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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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Cécile Vicier Lillian Werner Jonathan Chipman Lauren C. Harshman Dattatraya H. Patil Raina N. Fichorova Jennifer R. Rider Martin G. Sanda Lorelei A. Mucci Christopher J. Sweeney 《Clinical genitourinary cancer》2019,17(1):32-37
Background
Inflammation and infections have been associated with prostate cancer progression. We assessed whether elevated serum cytokines or T. vaginalis seropositivity at the time of diagnosis was associated with higher grade or lethal prostate cancer.Patients and Methods
Men with localized or metastatic prostate cancer were included in this study. Cytokine serum levels including interleukin (IL)-1α, IL-1β, IL-2, IL-6, IL-8, monocyte chemotactic protein 1 (CCL-2), tumor necrosis factor α, and growth-regulated oncogene α (CXCL-1) using a multiplex enzyme-linked immunosorbent assay and T. vaginalis serology were measured in blood samples at diagnosis.Results
A total of 324 patients were identified at time of localized disease and 118 at time of metastatic disease. Of the 189 patients with localized disease and clinical follow-up data (median, 73 months), 28 developed lethal disease. There was no association between circulating cytokine levels above median concentrations nor T. vaginalis seropositivity and risk of intermediate- to high-risk or lethal prostate cancer.Conclusion
Higher levels of serum cytokine levels and T. vaginalis seropositivity at diagnosis are not associated with high-grade or lethal prostate cancer and do not aid risk stratification of localized prostate cancer. 相似文献6.
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Darren R. Feldman MD Yasser Ged MBBS Chung-Han Lee PhD Andrea Knezevic MS Ana M. Molina MD Ying-Bei Chen PhD Joshua Chaim DO Devyn T. Coskey MS Samuel Murray MS Satish K. Tickoo MD Victor E. Reuter MD Sujata Patil PhD Han Xiao MD Jahan Aghalar MD Arlyn J. Apollo MD Maria I. Carlo MD Robert J. Motzer MD Martin H. Voss MD 《Cancer》2020,126(24):5247-5255
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山西省出生缺陷高发区土壤元素分布特征 总被引:6,自引:0,他引:6
目的 了解出生缺陷高发区土壤中元素分布特征,为出生缺陷的干预和治疗提供理论依据.方法 于2005年1-5月,选择山西省吕梁山区出生缺陷高发的中阳县和交口县作为出生缺陷高发区,以人口相对集中的河道两侧为采样点,共涉及8个乡镇,79个行政村;选择晋中盆地出生缺陷低发的祁县作为出生缺陷对照区,采样点均匀分布,共涉及6个乡镇,27个行政村.采集距耕地表层10~20cm深的土壤,共采集样品131件.采用ICP-电感耦合等离子发射光谱法,对土壤样品中的16种元素进行测定.结果 高发区土壤中元素总量明显高于低发区.与祁县相比,交口县土壤中元素含量偏高的有As、Mo、Pb、Ni、V,含量偏低的元素有Se,差异均有统计学意义(P<0.05);中阳县土壤中含量偏高的元素为Sn、Se、Mo、Zn、Sr、Pb、Ni、Fe、V、Ca、Cu、Al,偏低的元素为Mg和Na,差异均有统计学意义(P<0.05).土壤中元素含量(μg/g)与出生缺陷发病率的(1/万)逐步回归分析显示,交口县土壤中Mo、Al、As、Ni、Pb、Zn元素对病情影响有统计学意义(均P<0.01),其标准的逐步回归判别方程为:y=-1.321 1.106 Mo-0.509 Al 0.117 As 0.663 Ni-0.429 Pb-0.262 Zn(R2a=0.891);中阳县土壤中Pb、Mg、Ca、Al、Zn元素对病情影响有统计学意义(均P<0.05),其标准回归方程为:y=-1.757 0.441 Pb-0.264Mg 0.309 Ca-0.186Al 0.162Zn (R2a2=0.839).结论 交口县和中阳县土壤中Pb、Mo、Al等含量异常可能是两县出生缺陷高发的原因之一. 相似文献
9.
Samir K El-Mofty Sushama Patil 《Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics》2006,101(3):339-345
We have recently shown that HPV-positive tonsillar carcinoma in young patients exhibits nonkeratinizing basaloid morphology and a characteristic immunophenotype. The purpose of this study was to review a large number of cases of oropharyngeal carcinomas, in all age groups, and to identify tumors with nonkeratinizing morphology. Using polymerase chain reaction (PCR) the prevalence and type of HPV DNA was determined in representative cases and in a control group of conventional keratinizing squamous cell carcinomas. The tumors were further characterized with a panel of immunohistochemical stains. A total of 235 carcinomas were reviewed; 141 of the tonsils and 94 in the base of tongue. Ninety (36%) of the tonsillar and 30 (32%) of the base of tongue carcinomas were nonkeratinizing (NKCa) with basal cell features; the rest were classical keratinizing squamous cell carcinomas (KSCC). HPV DNA, particularly type 16, was identified in 10 (100%) of 10 of NKCA and in only 2 (20%) of 10 of KSCC (P = .0014). NKCas were strongly reactive to p16 antibodies while KSCC showed weak and focal reactivity. Higher Ki67 and lower p53 staining scores were observed in NKCa as compared to KSCC. It is concluded that NKCa of the tonsils and base of tongue is a distinct subtype of squamous cell carcinoma of the head and neck with high prevalence of HPV DNA and a characteristic immunophenotype. 相似文献
10.
Urodynamic studies in the evaluation of young men presenting with lower urinary tract symptoms 总被引:1,自引:0,他引:1
AIM: To evaluate the usefulness of urodynamic study in young men with lower urinary tract symptoms (LUTS). METHODS: We reviewed the charts of 50 men with LUTS aged 50 years and below. Those with neurological diseases, urethral trauma or strictures were excluded. All underwent multichannel urodynamic studies (UDS). The pre- and post-UDS diagnoses and treatment modalities were compared. RESULTS: Mean age was 38.1 years (17-49). The main pre-UDS diagnoses included prostatitis in seven (14%), overactive bladder in seventeen (34%) and benign prostatic hyperplasia in nine (18%). Pre-UDS management ranged from anticholingeric agents for thirteen (26%), alpha-adrenergic antagonists for nine (18%), antibiotics for six (12%). Abnormal UDS were noted in 36 (72%), including detrusor overactivity in 9 (18%), detrusor underactivity/acontractility in 5 (10%) and bladder outlet obstruction in 21 (42%). Fourteen (28%) had primary bladder neck dysfunction and five (10%) had benign prostatic hyperplasia. Post-UDS management included anticholingeric agents for ten (26%), alpha-adrenergic antagonists for seventeen (34%), catheterization for four (10%), behavioral therapy for three (6%), surgery for three (6%). None were prescribed antibiotics. Following UDS, the diagnosis had to be updated in 40 (80%) and concomitant change in management was required in 34 (68%). CONCLUSION: Young men presenting with LUTS have different underlying etiologies. Clinical diagnosis and treatment are often empiric and inaccurate. Urodynamic study is useful in the evaluation of this group of patients as it aids in arriving at an accurate diagnosis and guides treatment therapy. 相似文献