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1.
Usha Patel Manish Pandey Sadhana Kannan Tanuja A. Samant Poonam Gera Neha Mittal Swapnil Rane Asawari Patil Vanita Noronha Amit Joshi Vijay M. Patil Kumar Prabhash Manoj B. Mahimkar 《British journal of cancer》2020,123(12):1757
Background Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are greatly needed to identify the patients likely to be benefited from these targeted therapies. Here, we present the prognostic and predictive association of biomarkers in HPV-negative locally advanced (LA) HNSCC patients.Methods Treatment-naive tumour tissue samples of 404 patients, a subset of randomised Phase 3 trial comparing cisplatin radiation (CRT) versus nimotuzumab plus cisplatin radiation (NCRT) were analysed to evaluate the expression of HIF1α, EGFR and pEGFR by immunohistochemistry and EGFR gene copy change by FISH. Progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) were estimated by Kaplan–Meier method. Hazard ratios were estimated by Cox proportional hazard models.Results Baseline characteristics of the patients were balanced between two treatment groups (CRT vs NCRT) and were representative of the trial cohort. The median follow-up was of 39.13 months. Low HIF1α was associated with better PFS [HR (95% CI) = 0.62 (0.42–0.93)], LRC [HR (95% CI) = 0.56 (0.37–0.86)] and OS [HR (95% CI) = 0.63 (0.43–0.93)] in the CRT group. Multivariable analysis revealed HIF1α as an independent negative prognostic biomarker. For patients with high HIF1α, NCRT significantly improved the outcomes [PFS:HR (95% CI) = 0.55 (0.37–0.82), LRC:HR (95% CI) = 0.55 (0.36–0.85) and OS:HR (95% CI) = 0.54 (0.36–0.81)] compared to CRT. While in patients with low HIF1α, no difference in the clinical outcomes was observed between treatments. Interaction test suggested a predictive value of HIF1α for OS (P = 0.008).Conclusions High HIF1α expression is a predictor of poor clinical response to CRT in HPV-negative LA-HNSCC patients. These patients with high HIF1α significantly benefited with the addition of nimotuzumab to CRT.Clinical trial registration Registered with the Clinical Trial Registry of India (Trial registration identifier—CTRI/2014/09/004980).Subject terms: Tumour biomarkers, Head and neck cancer, Tumour biomarkers, Head and neck cancer, Predictive markers 相似文献
2.
Stress Testing Versus CT Angiography in Patients With Diabetes and Suspected Coronary Artery Disease
Abhinav Sharma Adrian Coles Nishant K. Sekaran Neha J. Pagidipati Michael T. Lu Daniel B. Mark Kerry L. Lee Hussein R. Al-Khalidi Udo Hoffmann Pamela S. Douglas 《Journal of the American College of Cardiology》2019,73(8):893-902
Background
The optimal noninvasive test (NIT) for patients with diabetes and stable symptoms of coronary artery disease (CAD) is unknown.Objectives
The purpose of this study was to assess whether a diagnostic strategy based on coronary computed tomographic angiography (CTA) is superior to functional stress testing in reducing adverse cardiovascular (CV) outcomes (CV death or myocardial infarction [MI]) among symptomatic patients with diabetes.Methods
PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) was a randomized trial evaluating an initial strategy of CTA versus functional testing in stable outpatients with symptoms suggestive of CAD. The study compared CV outcomes in patients with diabetes (n = 1,908 [21%]) and without diabetes (n = 7,058 [79%]) based on their randomization to CTA or functional testing.Results
Patients with diabetes (vs. without) were similar in age (median 61 years vs. 60 years) and sex (female 54% vs. 52%) but had a greater burden of CV comorbidities. Patients with diabetes who underwent CTA had a lower risk of CV death/MI compared with functional stress testing (CTA: 1.1% [10 of 936] vs. stress testing: 2.6% [25 of 972]; adjusted hazard ratio: 0.38; 95% confidence interval: 0.18 to 0.79; p = 0.01). There was no significant difference in nondiabetic patients (CTA: 1.4% [50 of 3,564] vs. stress testing: 1.3% [45 of 3,494]; adjusted hazard ratio: 1.03; 95% confidence interval: 0.69 to 1.54; p = 0.887; interaction term for diabetes p value = 0.02).Conclusions
In diabetic patients presenting with stable chest pain, a CTA strategy resulted in fewer adverse CV outcomes than a functional testing strategy. CTA may be considered as the initial diagnostic strategy in this subgroup. (PROspective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550) 相似文献3.
We report herein, a new method devised of producing neurogenic stress ulceration in rats. An experimental subarachnoid hemorrhage (SAH) was produced in rats by injecting 0.2 ml of arterial blood from other rats into the cisterna magna. Three days later, the rats were laparotomized for 1 hour under ether anesthesia, followed by restraint for 3 hours in wakefulness. The SAH rats were found to develop stress ulcers (UL-I) in the glandular stomach, which were significantly (p less than 0.001) more marked than those in non-SAH rats. Measurements were performed on gastric acid secretion, an important aggressive factor. It was found that the SAH rats undergoing the laparotomy-restraint stress showed a more marked increase in gastric acid secretion and a more marked reduction in MBF, than the non-SAH rats. The effects of bilateral vagotomy, upper abdominal sympathectomy and bilateral adrenalectomy were examined, and it was revealed that the SAH rats were under the condition of hyperreactivity both in the sympathetic and parasympathetic systems and, on this basis, the laparotomy-restraint stress caused the stress gastric ulceration. In this rat model, the laparotomy stress was applied under anesthesia and any exposure to low temperatures which may have interfered with blood circulation was avoided. 相似文献
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6.
Motohisa Kato Shigetoyo Saji Katsuyuki Kunieda Tatsuhiro Yasue Kimitoshi Nishio Mitsuri Adachi 《Surgery today》1997,27(8):766-768
We experienced a case of mediastinal lipoma, which is considered to be a relatively rare disease. A 3-year-old girl was referred
to Gifu University hospital because of fever and an abnormal shadow on her chest X-ray. The chest X-ray clearly showed a well-delineated
tumor shadow which seemed to oppress the diaphragm and the right atrium in the right lower lung area. A computed tomogram
(CT) of the chest showed a homogeneous mass localized on the right diaphragm and adjoining the right anterior chest wall and
heart. The mass showed a fat density measuring about-100 HU. Magnetic resonance imaging (MRI) showed a high-intensity mass
which was almost the same level as the subcutaneous fat on both the T1-weighted and T2-weighted images. Thoracotomy was performed and a fatty tumor was found. It arose from the right side of the pericardium and
adjoined the diaphragm, the anterior chest wall, and the thymus. There was no adhesion between the tumor and the surrounding
organs. It was resected easily and its contents were yellowish and homogeneous. The patient made an uneventful recovery and
was discharged 10 days after the operation. Light microscopy showed a lipoma consisting of mature adipose tissue and no malignancy
was found. 相似文献
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9.
Takahito Adachi Makoto Takeuchi Satomi Uno Motohisa Kato Kiichi Miya Shigetoyo Saji 《Surgery today》1997,27(12):1144-1149
Although tumor cryosurgery would be expected to produce beneficial immunological effects from the enhancement of anti-tumor
activity, under certain conditions the tumor may become enlarged and metastases promoted due to increased immunosuppressive
activity and a high zone tolerance. In the present study, we examined whether hepatocyteproliferating factors were produced
by the inoculation of freezing-thawing hepatic tissue (FTHT). Serum obtained from rats inoculated with FTHT increased DNA
synthesis, according to measurement by [3H]thymidine incorporation in primary cultured rat hepatocytes. This increase was dependent on the serum concentration, with
serum obtained on day 14 after the inoculation being the most potent for hepatocyte proliferation. The sensitized serum promoted
DNA synthesis nearly as much as serum obtained from a 70% hepatectomized rat, but slightly less than 10ng/ml hepatocyte growth
factor. The sensitized serum also protected hepatocytes from carbon tetrachloride (CCI4)-induced hepatotoxicity. Optical density measured by the 3-(4,5-dimethyl-thiazole-2-yl)-2,5-diphenyl tetrozolium bromide
(MTT) cytotoxicity assay was increased, and the release of aspartate aminotransferase, alanine aminotransferase, and lactate
dehydrogenase in medium was decreased by treating hepatocytes damaged by CCI4 with the sensitized serum. These results suggest that certain hepatocyte-proliferating and protective factors are induced
in serum by the inoculation of freezing-thawing hepatic tissue, and that the sensitized serum may be useful in the treatment
of liver failure. 相似文献
10.
Anjali Ramaswamy Nina N. Brodsky Tomokazu S. Sumida Michela Comi Hiromitsu Asashima Kenneth B. Hoehn Ningshan Li Yunqing Liu Aagam Shah Neal G. Ravindra Jason Bishai Alamzeb Khan William Lau Brian Sellers Neha Bansal Pamela Guerrerio Avraham Unterman Victoria Habet Carrie L. Lucas 《Immunity》2021,54(5):1083-1095.e7
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