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Radioiodine-refractory differentiated thyroid cancer: Molecular mechanisms and therapeutic strategies for radioiodine resistance.
Shen, H, Zhu, R, Liu, Y, Hong, Y, Ge, J, Xuan, J, Niu, W, Yu, X, Qin, JJ, Li, Q
Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy. 2024;:101013
Abstract
Radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) is difficult to treat with radioactive iodine because of the absence of the sodium iodide transporter in the basement membrane of thyroid follicular cells for iodine uptake. This is usually due to the mutation or rearrangement of genes and the aberrant activation of signal pathways, which result in abnormal expression of thyroid-specific genes, leading to resistance of differentiated thyroid cancer cells to radioiodine therapy. Therefore, inhibiting the proliferation and growth of RAIR-DTC with multikinase inhibitors and other drugs or restoring its differentiation and then carrying out radioiodine therapy have become the first-line treatment strategies and main research directions. The drugs that regulate these kinases or signaling pathways have been studied in clinical and preclinical settings. In this review, we summarized the major gene mutations, gene rearrangements and abnormal activation of signaling pathways that led to radioiodine resistance of RAIR-DTC, as well as the medicine that have been tested in clinical and preclinical trials.
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Targeting ferroptosis in gastric cancer: Strategies and opportunities.
Le, J, Pan, G, Zhang, C, Chen, Y, Tiwari, AK, Qin, JJ
Immunological reviews. 2024;(1):228-245
Abstract
Ferroptosis is a novel form of programmed cell death morphologically, genetically, and biochemically distinct from other cell death pathways and characterized by the accumulation of iron-dependent lipid peroxides and oxidative damage. It is now understood that ferroptosis plays an essential role in various biological processes, especially in the metabolism of iron, lipids, and amino acids. Gastric cancer (GC) is a prevalent malignant tumor worldwide with low early diagnosis rates and high metastasis rates, accounting for its relatively poor prognosis. Although chemotherapy is commonly used to treat GC, drug resistance often leads to poor therapeutic outcomes. In the last several years, extensive research on ferroptosis has highlighted its significant potential in GC therapy, providing a promising strategy to address drug resistance associated with standard cancer therapies. In this review, we offer an extensive summary of the key regulatory factors related to the mechanisms underlying ferroptosis. Various inducers and inhibitors specifically targeting ferroptosis are uncovered. Additionally, we explore the prospective applications and outcomes of these agents in the field of GC therapy, emphasizing their capacity to improve the outcomes of this patient population.
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Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes.
Zhu, L, She, ZG, Cheng, X, Qin, JJ, Zhang, XJ, Cai, J, Lei, F, Wang, H, Xie, J, Wang, W, et al
Cell metabolism. 2020;31(6):1068-1077.e3
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The novel coronavirus disease 2019 (COVID-19) is caused by infection from the newly emerged, highly contagious coronavirus SARS-CoV-2. The aim of this study was to analyse the association between plasma glucose levels and clinic outcomes in COVID-19 patients with type 2 diabetes (T2D). The study is a retrospective longitudinal, multi-centre study from a cohort of 7,337 COVID-19 cases enrolled among 19 hospitals. Results show that patients with pre-existing T2D received significantly more intensive integrated treatments to manage their symptoms of COVID-19 than the non-diabetic subjects. Furthermore, findings indicate that well-controlled blood glucose was associated with a markedly improved outcome of patients with COVID-19 and pre-existing T2D. Authors conclude that T2D is an important risk factor for COVID-19 progression and adverse endpoints, and well-controlled blood glucose is associated with a significant reduction in the composite adverse outcomes and death.
Abstract
Type 2 diabetes (T2D) is a major comorbidity of COVID-19. However, the impact of blood glucose (BG) control on the degree of required medical interventions and on mortality in patients with COVID-19 and T2D remains uncertain. Thus, we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. We found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio [HR], 1.49) and multiple organ injury than the non-diabetic individuals. Further, we found that well-controlled BG (glycemic variability within 3.9 to 10.0 mmol/L) was associated with markedly lower mortality compared to individuals with poorly controlled BG (upper limit of glycemic variability exceeding 10.0 mmol/L) (adjusted HR, 0.14) during hospitalization. These findings provide clinical evidence correlating improved glycemic control with better outcomes in patients with COVID-19 and pre-existing T2D.
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Integrated Bioinformatics Analysis Reveals Key Candidate Genes and Pathways Associated With Clinical Outcome in Hepatocellular Carcinoma.
Li, Y, Chen, R, Yang, J, Mo, S, Quek, K, Kok, CH, Cheng, XD, Tian, S, Zhang, W, Qin, JJ
Frontiers in genetics. 2020;:814
Abstract
Hepatocellular carcinoma (HCC) accounts for approximately 85-90% of all liver cancer cases and has poor relapse-free survival. There are many gene expression studies that have been performed to elucidate the genetic landscape and driver pathways leading to HCC. However, existing studies have been limited by the sample size and thus the pathogenesis of HCC is still unclear. In this study, we performed an integrated characterization using four independent datasets including 320 HCC samples and 270 normal liver tissues to identify the candidate genes and pathways in the progression of HCC. A total of 89 consistent differentially expression genes (DEGs) were identified. Gene-set enrichment analysis revealed that these genes were significantly enriched for cellular response to zinc ion in biological process group, collagen trimer in the cellular component group, extracellular matrix (ECM) structural constituent conferring tensile strength in the molecular function group, protein digestion and absorption, mineral absorption and ECM-receptor interaction. Network system biology based on the protein-protein interaction (PPI) network was also performed to identify the most connected and important genes based on our DEGs. The top five hub genes including osteopontin (SPP1), Collagen alpha-2(I) chain (COL1A2), Insulin-like growth factor I (IGF1), lipoprotein A (LPA), and Galectin-3 (LGALS3) were identified. Western blot and immunohistochemistry analysis were employed to verify the differential protein expression of hub genes in HCC patients. More importantly, we identified that these five hub genes were significantly associated with poor disease-free survival and overall survival. In summary, we have identified a potential clinical significance of these genes as prognostic biomarkers for HCC patients who would benefit from experimental approaches to obtain optimal outcome.
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Early oral feeding following thoracolaparoscopic oesophagectomy for oesophageal cancer.
Sun, HB, Liu, XB, Zhang, RX, Wang, ZF, Qin, JJ, Yan, M, Liu, BX, Wei, XF, Leng, CS, Zhu, JW, et al
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 2015;(2):227-33
Abstract
OBJECTIVES Nil-by-mouth with enteral tube feeding is widely practised for several days after resection and reconstruction of oesophageal cancer. This study investigates early changes in postoperative gastric emptying and the feasibility of early oral feeding after thoracolaparoscopic oesophagectomy for patients with oesophageal cancer. METHODS Between January 2013 and August 2013, gastric emptying of liquid food and the feasibility of early oral feeding after thoracolaparoscopic oesophagectomy was investigated in 68 patients. Sixty-five patients previously managed in the same unit who routinely took liquid food 7 days after thoracolaparoscopic oesophagectomy served as controls. RESULTS The mean preoperative half gastric emptying time (GET1/2) was 66.4 ± 38.4 min for all 68 patients, and the mean GET1/2 at postoperative day (POD) 1 and POD 7 was statistically significantly shorter than preoperative GET1/2 (23.9 ± 15.7 min and 24.1 ± 7.9 min, respectively, both P-values <0.001). Of the 68 patients who were enrolled to analyse the feasibility of early oral feeding, 2 (3.0%) patients could not take food as early as planned. The rate of total complication was 20.6% (14/68) and 29.2% (19/65) in the early oral feeding group and the late oral feeding group, respectively (P = 0.249). Compared with the late oral feeding group, time to first flatus and bowel movement was significantly shorter in the early oral feeding group. CONCLUSIONS Compared with preoperative gastric emptying, early postoperative gastric emptying for liquid food after oesophagectomy is significantly faster. Postoperative early oral feeding in patients with thoracolaparoscopic oesophagectomy is feasible and safe.
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Chemical constituents of plants from the genus Euonymus.
Zhu, JX, Qin, JJ, Chang, RJ, Zeng, Q, Cheng, XR, Zhang, F, Jin, HZ, Zhang, WD
Chemistry & biodiversity. 2012;(6):1055-76