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Topic Review
Telomeres in Liver Cancer
Liver cancer is one of the most common cancer types worldwide and the fourth leading cause of cancer-related death. Liver carcinoma is distinguished by a high heterogeneity in pathogenesis, histopathology and biological behavior. Dysregulated signaling pathways and various gene mutations are frequent in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), which represent the two most common types of liver tumors. Both tumor types are characterized by telomere shortening and reactivation of telomerase during carcinogenesis. The observation that TERT promoter mutations occur early during liver carcinogenesis highlights the importance of telomerase activity for tumor cell survival. Two possible scenarios are conceivable how telomerase contributes to tumorigenesis in liver cancer: On the one side, telomerase reactivation before entering the crisis checkpoint may stabilize critically short telomeres, providing growth advantage for cells with oncogenic mutations. On the other side, early reactivation of telomerase may be related to its non-canonical functions.  Similarities and differences between HCC and iCCA in telomere biology are depicted in this review article.
  • 678
  • 04 Aug 2020
Topic Review
Eotaxins in Colorectal Cancer
Colorectal cancer (CRC) is one of the most common malignancies in the world, with a global incidence of almost 2 million new cases every year. Despite the availability of many diagnostic tests, including laboratory tests and molecular diagnostics, an increasing number of new cases is observed. Thus, it is very important to search new markers that would show high diagnostic sensitivity and specificity in the detection of colorectal cancer in early stages of the disease. Eotaxins are proteins that belong to the cytokine group—small molecules with a variety of applications. Their main role is the activation of basophils and eosinophils involved in inflammatory processes. On the basis of available literature, we can assume that eotaxins accumulate in cancer cells in the course of CRC. This leads to a decrease in the chemotaxis of eosinophils, which are effector immune cells with anti-tumor activity. This may explain a decrease in their number as a defense mechanism of cancer cells against their destruction and may be useful when attempting anti-tumor therapy with the use of chemokines. Authors: Monika Zajkowska, Barbara Mroczko
  • 678
  • 10 Oct 2020
Topic Review
Three-Dimensional Printing for Cancer Applications
As a variety of novel technologies, 3D printing has been considerably applied in the field of health care, including cancer treatment. With its fast prototyping nature, 3D printing could transform basic oncology discoveries to clinical use quickly, speed up and even revolutionise the whole drug discovery and development process.
  • 678
  • 28 Sep 2021
Topic Review
Repurposing Nelfinavir for Cancer Therapy
Nelfinavir is an anti-infective agent that has extensively been used to treat acquired immunodeficiency syndrome (AIDS) in adult and pediatric patients. In addition to its anti-infective properties, nelfinavir has demonstrated potent off-target anti-cancer effects, suggesting that it could be a suitable candidate for drug repurposing for cancer.
  • 677
  • 07 Dec 2020
Topic Review
Alternative RNA Splicing
Alternative splicing relies on the distinction between intronic and exonic sections of DNA within genes. The pre-processed mRNA transcript bears these same sections, which are recognized and spliced together by the spliceosome, a large complex of five small nuclear ribonucleoproteins (snRNPs) and proteins. Specific consensus sequences such as 5′ dinucleotide GU and 3′ dinucleotide AG in introns are critical to intron recognition.
  • 677
  • 15 Nov 2021
Topic Review
LAT1 and ASCT2 Related microRNAs
The development and progression of colorectal cancer (CRC) have been associated with genetic and epigenetic alterations and more recently with changes in cell metabolism. Amino acid trans-porters are key players in tumor development, and it is described that tumor cells upregulate some AA transporters in order to support the increased amino acid (AA) intake to sustain the tumor additional needs for tumor growth and proliferation through the activation of several signaling pathways. LAT1 and ASCT2 are two AA transporters involved in the regulation of the mTOR pathway that has been reported as upregulated in CRC. Some attempts have been made in order to develop therapeutic approaches to target these AA transporters, however none have reached the clinical setting so far. MiRNA-based therapies have been gaining increasing attention from pharmaceutical companies and now several miRNA-based drugs are currently in clinical trials with promising results.
  • 676
  • 16 Mar 2021
Topic Review
EEF2K
Eukaryotic elongation factor 2 kinase (eEF2K or Ca2+/calmodulin-dependent protein kinase, CAMKIII) is a new member of an atypical α-kinase family different from conventional protein kinases that is now considered as a potential target for the treatment of cancer. 
  • 676
  • 22 Apr 2021
Topic Review
Immunotherapy Biomarkers Renal Cell Carcinoma
The treatment of metastatic renal cell carcinoma has evolved quickly over the last few years from a disease managed primarily with sequential oral tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor (VEGF) pathway, to now with a combination of therapies incorporating immune checkpoint blockade (ICB). Patient outcomes have improved with these innovations, however, controversy persists regarding the optimal sequence and patient selection amongst the available combinations. Ideally, predictive biomarkers would aid in guiding treatment decisions and personalizing care.
  • 676
  • 26 Nov 2020
Topic Review
Prognostic Biomarkers in Colorectal Cancer
Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide and is heterogeneous both morphologically and molecularly. In an era of personalized medicine, the greatest challenge is to predict individual response to therapy and distinguish patients likely to be cured with surgical resection of tumors and systemic therapy from those resistant or non-responsive to treatment. Patients would avoid futile treatments, including clinical trial regimes and ultimately this would prevent under- and over-treatment and reduce unnecessary adverse side effects.
  • 675
  • 25 May 2021
Topic Review
Tumor Immune Microenvironment in MPM
Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease that arises from pleural mesothelial cells, characterized by a median survival of approximately 13–15 months after diagnosis. The primary cause of this disease is asbestos exposure and the main issues associated with it are late diagnosis and lack of effective therapies. Asbestos-induced cellular damage is associated with the generation of an inflammatory microenvironment that influences and supports tumor growth, possibly in association with patients’ genetic predisposition and tumor genomic profile. The chronic inflammatory response to asbestos fibers leads to a unique tumor immune microenvironment (TIME) composed of a heterogeneous mixture of stromal, endothelial, and immune cells, and relative composition and interaction among them is suggested to bear prognostic and therapeutic implications. TIME in MPM is known to be constituted by immunosuppressive cells, such as type 2 tumor-associated macrophages and T regulatory lymphocytes, plus the expression of several immunosuppressive factors, such as tumor-associated PD-L1. Several studies in recent years have contributed to achieve a greater understanding of the pathogenetic mechanisms in tumor development and pathobiology of TIME, that opens the way to new therapeutic strategies. The study of TIME is fundamental in identifying appropriate prognostic and predictive tissue biomarkers. In the present review, we summarize the current knowledge about the pathological characterization of TIME in MPM.
  • 675
  • 23 Jun 2021
Topic Review
Melatonin and Oral Cancer
The wide variety of epigenetic controls available is rapidly expanding the knowledge of molecular biology even overflowing it. At the same time, it can illuminate unsuspected ways of understanding the etiology of cancer. New emerging therapeutic horizons, then, promise to overcome the current antitumor strategies need. The translational utility of this complexity is particularly welcome in oral cancer (OC), in which natural history is alarmingly disappointing due to the invasive and mutilating surgery, the high relapsing rate, the poor quality of life and the reduced survival after diagnosis. Melatonin activates protective receptor-dependent and receptor-independent processes that prevent tissue cancerisation and inhibit progressive tumor malignancy and metastasis. 
  • 675
  • 24 Aug 2021
Topic Review
Paraneoplastic Leukocytosis in Cervical Cancer
Tumor-associated leukocytosis has been associated with poor prognosis in cervical cancer. Leukemoid reaction (i.e., white blood cell count > 40,000/μL) is defined paraneoplastic (PLR) when it occurs in the presence of a cytokine-secreting tumor (CST) without neoplastic bone marrow infiltration. Cervical cancers displaying PLR represent a peculiar entity characterized by a rapidly progressive behavior typically associated with chemo-radioresistance.
  • 675
  • 30 Aug 2022
Topic Review
Boron Neutron Capture Therapy in Breast Cancer
Boron neutron capture (BNCT) is a biologically targeted, densely ionizing form of radiation therapy that allows for increased tumor cell kill, while reducing toxicity to surrounding normal tissues. 
  • 675
  • 28 Jun 2022
Topic Review
Mismatch Repair Deficiency
Universal MMR/MSI testing is standard of care for all patients with newly diagnosed CRC based on multi-society guidelines in the United States. Such testing is intended to identify patients with Lynch Syndrome due to a germline mutation in an MMR gene, but also detects those with sporadic dMMR/MSI-high CRCs.
  • 674
  • 19 Feb 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. 
  • 674
  • 17 Jun 2021
Topic Review
Biomarker for Thyroid Cancer
Thyroid cancer has the most rapidly increasing incidence rate among all major cancers, with a triple increase from 4.5 to 14.4 per 100,000 population during 1974–2013. It was estimated 52,890 new cases in the United States in 2020 and contributed to 0.36% of all cancer deaths. Most primary thyroid cancers are follicular cell-derived epithelial tumors, making up four main pathological carcinoma types: papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC).
  • 674
  • 29 Mar 2022
Topic Review
TGF-β and ROS in Cancer
Metabolic changes in tumor microenvironment play a critical role in cancer, related to the accumulated alterations in signaling pathways that control cellular metabolism. Cancer metabolic deregulation is related to specific events such as the control of oxidative stress, and in particular the redox imbalance with aberrant oxidant production and/or a deregulation of the efficacy of the antioxidant systems. In cancer cells, different cytokines are involved in the development and/or progression of cancer: among these cytokines, the transforming growth factor β (TGF-β) is central to tumorigenesis and cancer progression. In tumor cells, it has been demonstrated that there is a close correlation between oxidative stress and TGF-β: this crosstalk strongly contributes to tumorigenesis, both in tumor development and in mediating its invasiveness.
  • 674
  • 09 Jul 2021
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.
  • 672
  • 02 Mar 2022
Topic Review
Applications of Humanized Mice in Oncology
While chemotherapies remain the mainstay treatments for many cancers, the advent of new molecular techniques has opened doors for more targeted modalities towards cancer cells. Although immune checkpoint inhibitors (ICIs) have demonstrated therapeutic efficacy in treating cancer, adverse side effects related to excessive inflammation are often reported. There is a lack of clinically relevant animal models to probe the human immune response towards ICI-based interventions. Humanized mouse models have emerged as valuable tools for pre-clinical research to evaluate the efficacy and safety of immunotherapy. 
  • 672
  • 05 Jun 2023
Topic Review
Adenosine Targeting Strategy for Glioblastoma Aggressiveness
Glioblastoma is the most commonly malignant and aggressive brain tumor, with a high mortality rate. The role of the purine nucleotide adenosine and its interaction with its four subtypes receptors coupled to the different G proteins, A1, A2A, A2B, and A3, and its different physiological functions in different systems and organs, depending on the active receptor subtype, has been studied for years. Recently, several works have defined extracellular adenosine as a tumoral protector because of its accumulation in the tumor microenvironment. Its presence is due to both the interaction with the A2A receptor subtype and the increase in CD39 and CD73 gene expression induced by the hypoxic state. This fact has fueled preclinical and clinical research into the development of efficacious molecules acting on the adenosine pathway and blocking its accumulation. Given the success of anti-cancer immunotherapy, the new strategy is to develop selective A2A receptor antagonists that could competitively inhibit binding to its endogenous ligand, making them reliable candidates for the therapeutic management of brain tumors. 
  • 671
  • 05 Sep 2022
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