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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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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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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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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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The role of DNA damage response in chemo- and radio-resistance of cancer cells: Can DDR inhibitors sole the problem?
Sadoughi, F, Mirsafaei, L, Dana, PM, Hallajzadeh, J, Asemi, Z, Mansournia, MA, Montazer, M, Hosseinpour, M, Yousefi, B
DNA repair. 2021;:103074
Abstract
Up to now, many improvements have been made in providing more therapeutic strategies for cancer patients. The lack of susceptibility to common therapies like chemo- and radio-therapy is one of the reasons why we need more methods in the field of cancer therapy. DNA damage response (DDR) is a set of mechanisms which identifies DNA lesions and triggers the repair process for restoring DNA after causing an arrest in the cell cycle. The ability of DDR in maintaining the genome stability and integrity can be favorable to cancerous cells which are exposed to radiation therapy or are treated with chemotherapeutic agents. When DDR mechanisms are error-free in cancer cells, they can escape the expected cellular death and display resistance to treatment. In this regard, targeting different components of DDR can help to increase the susceptibility of advanced tumors to chemo- and radio-therapy.
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Platinum accumulation in oxaliplatin-induced peripheral neuropathy.
Wei, G, Gu, Z, Gu, J, Yu, J, Huang, X, Qin, F, Li, L, Ding, R, Huo, J
Journal of the peripheral nervous system : JPNS. 2021;(1):35-42
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Abstract
Oxaliplatin-induced peripheral neuropathy (OIPN) is a common and dose-limiting toxic effect that markedly limits the use of oxaliplatin and affects the quality of life. Although it is common, the underlying mechanisms of OIPN remain ambiguous. Recent studies have shown that the platinum accumulation in peripheral nervous system, especially in dorsal root ganglion, is a significant mechanism of OIPN. Several specific transporters, including organic cation transporters, high-affinity copper uptake protein1 (CTR1), ATPase copper transporting alpha (ATP7A) and multidrug and toxin extrusion protein 1 (MATE1), could be associated with this mechanism. This review summarizes the current research progress about the relationship between platinum accumulation and OIPN, as well as suggests trend for the future research.
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Beneficial Actions of Orostachys japonica and Its Compounds against Tumors via MAPK Signaling Pathways.
Hur, S, Jang, E, Lee, JH
Nutrients. 2021;(2)
Abstract
Tumors are one of the most life-threatening diseases, and a variety of cancer treatment options have been continuously introduced in order to overcome cancer and improve conventional therapy. Orostachys japonica (O. japonica), which is a perennial plant belonging to the genus Orostachys of the Crassulaceae family, has been revealed to exhibit pharmacological properties against various tumors in numerous studies. The present review aimed to discuss the biological actions and underlying molecular mechanisms of O. japonica and its representative compounds-kaempferol and quercetin-against tumors. O. japonica reportedly has antiproliferative, anti-angiogenic, and antimetastatic activities against various types of malignant tumors through the induction of apoptosis and cell cycle arrest, a blockade of downstream vascular endothelial growth factor (VEGF)-VEGFR2 pathways, and the regulation of epithelial-to-mesenchymal transition. In addition, emerging studies have highlighted the antitumor efficacy of kaempferol and quercetin. Interestingly, it was found that alterations of the mitogen-activated protein kinase (MAPK) signaling cascades are involved in the pivotal mechanisms of the antitumor effects of O. japonica and its two compounds against cancer cell overgrowth, angiogenesis, and metastasis. In summary, O. japonica could be considered a preventive and therapeutic medicinal plant which exhibits antitumor actions by reversing altered patterns of MAPK cascades, and kaempferol and quercetin might be potential components that can contribute to the efficacy and underlying mechanism of O. japonica.
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The Anticancer Effect of Natural Plant Alkaloid Isoquinolines.
Yun, D, Yoon, SY, Park, SJ, Park, YJ
International journal of molecular sciences. 2021;(4)
Abstract
Isoquinoline alkaloids-enriched herbal plants have been used as traditional folk medicine for their anti-inflammatory, antimicrobial, and analgesic effects. They induce cell cycle arrest, apoptosis, and autophagy, leading to cell death. While the molecular mechanisms of these effects are not fully understood, it has been suggested that binding to nucleic acids or proteins, enzyme inhibition, and epigenetic modulation by isoquinoline alkaloids may play a role in the effects. This review discusses recent evidence on the molecular mechanisms by which the isoquinoline alkaloids can be a therapeutic target of cancer treatment.
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Treatment for liver cancer: From sorafenib to natural products.
Man, S, Luo, C, Yan, M, Zhao, G, Ma, L, Gao, W
European journal of medicinal chemistry. 2021;:113690
Abstract
Liver cancer most commonly develops in patients with chronic liver disease, the etiology of which includes viral hepatitis (B and C), alcohol, obesity, dietary carcinogens, and so forth. The current treatment modalities, including surgical resection and liver transplantation, have been found far from effective. Hence, there is an obvious critical need to develop alternative strategies for the treatment of it. In this review, we discuss the formation process and therapeutic targets of liver cancer. Currently, targeted therapy is limited to sorafenib, lenvatinib, regorafenib, ramucirumab and cabozantinib which leads to a survival benefit in patients, but on the other hand is hampered by the occurrence of drug resistance. Pleasingly and importantly, there are multiple natural products undergoing clinical evaluation in liver cancer, such as polyphenols like icaritin, resveratrol, and silybin, saponins including ginsenoside Rg3 and glycyrrhizinate, alkaloid containing irinotecan and berberine and inorganic compound arsenic trioxide at present. Preclinical and clinical studies have shown that these compounds inhibit liver cancer formation owing to the influence on the anti-viral, anti-inflammation, anti-oxidant, anti-angiogenesis and anti-metastasis activity. Furthermore, a series of small molecule derivatives inspired by the aforementioned compounds are designed and synthesized according to structure-activity relationship studies. Drug combination and novel type of drug-targeted delivery system thereof have been well developed. This article is ended by a perspective remark of futuristic development of natural product-based therapeutic regimen for liver cancer treatment. We expect that this review is an account for current status of natural products as promising anti-liver cancer treatments and should contribute to its understanding.
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A Decade of Research on Coffee as an Anticarcinogenic Beverage.
Nigra, AD, Teodoro, AJ, Gil, GA
Oxidative medicine and cellular longevity. 2021;:4420479
Abstract
Coffee consumption has been investigated as a protective factor against cancer. Coffee is a complex beverage that contains more than 1000 described phytochemicals, which are responsible for its pleasant taste, aroma, and health-promoting properties. Many of these compounds have a potential therapeutic effect due to their antioxidant, anti-inflammatory, antifibrotic, and anticancer properties. The roasting process affects the phytochemical content, and undesirable compounds may be formed. In recent years, there have been contradictory publications regarding the effect of coffee drinking and cancer. Therefore, this study is aimed at evaluating the association of coffee consumption with the development of cancer. In PubMed, until July 2021, the terms "Coffee and cancer" resulted in about 2150 publications, and almost 50% of them have been published in the last 10 years. In general, studies published in recent years have shown negative associations between coffee consumption and the risk or development of different types of cancer, including breast, prostate, oral, oral and pharyngeal, melanoma, skin and skin nonmelanoma, kidney, gastric, colorectal, endometrial, liver, leukemic and hepatocellular carcinoma, brain, and thyroid cancer, among others. In contrast, only a few publications demonstrated a double association between coffee consumption and bladder, pancreatic, and lung cancer. In this review, we summarize the in vitro and in vivo studies that accumulate epidemiological evidence showing a consistent inverse association between coffee consumption and cancer.