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1.
Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations.
Zhu, H, Bi, D, Zhang, Y, Kong, C, Du, J, Wu, X, Wei, Q, Qin, H
Signal transduction and targeted therapy. 2022;(1):11
Abstract
The ketogenic diet (KD) is a high-fat, adequate-protein, and very-low-carbohydrate diet regimen that mimics the metabolism of the fasting state to induce the production of ketone bodies. The KD has long been established as a remarkably successful dietary approach for the treatment of intractable epilepsy and has increasingly garnered research attention rapidly in the past decade, subject to emerging evidence of the promising therapeutic potential of the KD for various diseases, besides epilepsy, from obesity to malignancies. In this review, we summarize the experimental and/or clinical evidence of the efficacy and safety of the KD in different diseases, and discuss the possible mechanisms of action based on recent advances in understanding the influence of the KD at the cellular and molecular levels. We emphasize that the KD may function through multiple mechanisms, which remain to be further elucidated. The challenges and future directions for the clinical implementation of the KD in the treatment of a spectrum of diseases have been discussed. We suggest that, with encouraging evidence of therapeutic effects and increasing insights into the mechanisms of action, randomized controlled trials should be conducted to elucidate a foundation for the clinical use of the KD.
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2.
Dosimetry study of three-dimensional print template for 125I implantation therapy.
Chen, E, Zhang, Y, Zhang, H, Jia, C, Liang, Y, Wang, J
Radiation oncology (London, England). 2021;(1):115
Abstract
BACKGROUND 125I seed implantation has been found to show good therapeutic effects on tumors. Recent studies showed that three-dimensional (3D) print template-assisted 125I seed implantation can optimize radiation dose distribution. This study aimed to compare the dose distribution differences in 125I seed implantation among 3D print noncoplanar template- (3DPNCT), 3D print coplanar template- (3DPCT) assisted implantation and traditional free-hand implantation. METHODS We systematically searched the PubMed, EMbase, Cochrane Library, Wan Fang Med Online, China National Knowledge Infrastructure (CNKI) from the earliest to November 2020 without time or language restrictions. And the references of primary literature were also searched. The outcome measures were dosimetry and operation time. This meta-analysis was carried out using Stata 12.0. RESULTS A total of 16 original articles were selected for inclusion. The differences of D90, D100, V90, and V100 values pre- and post-implantation with traditional free-hand implantation showed statistically significant (p < 0.05). The differences of D90, D100, V100, V150, V200, and D2cc of organs at risk (OAR) values pre- and post-implantation with 3D print template showed no statistically significant (p > 0.05). Compared with traditional free-hand implantation without any templates, 3D print template could improve postoperative D90 (Standard mean difference, SMD = 0.67, 95% confidence interval (CI) = 0.35 to 0.98, p < 0.001), D100 (SMD = 0.82, 95%CI = 0.40 to 1.23, p < 0.001), V90 (SMD = 1.48, 95%CI = 0.95 to 2.00, p < 0.001), V100 (SMD = 1.41, 95%CI = 0.96 to 1.86, p < 0.001), and reduce operation time (SMD = - 0.93, 95%CI = - 1.34 to - 0.51, p < 0.001). In three studies, both 3DPNCT and 3DPCT plans were designed for all patients. The prescribed dose and seed activity were same. Pooled analysis of D90, D100, V100, D2cc of OAR, number of seeds and number of needles showed no significant differences between 3DPNCT and 3DPCT groups (p > 0.05). However, in 3DPNCT group, V150 and V200 were increased (SMD = 0.35, 0.49; 95%CI = 0.04 to 0.67, 0.02 to 0.96; p = 0.028, 0.043); the number of through bone needles was reduced (SMD = - 1.03, 95%CI = - 1.43 to - 0.64, p < 0.001). CONCLUSIONS Compared with traditional free-hand implantation, 3D print template-assisted 125I seeds implantation can optimize dose distribution and reduce the implantation time at the same time. Compared with 3D print coplanar template, 3D print noncoplanar template can increase the volume of high dose within tumor target and is more safer in the respect of puncture route.
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3.
The RNA m6A writer METTL14 in cancers: Roles, structures, and applications.
Zhou, H, Yin, K, Zhang, Y, Tian, J, Wang, S
Biochimica et biophysica acta. Reviews on cancer. 2021;(2):188609
Abstract
N6-methyladenosine (m6A) is the most abundant and diverse epigenetic modification of mRNAs in eukaryotes, and it regulates biological metabolism, cell differentiation and cycles, and responses to heat shock stress, cancers and other diseases. RNA methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14) and other proteins possessing methyltransferase (MTase) capability including Wilms tumor 1-associated protein (WTAP), RNA-binding motif protein 15(RBM15), KIAA1429 and zinc finger CCCH-type containing 13 (ZC3H13) constitute the m6A writer complex. Although METTL3 is the catalytic subunit, its activity is strongly dependent on METTL14, which is crucial in maintaining complex integrity and recognizing special RNA substrates. Currently, the roles of m6A modification in cancers are being extensively reviewed. The critical functions of METTL14 in the occurrence and development of a variety of cancers as well as the potential targeting of METTL14 as a cancer treatment have not yet been highlighted. Therefore, in this review, we summarize the m6A modification and focus on the structure and functions of METTL14 as well as its roles in oncogenesis, metastasis progression, treatment and prognosis in cancer.
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4.
The Molecular Mechanisms of Regulating Oxidative Stress-Induced Ferroptosis and Therapeutic Strategy in Tumors.
Zhu, J, Xiong, Y, Zhang, Y, Wen, J, Cai, N, Cheng, K, Liang, H, Zhang, W
Oxidative medicine and cellular longevity. 2020;:8810785
Abstract
Ferroptosis is an atypical form of regulated cell death, which is different from apoptosis, necrosis, pyroptosis, and autophagy. Ferroptosis is characterized by iron-dependent oxidative destruction of cellular membranes following the antioxidant system's failure. The sensitivity of ferroptosis is tightly regulated by a series of biological processes, the metabolism of iron, amino acids, and polyunsaturated fatty acids, and the interaction of glutathione (GSH), NADPH, coenzyme Q10 (CoQ10), and phospholipids. Elevated oxidative stress (ROS) level is a hallmark of cancer, and ferroptosis serves as a link between nutrition metabolism and redox biology. Targeting ferroptosis may be an effective and selective way for cancer therapy. The underlying molecular mechanism of ferroptosis occurrence is still not enough. This review will briefly summarize the process of ferroptosis and introduce critical molecules in the ferroptotic cascade. Furthermore, we reviewed the occurrence and regulation of reduction-oxidation (redox) for ferroptosis in cancer metabolism. The role of the tumor suppressor and the epigenetic regulator in tumor cell ferroptosis will also be described. Finally, old drugs that can be repurposed to induce ferroptosis will be characterized, aiming for drug repurposing and novel drug combinations for cancer therapy more efficiently and economically.
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5.
Prognostic value of LAT-1 status in solid cancer: A systematic review and meta-analysis.
Lu, JJ, Li, P, Yang, Y, Wang, L, Zhang, Y, Zhu, JY, Zhu, XR, Chen, MB
PloS one. 2020;(5):e0233629
Abstract
BACKGROUND The expression of the L-type amino acid transporter 1 (LAT1) plays a significant role in tumor progression. However, it remains unclear whether high LAT1 expression correlates with poor prognosis of solid tumor patients. Here, we conducted a meta-analysis to assess the potential of LAT1 in predicting the prognosis of tumor patients. METHODS AND FINDINGS A total of 4,579 cases were analyzed from 35 qualified studies. In patients with solid tumors, elevated expression of LAT1 is associated with poor prognosis (overall survival [OS]: pooled hazard ratio (HR) = 1.848, 95% confidence interval (CI) = 1.620-2.108, P < 0.001; disease free survival [DFS]: pooled HR = 1.923, 95% CI = 1.585-2.333, P < 0.001; progression free survival [PFS]: pooled HR = 1.345, 95% CI = 1.133-1.597, P = 0.001). Furthermore, in subgroup analysis, we found an association between high LAT1 expression and poor OS in non-small cell lung cancer (HR = 1.554, 95% CI = 1.345-1.794, P < 0.001), pancreatic cancer (HR = 2.052, 95% CI = 1.613-2.724, P < 0.001) and biliary tract cancer (HR = 2.253, 95% CI = 1.562-3.227, P < 0.001). CONCLUSION The results of this meta-analysis indicate the reliability and potential of using LAT1 expression as a predictive biomarker in solid cancers prior to treatment. However, further studies with larger sample sizes would be beneficial for fully evaluating the predictive value of LAT1 expression for clinical applications.
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6.
Research Progress on Chemical Constituents and Anticancer Pharmacological Activities of Euphorbia lunulata Bunge.
Wang, Y, Yu, X, Wang, L, Zhang, F, Zhang, Y
BioMed research international. 2020;:3618941
Abstract
Euphorbia lunulata Bunge (ELB) is a traditional Chinese medicine possessing the functions of expectoration, cough relief, asthma relief, detoxification, and itching relief. Modern pharmacological studies have showed that ELB exhibits a variety of activities, such as antitumor, antibacterial, and antioxidant activities. In particular, the anticancer activities of ELB have attracted much attention. In this review, we summarize the recent research progress on the chemical constituents and anticancer activities of ELB by searching the PubMed, Web of Science, and China National Knowledge Infrastructure databases. The results show that more than 151 components have been identified from extracts of ELB, including 73 terpenoids, 28 flavonoids, 8 phenylpropanoids, 7 steroids, 19 phenols, and 5 alkaloids. ELB has been shown to exhibit significant inhibitory effects on lung, cervical, gastric, breast, and liver cancers, and its anticancer effects are mainly manifested in the 3 aspects, including cell cycle arrest, cell apoptosis, and inhibition of the migration of cancer cells.
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7.
Phytochemicals of garlic: Promising candidates for cancer therapy.
Zhang, Y, Liu, X, Ruan, J, Zhuang, X, Zhang, X, Li, Z
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2020;:109730
Abstract
Of the numerous health benefits of garlic, the anticancer effect is probably the most noticeable. Observations over the past years have shown that the consumption of garlic in the diet provides strong protection against cancer risk. Previous studies involving garlic phytochemicals have usually focused on the cancer chemopreventive properties, but there is little published evidence showing its therapeutic potential in cancer treatment. In view of the multitargeted carcinoma actions and lack of severe toxicity, some components of garlic are likely to play vital roles in the selective killing of cancer cells. However, the rational design of experimental studies and clinical trials are required to verify this concept. This paper discusses the promises and pitfalls of garlic for the treatment of cancer.
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8.
Reduction of Red and Processed Meat Intake and Cancer Mortality and Incidence: A Systematic Review and Meta-analysis of Cohort Studies.
Han, MA, Zeraatkar, D, Guyatt, GH, Vernooij, RWM, El Dib, R, Zhang, Y, Algarni, A, Leung, G, Storman, D, Valli, C, et al
Annals of internal medicine. 2019;(10):711-720
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Abstract
UNLABELLED This article has been corrected. The original version (PDF) is appended to this article as a Supplement. BACKGROUND Cancer incidence has continuously increased over the past few centuries and represents a major health burden worldwide. PURPOSE To evaluate the possible causal relationship between intake of red and processed meat and cancer mortality and incidence. DATA SOURCES Embase, Cochrane Central Register of Controlled Trials, Web of Science, CINAHL, and ProQuest from inception until July 2018 and MEDLINE from inception until April 2019 without language restrictions. STUDY SELECTION Cohort studies that included more than 1000 adults and reported the association between consumption of unprocessed red and processed meat and cancer mortality and incidence. DATA EXTRACTION Teams of 2 reviewers independently extracted data and assessed risk of bias; 1 reviewer evaluated the certainty of evidence, which was confirmed or revised by the senior reviewer. DATA SYNTHESIS Of 118 articles (56 cohorts) with more than 6 million participants, 73 articles were eligible for the dose-response meta-analyses, 30 addressed cancer mortality, and 80 reported cancer incidence. Low-certainty evidence suggested that an intake reduction of 3 servings of unprocessed meat per week was associated with a very small reduction in overall cancer mortality over a lifetime. Evidence of low to very low certainty suggested that each intake reduction of 3 servings of processed meat per week was associated with very small decreases in overall cancer mortality over a lifetime; prostate cancer mortality; and incidence of esophageal, colorectal, and breast cancer. LIMITATION Limited causal inferences due to residual confounding in observational studies, risk of bias due to limitations in diet assessment and adjustment for confounders, recall bias in dietary assessment, and insufficient data for planned subgroup analyses. CONCLUSION The possible absolute effects of red and processed meat consumption on cancer mortality and incidence are very small, and the certainty of evidence is low to very low. PRIMARY FUNDING SOURCE None. (PROSPERO CRD42017074074).
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Regulation of H2A ubiquitination and SLC7A11 expression by BAP1 and PRC1.
Zhang, Y, Koppula, P, Gan, B
Cell cycle (Georgetown, Tex.). 2019;(8):773-783
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Abstract
SLC7A11 (or xCT) imports extracellular cystine into cells to promote glutathione synthesis, thus inhibiting ferroptosis. SLC7A11 expression is tightly controlled in normal cells and its dysregulation results in aberrant expression of SLC7A11 in human cancers. We recently discovered that tumor suppressor BAP1, a H2A deubiquitinase, represses SLC7A11 expression by reducing H2A ubiquitination (H2Aub) on the SLC7A11 promoter. BAP1 inactivation in cancer cells leads to SLC7A11 de-repression, ferroptosis resistance, and tumor development. Here we show that BAP1 promotes ferroptosis induced by class I ferroptosis inducer (FIN) erastin but not by class II FIN RSL3, further supporting that BAP1 regulates ferroptosis through SLC7A11. In addition, we studied how BAP1 coordinates with other transcription factors to regulate SLC7A11 expression and show that BAP1-mediated SLC7A11 repression does not require NRF2 and ATF4 transcription factors. Finally, we show that, while BAP1 decreases whereas PRC1 (a major H2Aub ubiquitin ligase) increases H2Aub binding on the SLC7A11 promoter, both BAP1 and PRC1 represses SLC7A11 expression, suggesting that a dynamic regulation of H2Aub is important for SLC7A11 repression. Together, our data provide additional insights on epigenetic regulation of SLC7A11 expression in cancer cells.
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Mushroom polysaccharide lentinan for treating different types of cancers: A review of 12 years clinical studies in China.
Zhang, M, Zhang, Y, Zhang, L, Tian, Q
Progress in molecular biology and translational science. 2019;:297-328
Abstract
Lentinula edodes has been used to improve general health for thousands of years in Asia. It is the second largest cultivated and the most popular edible mushroom in the world known as "Xianggu" in China and "Shiitake" in Japan. Lentinan is a polysaccharide extracted from Lentinula edodes. β-Glucan is the major bioactive component in lentinan with immunostimulatory effect. The antitumor property of lentinan was reported in 1960s. Biochemical studies indicate that immunocytes can be activated by lentinan through multiple signaling pathways, such as TLR4/Dectin1-MAPK and Syk-PKC-NFκB pathways. Though it has been approved as an adjuvant therapeutic drug both in China and Japan for treating cancers since 1980s, a systematic review of clinical studies of lentinan has not been conducted elaborately. In this review, over 9474 reported lentinan-associated cancer treatment cases are evaluated and summarized from 135 independent studies in China during the past 12 years (2004-2016) based on CNKI (China National Knowledge Infrastructure), VIP (Chongqing VIP Chinese Scientific Journals Database) and Wanfang database. The 9474 reported lentinan-associated cancer treatment cases include lung cancer (3469 cases), gastric cancer (3039 cases), colorectal cancer (1646 cases), ovarian cancer (183 cases), cervical cancer (130 cases), Non-Hodgkin lymphoma (70 cases), pancreatic cancer (15 cases), cardiac cancer (15 cases), nasopharyngeal cancer (14 cases), duodenal cancer (1 case) and 110 cancer cases with no classifying patient information. Overall clinical data show solid effect of lentinan on improving the quality of life and on promoting the efficacy of chemotherapy and radiation therapy during cancer treatment.