize the pancreas and cause local inflammation by the action of its metabolites, which may lead to carcinogenesis. The mechanisms behind dysbiosis and pancreatic cancer (PC) development are not completely clear. An altered microbiota may induce oncogenomic changes, or, on the other hand, cancer mutations may have an impact on microbiota composition. Altered microbiota can also influence drug efficacy in PC chemo- and immunotherapies. Possible future scenarios are the intentional manipulation of the gut microbiota in combination with therapy or the utilization of microbial profiles for the noninvasive screening and monitoring of PC.
  • 1.0K
  • 13 Dec 2021
Topic Review
Splice Site Selection Abrogated in Cancer
Splicing and alternative splicing (AS) must be tightly regulated, as they have profound effects on gene expression. Various cis-regulatory elements control the fidelity and efficiency of splicing. These include the 5′ and 3′ splice sites (SSs), splicing enhancers, splicing silencers, branch points, and polypyrimidine tracts. A quality control mechanism of splice site selection termed Suppression of Splicing (SOS), was proposed to protect cells from splicing at the numerous intronic unused, latent 5′ splice sites (LSSs) sequences, which are not used under normal growth condition. However, under stress and in cancer thousands of LSSs are activated in splicing resulting in the expression of thousands of aberrant nonsense mRNAs that may be toxic to cells. 
  • 1.0K
  • 20 Jun 2022
Topic Review
Tumor Microenvironment and Metabolism
There is a growing appreciation that the cells of the tumor microenvironment interact via variations in their dynamic regulation of mitochondrial function. The melatonergic pathway is a core aspect of mitochondrial function, with tumors 'domineering' the homeostasis established in the tumor microenvironment by regulating the core functioning of other cells. This is predominantly achieved by regulating the levels of melatonin and its immediate precursor, N-acetylserotonin (NAS). Applying melatonin to any tumor drives tumor death via apoptosis, whilst NAS can activate the trophic receptor, TrkB, to increase the survival and proliferation of tumors. Given such contrasting effects of melatonin and NAS, it is crucial for tumors to regulate the NAS/melatonin ratio within the tumor microenvironment. Two immune cells can readily kill cancer cells, namely natural killer (NK) cells and CD8+ t cells. The tumor inactivates these cells by releasing kynurenine, which activates the aryl hydrocarbon receptor (AhR) on these immune cells, leading to their inactivation ('exhaustion'), with AhR activation also increasing the NAS/melatonin ratio. NAS release enhances the survival and proliferation of cancer stem-like cells, thereby driving tumor maintenance and spread (metastasis). The cells that can readily kill cancer cells are therefore turned into providers of support for tumor survival and spread. This is achieved via the tumor's regulation of the mitochondrial melatonergic pathway. Similar tumor interactions with the mitochondrial melatonergic pathway allows the tumor to regulate other cells in the tumor microenvironment, as well as influencing how these cells interact with each other. This is predominantly achieved by the altered metabolism and mitochondrial function in the tumor shaping the mitochondrial function of other cells in the tumor microenvironment. As mitochondria evolved over evolution from ancient bacteria, these interactions across cell types in the tumor microenvironment may be viewed as evolutionary modified bacteria dynamically interacting with each other within a quest to achieve 'dominance' via the regulation of mitochondrial melatonergic pathway. This is a novel conceptualization of the tumor microenvironment that emphasizes core metabolic processes, and their regulation by the melatonergic pathway. As a frame of reference this allows the incorporation of previously disparate pieces of data on the tumor microenvironment and also provides a clearer pathway to new research, coupled to treatment implications. 
  • 1.0K
  • 05 Jan 2023
Topic Review
Primary cilia and cancer
Primacy cilia are antenna-like structures present in many vertebrate cells. These organelles detect extracellular cues, transduce signals into the cell, and play an essential role in ensuring correct cell proliferation, migration, and differentiation in a spatiotemporal manner. Not surprisingly, dysregulation of primary cilia can cause various diseases, including cancer. The structure and function of primary cilia are dynamically regulated through many proteins and various posttranslational mechanisms of these proteins, including phosphorylation, acetylation, and ubiquitination. Targeting these signaling that regulates the assembly and disassembly of primary cilia may be a promising approach for cancer treatment.
  • 1.0K
  • 27 Aug 2020
Topic Review
UPS in Human Malignancies
The ubiquitin proteasome system (UPS) governs the non-lysosomal degradation of oxidized, damaged, or misfolded proteins in eukaryotic cells. This process is tightly regulated through the activation and transfer of polyubiquitin chains to target proteins which are then recognized and degraded by the 26S proteasome complex. The role of UPS is crucial in regulating protein levels through degradation to maintain fundamental cellular processes such as growth, division, signal transduction, and stress response. Dysregulation of the UPS, resulting in loss of ability to maintain protein quality through proteolysis, is closely related to the development of various malignancies and tumorigenesis.
  • 1.0K
  • 13 Apr 2021
Topic Review
Hypoxia in Lung Cancer Management
Lung cancer represents the first cause of death by cancer worldwide and remains a challenging public health issue. Hypoxia, as a relevant biomarker, has raised high expectations for clinical practice.
  • 1.0K
  • 22 Sep 2021
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