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Topic Review
Tumor Cell Signaling Pathways
Increasing the understanding of carcinogenesis has allowed the delineation of crucial signaling pathways, which have shown essential roles in the regulation of stem cell functions
  • 1.1K
  • 09 Sep 2022
Topic Review
Obesity and Immunometabolic Changes in Adipose Tissue
White adipose tissue (WAT) represents an endocrinologically and immunologically active tissue whose primary role is energy storage and homeostasis. Breast WAT is involved in the secretion of hormones and proinflammatory molecules that are associated with breast cancer development and progression.
  • 1.1K
  • 12 May 2023
Topic Review
Pancreatic Enzyme Replacement Therapy
Pancreatic cancer is an aggressive malignancy and the seventh leading cause of global cancer deaths in industrialised countries. More than 80% of patients suffer from significant weight loss at diagnosis and over time tend to develop severe cachexia. A major cause of weight loss is malnutrition. Patients may experience pancreatic exocrine insufficiency (PEI) before diagnosis, during nonsurgical treatment, and/or following surgery. PEI is difficult to diagnose because testing is cumbersome. Consequently, PEI is often detected clinically, especially in non-specialised centres, and treated empirically.
  • 1.1K
  • 25 Jun 2021
Topic Review
Revisiting Hepatic Artery Infusion Chemotherapy
Hepatic artery infusion chemotherapy (HAIC) is a well-established and common treatment for advanced hepatocellular carcinoma (HCC), particularly in East Asia. However, HAIC is not recognized internationally. Although several trials have demonstrated the safety and efficacy of HAIC, evidence corroborating its overall survival (OS) benefits compared with standard treatments is insufficient. Nevertheless, HAIC may provide prominent benefits in selected patients such as patients with portal vein thrombosis or high intrahepatic tumor burden. Moreover, HAIC has been combined with several therapeutic agents and modalities, including interferon-alpha, multikinase inhibitors, radiation therapy, and immunotherapy, to augment its treatment efficacy. Most of these combinations appeared to increase overall response rates compared with HAIC alone, but results regarding OS are inconclusive. Two prospective randomized controlled trials comparing HAIC plus sorafenib with sorafenib alone have reported conflicting results, necessitating further research. As immunotherapy-based combinations became the mainstream treatments for advanced HCC, HAIC plus immunotherapy-based treatments also showed encouraging preliminary results. The trials of HAIC were heterogeneous in terms of patient selection, chemotherapy regimens and doses, HAIC combination agent selections, and HAIC technical protocols. These heterogeneities may contribute to differences in treatment efficacy, thus increasing the difficulty of interpreting trial results.
  • 1.1K
  • 29 Mar 2022
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.
  • 1.1K
  • 30 Aug 2022
Topic Review
Metal-Based Chemotherapeutic Treatments
Herein we provides an overview of the various research approaches we have explored in recent years to improve metal-based agents for cancer or infection treatments. Although cisplatin, carboplatin, and oxaliplatin remain the cornerstones in tumor chemotherapy, the discovery and approval of novel inorganic anticancer drugs is a very slow process. Analogously, although a few promising inorganic drugs have found clinical application against parasitic or bacterial infections, their use remains relatively limited. Moreover, the discovery process is often affected by small therapeutic enhancements that are not attractive for the pharmaceutical industry. However, the availability of increasing mechanistic information for the modes of action of established inorganic drugs is fueling the exploration of various approaches for developing effective inorganic chemotherapy agents. Through a series of examples, some from our own research experience, we focus our attention on a number of promising strategies, including (1) drug repurposing, (2) the simple modification of the chemical structures of approved metal-based drugs, (3) testing novel drug combinations, and (4) newly synthesized complexes coupling different anticancer drugs. Accordingly, we aim to suggest and summarize a series of reliable approaches that are exploitable for the development of improved and innovative treatments.
  • 1.1K
  • 25 May 2021
Topic Review
Antitumor Potential of Stingless Bee Propolis and Geopropolis
Stingless bees, also known as meliponines, live in colonies and are characterized by having atrophied stingers. Propolis is a mixture of salivary secretions and plant resins collected by bees and is produced to seal the hive and prevent the entry of air and invading insects, besides having antimicrobial activity, protecting the colony from diseases. The investigation of the biological activities of stingless bee products, especially propolis and geopropolis, has revealed promising therapeutic properties, especially in the research on new antineoplastic agents.
  • 1.1K
  • 17 Nov 2021
Topic Review
Lateralized and Segmental Overgrowth in Children
Lateralized overgrowth (LO), or segmental overgrowth, is defined as an increase in tissue growth of various origins (skeletal, muscular, fibrous, vascular, adipose, or any association of these) in any region of the body.
  • 1.1K
  • 14 Dec 2021
Topic Review
Leptomeningeal Disease Treatment
Leptomeningeal disease (LMD) is a devastating complication caused by seeding malignant cells to the cerebrospinal fluid (CSF) and the leptomeningeal membrane. LMD is diagnosed in 5–15% of patients with systemic malignancy. Management of LMD is challenging due to the biological and metabolic tumor microenvironment of LMD being largely unknown. Patients with LMD can present with a wide variety of signs and/or symptoms that could be multifocal and include headache, nausea, vomiting, diplopia, and weakness, among others. The median survival time for patients with LMD is measured in weeks and up to 3–6 months with aggressive management, and death usually occurs due to progressive neurologic dysfunction. In melanoma, LMD is associated with a suppressive immune microenvironment characterized by a high number of apoptotic and exhausted CD4+ T-cells, myeloid-derived suppressor cells, and a low number of CD8+ T-cells. Proteomics analysis revealed enrichment of complement cascade, which may disrupt the blood–CSF barrier. Clinical management of melanoma LMD consists primarily of radiation therapy, BRAF/MEK inhibitors as targeted therapy, and immunotherapy with anti-PD-1, anti-CTLA-4, and anti-LAG-3 immune checkpoint inhibitors.
  • 1.1K
  • 31 Mar 2023
Topic Review
Galectins in Esophageal Cancer
The overall 5-year survival rate of esophageal cancer patients is poor. Galectins are glycan-binding proteins known to contribute to tumor initiation and progression. To get insight in the expression and potential function of galectins in esophageal cancer, a literature review is performed. The researchers found that galectins have been mainly studied in the context of esophageal squamous cell carcinoma and that galectin-1, -3, and -9 expression are most frequently reported. More research is required to provide better insights in the diagnostic, prognostic, and predictive value of galectins in esophageal cancer as well as their functional role in tumor progression.
  • 1.1K
  • 05 Dec 2022
Topic Review
Neurokinin-1 Receptor Antagonists as Therapeutic Agent for Osteosarcoma
Osteosarcoma is a bone tumor predominantly affecting children and adolescents with high malignant potential. It is a cause of serious public health challenges due to its high morbidity rates and metastatic potential. Metastasis in osteosarcoma may manifest either during treatment of the primary tumor, shortly after treatment, or a long time after the end of the treatment. So far, there are no therapeutics that can prevent or treat osteosarcoma metastasis. The peptide substance P (SP) and its high-affinity receptor, Neurokinin-1 (NK-1R), are known to positively correlate with osteosarcoma progression. Osteosarcoma cells overexpress NK-1R. SP is known to elicit the proliferation of osteosarcoma cells and induce angiogenesis and migration, leading to the invasion and metastasis of tumor cells. In contrast, NK-1R antagonists, such as aprepitant, inhibit the proliferation and induce the apoptosis of osteosarcoma cells. Aprepitant is also known to inhibit the migration of osteosarcoma cells, as well as reduce the expression levels and activities of transcriptional regulators of metastasis-related genes such as matrix metalloproteinases (MMP-2 and MMP-9), vascular endothelial growth factor (VEGF), and nuclear factor kappa B (NF-κB). These preceding studies highlighted the antimetastatic role of aprepitant in osteosarcoma Moreover, combination therapy consisting of chemotherapy and NK-1R antagonist increases the chemosensitization of osteosarcoma cells.
  • 1.1K
  • 28 Mar 2023
Topic Review
Targeted Therapy for EWS-FLI1 in Ewing Sarcoma
Ewing sarcoma (EwS) is a highly aggressive and metastatic cancer in children and adolescents. Canonical therapy mainly comprises the combination of intensive chemotherapy, radiation, and local surgery, which give rise to acute and chronic adverse effects. Drugs targeting EwS without side effects are in urgent demand. Genetically, EwS is characterized by chromosomal translocations with a low mutation burden. As a result, the chimeric protein EWS-ETS, mainly EWS-FLI1(85%), is critical for the malignancy of EwS. EWS-FLI1 directly binds to GGAA microsatellites in enhancers and promotors of the target genes and recruits multiple transcription factors or epigenetic regulators to reprogramme the epigenome.
  • 1.1K
  • 17 Aug 2023
Topic Review
D Adenovirus Oncolytic Viral Vectors
Oncolytic adenoviruses (Ad) have shown promising results in the therapeutic treatment of cancer. Ad type 5 (Ad5) is the most extensively utilized Ad type. However, several limitations exist to using Ad5 as an oncolytic virus, including high levels of anti-Ad5 neutralizing antibodies in the population, binding of the Ad5 hexon to blood coagulation factor X leading to liver sequestration and toxicity, and reduced expression of the primary receptor CAR on many tumors. Here, we use in vitro methods to explore the oncolytic potential of four alternative Ad types (Ad26, 28, 45, and 48) belonging to the species D Ad subgroup and developed replication-competent species D Ads expressing the human sodium iodide symporter protein (hNIS) for combination radiovirotherapy. We evaluated the species D Ad vectors transduction, replication, cytotoxicity, and gene expression in six different cancer cell lines. Species D Ads showed the greatest transduction and cytotoxic killing in the SKBR3 breast cancer cells, followed by 293, A549, and HepG2 cells, however the cytotoxicity was less than the wild type Ad5 virus. In contrast, species D Ads showed limited transduction and cytotoxicity in the Hela and SKOV3 cancer cell lines. These species D Ad vectors also successfully expressed the hNIS gene during infection leading to increased iodide uptake in multiple cancer cell lines. These results, the low seroprevalence of anti-species D antibodies, and the lack of binding to blood coagulation FX, support further exploration of species D Ads as alternative oncolytic adenoviruses against multiple types of cancer.
  • 1.1K
  • 22 Sep 2021
Topic Review
HCV and Hepatic Extracellular Matrix
Chronic infection by the hepatitis C virus (HCV) is a major cause of liver diseases, predisposing to fibrosis and hepatocellular carcinoma. Liver fibrosis is characterized by an overly abundant accumulation of components of the hepatic extracellular matrix, such as collagen and elastin, with consequences on the properties of this microenvironment and cancer initiation and growth. This review will provide an update on mechanistic concepts of HCV-related liver fibrosis/cirrhosis and early stages of carcinogenesis, with a dissection of the molecular details of the cross-talk during disease progression between hepatocytes, the extracellular matrix and hepatic stellate cells.
  • 1.1K
  • 22 Sep 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.
  • 1.1K
  • 26 Nov 2020
Topic Review
Molecular Markers and Targets in Melanoma
Melanoma develops as a result of several genetic alterations, with UV radiation often acting as a mutagenic risk factor. Deep knowledge of the molecular signaling pathways of different types of melanoma allows better characterization and provides tools for the development of therapies based on the intervention of signals promoted by these cascades. The latest World Health Organization classification acknowledged the specific genetic drivers leading to melanoma and classifies melanocytic lesions into nine distinct categories according to the associate cumulative sun damage (CSD), which correlates with the molecular alterations of tumors. The largest groups are melanomas associated with low-CSD or superficial spreading melanomas, characterized by frequent presentation of the BRAFV600 mutation. High-CSD melanomas include lentigo maligna type and desmoplastic melanomas, which often have a high mutation burden and can harbor NRAS, BRAFnon-V600E, or NF1 mutations. Non-CSD-associated melanomas encompass acral and mucosal melanomas that usually do not show BRAF, NRAS, or NF1 mutations (triple wild-type), but in a subset may have KIT or SF3B1 mutations. To improve survival, these driver alterations can be treated with targeted therapy achieving significant antitumor activity.
  • 1.1K
  • 22 Apr 2022
Topic Review
Nuclear Matrix Metalloproteinases
Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are responsible for the degradation of a wide range of extracellular matrix proteins, which are involved in many cellular processes to ensure the normal development of tissues and organs. Overexpression of MMPs has been observed to facilitate cellular growth, migration, and metastasis of tumor cells during cancer progression. A growing number of these proteins are being found to exist in the nuclei of both healthy and tumor cells, thus highlighting their localization as having a genuine purpose in cellular homeostasis. The mechanism underlying nuclear transport and the effects of MMP nuclear translocation have not yet been fully elucidated. To date, nuclear MMPs appear to have a unique impact on cellular apoptosis and gene regulation, which can have effects on immune response and tumor progression, and thus present themselves as potential therapeutic targets in certain types of cancer or disease. Herein, we highlight and evaluate what progress has been made in this area of research, which clearly has some value as a specific and unique way of targeting the activity of nuclear matrix metalloproteinases within various cell types. 
  • 1.1K
  • 05 Jan 2021
Topic Review
Microneedles in Cancer Therapy and Diagnosis
The tumor is an uncontrolled growth of tissue that can be localized (benign) or possesses the capability of metastasis (malignant). The conventional methods of tumor diagnosis, such as acupuncture, endoscopy, and histopathology, and treatment methods, such as injections, chemotherapy, surgery, and radiotherapy, are invasive, expensive, and pose severe safety and management issues for the patients. Microneedle technology is minimally invasive, self-administrable, bypasses the first-pass effect, effectively delivers chemotherapeutics and drugs at low doses, and provides drug diffusion into the tumor areas, thus, overcoming the drawbacks of conventional delivery systems.
  • 1.1K
  • 12 Jan 2023
Topic Review
Metabolic Reprogramming in Tumor Endothelial Cells
The dynamic crosstalk between the different components of the tumor microenvironment is critical to determine cancer progression, metastatic dissemination, tumor immunity, and therapeutic responses. Angiogenesis is critical for tumor growth, and abnormal blood vessels contribute to hypoxia and acidosis in the tumor microenvironment. In this hostile environment, cancer and stromal cells have the ability to alter their metabolism in order to support the high energetic demands and favor rapid tumor proliferation. 
  • 1.1K
  • 12 Oct 2022
Topic Review
Cold-Shock Domains
The cold-shock domain has a deceptively simple architecture but supports a complex biology. Cold-shock domains in human proteins are often associated with natively unfolded protein segments and more rarely with other folded domains. Human proteins containing cold-shock domains bind single-stranded DNA and/or RNA and serve a large variety of roles in regulating transcription, DNA-damage repair, RNA splicing, translation, stability and sequestration.
  • 1.1K
  • 23 Feb 2021
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