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1.
AGA Technical Review on Systemic Therapies for Hepatocellular Carcinoma.
Altayar, O, Shah, R, Chang, CY, Falck-Ytter, Y, Muir, AJ
Gastroenterology. 2022;(3):937-951
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2.
Modulators of TRPM7 and its potential as a drug target for brain tumours.
Ji, D, Fleig, A, Horgen, FD, Feng, ZP, Sun, HS
Cell calcium. 2022;:102521
Abstract
TRPM7 is a non-selective divalent cation channel with an alpha-kinase domain. Corresponding with its broad expression, TRPM7 has a role in a wide range of cell functions, including proliferation, migration, and survival. Growing evidence shows that TRPM7 is also aberrantly expressed in various cancers, including brain cancers. Because ion channels have widespread tissue distribution and result in extensive physiological consequences when dysfunctional, these proteins can be compelling drug targets. In fact, ion channels comprise the third-largest drug target type, following enzymes and receptors. Literature has shown that suppression of TRPM7 results in inhibition of migration, invasion, and proliferation in several human brain tumours. Therefore, TRPM7 presents a potential target for therapeutic brain tumour interventions. This article reviews current literature on TRPM7 as a potential drug target in the context of brain tumours and provides an overview of various selective and non-selective modulators of the channel relevant to pharmacology, oncology, and ion channel function.
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3.
Fungal Naphthalenones; Promising Metabolites for Drug Discovery: Structures, Biosynthesis, Sources, and Pharmacological Potential.
Ibrahim, SRM, Fadil, SA, Fadil, HA, Eshmawi, BA, Mohamed, SGA, Mohamed, GA
Toxins. 2022;(2)
Abstract
Fungi are well-known for their abundant supply of metabolites with unrivaled structure and promising bioactivities. Naphthalenones are among these fungal metabolites, that are biosynthesized through the 1,8-dihydroxy-naphthalene polyketide pathway. They revealed a wide spectrum of bioactivities, including phytotoxic, neuro-protective, cytotoxic, antiviral, nematocidal, antimycobacterial, antimalarial, antimicrobial, and anti-inflammatory. The current review emphasizes the reported naphthalenone derivatives produced by various fungal species, including their sources, structures, biosynthesis, and bioactivities in the period from 1972 to 2021. Overall, more than 167 references with 159 metabolites are listed.
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4.
Efficacy of combined transarterial radioembolization and sorafenib in the treatment of hepatocarcinoma: A meta-analysis.
Facciorusso, A, Paolillo, R, Tartaglia, N, Ramai, D, Mohan, BP, Cotsoglou, C, Chandan, S, Ambrosi, A, Bargellini, I, Renzulli, M, et al
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2022;(3):316-323
Abstract
BACKGROUND Adjuvant sorafenib may further enhance the efficacy of transarterial radioembolization for the treatment of hepatocellular carcinoma. AIMS To evaluate the efficacy and safety of radioembolization plus sorafenib in hepatocellular carcinoma patients. METHODS With a literature search through October 2020, we identified 9 studies (632 patients). Primary outcome was overall survival. Results were expressed as pooled median, odds ratio, or hazard ratio and 95% confidence intervals. RESULTS Pooled overall survival after radioembolization plus sorafenib was 10.79 months (95% confidence interval 9.19-12.39) and it was longer in Barcelona Clinic Liver Cancer (BCLC) B (14.47 months, 9.07-19.86) as compared to BCLC C patients (10.22 months, 7.53-12.9). No difference between combined therapy versus radioembolization alone was observed in terms of overall survival (hazard ratio 1.07, 0.89-1.30). Pooled median progression-free survival was 6.32 months (5.68-6.98), with 1-year progression-free survival pooled rate of 38.5% (12.7%-44.2%). No difference in progression-free survival (hazard ratio 0.94, 0.79-1.12) between the two treatments was observed. Pooled rate of severe adverse events was 48.9% (26.7%-71.2%), again with no difference between the two treatment regimens (odds ratio 1.52, 0.15-15.02). CONCLUSIONS The association of sorafenib does not seem to prolong survival nor delay disease progression in patients treated with radioembolization.
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5.
Recent Research Progress in Taxol Biosynthetic Pathway and Acylation Reactions Mediated by Taxus Acyltransferases.
Wang, T, Li, L, Zhuang, W, Zhang, F, Shu, X, Wang, N, Wang, Z
Molecules (Basel, Switzerland). 2021;(10)
Abstract
Taxol is one of the most effective anticancer drugs in the world that is widely used in the treatments of breast, lung and ovarian cancer. The elucidation of the taxol biosynthetic pathway is the key to solve the problem of taxol supply. So far, the taxol biosynthetic pathway has been reported to require an estimated 20 steps of enzymatic reactions, and sixteen enzymes involved in the taxol pathway have been well characterized, including a novel taxane-10β-hydroxylase (T10βOH) and a newly putative β-phenylalanyl-CoA ligase (PCL). Moreover, the source and formation of the taxane core and the details of the downstream synthetic pathway have been basically depicted, while the modification of the core taxane skeleton has not been fully reported, mainly concerning the developments from diol intermediates to 2-debenzoyltaxane. The acylation reaction mediated by specialized Taxus BAHD family acyltransferases (ACTs) is recognized as one of the most important steps in the modification of core taxane skeleton that contribute to the increase of taxol yield. Recently, the influence of acylation on the functional and structural diversity of taxanes has also been continuously revealed. This review summarizes the latest research advances of the taxol biosynthetic pathway and systematically discusses the acylation reactions supported by Taxus ACTs. The underlying mechanism could improve the understanding of taxol biosynthesis, and provide a theoretical basis for the mass production of taxol.
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6.
Cytolethal distending toxin: from genotoxin to a potential biomarker and anti-tumor target.
Kailoo, S, Shreya, , Kumar, Y
World journal of microbiology & biotechnology. 2021;(9):150
Abstract
Cytolethal Distending Toxin (CDT) belongs to the AB toxin family and is produced by a plethora of Gram-negative bacteria. Eight human-affecting enteropathogens harbor CDT that causes irritable bowel syndrome (IBS), dysentery, chancroid, and periodontitis worldwide. They have a novel molecular mode of action as they interfere in the eukaryotic cell-cycle progression leading to G2/M arrest and apoptosis. CDT, the first bacterial genotoxin described, is encoded in a single operon possessing three proteins, CdtA, CdtB, and CdtC. CdtA and CdtC are needed for the binding of the CDT toxin complex to the cholesterol-rich lipid domains of the host cell while the CdtB is the active moiety. Sequence and 3D structural-based analysis of CdtB showed similarities with nucleases and phosphatases, it was hypothesized that CdtB exercises a biochemical function identical to both these enzymes. CDT is secreted through the outer membrane vesicles from the producing bacteria. It is internalized in the target cells via clathrin-dependent endocytosis and translocated to the host cell nucleus through the Golgi complex and ER. This study discusses the virulence role of CDT, causing pathogenicity by acting as a tri-perditious complex in the CDT-producing species with an emphasis on its potential role as a biomarker and an anti-tumor agent.
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7.
Combinations of Calcitriol with Anticancer Treatments for Breast Cancer: An Update.
Segovia-Mendoza, M, García-Quiroz, J, Díaz, L, García-Becerra, R
International journal of molecular sciences. 2021;(23)
Abstract
Preclinical, clinical, and epidemiological studies indicate that vitamin D3 (VD) deficiency is a risk factor for the development of breast cancer. Underlying mechanisms include the ability of calcitriol to induce cell differentiation, inhibit oncogenes expression, and modify different signaling pathways involved in the control of cell proliferation. In addition, calcitriol combined with different kinds of antineoplastic drugs has been demonstrated to enhance their beneficial effects in an additive or synergistic fashion. However, a recognized adjuvant regimen based on calcitriol for treating patients with breast cancer has not yet been fully established. Accordingly, in the present work, we review and discuss the preclinical and clinical studies about the combination of calcitriol with different oncological drugs, aiming to emphasize its main therapeutic benefits and opportunities for the treatment of this pathology.
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8.
Cisplatin-induced nephrotoxicity in children: what is the best protective strategy?
Ruggiero, A, Ariano, A, Triarico, S, Capozza, MA, Romano, A, Maurizi, P, Mastrangelo, S, Attinà, G
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2021;(1):180-186
Abstract
INTRODUCTION Platinum compounds, which are considerably effective for the treatment of childhood malignancies, have significantly contributed to the increase in long-term survival of children with cancer. Unfortunately, children receiving cisplatin-based chemotherapy have been known to be at risk for severe disabling adverse effects, such as nephrotoxicity. METHODS A literature research of the MEDLINE PubMed database was conducted to identify articles published between 1980 and 2019 reviewing "Cisplatin AND mannitol." RESULTS The primary pharmacodynamics and clinical characteristics of cisplatin were described, focusing on its renal toxic effects and potential preventive strategies, in order to improve clinical outcomes among children with cancer aged 1 to 14 years. Currently, selecting either hydration alone or hydration plus mannitol for preventing nephrotoxicity has been controversial considering the lack of guidelines to provide treatment recommendations both among adults and children. CONCLUSIONS Appropriate knowledge regarding the pharmacokinetics and toxicological profile of cisplatin may help physicians prevent renal toxicity. Unfortunately, published data regarding the nephroprotective utility of adding mannitol appear to be inconclusive. As such, appropriate hydration remains the main fundamental strategy for reducing the risk of cisplatin-induced nephrotoxicity. Considering the increasing number of children safely cured of their tumours, it is imperative that those treated with cisplatin receive the most appropriate nephroprotective strategy for reducing the negative impact of platinum compounds on quality of life.
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9.
Multikinase inhibitors in thyroid cancer: timing of targeted therapy.
Gild, ML, Tsang, VHM, Clifton-Bligh, RJ, Robinson, BG
Nature reviews. Endocrinology. 2021;(4):225-234
Abstract
In the 9 years since the publication of our 2011 review of targeted treatment of thyroid cancer with multikinase inhibitors, much has changed in the landscape of this heterogeneous disease. New multikinase and selective inhibitor treatments for medullary thyroid cancer, radioiodine-refractory thyroid cancer and anaplastic thyroid cancer have completed trials and improved progression-free survival. Many physicians are concerned by dose-limiting adverse effects of these drugs and are wary to begin treatment in patients who are systemically well but have marked disease burden, which makes the timing of treatment initiation challenging. Published mechanistic data on tyrosine kinase inhibitors (TKIs) have helped guide our understanding of how to dose effectively with these drugs. A major goal in TKI therapy is to optimize inhibition of oncogenic kinase drivers while maintaining patient quality of life. Real-world data have now been published on how TKIs have fared outside the clinical trial environment. In this Review, we provide a summary of published data on the efficacy of TKIs in clinical practice, to provide clinicians with a more realistic view of how their patients will manage and respond to TKI therapy. Furthermore, we review the data on mechanisms of inhibition, outcomes and adverse effects of TKIs and provide an update on targeted treatment of thyroid cancer, focusing on optimizing the timing of treatment initiation.
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10.
Strategies to Mitigate Chemotherapy and Radiation Toxicities That Affect Eating.
Anderson, PM, Thomas, SM, Sartoski, S, Scott, JG, Sobilo, K, Bewley, S, Salvador, LK, Salazar-Abshire, M
Nutrients. 2021;(12)
Abstract
BACKGROUND Cancer and its therapy is commonly associated with a variety of side effects that impact eating behaviors that reduce nutritional intake. This review will outline potential causes of chemotherapy and radiation damage as well as approaches for the amelioration of the side effects of cancer during therapy. METHODS Information for clinicians, patients, and their caregivers about toxicity mitigation including nausea reduction, damage to epithelial structures such as skin and mucosa, organ toxicity, and education is reviewed. RESULTS How to anticipate, reduce, and prevent some toxicities encountered during chemotherapy and radiation is detailed with the goal to improve eating behaviors. Strategies for health care professionals, caregivers, and patients to consider include (a) the reduction in nausea and vomiting, (b) decreasing damage to the mucosa, (c) avoiding a catabolic state and muscle wasting (sarcopenia), and (d) developing therapeutic alliances with patients, caregivers, and oncologists. CONCLUSIONS Although the reduction of side effects involves anticipatory guidance and proactive team effort (e.g., forward observation, electronic interactions, patient reported outcomes), toxicity reduction can be satisfying for not only the patient, but everyone involved in cancer care.