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1.
Ali Soroush Reza Malekzadeh Gholamreza Roshandel Masoud Khoshnia Hossein Poustchi Farin Kamangar Paul Brennan Paolo Boffetta Sanford M. Dawsey Christian C. Abnet Julian A. Abrams Arash Etemadi 《International journal of cancer. Journal international du cancer》2023,152(6):1137-1149
Prior studies have conflicting findings regarding the association between gastroesophageal reflux disease (GERD) and esophageal squamous cell carcinoma (ESCC). We examined this relationship in a prospective cohort in a region of high ESCC incidence. Baseline exposure data were collected from 50 045 individuals using in-person interviews at the time of cohort entry. Participants were followed until they developed cancer, died, or were lost to follow up. Participants with GERD symptoms were categorized into any GERD (heartburn or regurgitation), mixed symptoms, or heartburn alone. Multivariable Cox regression was used to assess the relationship between GERD symptom group and histologically confirmed ESCC. The model was adjusted for known risk factors for GERD and ESCC. 49 559 individuals were included in this study, of which 9005 had GERD symptoms. Over 13.0 years of median follow up, 290 individuals were diagnosed with ESCC. We found no association between any GERD and risk of ESCC (aHR 0.90, 95% CI: 0.66-1.24, P = .54). Similar findings were observed for the GERD symptom subtypes. Significant interactions between any GERD and sex (P = .013) as well as tobacco smoking (P = .028) were observed. In post-hoc analyses, GERD was associated with a decreased risk of ESCC in men (aHR 0.51, 95% CI: 0.27-0.98 P = .04) and in smokers (aHR 0.26, 95% CI: 0.08-0.83 P = .02). While there was little evidence for an overall association between GERD symptoms and ESCC risk, significant interactions with sex and smoking were observed. Men and smokers with GERD symptoms had a lower risk of ESCC development. 相似文献
2.
David G. Darcy Rachel Chiaroni-Clarke Jennifer M. Murphy Joshua N. Honeyman Umesh Bhanot Michael P. LaQuaglia Sanford M. Simon 《Oncotarget》2015,6(2):755-770
Fibrolamellar hepatocellular carcinoma is a rare, malignant liver tumor that often arises in the otherwise normal liver of adolescents and young adults. Previous studies have focused on biomarkers and comparisons to traditional hepatocellular carcinoma, and have yielded little data on the underlying pathophysiology. We performed whole genome sequencing on paired tumor and normal samples from 10 patients to identify recurrent mutations and structural variations that could predispose to oncogenesis. There are relatively few coding, somatic mutations in this cancer, putting it on the low end of the mutational spectrum. Aside from a previously described heterozygous deletion on chromosome 19 that encodes for a functional, chimeric protein, there were no other recurrent structural variations that contribute to the tumor genotype. The lack of a second-hit mutation in the genomic landscape of fibrolamellar hepatocellular carcinoma makes the DNAJB1-PRKACA fusion protein the best target for diagnostic and therapeutic advancements. The mutations, altered pathways and structural variants that characterized fibrolamellar hepatocellular carcinoma were distinct from those in hepatocellular carcinoma, further defining it as a distinct carcinoma. 相似文献
3.
Shahed N. Badiyan Michael S. Rutenberg Bradford S. Hoppe Pranshu Mohindra Gary Larson William F. Hartsell Henry Tsai Jing Zeng Ramesh Rengan Erica Glass Sanford Katz Carlos Vargas Steven J. Feigenberg Charles B. Simone 《Practical radiation oncology》2019,9(4):280-288
PurposeWe sought to assess clinical outcomes and toxicities of patients with recurrent lung cancer reirradiated with proton beam therapy (PBT) who were enrolled in 2 prospective registry trials.Methods and MaterialsSeventy-nine consecutive patients were reirradiated with PBT at 8 institutions. Conventionally fractionated radiation therapy was used to treat the previous lung cancer in 68% of patients (median equivalent dose in 2 Gy fractions [EQD2], 60.2 Gy) and hypofractionated/stereotactic body radiation therapy in 32% (median EQD2, 83.3 Gy). Nine patients (11%) received ≥2 courses of thoracic irradiation before PBT. Eastern Cooperative Oncology Group (ECOG) performance status was 2 to 3 in 13%. Median time from prior radiation therapy to PBT was 19.9 months. PBT was delivered with conventional fractionation in 58% (median EQD2, 60 Gy), hyperfractionation in 3% (median EQD2, 62.7 Gy), and hypofractionation in 39% (median EQD2, 60.4 Gy). Twenty-four patients (30%) received chemotherapy concurrently with PBT.ResultsAll patients completed PBT as planned. At a median follow-up of 10.7 months after PBT, median overall survival (OS) and progression-free survival (PFS) were 15.2 months and 10.5 months, respectively. Acute and late grade 3 toxicities occurred in 6% and 1%, respectively. Three patients died after PBT from possible radiation toxicity. On multivariate analysis, ECOG performance status ≤1 was associated with OS (hazard ratio, 0.35; 95% confidence interval, 0.15-0.80; P = .014) and PFS (hazard ratio, 0.32; 95% confidence interval, 0.14-0.73; P = .007).ConclusionsThis is the largest series to date of PBT reirradiation for recurrent lung cancer and indicates that reirradiation with PBT is well tolerated with acceptable toxicity and encouraging efficacy. ECOG performance status was associated with OS and PFS. 相似文献
4.
Bruce A Dye Ru Wang Ruth Lashley Wenqiang Wei Christian C Abnet Guoqing Wang Sanford M Dawsey Wei Cong Mark J Roth Xiaojie Li Youlin Qiao 《BMC oral health》2007,7(1):1-15
Background
The oral health status of rural residents in the People's Republic of China has not been extensively studied and the relationship between poor oral health and esophageal cancer (EC) is unclear. We aim to report the oral health status of adults participating in an EC screening study conducted in a rural high-risk EC area of China and to explore the relationship between oral health and esophageal dysplasia.Methods
National Health and Nutrition Examination Survey (NHANES) oral health examination procedures and the Modified Gingival Index (MGI) were used in a clinical study designed to examine risk factors for esophageal cancer and to test a new esophageal cytology sampling device. This study was conducted in three rural villages in China with high rates of EC in 2002 and was a collaborative effort involving investigators from the National Institutes of Health and the Cancer Institute of the Chinese Academy of Medical Sciences.Results
Nearly 17% of the study participants aged 40–67 years old were edentulous. Overall, the mean number of adjusted missing teeth (including third molars and retained dental roots) was 13.8 and 35% had 7 contacts or less. Women were more likely to experience greater tooth loss than men. The average age at the time of first tooth loss for those with no posterior functional contacts was approximately 41 years for men and 36 years for women. The mean DMFT (decayed, missing, and filled teeth) score for the study population was 8.5. Older persons, females, and individuals having lower educational attainment had higher DMFT scores. The prevalence of periodontal disease (defined as at least one site with 3 mm of attachment loss and 4 mm of pocket depth) was 44.7%, and 36.7% of the study participants had at least one site with 6 mm or more of attachment loss. Results from a parsimonious multivariate model indicate that participants with poor oral health wemore likely to have esophageal dysplasia (OR = 1.59; 95% CI 1.06, 2.39).Conclusion
This report describes the first use of NHANES oral health protocols employed in a clinical study conducted outside of the United States. The extent and severity of poor oral health in this Chinese study group may be an important health problem and contributing factor to the prevalence of EC. 相似文献5.
Roxanne Charles Asoke Basu Bryan Sanford Auria King‐Cenac Sharmine Melville‐Edwin Patricia Pow‐Brown Candice Sant Karla Georges 《Transboundary and Emerging Diseases》2020,67(Z2):129-134
Ticks and the pathogens they transmit can cause high morbidity and mortality in domestic animals. As part of a larger study to determine the tick‐borne pathogens infesting domestic animals and wildlife, the aim of this study was to survey the tick species infesting the canine and cattle populations in Trinidad, Tobago and St. Lucia. A total of 1,990 ticks were collected off 179 dogs in Trinidad (n = 163) and Tobago (n = 16) between June 2016 and 2018. Ticks were also collected from cattle throughout Trinidad (n = 1,098), Tobago (n = 306) and St. Lucia (n = 176). Collected ticks were morphologically identified using standard taxonomic keys. Tick‐infested dogs were characterized as pets (n = 161) or hunting dogs (n = 18). Only two tick species, Rhipicephalus sanguineus (1,926; 96.8%) and Amblyomma ovale (64; 3.2%), were found on the dogs. A total of 169 (94.4%) dogs and 10 (5.6%) dogs were infested with R. sanguineus and A. ovale, respectively. Three dogs (1.7%) were infested with both tick species. Hunting dogs or those closely associated with them were infested with A. ovale. Rhipicephalus sanguineus was widely distributed throughout both islands, whereas A. ovale was restricted to small foci in three rural settlements in both Trinidad (n = 2) and Tobago (n = 1). Rhipicephalus (Boophilus) microplus (n = 1,404) was the only tick species found in cattle from Trinidad (n = 62) and Tobago (n = 20), whilst R. B. microplus (n = 171) and Amblyomma variegatum (n = 5) were found infesting 14 and two heads of cattle, respectively, in St. Lucia. These preliminary findings will aid in determining whether there are links between ticks and tick‐borne pathogens associated with domestic, wildlife species and humans and give further insight into the potential movement of ticks and their pathogens between the human, animal and tropical forest interface. 相似文献
6.
The antithrombotic potential of selective blockade of talin-dependent integrin alpha IIb beta 3 (platelet GPIIb-IIIa) activation 下载免费PDF全文
Petrich BG Fogelstrand P Partridge AW Yousefi N Ablooglu AJ Shattil SJ Ginsberg MH 《The Journal of clinical investigation》2007,117(8):2250-2259
In vitro studies indicate that binding of talin to the beta(3) integrin cytoplasmic domain (tail) results in integrin alpha(IIb)beta(3) (GPIIb-IIIa) activation. Here we tested the importance of talin binding for integrin activation in vivo and its biological significance by generating mice harboring point mutations in the beta(3) tail. We introduced a beta(3)(Y747A) substitution that disrupts the binding of talin, filamin, and other cytoplasmic proteins and a beta(3)(L746A) substitution that selectively disrupts interactions only with talin. Platelets from animals homozygous for each mutation showed impaired agonist-induced fibrinogen binding and platelet aggregation, providing proof that inside-out signals that activate alpha(IIb)beta(3) require binding of talin to the beta(3) tail. beta(3)(L746A) mice were resistant to both pulmonary thromboembolism and to ferric chloride-induced thrombosis of the carotid artery. Pathological bleeding, measured by the presence of fecal blood and development of anemia, occurred in 53% of beta(3)(Y747A) and virtually all beta(3)-null animals examined. Remarkably, less than 5% of beta(3)(L746A) animals exhibited this form of bleeding. These results establish that alpha(IIb)beta(3) activation in vivo is dependent on the interaction of talin with the beta(3) integrin cytoplasmic domain. Furthermore, they suggest that modulation of beta(3) integrin-talin interactions may provide an attractive target for antithrombotics and result in a reduced risk of pathological bleeding. 相似文献
7.
8.
Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis 总被引:85,自引:19,他引:85
Koopman G; Reutelingsperger CP; Kuijten GA; Keehnen RM; Pals ST; van Oers MH 《Blood》1994,84(5):1415-1420
Apoptosis, or programmed cell death, is a general mechanism for removal of unwanted cells from the immune system. It is characterized by chromatin condensation, a reduction in cell volume, and endonuclease cleavage of DNA into oligonucleosomal length fragments. Apoptosis is also accompanied by a loss of membrane phospholipid asymmetry, resulting in the exposure of phosphatidylserine at the surface of the cell. Expression of phosphatidylserine at the cell surface plays an important role in the recognition and removal of apoptotic cells by macrophages. Here we describe a new method for the detection of apoptotic cells by flow cytometry, using the binding of fluorescein isothiocyanate-labeled annexin V to phosphatidylserine. When Burkitt lymphoma cell lines and freshly isolated germinal center B cells are cultured under apoptosis inducing conditions, all cells showing chromatin condensation strongly stain with annexin V, whereas normal cells are annexin V negative. Moreover, DNA fragmentation is only found in the annexin V-positive cells. The nonvital dye ethidium bromide was found to stain a subpopulation of the annexin V-positive apoptotic cells, increasing with time. Our results indicate that the phase in apoptosis that is characterized by chromatin condensation coincides with phosphatidylserine exposure. Importantly, it precedes membrane damage that might lead to release from the cells of enzymes that are harmful to the surrounding tissues. Annexin V may prove important in further unravelling the regulation of apoptosis. 相似文献
9.
Recently, the JAK2(V617F) mutation was found in patients with myeloproliferative disorders (MPDs), including most with polycythemia vera (PV). The mutant JAK2 has increased kinase activity, and it was shown to be pathogenic in mouse models. Herein, we analyzed blood samples randomly collected from a clinical laboratory. Surprisingly, as many as 37 samples from a total of 3935 were found positive for the JAK2 mutation. However, only one of these samples had blood test results indicative for probable PV, but several had nonhematologic diseases. On average, samples with the mutation had normal red cell counts but significantly higher white blood cell and platelet counts, although most were within the normal range. The data suggest that the JAK2(V617F) mutation is apparently much more common than MPDs. Its occurrence may be a prelude to full blood cell abnormalities and other diseases, but it cannot by itself diagnose MPDs. 相似文献