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Serum Levels of Androgens, Estrogens, and Sex Hormone Binding Globulin and Risk of Primary Gastric Cancer in Chinese Men: A Nested Case-Control Study.
Zhu, Z, Chen, Y, Ren, J, Dawsey, SM, Yin, J, Freedman, ND, Fan, JH, Taylor, PR, Liu, Y, Qiao, YL, et al
Cancer prevention research (Philadelphia, Pa.). 2021;(6):659-666
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Abstract
Gastric cancer shows a strong male predominance, and sex steroid hormones have been hypothesized to explain this sex disparity. Previous studies examining the associations between sex hormones and sex hormone binding globulin (SHBG) and risk of gastric cancer come primarily from western populations and additional studies in diverse populations will help us better understand the association. We performed a nested case-control study in Linxian Nutrition Intervention Trials cohorts to evaluate the associations among Chinese men, where we had sufficient cases to perform a well-powered study. Using radioimmunoassays and immunoassays, we quantitated androgens, estrogens, and SHBG in baseline serum from 328 men that developed noncardia gastric cancer and matched controls. We used multivariable unconditional logistic regression to calculate ORs and 95% confidence intervals (CI) and explored interactions with body mass index (BMI), age, alcohol drinking, smoking, and follow-up time. Subjects with SHBG in the highest quartile, as compared with those in the lowest quartile, had a significantly increased risk of gastric cancer (OR = 1.87; 95% CI, 1.01-3.44). We found some evidence for associations of sex steroid hormones in men with lower BMI. Our study found a novel association suggesting that higher serum concentrations of SHBG may be associated with risk of gastric cancer in men. We found no overall associations with sex hormones themselves, but future studies should expand the scope of these studies to include women and further explore whether BMI modifies a potential association. PREVENTION RELEVANCE It was the first study to investigate the association of gastric cancer with prediagnostic sex steroid hormones and SHBG in an Asian male population. Although there were no overall associations for sex steroid hormone concentrations, higher concentrations of SHBG was associated with increased risk of noncardia gastric cancer.
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Exercise training and detraining effects on body composition, muscle strength and lipid, inflammatory and oxidative markers in breast cancer survivors under tamoxifen treatment.
de Jesus Leite, MAF, Mariano, IM, Dechichi, JGC, Giolo, JS, Gonçalves, ÁC, Puga, GM
Life sciences. 2021;:119924
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Abstract
AIMS: The present study aimed to verify the effects of resistance training (RT) and successive detraining on body composition, muscle strength and lipid profile as primary outcome, and the oxidative stress and inflammatory markers as second outcome of postmenopausal Breast Cancer (BC) survivors undergoing tamoxifen (TA). MAIN METHODS Fourteen postmenopausal BC survivors underwent 12 weeks of resistance exercise training and subsequently 12 weeks of detraining. Anthropometric parameters, lipid profile, muscle strength, inflammatory cytokines and the oxidative stress markers, were assessed before, after the training period and after detraining period. KEY FINDINGS One-way ANOVA showed that fat mass decrease (39.4 ± 6.9 to 37.7 ± 6.8%) and free-fat mass increase (39.3 ± 4.9 to 40.3 ± 5.6%) after RT. Muscle strength increased in response to training but decreased after the detraining period. Triglycerides (156 ± 45 to 123 ± 43 mg/dL) and total cholesterol (202 ± 13 to 186 ± 16 mg/dL) decreased after the RT and HDL-cholesterol (47 ± 9 to 56 ± 9 mg/dL) increased after RT and remained higher (53 ± 10 mg/dL) than after detraining. IL-6 increases (24.65 ± 10.85 to 41.42 ± 22.88 pg/mL) and IL-17 (2.42 ± 0.32 to 1.69 ± 0.19 pg/mL), TBARS (1.91 ± 0.19 to 1.03 ± 0.1 μmol/L), SOD (24.65 ± 10.85 to 41.42 ± 22.88 U/gHb) and Catalase activity (445.9 ± 113.0 to 345.8 ± 81.7 k/gHb·s) reduced after RT and remained lower after detraining. SIGNIFICANCE Resistance exercise training improves health markers of BC survivors undergoing TA and detraining are not sufficient to reverse the positive effects in oxidative stress markers.
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Blood biomarkers of bone metastasis in digestive tract malignant tumors.
Ma, X, Fan, Y, Chen, Z, Zhang, Y, Wang, S, Yu, J
Future oncology (London, England). 2021;(12):1507-1518
Abstract
Aim: To evaluate the role of clinical features and blood markers in patients with malignant digestive tract tumors bone metastasis. Materials & methods: A total of 267 patients were included in this trial. Age, gender, primary tumor site, metastatic sites, T/N stage, high-density lipoprotein, low-density lipoprotein, total cholesterol, triglycerides, alkaline phosphatase, LDH, Ca levels, platelet, neutrophils to absolute value of lymphocytes (NLR), ratio of platelets to absolute values of lymphocytes (PLR) were analyzed. Results: T stage, lymph node metastasis, N stage and liver and lung metastasis were independent risk factors. LDH + alkaline phosphatase + NLR + PLR and LDH + NLR, respectively have higher predictive value for bone metastasis compared with patients with early-stage malignant digestive tract tumor and patients with advanced malignant digestive tract tumor without bone metastasis. Conclusion: Some clinical features or blood markers have the potential to detect bone metastasis early to avoid skeletal complications.
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Prognostic value of aldo-keto reductase family 1 member B10 (AKR1B10) in digestive system cancers: A meta-analysis.
Liu, R, Zheng, S, Yang, CY, Yu, Y, Peng, S, Ge, Q, Lin, Q, Li, Q, Shi, W, Shao, Y
Medicine. 2021;(14):e25454
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Abstract
BACKGROUND Numbers of studies have reported that the expression of aldo-keto reductase family 1 member B10 (AKR1B10) is abnormal in digestive system cancers, and could be used as a prognostic biomarker. However, the results are argued. Therefore, we conduct a meta-analysis to comprehensively evaluate the prognostic value of high AKR1B10 expression for overall survival (OS), disease specific survival (DSS), and disease-free survival/recurrence-free survival (DFS/PFS) in digestive system cancers. METHODS Hazard ratios (HRs) with its 95% confidence intervals (CIs) were calculated to assess the prognostic value of AKR1B10 by using the random effects model. The STATA version 12.0 software were used to perform all the analyses. RESULTS Eleven articles including 1428 patients involved in this meta-analysis. The pooled analysis suggested that high AKR1B10 expression was not associated with OS (HR: 1.18; 95% CI: 0.69-2.00) and DFS/PFS (HR: 1.08, 95% CI: 0.67-1.76) in digestive system cancers. However, Further analysis revealed that high AKR1B10 expression indicated poor OS in oral squamous cell carcinomas (OSCC) (HR: 2.92, 95% CI: 1.86-4.58) and favorable DSS in hepatocellular carcinoma (HCC) (HR: 0.71, 95% CI: 0.52-0.97). CONCLUSIONS The prognostic value of high AKR1B10 expression varied in different types of digestive system cancers. Further studies exploring the prognostic role of AKR1B10 in digestive system cancers are needed.
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Inflammation-Related Biomarkers for the Prediction of Prognosis in Colorectal Cancer Patients.
Yamamoto, T, Kawada, K, Obama, K
International journal of molecular sciences. 2021;(15)
Abstract
Colorectal cancer (CRC) is the leading cause of cancer deaths around the world. It is necessary to identify patients with poor prognosis or with high risk for recurrence so that we can selectively perform intensive treatments such as preoperative and/or postoperative chemotherapy and extended surgery. The clinical usefulness of inflammation-related prognostic biomarkers available from routine blood examination has been reported in many types of cancer, e.g., neutrophil-lymphocyte ratio (NLR), lymphocyte-C-reactive protein ratio (LCR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and so on. Moreover, some scoring systems based on circulating blood cell counts and albumin concentration have been also reported to predict cancer patients' prognosis, such as the Glasgow prognostic score (GPS), systemic inflammation score (SIS), and prognostic nutritional index (PNI). The optimal biomarker and optimal cutoff value of the markers can be different depending on the cancer type. In this review, we summarize the prognostic impact of each inflammation-related marker in CRC.
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Urinary Angiogenin as a Marker for Bladder Cancer: A Meta-Analysis.
Aalami, AH, Abdeahad, H, Mesgari, M, Sathyapalan, T, Sahebkar, A
BioMed research international. 2021;:5557309
Abstract
AIMS: Bladder cancer (BCa) is a common cancer in North America and Europe that carries considerable morbidity and mortality. A reliable biomarker for early detection of the bladder is crucial for improving the prognosis of BCA. In this meta-analysis, we examine the diagnostic role of the angiogenin (ANG) protein in patients' urine with bladder neoplasm. METHODS We performed a systematic literature search using ScienceDirect, Web of Science, PubMed/MEDLINE, Scopus, Google Scholar, and Embase, up to 10th October 2020 databases. Meta-Disc V.1.4 and Comprehensive Meta-Analysis V.2.2 software calculated the pooled specificity, sensitivity, area under the curve (AUC), diagnostic odds ratio (DOR), positive likelihood ratio (LR+), negative likelihood ratio (LR-), Q ∗ index, and summary receiver-operating characteristic (SROC) for the role of ANG as a urinary biomarker for BCa patients. RESULTS Four case-control studies were included with 656 participants (417 cases and 239 controls) in this meta-analysis. The pooled sensitivity of 0.71 (95% CI: 0.66-0.75), specificity of 0.78 (95% CI: 0.73-0.81), LR+ of 3.34 (95% CI: 2.02-5.53), LR- of 0.37 (95% CI: 0.32-0.44), DOR of 9.99 (95% CI: 4.69-21.28), and AUC of 0.789 and Q ∗ index of 0.726 demonstrate acceptable diagnostic precision of ANG in identifying BCa. CONCLUSION This meta-analysis showed that ANG could be a fair biomarker for the diagnosis of BCa patients.
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An Exploratory Phase II Study of Eribulin Re-challenge After Short Term Therapy of 5-Fluorouracil for HER2 Negative, Advanced or Recurrent Breast Cancer.
Takashima, T, Nishimura, S, Kawajiri, H, Mizuyama, Y, Nishimori, T, Yamagata, S, Tokunaga, S, Tezuka, K, Tei, S, Sunami, T, et al
Anticancer research. 2021;(10):5007-5014
Abstract
BACKGROUND/AIM: In our previous study, first-line eribulin (ERI) showed 25 weeks of progression-free survival (PFS). This study investigated the efficacy and safety of ERI re-administration in metastatic breast cancer (MBC) patients. PATIENTS AND METHODS HER2-negative MBC patients who had never received chemotherapy for MBC received first-line ERI for 18 weeks if they did not have disease progression, and then one cycle of S-1 before ERI re-administration. RESULTS Twelve patients received ERI re-administration. The PFS of re-administered ERI was 13 weeks. Total duration of ERI use was 30 weeks. The incidence and severity of adverse events were consistent with previous reports. CONCLUSION In the first-line setting, the total PFS of eribulin was extended by S-1 administration before disease progression, compared with that of our previous report.
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Calcitonin Stimulation Tests: Rationale, Technical Issues and Side Effects: A Review.
Băetu, M, Olariu, CA, Moldoveanu, G, Corneci, C, Badiu, C
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2021;(6):355-363
Abstract
Calcitonin (CT) stimulation tests have great value and could help to: differentiate thyroid causes of elevated CT apart from non-thyroid sources, determine whether the patients with slightly elevated basal CT could/could not be candidates for surgery, and indicate the right moment for prophylactic thyroidectomy in children with MEN syndromes when with normal basal CT. This triggered the requests for development of CT stimulation tests, taking into consideration their safety and aimed us to write a systematic review of literature regarding the rationale, technical issues, and side effects of CT stimulating tests used for diagnosis of MTC. After a thorough review of the literature, we classified the reported side effects by severity, as defined by United States Food and Drug Administration. A statistical analysis was performed using IBM SPSS Statistics version 20. Various side effects were noticed during stimulation tests that differ by intensity, duration and severity, depending on types of substances and protocols used. The side effects after pentagastrin test were significantly more severe than those reported after calcium stimulation test (p=0.0396). There are also significant gender-specific differences in side effects induced by stimulation tests. In conclusion, we recommend performing Ca CT stimulation test when needed, considering preventive evaluation of some clinical, instrumental, and biochemical aspects of each patient. Precise instructions should be followed before a stimulation test and furthermore continuous cardiac monitoring is essential during and after the test to minimize the possibility of a serious event.
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Orphan nuclear receptors as regulators of intratumoral androgen biosynthesis in castration-resistant prostate cancer.
Zhou, J, Wang, Y, Wu, D, Wang, S, Chen, Z, Xiang, S, Chan, FL
Oncogene. 2021;(15):2625-2634
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Abstract
Castration-resistant prostate cancer (CRPC) almost invariably occurs after androgen-deprivation therapy (ADT) for the advanced metastatic disease. It is generally believed that among multiple mechanisms and signaling pathways, CRPC is significantly driven by the reactivation of androgen receptor (AR) signaling in ADT-treated patients with castrate levels of androgen, partially at least mediated by the androgen biosynthesis within the tumor, also known as intratumoral or intraprostatic androgen biosynthesis. Steroidogenic enzymes, such as CYP11A1, CYP17A1, HSD3B1, AKR1C3 and SRD5A, are essential to catalyze the conversion of the initial substrate cholesterol into potent androgens that confers the CRPC progression. Accumulating evidences indicate that many steroidogenic enzymes are upregulated in the progression setting; however, little is known about the dysregulation of these enzymes in CRPC. Orphan nuclear receptors (ONRs) are members of the nuclear receptor superfamily, of which endogenous physiological ligands are unknown and which are constitutively active independent of any physiological ligands. Studies have validated that besides AR, ONRs could be the potential therapeutic targets for prostate cancer, particularly the lethal CRPC progression. Early studies reveal that ONRs play crucial roles in the transcriptional regulation of steroidogenic enzyme genes. Notably, we and others show that three distinct ONRs, including liver receptor homolog-1 (LRH-1, NR5A2), steroidogenic factor 1 (SF-1, AD4BP, NR5A1) and estrogen-related receptor α (ERRα, NR3B1), can contribute to the CRPC progression by promotion of the intratumoral androgen synthesis via their direct transcriptional regulation on multiple steroidogenic enzymes. This review presents an overview of the current understanding on the intratumoral androgen biosynthesis in CRPC, with a special focus on the emerging roles of ONRs in this process.
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Identifying Novel Susceptibility Genes for Colorectal Cancer Risk From a Transcriptome-Wide Association Study of 125,478 Subjects.
Guo, X, Lin, W, Wen, W, Huyghe, J, Bien, S, Cai, Q, Harrison, T, Chen, Z, Qu, C, Bao, J, et al
Gastroenterology. 2021;(4):1164-1178.e6
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Abstract
BACKGROUND AND AIMS Susceptibility genes and the underlying mechanisms for the majority of risk loci identified by genome-wide association studies (GWAS) for colorectal cancer (CRC) risk remain largely unknown. We conducted a transcriptome-wide association study (TWAS) to identify putative susceptibility genes. METHODS Gene-expression prediction models were built using transcriptome and genetic data from the 284 normal transverse colon tissues of European descendants from the Genotype-Tissue Expression (GTEx), and model performance was evaluated using data from The Cancer Genome Atlas (n = 355). We applied the gene-expression prediction models and GWAS data to evaluate associations of genetically predicted gene-expression with CRC risk in 58,131 CRC cases and 67,347 controls of European ancestry. Dual-luciferase reporter assays and knockdown experiments in CRC cells and tumor xenografts were conducted. RESULTS We identified 25 genes associated with CRC risk at a Bonferroni-corrected threshold of P < 9.1 × 10-6, including genes in 4 novel loci, PYGL (14q22.1), RPL28 (19q13.42), CAPN12 (19q13.2), MYH7B (20q11.22), and MAP1L3CA (20q11.22). In 9 known GWAS-identified loci, we uncovered 9 genes that have not been reported previously, whereas 4 genes remained statistically significant after adjusting for the lead risk variant of the locus. Through colocalization analysis in GWAS loci, we additionally identified 12 putative susceptibility genes that were supported by TWAS analysis at P < .01. We showed that risk allele of the lead risk variant rs1741640 affected the promoter activity of CABLES2. Knockdown experiments confirmed that CABLES2 plays a vital role in colorectal carcinogenesis. CONCLUSIONS Our study reveals new putative susceptibility genes and provides new insight into the biological mechanisms underlying CRC development.