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Predictive biomarkers in precision medicine and drug development against lung cancer

Chinese Journal of Cancer 2015年第7期34卷 295-309页

作者： Bingliang Fang Reza J Mehran John V Heymach stephen G swisher Department of Thoracic and Cardiovascular Surgery The University of Texas MD Anderson Cancer Center Department of Thoracic and Head/Neck Medical Oncology The University of Texas MD Anderson Cancer Center

The molecular characterization of various cancers has shown that cancers with the same origins,histopathologic diagnoses,and clinical stages can be highly heterogeneous in their genetic and epigenetic alterations that cause tumorigenesis.A number of cancer driver genes with functional abnormalities that trigger malignant transformation and that are required for the survival of cancer cells have been *** agents targeting some of these cancer drivers have been successfully developed,resulting in substantial improvements in clinical symptom amelioration and outcomes in a subset of cancer ***,because such therapeutic drugs often benefit only a limited number of patients,the successes of clinical development and applications rely on the ability to identify those patients who are sensitive to the targeted ***,biomarkers that can predict treatment responses are critical for the success of precision therapy for cancer patients and of anticancer drug *** review discusses the molecular heterogeneity of lung cancer pathogenesis;predictive biomarkers for precision medicine in lung cancer therapy with drugs targeting epidermal growth factor receptor(EGFR),anaplastic lymphoma kinase(ALK),c-ros oncogene 1 receptor tyrosine kinase[ROSl),and immune checkpoints;biomarkers associated with resistance to these therapeutics;and approaches to identify predictive biomarkers in anticancer drug *** identification of predictive biomarkers during anticancer drug development is expected to greatly facilitate such development because it will increase the chance of success or reduce the attrition ***,such identification will accelerate the drug approval process by providing effective patient stratification strategies in clinical trials to reduce the sample size required to demonstrate clinical benefits.

关键词：生物标志物药物开发预测肺癌医学受体酪氨酸激酶表皮生长因子受体治疗药物

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Intensity-modulated radiation therapy with concurrent chemotherapy for locally advanced cervical and upper thoracic esophageal cancer

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World Journal of Gastroenterology 2006年第34期12卷 5501-5508页

作者： Shu-Lian Wang Zhongxing Liao Helen Liu( Jaffer Ajani stephen swisher James D Cox Ritsuko Komaki Department of Radiation Oncology Cancer Hospital Peking Union Medical College and Chinese Academy of Medical Sciences Beijing China Department of Radiation Oncology the University of Texas M D Anderson Cancer Center United States Department of Gastrointestinal Medical Oncology the University of Texas M D Anderson Cancer CenterUnited States Department of Cardiovascular and Thoracic Surgical Oncology the University of Texas M D Anderson Cancer Center United States

AIM： To evaluate the dosimetry, efficacy and toxicity of intensity-modulated radiation therapy （IMRT） and concurrent chemotherapy for patients with locally advanced cervical and upper thoracic esophageal cancer. METHODS： A retrospective study was performed on 7 patients who were definitively treated with IMRT and concurrent chemotherapy. Patients who did not receive IMRT radiation and concurrent chemotherapy were not included in this analysis. IMRT plans were evaluated to assess the tumor coverage and normal tissue avoidance. Treatment response was evaluated and toxicities were assessed. RESULTS： Five- to nine-beam IMRT were used to deliver a total dose of 59.4-66 Gy （median： 64.8 Gy） to the primary tumor with 6-MV photons. The minimum dose received by the planning tumor volume （PTV） of the gross tumor volume boost was 91.2%-98.2% of the prescription dose （standard deviation [SD]： 3.7%-5.7%）. The minimum dose received by the PTV Of the clinical tumor volume was 93.8%-104.8% （SD： 4.3%-11.1%） of the prescribed dose. With a median follow-up of 15 rno （range： 3-21 too）, all 6 evaluable patients achieved complete response. Of them, 2 developed local recurrences and 2 had distant metastases, 3 survived with no evidence of disease. After treatment, 2 patients developed esophageal stricture requiring frequent dilation and 1 patient developed tracheal-esophageal fistula. CONCLUSION： Concurrent IMRT and chemotherapy resulted in an excellent early response in patients with locally advanced cervical and upper thoracic esophageal cancer. However, local and distant recurrence and toxicity remain to be a problem. Innovative approaches are needed to improve the outcome.

关键词： Esophageal cancer Intensity-modulated radiation therapy Chemotherapy

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Large-area photonic lift-off process for flexible thin-film transistors

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npj Flexible Electronics 2022年第1期6卷 115-124页

作者： Adam M.Weidling Vikram STurkani Vahid Akhavan Kurt A.Schroder Sarah L.swisher Department of Electrical and Computer Engineering University of Minnesota Twin Cities4-174 Keller Hall200 Union Street S.E.MinneapolisMN 55455USA NovaCentrix 400 Parker DriveSuite 1110AustinTX 78728USA

Fabricating flexible electronics on plastic is often limited by the poor dimensional stability of polymer *** mitigate,glass carriers are used during fabrication,but removing the plastic substrate from a carrier without damaging the electronics remains *** we utilize a large-area,high-throughput photonic lift-off(PLO)process to rapidly separate polymer films from rigid *** uses a 150µs pulse of broadband light from flashlamps to lift-off functional thin films from glass carrier substrates coated with a light absorber layer(LAL).Modeling indicates that the polymer/LAL interface reaches above 800℃ during PLO,but the top surface of the PI remains below 120℃.An array of indium zinc oxide(IZO)thin-film transistors(TFTs)was fabricated on a polyimide substrate and photonically lifted off from the glass *** TFT mobility was unchanged by *** flexible TFTs were mechanically robust,with no reduction in mobility while flexed.

关键词： film process absorber

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并购前申报实务手册

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作者： (swisher Anthony W.)斯威瑟 (Imus Neil W.)伊姆斯

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Further support for a Cretaceous age for the feathered-dinosaur beds of Liaoning,China:New ^(40)Ar/^(39)Ar dating of the Yixian and Tuchengzi Formations

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Chinese Science Bulletin 2002年第2期47卷 135-138页

作者： C. C. swisher III, WANG Xiaolin, ZHOU Zhonghe, WANG Yuanqing, JIN Fan, ZHANG Jiangyong , XU Xing, ZHANG Fucheng & WANG YuanDepartment of Geological Sciences, Wright Labs, Rutgers University, Piscataway, New Jersey 08854, USA (e-mail: cswish@rutgers. rci.e Department of Geological Sciences Wright Labs Rutgers University Piscataway NJ 08854 United States

We report new 40Ar/39Ar dating results ob-tained from total fusion and incremental-heating analyses of sanidine and biotite from three tuffs found interbedded within the fossil-bearing deposits of Liaoning, northeast China. The first is a new sample of the Bed 6 Sihetun tuff from the Yixian Formation, previously dated by our team as middle Early Cretaceous, and recently considered by Lo et al., partially reset due to metamorphism from a nearby ba-saltic sill. The second is the Yixian Bed 9 tuff from Heng-daozi considered by Lo et al. to be unaffected by metamor-phism and whose age, based on total fusion 40Ar/39Ar dating of biotite, argues for a Jurassic age for the Yixian Formation. The third tuff is a previously undated tuff from the upper part of the underlying Tuchengzi Formation. Single crystal total fusion 40Ar/39Ar analyses of the Sihetun sanidine showed homogeneous radiogenic Ar, Ca/K ratios, excellent reproducibility and gave a mean age of 125.0 ± 0.18 (1SD) ± 0.04 (SE) Ma. Single sanidine

关键词： 40Ar/39Ar dating Cretaceous Yixian Formation Tu-chengzi Formation western Liaoning.

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Jawbone启动2.5亿美元融资计划

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投资与合作 2014年第7期 112-112页

作者： Kara swisher

Jawbone是一家创新型消费电子设备制造商,其代表性产品是“UP智能腕带”(Up wristband)。据多名知情人士透露,这家公司正在开展新一轮融资,计划融资2.5亿美元。同样来自这些人士的消息表明,该轮融资已获得超额认购,融资总额或将升至3亿...

Jawbone是一家创新型消费电子设备制造商,其代表性产品是“UP智能腕带”(Up wristband)。据多名知情人士透露,这家公司正在开展新一轮融资,计划融资2.5亿美元。同样来自这些人士的消息表明,该轮融资已获得超额认购,融资总额或将升至3亿美元。这轮融资的领投者是总部位于旧金山的Rizvi Traverse,它也是推特、Square等当红科技企业的大股东,公司领导苏哈尔·利兹维(Suhail Rizvi)将进入Jawbone公司董事会。俄罗斯投资人尤里·米尔纳(Yuri Milner)也参与了投资,他的投资额与Rizvi

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Gastric intestinal metaplasia development in African American predominant United States population

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World Journal of Gastrointestinal Endoscopy 2022年第10期14卷 597-607页

作者： Akram I Ahmad Arielle Lee Claire Caplan Colin Wikholm Ioannis Pothoulakis Zaynab Almothafer NishthaRaval Samantha Marshall Ankit Mishra Nicole Hodgins In Guk Kang Raymond K Chang Zachary Dailey Arvin Daneshmand Anjani Kapadia Jae Hak Oh Brittney Rodriguez Abhinav Sehgal Matthew Sweeney Christopher B swisher Daniel F Childers Corinne O'Connor Lynette M Sequeira Won Cho Department of Internal Medicine MedStar Washington Hospital CenterWashingtonDC 20010United States Department of Internal Medicine Georgetown University School of MedicineWashingtonDC 20007United States Department of Gastroenterology and Hepatology INOVA Medical SystemLeesburgVA 20176United States

BACKGROUND Gastric cancer significantly contributes to cancer mortality *** intestinal metaplasia(GIM)is a stage in the Correa cascade and a premalignant lesion of gastric *** natural history of GIM formation and progression over time is not fully ***,there are no clear guidelines on GIM surveillance or management in the United *** To investigate factors associated with GIM development over time in African American-predominant study *** This is a retrospective longitudinal study in a single tertiary hospital in Washington *** retrieved upper esophagogastroduodenoscopies(EGDs)with gastric biopsies from the pathology department database from January 2015 to December *** included in the study had undergone two or more EGDswith gastric *** with no GIM at baseline were followed up until they developed GIM or until the last available *** criteria consisted of patients age<18,pregnancy,previous diagnosis of gastric cancer,and missing data including pathology results or endoscopy *** study population was divided into two groups based on GIM *** and multivariate Cox regression was used to estimate the hazard induced by patient demographics,EGD findings,and Helicobacter pylori(***)status on the GIM *** Of 2375 patients who had at least 1 EGD with gastric biopsy,579 patients were included in the study.138 patients developed GIM during the study follow-up period of 1087 d on average,compared to 857 d in patients without GIM(P=0.247).The average age of GIM group was 64 years compared to 56 years in the non-GIM group(P<0.001).In the GIM group,adding one year to the age increases the risk for GIM formation by 4%(P<0.001).Over time,African Americans,Hispanic,and other ethnicities/races had an increased risk of GIM compared to Caucasians with a hazard ratio(HR)of 2.12(1.16,3.87),2.79(1.09,7.13),and 3.19(1.5,6.76)*** gender difference was obse

关键词： Gastric intestinal metaplasia Gastric cancer Helicobacter pylori Retrospective longitudinal study Esophagogastroduodenoscopy African American population

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接受预防性输卵管卵巢切除术妇女隐性肿瘤的预测因子

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世界核心医学期刊文摘（妇产科学分册） 2006年第11期2卷 4-4页

作者： Lamb J.D. Garcia R.L. Goff B.A. E.M. swisher 朱磊 Departments of Obstetrics and Gynecology Dr.

Objective: The purpose of this study was to define the rate of neoplasia in prophylactic surgical specimens with the use of a careful surgical and pathologic protocol in a prospective study of high-risk women who were undergoing risk-redu-cing salpingo-oophorectomy. Outcomes of interest were neoplasia that was identified in surgical specimens and clinical outcomes of women who were undergoing risk-re-ducing salpingo-oophorectomy. We hypothesized that older age and having a BRCA1 mutation would be predictors for tubal or ovarian neoplasia and that a careful surgical and pathologic protocol would lead to a low rate of subsequent primary peritoneal cancer. Study design: A prospective tissue and research database enrolled patients who underwent risk-reducing salpingo-oophorectomy for prevention of ovarian cancer. Clinical and pathologic data were extracted for those patients after the initiation of a de- fined surgical and pathologic protocol in 1999. Results: One hundred thirteen women met the high-risk criteria; 40 of the women (45% ) who were tested had a deleterious mutation in BRCA1, and 22 women (25% ) had a mutation in BRCA2. Seven women had ovarian or tubal neoplasia (6.2% ). One woman had occult endometrial cancer. Age ≥ 45 years and having a BRCA1 or BRCA2 mutation were significant predictors of occult neoplasia. Two patients with neoplasia that was identified at risk-reducing salpingo-oophorectomy experienced recurrence. Three patients with BRCA1 mutations have subsequent new diagnoses of breast cancer. No patients had primary peritoneal cancer after risk-reducing salpingo-oophorectomy. Conclusion: Age ≥ 45 years and mutations in BRCA1 or BRCA2 predict occult neoplasia in women who undergo risk-reducing salpingo-oophorectomy. A thorough pathologic and surgical protocol at the time of risk-reducing salpingo-oophorectomy may improve the risk of subsequent primary peritoneal cancer.

关键词： BRCA 输卵管卵巢临床结局腹膜癌病理检查基因突变病理学检查癌发生率研究设计试验计划

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