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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.
G. Michael Taylor Thomas J. Neuhaus Vanita Shah Susannah Dillon T. Martin Barratt 《Pediatric nephrology (Berlin, Germany)》1997,11(4):404-410
Experimental studies have pointed to charge selectivity as an important determinant of glomerular permeability to macromolecules.
Loss of glomerular basement membrane (GBM) polyanion has been proposed as a cause of the selective proteinuria in minimal
change nephrotic syndrome (MCNS). However, the presence of less-anionic albumin in urine than plasma from MCNS and focal and
segmental glomerulosclerosis (FSGS) patients has been interpreted both as evidence for partial maintenance of charge selectivity
and for involvement of other pathogenic mechanisms. The exact role of charge selectivity in the pathogenesis of nephrotic
proteinuria remains controversial. We have examined the clearance of endogenous proteins of differing size and charge in children
with idiopathic nephrotic syndrome (NS). Chromatofocusing was used to determine the isoelectric points (pIs) of albumins in
paired plasma and urine samples from patients with FSGS (n = 6) and MCNS (n = 6). Charge selectivity was assessed by comparing the pIs of the fractions with the highest albumin concentration (modal
pI) in plasma and urine. The difference between the modal pIs was defined as the delta modal pI. Charge selectivity was also
assessed from the albumin/transferrin and IgG4/IgG1 clearance ratios; size selectivity from the IgG1/albumin and IgG1/transferrin
as well as the IgG4/albumin and IgG4/transferrin clearances. In children with FSGS, the mean (± SD) delta modal pI was – 0.05
± 0.16, and in MCNS – 0.05 ± 0.11. Neither value differed significantly from zero. The albumin/transferrin clearance ratio
showed no significant difference between FSGS and MCNS, but the IgG4/IgG1 clearance ratio was significantly higher in MCNS
(P<0.05). Size selectivity was significantly reduced in FSGS compared with MCNS (for IgG1/transferrin P<0.01 and for IgG1/albumin P<0.05). For IgG4/transferrin and IgG4/albumin, P was <0.05. In conclusion, there was no evidence for residual charge selectivity in idiopathic NS associated with either MCNS
or FSGS during nephrotic-range proteinuria. There was a significant loss of GBM size selectivity in children with FSGS with
heavy proteinuria compared with children with MCNS with heavy proteinuria.
Received August 7, 1996; received in revised form and accepted December 16, 1996 相似文献
3.
Daniel Einhorn Vanita R Aroda Robert R Henry 《Endocrinology & Metabolism Clinics of North America》2004,33(3):595-616, vii-viii
Thiazolidinediones (glitazones) are the only compounds currently available that specifically target tissue insulin resistance. The two currently available drugs in this class, pioglitazone and rosiglitazone,are approved by the Food and Drug Administration for the treatment of type 2 diabetes mellitus only. The therapeutic potential of the glitazones for other consequences of insulin resistance has stirred considerable interest, especially with regard to their potential beneficial impact on atherosclerotic cardiovascular disease and diabetes prevention. They also have been considered in the management of polycystic ovarian syndrome, nonalcoholic fatty liver disease, and other consequences of insulin resistance. The nonglycemic potential of glitazones is a clinical area in rapid evolution, wherein most data are on the impact of the glitazones onsurrogate markers that are associated with diseases, not on disease outcomes. This article provides insight and guidance to clinicians on the diverse nonglycemic potential of glitazones until conclusive outcome data become available. 相似文献
4.
Hersha Rathod Archibald J. Malcolm James I. Gillespie Vanita Berry Joseph Pooley Nigel H. Piggott Harish K. Datta 《The Journal of pathology》1994,174(4):293-299
We report here a case of primary osteoclastoma that despite possessing HLA-DR-positive status and ‘functional’ calcitonin receptors, exhibited aggressive in vitro and in vivo bone resorptive activity. In the osteoclast bone slice assay employing scanning electron microscopy, the giant cell-mediated bone resorption was uninhibited by salmon calcitonin (10 nM) and significantly inhibited by raised extracellular calcium (20 mM). In Fura-2AM based microspectrofluorimetric assays, the presence of the ‘functional’ calcitonin receptors was ascertained by a rise in intracellular calcium induced by calcitonin and high extracellular calcium. These findings provide evidence for a hitherto unrecognized subtype of giant cells that have HLA-DR-positive status, exhibit avid bone resorptive activity, but remain insensitive to calcitonin despite possessing calcitonin receptors. 相似文献
5.
Glomerular and tubular function in glycogen storage disease 总被引:4,自引:0,他引:4
Philip J. Lee R. Neil Dalton Vanita Shah Peter C. Hindmarsh James V. Leonard 《Pediatric nephrology (Berlin, Germany)》1995,9(6):705-710
Urinary protein and calcium excretion were assessed in 77 patients with the hepatic glycogen storage diseases (GSD): 30 with GSD-I (median age 12.4 years, range 3.2–32.9 years), 25 with GSD-III (median age 10.5 years, range 4.2–31.3 years) and 22 with GSD-IX (median age 11.8 years, range 1.2–35.4 years). Inulin (C
inulin) and para-aminohippuric acid (C
PAH) clearances were also measured in 33 of these patients. Those with GSD-I had significantly greater albumin (F=15.07,P<0.001), retinolbinding protein (RBP) (F=14.66,P<0.001),N-acetyl--d glucosaminidase (NAG) (F=9.41,P<0.001) and calcium (F=7.41,P=0.001) excretion than those with GSD-III and GSD-IX. GSD-I patients (n=18) also had significantly higherC
inulin (F=5.57,P=0.009), butC
PAH did not differ (F=0.77, NS). Renal function was normal in GSD-III and GSD-IX patients. In GSD-I,C
inulin (r=–0.51,P=0.03) and NAG excretion (r=–0.40,P=0.03) were inversely correlated with age, whereas albumin excretion was positively correlated with age (r=+0.41,P=0.03). RBP and calcium excretion were generally high throughout all age groups. Hyperfiltration in GSD-I is associated with renal tubular proteinuria that occurs before the onset of significant albuminuria. Deficiency of glucose-6-phosphatase within the proximal renal tubule may primarily cause tubular dysfunction, glomerular hyperfiltration being a secondary phenomenon. 相似文献
6.
Rehan Asif Kamlesh Chandra Vanita Chopra M. L. B. Bhatt 《Indian journal of otolaryngology and head and neck surgery》2003,55(2):94-96
Management of Head and Neck Cancers poses a challenge inspite of several advances because of poor success in terms of response
rate, survival and reduced morbidity of the patients. In the present study 30 untreated histologically proven cases of head
and neck cancers were subjected to weekly radiotherapy with adjuvant chemotherapy (cisplatin 30 mg/m2 intravenously). This study group was compared with a group of 30 patients who were given only radiotherapy. Results have
shown that combination of chemotherapy with radiotherapy gives a significantly better results in tumour as well as nodal response
with minimal toxicities. 相似文献
7.
The impact of post-partum haemorrhage in “near-miss” morbidity and mortality in developing countries
The global maternal mortality ratio (MMR) of 400 per 100,000 live births results in an estimated 529,000 maternal deaths annually. Most of these deaths occur in developing countries and only about 1% in developed countries. Besides mortality data, the identification and accurate documentation of “near-miss” morbidity (a more sensitive index) is extremely important to assess the quality of health care systems. It can suitably guide to adopt appropriate measures to reduce maternal mortality and morbidity. Haemorrhage remains a major cause of maternal mortality in both developing and developed countries followed by anaemia and infection, which are more common in developing countries. Post-partum haemorrhage (PPH) is a frequent complication of delivery. PPH occurred in 10.5% of all live births worldwide resulting in 13,795,000 cases in the year 2000. The case fatality rate for PPH was 1% and there were 132,000 deaths attributable to PPH. Anaemia as a consequence of PPH was estimated to occur in 1.6 million women every year. Thus, the prevention and adequate management of obstetric haemorrhage are likely to result in a significant reduction in the MMR and in the less frequently monitored “near-miss” morbidity. Strategies to be adopted with regard to PPH in developing countries may differ from those routinely available and practised in developed countries because of limited access to health care facilities and low institutional delivery rate in the former countries. Some low cost, simple techniques to prevent and manage PPH are described. These need to be tested in a wider population to determine which is most suitable for a particular area or country. The mortality and “near-miss” morbidity data should be continually assessed and only then will the impact of these strategies be known. First level midwifery care plus backup by well-equipped hospitals must be developed concomitantly. Anyone can conduct a normal delivery when all is going well but only those with good clinical judgement and the necessary skills will be able to anticipate and manage a problem. This is especially important in the context of PPH where the under-estimation of blood loss coupled with the rapidity of development of serious consequences is the key issue. 相似文献
8.
Jonah A. Hoyt BS Emily Cozzi PhD David A. D'Alessio MD Chris C. Thompson MD Vanita R. Aroda MD 《Diabetes, obesity & metabolism》2024,26(6):2017-2028
Affecting 5%–10% of the world population, type 2 diabetes (T2DM) is firmly established as one of the major health burdens of modern society. People with T2DM require long-term therapies to reduce blood glucose, an approach that can mitigate the vascular complications. However, fewer than half of those living with T2DM reach their glycaemic targets despite the availability of multiple oral and injectable medications. Adherence and access to medications are major barriers contributing to suboptimal diabetes treatment. The gastrointestinal tract has recently emerged as a target for treating T2DM and altering the underlying disease course. Preclinical and clinical analyses have elucidated changes in the mucosal layer of the duodenum potentially caused by dietary excess and obesity, which seem to be prevalent among individuals with metabolic disease. Supporting these findings, gastric bypass, a surgical procedure which removes the duodenum from the intestinal nutrient flow, has remarkable effects that improve, and often cause remission of, diabetes. From this perspective, we explore the rationale for targeting the duodenum with duodenal mucosal resurfacing (DMR). We examine the underlying physiology of the duodenum and its emerging role in T2DM pathogenesis, the rationale for targeting the duodenum by DMR as a potential treatment for T2DM, and current data surrounding DMR. Importantly, DMR has been demonstrated to change mucosal abnormalities common in those with obesity and diabetes. Given the multifactorial aetiology of T2DM, understanding proximate contributors to disease pathogenesis opens the door to rethinking therapeutic approaches to T2DM, from symptom management toward disease modification. 相似文献
9.
10.
Jayasree Vanukuru Tanuja Muthyala Vikas Gautam Sunil Sethi Vanita Jain 《The journal of maternal-fetal & neonatal medicine》2019,32(12):1931-1937
Objective: This prospective study was carried out to evaluate the clinical profile and bacterial isolates among women with puerperal sepsis in a tertiary hospital in North India.Materials and methods: Women with puerperal sepsis (n?=?45) admitted from January 2015 to April 2016 were followed prospectively. Cultures were obtained from cervix, blood, urine, and pyoperitoneum. Initial antibiotics were cefotaxime or piperacillin with tazobactam plus amikacin plus clindamycin or metronidazole and were changed according to sensitivity.Results: Out of 7887 deliveries during this period, 45 (0.2%) women had puerperal sepsis. 16 (35.5%) delivered in the present hospital, 25 (55.5%) at another health care facility, and 4 (8.9%) at home. Delivery was by cesarean section (CS) in 24/45 (53.3%) and vaginal in 21/45 (46.6%). Grade 1 sepsis occurred in 21, grade 2 in two, and grade 3 in 22 women. Majority (29/45 or 64.5%) had no risk factor for puerperal sepsis. There were two (4.4%) deaths and 13/45 (28.8%) had near-miss morbidity. Pathogenic bacteria were isolated in 33/45 (73.3%) in cervical swab (69%), blood, urine, or pus culture with no significant difference in the bacterial yield or species isolated between cotton or polyester swabs (p?>?.05). Escherichia coli were the commonest isolate and was sensitive to amikacin in all. Five had stillbirths and 4/40 neonates developed sepsis but recovered.Conclusions: Escherichia coli was the commonest pathogen and was uniformly sensitive to amikacin, which may be included among the initial antibiotics to treat puerperal sepsis in India. 相似文献