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Topic Review
Benign Prostatic Hyperplasia
The apoptosis machinery is a promising target against benign prostatic hyperplasia (BPH). Inhibitors of apoptosis proteins (IAPs) modulate apoptosis by direct inhibition of caspases. Serenoa Repens (SeR) may be combined with other natural compounds such as Lycopene (Ly) and Selenium (Se) to maximize its therapeutic activity in BPH. We investigated the effects of SeR, Se and Ly, alone or in association, on the expression of four IAPs, cIAP-1, cIAP-2, NAIP and survivin in rats with experimental testosterone-dependent BPH. Moreover, caspase-3, interleukin-6 (IL-6) and prostate specific membrane antigen (PSMA) have been evaluated. Rats were administered, daily, with testosterone propionate (3 mg/kg/sc) or its vehicle for 14 days. Testosterone injected animals (BPH) were randomized to receive vehicle, SeR (25 mg/kg/sc), Se (3 mg/kg/sc), Ly (1 mg/kg/sc) or the SeR-Se-Ly association for 14 days. Animals were sacrificed and prostate removed for analysis. BPH animals treated with vehicle showed unchanged expression of cIAP-1 and cIAP-2 and increased expression of NAIP, survivin, caspase-3, IL-6 and PSMA levels when compared with sham animals. Immunofluorescence studies confirmed the enhanced expression of NAIP and survivin with a characteristic pattern of cellular localization. SeR-Se-Ly association showed the highest efficacy in reawakening apoptosis; additionally, this therapeutic cocktail significantly reduced IL-6 and PSMA levels. The administration of SeR, Se and Ly significantly blunted prostate overweight and growth; moreover, the SeR-Se-Ly association was most effective in reducing prostate enlargement and growth by 43.3% in treated animals. The results indicate that IAPs may represent interesting targets for drug therapy of BPH.
  • 886
  • 01 Nov 2020
Topic Review
RadioIodine Treatment
Thyroid radioiodide or radioiodine therapy (RAI) is one of the oldest known and used targeted therapies. In thyroid cancer, it has been used for more than eight decades and is still being used to improve thyroid tumor treatment to eliminate remnants after thyroid surgery, and tumor metastases. Knowledge at the molecular level of the genes/proteins involved in the process has led to improvements in therapy, both from the point of view of when, how much, and how to use the therapy according to tumor type. The effectiveness of this therapy has spread into other types of targeted therapies, and this has made sodium/iodide symporter (NIS) one of the favorite theragnostic tools. 
  • 886
  • 29 Mar 2021
Topic Review
Tripartite Motif Family
The tripartite motif (TRIM) family comprises at least 80 members in humans, with most having ubiquitin or SUMO E3 ligase activity conferred by their N-terminal RING domain. TRIMs regulate a wide range of processes in ubiquitination- or sumoylation-dependent manners in most cases, and fewer as adaptors. Their roles in the regulation of viral infections, autophagy, cell cycle progression, DNA damage and other stress responses, and carcinogenesis are being increasingly appreciated, and their E3 ligase activities are attractive targets for developing specific immunotherapeutic strategies for immune diseases and cancers.
  • 886
  • 22 Sep 2021
Topic Review
LncRNAs in Cervical Cancer
Cervical cancer (CC) continues to be one of the leading causes of death for women across the world. Although it has been determined that papillomavirus infection is one of the main causes of the etiology of the disease, genetic and epigenetic factors are also required for its progression. Among the epigenetic factors are included the long noncoding RNAs (lncRNAs), transcripts of more than 200 nucleotides (nt) that generally do not code for proteins and have been associated with diverse functions such as the regulation of transcription, translation, RNA metabolism, as well as stem cell maintenance and differentiation, cell autophagy and apoptosis. Recently, studies have begun to characterize the aberrant regulation of lncRNAs in CC cells and tissues, including Homeobox transcript antisense RNA (HOTAIR), H19, Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), Cervical Carcinoma High-Expressed 1 (CCHE1), Antisense noncoding RNA in the inhibitors of cyclin-dependent kinase 4 (ANRIL), Growth arrest special 5 (GAS5) and Plasmacytoma variant translocation 1 (PVT1). They have been associated with several disease-related processes such as cell growth, cell proliferation, cell survival, metastasis and invasion as well as therapeutic resistance, and are novel potential biomarkers for diagnosis and prognosis in CC.
  • 885
  • 13 Jan 2021
Topic Review
Brain Cancer Chemotherapy Using Monoclonal Antibody Conjugates
Central nervous system (CNS) drug delivery into the brain across the endothelium is difficult due to the blood-brain barrier (BBB), which is composed mainly of tight junctions and efflux transporters, such as multiple drug resistance 1 (MDR1) (P-glycoprotein). On the other hand, the development of anti-cancer drugs is a challenging task due to their frequent off-target side effects and the complicated mechanisms of cancer pathogenesis and progression. Brain cancer treatment options are surgery, radiation therapy, and chemotherapy. It is difficult to remove all tumor cells, even by surgical removal after a craniotomy. Accordingly, innovative brain cancer drugs are needed. Currently, antibody (Ab) drugs that show high therapeutic effects are often used clinically. Furthermore, antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan, an anti-HER2 (human epidermal receptor 2) ADC with low-molecular cancer drugs through the suitable linker, have been developed. In the case of trastuzumab deruxtecan, it is internalized into cancer cells across the membrane via receptor-mediated endocytosis. Moreover, it is reported that drug delivery into the brain across the BBB was carried out via receptor-mediated transcytosis (RMT), using anti-receptor Abs as a vector against the transferrin receptor (TfR) or insulin receptor (InsR). Thus, anti-TfR ADCs with cancer drugs are promising brain cancer agents due to their precise distribution and low side effects.
  • 885
  • 20 Jul 2022
Topic Review
Genetic Alterations Featuring Biological Models
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death worldwide. This high mortality rate is due to the disease’s lack of symptoms, resulting in a late diagnosis. Biomarkers and treatment options for pancreatic cancer are also limited. In order to overcome this, new research models and novel approaches to discovering PDAC biomarkers are required. In this review, we outline the hereditary and somatic causes of PDAC and provide an overview of the recent genome wide association studies (GWAS) and pathway analysis studies. We also provide a summary of some of the systems used to study PDAC, including established and primary cell lines, patient-derived xenografts (PDX), and newer models such as organoids and organ-on-chip. These ex vitro laboratory systems allow for critical research into the development and progression of PDAC.
  • 884
  • 16 Oct 2020
Topic Review
Belantamab Mafodotin and Multiple Myeloma
Multiple myeloma (MM) is a hematologic malignancy characterized by excessive clonal proliferation of plasma cells. The treatment of multiple myeloma presents a variety of unique challenges due to the complex molecular pathophysiology and incurable status of the disease at this time. Given that MM is the second most common blood cancer with a characteristic and unavoidable relapse/refractory state during the course of the disease, the development of new therapeutic modalities is crucial. Belantamab mafodotin (belamaf, GSK2857916) is a first-in-class therapeutic, indicated for patients who have previously attempted four other treatments, including an anti-CD38 monoclonal antibody, a proteosome inhibitor, and an immunomodulatory agent. In November 2017, the FDA designated belamaf as a breakthrough therapy for heavily pretreated patients with relapsed/refractory multiple myeloma. In August 2020, the FDA granted accelerated approval as a monotherapy for relapsed or treatment-refractory multiple myeloma. The drug was also approved in the EU for this indication in late August 2020. Of note, belamaf is associated with the following adverse events: decreased platelets, corneal disease, decreased or blurred vision, anemia, infusion-related reactions, pyrexia, and fetal risk, among others. Further studies are necessary to evaluate efficacy in comparison to other standard treatment modalities and as future drugs in this class are developed
  • 883
  • 24 Feb 2021
Topic Review
3D Pancreatic Cancer Models
Pancreatic cancer is an extremely lethal malignancy with a survival rate lower than any other cancer type. For decades, two-dimensional (2D) cultures have been the cornerstone for studying cancer cell biology and drug testing, due to their simplicity and cost. However, their inability to reconstitute the tumor architecture, the absence of nutrient and oxygen supply gradients, as well as the lack of appropriate mechano-forces that mimic the extracellular microenvironment, make them an inadequate model to accurately reproduce tissue level-specific characteristics. Bioengineering systems, such as three-dimensional (3D) patient-specific models, are progressively emerging as systems better able to mimic the biology of pancreatic tumors and to test new anticancer therapies, as they more efficiently recapitulate the complex tumor microenvironment characteristic of pancreatic tumors.
  • 883
  • 22 Mar 2021
Topic Review
Significance of Mitochondrial-Dysfunction in Cancer
       Mitochondria are semi-autonomous intracellular double membrane-bound organelles, which include an outer membrane, a highly folded inner membrane (crista), a matrix space surrounded by the inner membrane, and an inter-membrane space between the inner and outer membranes. Usually, a cell has hundreds or thousands of mitochondria, which can occupy up to 25% of the cellular cytoplasm. Mitochondria are a convergence point for glucose, glutamine, and lipid metabolism. The primary function of mitochondria is to support the TCA cycle and aerobic respiration by oxidative phosphorylation, generating ATP through the mitochondrial respiratory chain to fulfill the energy needs for cell survival. One unique feature of mitochondria is that they possess their own supercoiled, double-stranded circular genetic material called mitochondrial DNA (mtDNA) that encodes rRNAs, tRNAs, and proteins essential for electron transport and oxidative phosphorylation, as well as their own genetic repair mechanisms. Mitochondrial biogenesis requires the coordinated expression of both mtDNA- and nuclear DNA-encoded genes. Thirteen proteins are encoded by mtDNA, while approximately 1000 mitochondrial proteins are encoded by the nuclear genome, translated in the cytoplasm and transported into the mitochondria by a specific transport system. These two pools of proteins are required to maintain mitochondria as a cellular power hub and a signaling nexus that are essential for normal cell function. Defects in many of the mitochondrial components are causal for a multitude of cellular diseases. Of note, the reprogramming of cellular metabolism and the aberrant redox status have been heralded as major emerging hallmarks of neoplastic transformation. Overall, mitochondrial dysfunction caused by mtDNA mutations, malfunctioned TCA cycle enzymes, electron respiratory chain leakage and subsequent oxidative stress, and/or aberrant oncogenic and tumor suppressor signaling is known to alter cellular metabolic pathways, disrupt redox balance, and cause resistance to apoptosis and therapies that significantly contribute to the development of multiple types of human cancers. In the following sections, we will present current knowledge on these aspects of mitochondrial dysfunction pertaining to the pathologies of various forms of human malignancies.
  • 882
  • 27 Aug 2020
Topic Review
Pitfalls and Limitations of Glioblastoma Diagnosis and Follow-Up
Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Glioblastoma is mainly diagnosed by neuroimaging techniques followed by histopathological and molecular analysis of the resected or biopsied tissue.
  • 880
  • 05 Aug 2022
Topic Review
Anticancer Potential of Furanocoumarins
       Cancer is one of the most extreme medical conditions in both developing and developed countries around the world, causing millions of deaths each year. Chemotherapy and/or radiotherapy are key for treatment approaches, but both have numerous adverse health effects. Furthermore, the resistance of cancerous cells to anticancer medication leads to treatment failure. The rising burden of cancer overall requires novel efficacious treatment modalities. Natural medications offer feasible alternative options against malignancy in contrast to western medication.        This review highlights the potential for furanocoumarins to be clinically beneficial in cancer, particularly given their specificity to tumor cells (while sparing normal cells). In vitro investigations have shown that furanocoumarins affect a range of cellular mechanisms, such as apoptosis, autophagy, and cell cycle arrest. ER stress induction mainly caused by NF-κB inactivation, PI3K/Akt inhibition, and p53 modulation. Furanocoumarins are also effective in different MDR cancers that are the main cause of anticancer therapeutics failure.       Compounds in this class have also have been shown to positively synergize with commonly used anticancer drugs. The fast absorption of furanocoumarins from food into the human bloodstream is also noteworthy.  Furanocoumarins, by inhibiting CYP P450 3A4, not only have anticancer properties but also when co-administered with a low bioavailability anticancer compound can increase oral bioavailability. To date, most focus has been on in vitro studies, making it hard to reach solid conclusions on the efficacy of furanocoumarins in vivo.       Nonetheless, studies aimed at characterizing furanocoumarin’s efficacy in vivo as well as clinical studies are encouraging, supporting the need for future studies to better characterize furanocoumarin’s potential as efficacious anticancer treatment modalities.
  • 878
  • 27 Aug 2020
Topic Review
Transcriptional Spatial Profiling
Transcriptional spatial profiling enables characterization of the cancer immune profile by providing quantitative gene expression data that retains critical spatial information. It encompasses both well-known technologies such as in-situ hybridization and digital spatial profiling as well as emerging technologies such as Visium Spatial Gene Expression Solution. These technologies may be used to identify and subsequently block the source of tumour heterogeneity that underlies treatment resistance, disease progression and cancer relapse. By combining sequencing data with spatial information, transcriptional spatial profiling technologies hold great promise in uncovering novel biomarkers, potential drug targets and pathogenic mechanisms. 
  • 878
  • 22 Sep 2020
Topic Review
Diagnosis of Glioblastoma by Immuno-Positron Emission Tomography
Resonance Imaging (MRI) is the most widely used non-invasive technique in the primary diagnosis of glioblastoma. Although MRI provides very powerful anatomical information, it has proven to be of limited value for diagnosing glioblastomas in some situations. The final diagnosis requires a brain biopsy that may not depict the high intratumoral heterogeneity present in this tumor type. The gold standard tracer for most PET cancer imaging is 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), a fluorine-18 glucose analog, being the most widely used in clinical radiopharmaceutical practice, and accounting for more than 90% of total PET scans. [18F]FDG is ineffective for diagnosing gliomas due to the high glucose metabolism in the normal brain, which results in suboptimal tumor detection and delineation, especially upon treatment. An innovative option for biomarker identification in vivo is termed “immunotargeted imaging”. By merging the high target specificity of antibodies with the high spatial resolution, sensitivity, and quantitative capabilities of positron emission tomography (PET), “Immuno-PET” allows us to conduct the non-invasive diagnosis and monitoring of patients over time using antibody-based probes as an in vivo, integrated, quantifiable, 3D, full-body “immunohistochemistry” in patients.
  • 878
  • 05 Jan 2022
Topic Review
Peripheral Neuropathy Associated with Dinutuximab in Neuroblastoma Patients
Neuroblastoma is the most common extracranial solid tumor of childhood, with a median age at diagnosis of 17 months. Its incidence is 10.2 cases per million children aged <15 years. Neuroblastoma arises in tissues of the sympathetic nervous system, mostly in the adrenal medulla or paraspinal ganglia. It appears as a mass in the abdomen, pelvis, neck, or chest, with about half of the patients having metastatic disease at diagnosis. The presence of metastatic diseases over the age of 12 or 18 months and aggressive biological features (e.g., MYCN oncogene amplification) define high-risk neuroblastoma. The prognosis for such patients is poor, with a long-term survival rate of only 40%.
  • 877
  • 07 Jan 2022
Topic Review
Salvia miltiorrhiza
Salvia miltiorrhiza Bunge, also known as red sage, is a valued herbal plant in the traditional medicine in Korea, China and Japan. It is called as Dansam in Korea, Danshen in China. It is well known for its highly medicinal properties in treating of heart and vascular diseases, chronic renal failure, Alzheimer’s disease, hepatitis and so forth. Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. 
  • 874
  • 28 Sep 2021
Topic Review
Gastric Intestinal Metaplasia
Gastric cancer (GC) remains one of the most common causes of mortality worldwide. Intestinal metaplasia (IM) is one of the preneoplastic gastric lesions and is considered an essential predisposing factor in GC development. Here we present a review of recent most relevant papers to summarize major findings on the molecular alterations in gastric IM. The latest progress in novel diagnostic methods allows scientists to identify various types of molecular alterations in IM, such as polymorphisms in various genes, changes in the expression of micro-RNAs and long noncoding RNAs, and altered microbiome profiles. The results have shown that some of these alterations have strong associations with IM and a potential to be used for screening, treatment, and prognostic purposes; however, one of the most important limiting factors is the inhomogeneity of the studies. Therefore, further large-scale studies and clinical trials with standardized methods designed by multicenter consortiums are needed. As of today, various molecular alterations in IM could become a part of personalized medicine in the near future, which would help us deliver a personalized approach for each patient and identify those at risk of progression to GC.
  • 873
  • 24 Jun 2021
Topic Review
Vimentin at the Heart of Epithelial Mesenchymal Transition
Epithelial-mesenchymal transition (EMT) is a reversible plethora of molecular events where epithelial cells gain the phenotype of mesenchymal cells to invade the surrounding tissues. EMT is a physiological event during embryogenesis (type I) but also happens during fibrosis (type II) and cancer metastasis (type III). It is a multifaceted phenomenon governed by the activation of genes associated with cell migration, extracellular matrix degradation, DNA repair, and angiogenesis. The cancer cells employ EMT to acquire the ability to migrate, resist therapeutic agents and escape immunity. One of the key biomarkers of EMT is vimentin, a type III intermediate filament that is normally expressed in mesenchymal cells but is upregulated during cancer metastasis. 
  • 873
  • 22 Oct 2021
Topic Review
HERC Ubiquitin Ligases in Cancer
HERC proteins are ubiquitin E3 ligases of the HECT family. The HERC subfamily is composed of six members classified by size into large (HERC1 and HERC2) and small (HERC3–HERC6). HERC family ubiquitin ligases regulate important cellular processes, such as neurodevelopment, DNA damage response, cell proliferation, cell migration, and immune responses. Accumulating evidence also shows that this family plays critical roles in cancer. In this review, we provide an integrated view of the role of these ligases in cancer, highlighting their bivalent functions as either oncogenes or tumor suppressors, depending on the tumor type.
  • 870
  • 21 Oct 2020
Topic Review
Systemic Chemotherapy for Gastric Cancer
Gastric cancer (GC) is a molecularly heterogeneous disease. Its molecular background, epidemiology, and standard of care are quite different between Eastern and Western countries. Many efforts have been made in developing more effective surgeries and adjuvant chemotherapies for resectable GC in each region. Recently, an intensive combination of cytotoxic agents has been established as a new standard of adjuvant treatment. Meanwhile, palliative chemotherapy is a uniform standard treatment for unresectable GC worldwide. Recently, one of the most remarkable advances in therapy for unresectable GC has been the approval of immune checkpoint inhibitors (ICIs). The use of ICIs as frontline treatment is currently being investigated. In addition, novel combinations of ICIs and targeted drugs are being evaluated in clinical trials. Despite these advances, the complex biology of GC has resulted in the failure of targeted therapies, with the exceptions of HER2-targeted trastuzumab and VEGFR2-targeted ramucirumab. GC harbors many redundant oncogenic pathways, and small subsets of tumors are driven by different specific pathways. Therefore, a combination strategy simultaneously inhibiting several pathways and/or stricter patient selection for better response to targeted drugs are needed to improve clinical outcomes in this field.
  • 867
  • 22 Oct 2020
Topic Review
Anticancer Activity of Berberine
Berberine is a plant metabolite belonging to the group of isoquinoline alkaloids with strong biological and pharmacological activity. Currently, berberine is receiving considerable interest due to its anticancer activity based on many biochemical pathways, especially its proapoptotic and anti-inflammatory activity. Therefore, the growing number of papers on berberine demands summarizing the knowledge and research trends. The efficacy of berberine in breast and colon cancers seems to be the most promising aspect. Many papers focus on novel therapeutic strategies based on new formulations or search for new active derivatives. The activity of berberine is very important as regards sensitization and support of anticancer therapy in combination with well-known but in some cases inefficient therapeutics. Currently, the compound is being assessed in many important clinical trials and is one of the most promising and intensively examined natural agents.
  • 866
  • 23 Nov 2020
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