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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
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The abdominal compartment syndrome is a life threatening condition resulting from pathologic elevation of the intraabdominal pressure. Prompt diagnosis is required to avoid significant sequelae. Diagnosis of this syndrome is based on clinical findings and intra abdominal pressure monitoring. Treatment consists of decompressive laparotomy, which corrects the pathology. Various surgical techniques are described to manage the open abdomen. Despite considerable attention accorded to this disorder, it is still associated with high morbidity and mortality. This review article deals with the identification of risk factors, pathophysiology, diagnostic criteria and treatment of critically ill patients with the abdominal compartment syndrome. 相似文献
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Carcinoma gallbladder is the commonest malignancy in the Northern part of India. The heavy metals are known carcinogens while trace metals have protective effect. Aim The aim of the study is to estimate the heavy and trace metal (Lead, Zinc, Copper, Cadmium, Chromium, Manganese and Selenium) concentration in serum, bile, tissue and gallstone in patients with gallbladder diseases. Method This is a pilot study conducted in 45 cases (Group – I: 15 cases of carcinoma gallbladder, Group II: 15 patients of cholecystitis with cholelithiasis and Group – III: 15 patients of healthy control), to detect the relationship between the heavy and trace metal concentration and gall bladder carcinoma. Analysis of metal was done using Perkins‐Elmer model 2380 atomic absorption spectrophotometer. Results The serum concentration of copper and nickel was significantly high in carcinoma gallbladder patients as compared to patients with cholecystitis while zinc and selenium is low in carcinoma gallbladder patients. Bile concentration of zinc, selenium and manganese was significantly low in carcinoma gallbladder patients (p < 0.05) as compared to patients of cholelithiasis while cadmium and nickel was high. Tissue concentration of manganese was significantly low in carcinoma gallbladder patients as compared to patients of cholelithiasis while chromium was high. Gallstone concentration of copper, manganese and lead was significantly low in carcinoma gallbladder patients as compared to patients of cholelithiasis. Conclusion The heavy metals are in higher concentration in carcinoma gallbladder while trace metals are in lower concentration indicating possible role of heavy metal in gallbladder carcinogenesis. 相似文献
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Girja S. Shukla S. V. Chandra 《Archives of environmental contamination and toxicology》1987,16(3):303-310
Growing rats were exposed to 5 mg/L Pb,ad libitum in drinking water, and administered low or high doses of Mn and Cd intraperitoneal (i.p.) for 30 days. Some groups of animals were also administered combinations of Pb + Mn and Pb + Cd in an identical manner. Analysis of Pb, Mn, and Cd in tissue samples showed the expected dose-dependent accumulation when the metal was administered singly. However, combined treatment produced different types of metal shift in different tissues. Enhanced accumulation of all three metals in the brain, Mn in liver, Pb in kidney and Cd in testis and kidney after combined exposure may make target organs vulnerable to the toxic effects of metals, even when encountered at low concentrations. Further, the decreased levels of blood Pb after combined treatment with Cd or Mn suggests that the significance of blood Pb level as a diagnostic aid for Pb toxicity in coexposed conditions may not be of much value. Changes in the metallic distribution within the tissues after coexposure may be the result of a competition between the administered metals for common binding sites. 相似文献
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A sublethal concentration of technical grade endosulfan (END) inhibited 35 to 55% of the activities of cytoplasmic malate dehydrogenase (cMDH), mitochondrial malate dehydrogenase (mMDH), and lactate dehydrogenase (LDH) in the liver and the skeletal muscle of a freshwater catfish, Clarias batrachus, after 7 days of exposure. The activity remained in the inhibited state up to 28 days. The withdrawal of END from the medium after 1 week of exposure gradually restored the activities to control levels within 21 days in the skeletal muscle and 28 days in the liver. The administration of actinomycin D or cycloheximide between the 14th and the 21st day of the withdrawal of END almost completely inhibited the withdrawal-dependent recovery in the activities of all the three enzymes. This indicates de novo synthesis of the enzymes during the recovery period. A conjoint treatment of END and triiodothyronine (T3) raised the activities of cMDH, mMDH, and LDH in the liver and the skeletal muscle up to the control levels. This shows that the inhibitory effect of END may be relieved in presence of T3. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed few changes in the pattern of cytoplasmic proteins of the liver and the skeletal muscle in response to exposure to END. 相似文献
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Asymptomatic infection with Loa loa, an eye worm, is reported in a 32-year old Zambian woman. The patient revealed up to 28% eosinophilia but microfileraemia was not noticed. One gravid female parasite 56 X 0.56 mm, extracted from lower lid of left eye of the patient, is described. Treatment with diethylcarbamazine (DEC) extended over three weeks was successful against another parasite in tissues. 相似文献
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Objective: To determine if drip infusion should be discontinued after full recovery of the patient from anaesthesia after minilaparotomy cholecystectomy in uncomplicated cases.Design: A randomised controlled clinical trial on 60 patients, from the waiting list, of cholelithiasis/cholecystitis operated by minilaparotomy cholecystectomy between November 1995 to March 1996. 30 patients did not receive postoperative IV drip infusion and in 30 patients 12–24 hours of standard drip transfusion was continued according to the current practice.Setting: Single Surgical Unit, SS Hospital, Banaras Hindu University, Varanasi, India.Main outcome measure: Recognition of clinical indication for continuation of. IV drip infusion after full recovery from anaesthesia.Results: In the cohorts of 30 patients each who were or were not given IV drip infusion after full recovery from anaesthesia following minilaparotomy cholecystectomy the observations on pulse rate, blood pressure, time to first voiding of urine and time to start first oral intake of fluids were identical. However postoperative urinary retention occured in 6 (20%) patients in whom the IV drip infusion was given.Conclusion: There is no clinical indication to continue IV drip infusion after full recovery from anaesthesia in patients operated for minilaparotomy cholecystectomy. 相似文献