Background
Thyroid cancer (TC) is one of the most commonly seen secondary malignancy in breast cancer (BC) survivors.
Materials and methods
A retrospective study was conducted in BC patients in our ...center from 1999 to 2013. Patients were divided into BC‐TC group and BC‐alone group.
Results
In total, 13 978 BC patients were identified, among whom 247 (1.8%) had TC. The standardized incidence ratio (SIR) of TC was 4.48 compared with Chinese females, and up to 98.0% of cases were thyroid papillary carcinomas. A family history of malignancy was the only independent risk factor (odds ratio = 1.457, P = 0.025) for development of TC in patients with BC. We also identified inferior survival in patients with synchronous versus metachronous BC‐TC (P = 0.016). Synchronous BC‐TC (risk ratio = 5.597, P = 0.018) was an independent prognostic factor for inferior RFS.
Conclusions
We observed high co‐occurrence of TC in patients with BC. There might be different mechanisms behind synchronous and metachronous BC‐TC.
In the current study, we investigated the association of thyroid cancer incidence in a cohort of 13 978 breast cancer patients. We identified that the standardized incidence ratio of secondary thyroid cancer was significantly increased and a family history of malignancy was the only independent risk factor, which provided a new insight into the association of breast cancer and thyroid cancer.
Abstract
NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluate the safety and ...immunogenicity of NVSI-06-08 as a heterologous booster dose in BBIBP-CorV recipients in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who have administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, are randomized 1:1 to receive either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The incidence of adverse reactions is low, and the overall safety profile is quite similar between two booster regimens. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster are significantly higher than those by BBIBP-CorV booster against not only SARS-CoV-2 prototype strain but also multiple variants of concerns (VOCs). Especially, the neutralizing antibody GMT against Omicron variant induced by heterologous NVSI-06-08 booster reaches 367.67, which is substantially greater than that boosted by BBIBP-CorV (GMT: 45.03). In summary, NVSI-06-08 is safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which is immunogenically superior to the homologous boost with another dose of BBIBP-CorV.
The benefit of adjuvant trastuzumab in disease-free and overall survival for human epidermal receptor 2-positive (HER2+) breast cancer patients is well established. However, the effect of trastuzumab ...on locoregional control remains unclear, particularly in patients treated with adjuvant radiotherapy (RT). In this study, we investigated the locoregional benefit of trastuzumab in patients with HER2+ breast cancer after adjuvant RT.Using a single institutional database, we identified 278 patients with stage II/III invasive HER2+ breast tumors receiving adjuvant RT between January 2008 and July 2011. We compared the locoregional outcomes of 134 patients who received trastuzumab to 144 patients without trastuzumab within the same period. Clinical and biological factors that might impact on the locoregional benefit of trastuzumab were also assessed.At the median follow-up of 45 months, trastuzumab significantly lowered the risk of locoregional recurrence (LRR) with a 3-year LRR rate of 2.4% versus 7.5% for the cohort with and without trastuzumab (P = 0.019). Trastuzumab was associated with a more significant locoregional benefit in the hormone receptor-positive (HR+)/HER2+ subgroup, with a 3-year LRR of 0% versus 6.7% in the cohort with and without trastuzumab (P = 0.027). For HR-/HER2+ breast tumor patients, the 3-year LRR rate was still lower for the cohort with trastuzumab (4.7% vs 8.6%). However, statistical significance was not found (P = 0.179). Both univariate and multivariate analyses confirmed that trastuzumab treatment was the only significant predictive factor for LRR (hazard ratio, 4.05; 95% confidence interval, 1.07-15.35; P = 0.039).Adjuvant trastuzumab in addition to RT is associated with significant reduced LRR risk in HER2+ breast cancer.
Background and Objective
Congestive heart failure (CHF) risk with bevacizumab in breast cancer has been previously investigated in a meta-analysis, but its incidence and the risk of CHF in other ...tumor types remain unclear. Thus, we performed this meta-analysis to gather current data and evaluate the risk of CHF with bevacizumab in cancer patients, with a focus on different subgroups.
Methods
The databases of PubMed and abstracts presented at the American Society of Clinical Oncology up to 31 December 2013 were searched for relevant articles. Statistical analyses were conducted to calculate the summary incidence, relative risk (RR), and 95 % confidence intervals (CIs) by using either random-effects or fixed-effect models according to the heterogeneity of included studies.
Results
A total of 16,962 patients from 19 RCTs were included. The use of bevacizumab significantly increased the risk of developing high-grade CHF in cancer patients (RR 1.98, 95 % CI 1.30–3.02,
p
= 0.002), but not for all-grade CHF (RR 1.14, 95 % CI 0.87–1.49,
p
= 0.33). Risk might vary with bevacizumab dose and tumor types. RRs for patients receiving bevacizumab at 5 and 2.5 mg/kg/week were 2.25 (95 % CI 1.43–3.56) and 1.00 (95 % CI 0.33–3.05), respectively. High risks were observed in patients with breast cancer (RR 2.43, 95 % CI 1.48–3.98), renal cell cancer (RR 3.66, 95 % CI 0.41–33.01), and glioblastoma (RR 4.90, 95 % CI 0.24–102.39). Additionally, bevacizumab in combination with taxanes significantly increased the risk of high-grade CHF (RR 2.15, 95 % CI 1.09–4.25,
p
= 0.027).
Conclusions
Bevacizumab treatment significantly increases the risk of developing high-grade CHF in cancer patients. The risk may vary with bevacizumab dose and tumor types. Clinicians should be aware of the risks of CHF with the administration of this drug in cancer patients.
Ankylosing spondylitis (AS) is a chronic and progressive autoimmune disease affecting the invasion of the spine, sacroiliac joints and peripheral joints. T cells play a vital role in the underlying ...pathogenesis of AS, which mediated autoimmune and inflammatory responses via specific recognition of autoantigen peptides presented by susceptibility HLA. Antigen-specific T cells triggered by HLA/antigen complexes will undergo a massive expansion that forming an uneven T cell repertoire. To enhance our understanding of T-cell-mediated autoimmune in AS, we applied TCR β chains high-throughput sequencing to AS patients for in-depth TCR repertoire analysis. A significantly lower TCR repertoire diversity was observed in peripheral blood of AS patients relative to controls. And severe patients in our AS cohort have a more restricted TCR repertoire than mild patients, suggesting that the TCR repertoire diversity might be associated with the clinical severity of disease. No V, J and VJ pairs with significant biased usage were identified, which indicated that the usage frequency deviation of certain V/J/V-J genes in AS patients is little. This is a pilot study with potentially interesting observation on reduced diversity of T cells repertoire in peripheral blood of AS patients and further studies are needed.
To evaluate the effect of short-term intensive insulin therapy on circulating T cell subpopulations in patients with newly diagnosed type 2 diabetes mellitus (T2DM).
A total of 113 patients with T2DM ...and 28 normal subjects were enrolled. Demographic parameters and biochemical markers were collected at baseline, and flow cytometry was applied to determine the proportion of T cell subpopulations in participants. Then the patients underwent continuous subcutaneous insulin injection (CSII) treatment with euglycemia for 2 weeks, and the T cell subpopulations were measured again after CSII treatment.
Compared with normal subjects, the proportion of Th1 cells and the ratio of Th1/Th2 increased, the proportion of Treg cells decreased in patients with T2DM (p < 0.05 for all). The ratio of Th1/Th2 was positively correlated with glycosylated hemoglobin A1c (HbA1c) and negatively correlated with high density lipoprotein cholesterol (HDL-C). Furthermore, there were negative associations between the proportion of Treg cells and fasting plasma glucose, HbA1c, triglyceride, low density lipoprotein cholesterol, and positive association between the proportion of Treg cells and HDL-C. After CSII treatment, the proportion of Th1 cells and the ratio of Th1/Th2 decreased (p < 0.05 for both), the proportion of Treg cells increased in patients with T2DM (p < 0.05).
Short-term intensive insulin therapy could modulate circulating T cell subpopulations in patients with T2DM, which might alleviate inflammatory responses caused by hyperglycemia.
This study was registered with ChiCTR-OPN-17010405.
Bemisia tabaci has developed a high level of resistance to thiamethoxam, a second generation neonicotinoid insecticide that has been widely used to control this pest. In this study, we investigated ...whether hydroxyacid-oxoacid transhydrogenase (HOT) is involved in resistance to the neonicotinoid insecticide thiamethoxam in the whitefly. We cloned the full-length gene that encodes HOT in B. tabaci. Its cDNA contains a 1428-bp open reading frame encoding 475 amino acid residues. Then we evaluated the mRNA expression level of HOT in different developmental stages, and found HOT expression was significantly greater in thiamethoxam resistance adults than in thiamethoxam susceptible adults. Subsequently, seven field populations of B. tabaci adults were sampled, the expression of mRNA level of HOT significant positive correlated with thiamethoxam resistance level. At last, we used a modified gene silencing system to knock-down HOT expression in B. tabaci adults. The results showed that the HOT mRNA levels decreased by 57% and thiamethoxam resistance decreased significantly after 2 days of feeding on a diet containing HOT dsRNA. The results indicated that down-regulation of HOT expression decreases thiamethoxam resistance in B. tabaci adults.
This meta-analysis aims to provide more evidence on the role of postoperative chemoradiotherapy (CRT) for gastric cancer (GC) patients in Asian countries where D2 lymphadenectomy is prevalent.
We ...conducted a systematic review of randomized controlled trials (RCTs), extracted data of survival and toxicities, and pooled data to evaluate the efficacy and toxicities of CRT compared with chemotherapy (CT) after D2 lymphadenectomy.
A total of 960 patients from four RCTs were selected. The results showed that postoperative CRT significantly reduced loco-regional recurrence rate (LRRR: RR = 0.50, 95 % CI = 0.34-0.74, P = 0.0005) and improved disease-free survival (DFS: HR = 0.73, 95 % CI = 0.60-0.89, P = 0.002). However, CRT did not affect distant metastasis rate (DMR: RR = 0.81, 95 % CI = 0.60-1.08, P = 0.15) and overall survival (OS: HR = 0.91, 95 % CI = 0.74-1.11, P = 0.34). The main grade 3-4 toxicities manifested no significant differences between the two groups.
Overall, CRT after D2 lymphadenectomy may reduce LRRR and prolong DFS. The role of postoperative CRT should be further investigated in the population with high risk of loco-regional recurrence.
The present study aimed to detect the role of 3, 4-dihydroxyl-phenyl lactic acid (DLA) during ischemia/reperfusion (I/R) induced myocardial injury with emphasis on the underlying mechanism of DLA ...antioxidant. Male Spragu-Dawley (SD) rats were subjected to left descending artery occlusion followed by reperfusion. Treatment with DLA ameliorated myocardial structure and function disorder, blunted the impairment of Complex I activity and mitochondrial function after I/R. The results of 2-D fluorescence difference gel electrophoresis revealed that DLA prevented the decrease in NDUFA10 expression, one of the subunits of Complex I. To find the target of DLA, the binding affinity of Sirtuin 1 (SIRT1) to DLA and DLA derivatives with replaced two phenolic hydroxyls was detected using surface plasmon resonance and bilayer interferometry. The results showed that DLA could activate SIRT1 after I/R probably by binding to this protein, depending on phenolic hydroxyl. Moreover, the importance of SIRT1 to DLA effectiveness was confirmed through siRNA transfection in vitro. These results demonstrated that DLA was able to prevent I/R induced decrease in NDUFA10 expression, improve Complex I activity and mitochondrial function, eventually attenuate cardiac structure and function injury after I/R, which was possibly related to its ability of binding to and activating SIRT1.
This study explored the effect of the implant position of stents across the Vater's ampulla on treatment outcomes in patients with lower bile duct obstruction.In the retrospective study, 41 patients ...with malignant obstruction of the lower bile duct and obstructive jaundice received percutaneous transhepatic biliary placement of bare-metal stents. Basic demographic data on patients, such as sex, age, and primary diseases, and follow-up data, including postoperative complications and jaundice-free survival, were recorded. The follow-up data on patients with an involved ampulla, patients with an uninvolved ampulla, patients with a stent across the ampulla, and patients with a stent at a site other than the ampulla were compared. Furthermore, prognostic factors for jaundice- free survival were investigated using Cox proportional hazards regression analysis.Among the 41 patients, 38 patients experienced subsiding of jaundice, whereas 3 cases had unsuccessful stent patency. Whether or not the ampulla was involved did not influence the incidence rates of postoperative complications and the jaundice-free survival time. Notably, when stents were placed across the ampulla, the jaundice-free survival time was significantly longer than when stents were placed at sites other than across the ampulla (P < .05). Furthermore, placement of the stent across the ampulla or at other sites was an independent prognostic factor (hazard ratio = 0.154, 95% confidence interval 0.042-0.560, P = .005) for jaundice-free survival of patients.The current study revealed that the implant position of a stent across the ampulla resulted in maintenance of stent patency and prolongation of the jaundice-free survival time.
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