tbuckley/cabot-search huggingface dataset:
Attenuated FOLFIRINOX in the salvage treatment of gemcitabine‐refractory advanced pancreatic cancer: a phase II study
Authors: Jung Hoon Kim, Sang‐Cheol Lee, Sung Yong Oh, Seo‐Young Song, Namsu Lee, Eun Mi Nam, Soonil Lee, In Gyu Hwang, Hyo Rak Lee, Kyu Taek Lee, Sang‐Byung Bae, Han Jo Kim, Joung Soon Jang, Do Hyoung Lim, Hyun Woo Lee, Seok Yun Kang, Jung Hun Kang
Journal: Cancer Communications (2018)

Abstract Background Combination therapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) chemotherapy drastically improves survival of advanced pancreatic cancer patients. However, the efficacy of FOLFIRINOX as a second‐line treatment after gemcitabine failure has not been tested prospectively. We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine‐refractory advanced pancreatic cancer. Methods A multicenter phase II prospective open‐label, single‐arm study was conducted at 14 hospitals. Patients with histologically proven invasive ductal pancreatic adenocarcinoma, a measurable or evaluable lesion, Eastern Cooperative Oncology Group performance status 0 or 1, adequate organ function, and aged 19 years or older were eligible. Attenuated FOLFIRINOX consisted of oxaliplatin 65 mg/m 2 , irinotecan 135 mg/m 2 , and leucovorin 400 mg/m 2 injected intravenously on day 1 and 5‐fluorouracil 2000 mg/m 2 continuously infused intravenously over 46 h on days 1–2, repeated every 2 weeks. The primary endpoint was progression‐free survival from the initiation of FOLFIRINOX. Secondary endpoints were the objective response rate, disease control rate, overall survival, safety, and tolerability. We estimated overall survival and progression‐free survival using the Kaplan–Meier methods. Results We enrolled 39 patients from 14 institutions. The objective response rate was 10.3%, while the disease control rate was 64.1%. The 6‐month and 1‐year overall survival rates were 59.0% and 15.4%, respectively. Median progression‐free survival and overall survival were 3.8 months (95% confidence interval [CI] 1.5–6.0 months) and 8.5 months (95% CI 5.6–11.4 months), respectively. Grade 3 or 4 adverse events were neutropenia (41.0%), nausea (10.3%), anorexia (10.3%), anemia (7.7%), mucositis (7.7%), pneumonia/pleural effusion (5.1%), and fatigue (5.1%). One treatment‐related death attributable to septic shock occurred. Conclusion Attenuated FOLFIRINOX may be promising as a second‐line therapy for gemcitabine‐refractory pancreatic cancer.
Effect of Preschool Home Visiting on School Readiness and Need for Services in Elementary School
Authors: Karen L. Bierman, Janet Welsh, Brenda S. Heinrichs, Robert L. Nix
Journal: JAMA Pediatrics (2018)

Home visiting programs targeting the school readiness of preschool children (age range, 4-5 years) show promise in short-term and quasi-experimental studies but rarely are evaluated with rigorous designs and follow-up assessments.To examine the sustained effects of a preschool home visiting program on child and family competencies and on child need for services 4 years later.In a randomized clinical trial, individual families with preschool children were assigned to receive the Research-Based and Developmentally Informed-Parent home visiting program (REDI-P) (intervention group) or math home learning games in the mail (control group). Follow-up assessments occurred in third grade. Families were recruited from 24 Head Start centers in 3 Pennsylvania counties serving rural and urban areas. Four-year-old children from 200 low-income families participated. Families were recruited in fall 2008 and fall 2009. The follow-up data used were collected in spring 2013 and spring 2014. The analyses were conducted in 2016 to 2017.REDI-P visits followed a well-specified curriculum, with 10 home visits during preschool and 6 booster visits in kindergarten. Parents received coaching to enhance parent-child relationships and home learning materials to support child development and school readiness.Intervention focused on boosting competencies in academic performance and social-emotional adjustment and reducing child problems at home. Direct assessments, teacher ratings, and parent reports were collected. In addition, third-grade teachers recorded all services that children needed and received at school.Two hundred participating children (110 [55.0%] white, 52 [26.0%] black, and 38 [19.0%] Latino; 112 [56.0%] male) had a mean (SD) age of 4.45 (0.29) years at the start of intervention. Third-grade outcomes were available for 153 (76.5%) of the initial sample and revealed statistically significant effects on multiple measures in each competency domain. In addition, REDI-P reduced child need for educational and mental health services at school. Significant effect sizes were small to moderate, averaging approximately one-third of 1 SD (Cohen d = 0.27 to 0.45). Mediation models demonstrated that intervention effects on services were accounted for by intervention effects on the targeted competencies.REDI-P produced sustained benefits evident 4 years after intervention, significantly reducing child need for school services. The results of this study appear to validate the value of preschool home visiting as a strategy to help close the gap in school readiness and child well-being associated with poverty.
Synergism in Carcinogenesis
Authors: Frédéric Yves Bois, Paule Vasseur
Journal: JNCI Journal of the National Cancer Institute (1985)

Synergism in Carcinogenesis Get access Frédéric Yves Bois, Frédéric Yves Bois Centre des Sciences de l'Environnement, Université de Metz, 1, rue des Recollets 57000 Metz, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Paule Vasseur Paule Vasseur Centre des Sciences de l'Environnement, Université de Metz, 1, rue des Recollets 57000 Metz, France Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 74, Issue 3, March 1985, Page 729, https://doi.org/10.1093/jnci/74.3.729 Published: 01 March 1985
Adjuvant Anti-HER2 Therapy, Treatment-Related Amenorrhea, and Survival in Premenopausal HER2-Positive Early Breast Cancer Patients
Authors: Matteo Lambertini, Christine Campbell, José Bines, Larissa A Korde, Miguel Izquierdo, Debora Fumagalli, Lucia Del Mastro, Michail Ignatiadis, Kathleen Pritchard, Antonio C Wolff, Christian Jackisch, Istvan Lang, Michael Untch, Ian Smith, Frances Boyle, Binghe Xu, Carlos H Barrios, José Baselga, Alvaro Moreno-Aspitia, Martine Piccart, Richard D Gelber, Evandro de Azambuja
Journal: JNCI Journal of the National Cancer Institute (2018)

In premenopausal patients with human epidermal growth factor receptor 2 (HER2)–positive early breast cancer, the gonadotoxicity of trastuzumab and lapatinib remains largely uncertain, and the prognostic effect of treatment-related amenorrhea (TRA) is unknown. In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (BIG 2-06) phase III trial, HER2-positive early breast cancer patients were randomized (1:1:1:1) to receive one year of trastuzumab, lapatinib, their sequence, or their combination. As per study protocol, menopausal status was collected in all patients at random assignment and at week 37 visit. We investigated TRA rates and whether TRA in patients with hormone receptor–positive and –negative tumors would impact disease-free survival (DFS) and overall survival (OS). Landmark and time-dependent modeling were used to account for guarantee-time bias. All statistical tests were two-sided. A total of 2862 premenopausal women were included, of whom 1679 (58.7%) had hormone receptor–positive disease. Median age was 43 (interquartile range = 38–47) years. Similar TRA rates were observed in the trastuzumab (72.6%), lapatinib (74.0%), trastuzumab→lapatinib (72.1%), and trastuzumab+lapatinib (74.8%) arms (P = .64). The association between TRA and survival outcomes differed according to hormone-receptor status (Pinteraction for DFS = .007; Pinteraction for OS = .003). For hormone receptor–positive patients, the TRA cohort had statistically significantly better DFS (adjusted hazard ratio [aHR] = 0.58, 95% confidence interval [CI] = 0.45 to 0.76) and OS (aHR = 0.63, 95% CI = 0.40 to 0.99) than the no TRA cohort. No difference was observed in hormone receptor–negative patients. In this unplanned analysis, no association between TRA rate and type of anti-HER2 treatment was observed. TRA was associated with statistically significant survival benefits in premenopausal hormone receptor–positive/HER2-positive early breast cancer patients.
Fluorescent endoscopic breast surgery to detect the sentinel node and the tumor for aesthetics of breast conserving therapy.
Authors: Koji Yamashita
Journal: Journal of Clinical Oncology (2018)

e12610 Background: As the breast conserving surgery for early breast cancer, video-assisted breast surgery (VABS) has been reported to manipulate all performance only through the axillary minimum incision, not to need any wound on the breast skin, and to exceed the aesthetics after surgery. We utilized the fluorescent endoscopic system for VABS to detect a tiny fluorescence of the enhanced tumor from some distance away. We can find the tumor location and the extended area. We get the possibility to minimize the breast resection volume accurately for the better aesthetics. Methods: As sentinel node (SN) biopsy, the location of SN is detected by 3D-CT mammary lymphography before surgery, 0.25% indocyanine green is injected intracutaneously, and SN is detected and biopsied by fluorescent endoscopy. Trans-axillary retromammary approach (TARM) is a single port surgery with an axillary skin incision. The wound length is usually 2.5cm. We cut the mammary gland with clear surgical margin from behind the mammary gland by using tumor enhancement of fluorescence. The postoperative aesthetic results were evaluated by the original scoring system as ABNSW. Results: BCS was performed on 450 patients and fluorescent surgery on 20 patients. The operative cost is very low as the conventional one. There was no significant difference in operational infestation. There was no serious complication after surgery. The fluorescent effect can be detected more the 90% of cases, and more than 1 cm distance. It was accurate to recognize the surgical margin and to decrease the resection volume. The original shapes of the breast were preserved well. The postoperative esthetic results were excellent and better. The sensory disturbance was minimal. All patients expressed great satisfaction. Conclusions: VABS can be considered as a best surgical procedure in curability and esthetics. The fluorescent endoscopic surgery will decrease the resection volume and improve the breast aesthetics.
Walking on sunshine: scoping review of the evidence for walking and mental health
Authors: Paul Kelly, Chloë Williamson, Ailsa G Niven, Ruth Hunter, Nanette Mutrie, Justin Richards
Journal: British Journal of Sports Medicine (2018)

Walking has well-established positive relationships with, and effects on, physical health. In contrast, while poor mental health contributes substantially to global health burden, an overview of the benefits from walking has not previously been published. We aimed to scope the literature and present what is known, and highlight what is not known, about walking and mental health.Design: Scoping review.Ovid (Medline), ProQuest, Web of Science.Screening and reporting: 13 014 records were identified and screened by a team of researchers. Included full texts were analysed and reported according to mental health outcome.For the 8 mental health outcomes (identified a priori), there were a total of 5 systematic reviews and 50 individual papers included. Depression had the most evidence and existing systematic reviews were reported. Evidence for anxiety, psychological stress, psychological well-being, subjective well-being and social isolation and loneliness varied in volume and effectiveness, but no harmful effects were identified. There were no studies for walking and resilience. The setting and context of walking seems to be important variables.The evidence base that suggests walking benefits mental health is growing, but remains fragmented and incomplete for some important outcomes. Policy and national guidelines should promote the known mental health benefits of increased walking and future research should directly address the gaps we have identified.
Detection of Gastric Cancer with Novel Methylated DNA Markers: Discovery, Tissue Validation, and Pilot Testing in Plasma
Authors: Bradley W. Anderson, Yun-Suhk Suh, Boram Choi, Hyuk-Joon Lee, Tracy C. Yab, William R. Taylor, Brian A. Dukek, Calise K. Berger, Xiaoming Cao, Patrick H. Foote, Mary E. Devens, Lisa A. Boardman, John B. Kisiel, Douglas W. Mahoney, Seth W. Slettedahl, Hatim T. Allawi, Graham P. Lidgard, Thomas C. Smyrk, Han-Kwang Yang, David A. Ahlquist
Journal: Clinical Cancer Research (2018)

Purpose: Gastric adenocarcinoma is the third most common cause of cancer mortality worldwide. Accurate and affordable noninvasive detection methods have potential value for screening and surveillance. Herein, we identify novel methylated DNA markers (MDM) for gastric adenocarcinoma, validate their discrimination for gastric adenocarcinoma in tissues from geographically separate cohorts, explore marker acquisition through the oncogenic cascade, and describe distributions of candidate MDMs in plasma from gastric adenocarcinoma cases and normal controls.Experimental Design: Following discovery by unbiased whole-methylome sequencing, candidate MDMs were validated by blinded methylation-specific PCR in archival case-control tissues from U.S. and South Korean patients. Top MDMs were then assayed by an analytically sensitive method (quantitative real-time allele-specific target and signal amplification) in a blinded pilot study on archival plasma from gastric adenocarcinoma cases and normal controls.Results: Whole-methylome discovery yielded novel and highly discriminant candidate MDMs. In tissue, a panel of candidate MDMs detected gastric adenocarcinoma in 92% to 100% of U.S. and South Korean cohorts at 100% specificity. Levels of most MDMs increased progressively from normal mucosa through metaplasia, adenoma, and gastric adenocarcinoma with variation in points of greatest marker acquisition. In plasma, a 3-marker panel (ELMO1, ZNF569, C13orf18) detected 86% (95% CI, 71-95) of gastric adenocarcinomas at 95% specificity.Conclusions: Novel MDMs appear to accurately discriminate gastric adenocarcinoma from normal controls in both tissue and plasma. The point of aberrant methylation during oncogenesis varies by MDM, which may have relevance to marker selection in clinical applications. Further exploration of these MDMs for gastric adenocarcinoma screening and surveillance is warranted. Clin Cancer Res; 24(22); 5724-34. ©2018 AACR.
Junior doctors see “substantial improvements” to their working lives, progress report shows
Authors: Jacqui Wise
Journal: BMJ (2018)

The BMA has welcomed what it describes as “substantial improvements” to the working conditions for junior doctors in England, including more flexible training opportunities and greater support.

Health Education England’s second report into the effects of the Enhancing Junior Doctors Working Lives programme was published on 30 May.1 The programme was the result of collaboration between the BMA, General Medical Council, NHS Employers, and the Academy of Medical Royal Colleges who were brought together after the junior doctors dispute two years ago to see what could be done to improve junior doctors’ training and working environments.

According to the BMA, the programme has initiated the most significant changes to postgraduate medical training for a number of years.2 Jeeves Wijesuriya, BMA Junior Doctors’ …
Bone Mechanical Properties in Healthy and Diseased States
Authors: Elise F. Morgan, Ginu U. Unnikrisnan, Amira I. Hussein
Journal: Annual Review of Biomedical Engineering (2018)

The mechanical properties of bone are fundamental to the ability of our skeletons to support movement and to provide protection to our vital organs. As such, deterioration in mechanical behavior with aging and/or diseases such as osteoporosis and diabetes can have profound consequences for individuals’ quality of life. This article reviews current knowledge of the basic mechanical behavior of bone at length scales ranging from hundreds of nanometers to tens of centimeters. We present the basic tenets of bone mechanics and connect them to some of the arcs of research that have brought the field to recent advances. We also discuss cortical bone, trabecular bone, and whole bones, as well as multiple aspects of material behavior, including elasticity, yield, fracture, fatigue, and damage. We describe the roles of bone quantity (e.g., density, porosity) and bone quality (e.g., cross-linking, protein composition), along with several avenues of future research.
A community based consultative survivorship program for breast cancer survivors.
Authors: Kit Yu Lu, Theresa M. Lee, Megan Lanigan, Beth Rudge, Lisa Torp
Journal: Journal of Clinical Oncology (2018)

47 Background: Many organizations have recognized the importance of longitudinal care for Breast Cancer Survivors (BCS) as they remained at risk for treatment related side effects (TRSE) that can greatly impact their health and quality of life. Various models of Breast Cancer Survivorship Program (BCSP) have been proposed. In October 2016, we implemented a BCSP using a consultative model with the goals to create a systematic approach to capture patients’ concerns, coordinate on-going care, standardize survivorship recommendations, and track care plan delivery compliance. Methods: Our Survivorship Nurse Practitioner (SNP) meets with patients in a one-on- one consultative visit after receiving electronic referral. Patients are given a comprehensive survey to assess symptoms and concerns following their treatment. Based on survey, SNP provides personalized education about their concerns. SNP also makes appropriate interventions and arranges referrals for supportive care services. After the visit, SNP generates a care plan and a consultative letter detailing the patient’s concerns and provides further recommendations for interventions and follow up care. SNP leads a quarterly Multidisciplinary Conference to educate treating providers and supporting staff regarding TRSE management according to standard guidelines and evidenced based approaches. Results: From Oct 2016-Oct 2017, 252 BCS were seen at our BCSP. BCS reported high satisfaction with better understanding and coping with their symptoms after being seen. 100% of oncology providers reported better understanding about BCS's concerns and felt more confident about TRSE management. Primary providers also reported higher satisfaction with communication across specialty. The ability to identify BCS and to track care plan delivery compliance was also more streamlined. Conclusions: We elected for a consultative approach because it allowed for a dedicate time to review all components of survivorship. It also created a formalized way to better understand the needs of our survivors. In addition, this approach empowered the patients to discuss TRSE with their providers and enabled the care team to integrate survivorship care throughout their subsequent visits.
Plasma and tumor genomic correlates of response to BYL719 in <i>PI3KCA</i> mutated metastatic ER-positive breast cancer (ER+/HER2- BC).
Authors: Sarah-Jane Dawson, Lironne Wein, Maria Joao Silva, Stephen James Luen, Courtney VanGeelen, Kate Moodie, Peter Savas, Chen-Fang Weng, Andjelija Zivanovic Bujak, Miriam M Yeung, Sarah Ftouni, Keilly Kuykhoven, Rodney J Hicks, Prudence A. Francis, Chee Khoon Lee, Sherene Loi
Journal: Journal of Clinical Oncology (2018)

1055 Background: Mutations of genes involved in the PI3K signalling pathway occur frequently in BC. We performed a phase II study of BYL719, a selective PI3Kα inhibitor, in BC to evaluate its efficacy and identify biomarkers that correlate with tumor response. Methods: Eligible patients had advanced ER+/HER2- BC and documented genetic alteration of the PI3K pathway detected in either tumor or plasma. Patients received BYL719 350mg orally daily. The primary end point was RECIST objective response rate (ORR). Secondary endpoints were clinical benefit rate (CBR) including stable disease for ≥24 weeks, progression-free survival (PFS) and efficacy according to baseline and week 8 change in ctDNA levels. ctDNA analysis was performed through droplet digital PCR. Results: Of the total 17 patients treated, 16 (94%) had a PIK3CA mutation (mt) and 1 had a PTEN deletion. Of the PI3KCA mutant patients, 8 (47%) had a kinase domain mt, 7 (41%) had a helical domain mt and 1 (6%) patient had 2 PIK3CA mts. 16/17 (94%) patients had their alteration detected in plasma at baseline; concordance between plasma and tumor was 94% (15/16). Median age was 60 years (45-77). Patients had received a median of 3 prior treatment lines (1-7) in the metastatic setting; 16 (94%) had received prior endocrine therapy and 14 (82%) prior chemotherapy. 15 (88%) had visceral disease. The ORR (centrally reviewed) was 41% (7/17) and CBR was 59% (10/17). Median PFS (mPFS) was 5.49 months (mo) (95% CI, 3.63 – 13.78). The most common grade ≥ 3 adverse event was hyperglycaemia (5/17; 29%). Co-existent MAP3K1 or ESR1 mt (N = 7, 41%) had a longer clinical benefit (mPFS 11.02 mo (95%CI, 5.44-NR) with 3 (18%) ≥1 yr) compared with co-existent TP53 mt, CCND1 or FGFR1 amplification (N = 10, 59%) (mPFS 3.66 mo (95%CI, 3.63-NR)). Patients who achieved clinical benefit had a significantly greater decrease in ctDNA levels at week 8 from baseline (median 97.34% vs 9.14% decrease, p = 0.04). Conclusions: BYL719 in previously treated advanced ER+/HER2- BC with PIK3CA mt detectable in plasma at baseline demonstrated robust clinical benefit. This biomarker should be considered in the Phase III setting. Clinical trial information: NCT02506556.
A tightly controlled Src-YAP signaling axis determines therapeutic response to dasatinib in renal cell carcinoma
Authors: Jingya Sun, Xin Wang, Boyun Tang, Hongchun Liu, Minmin Zhang, Yueqin Wang, Fangfang Ping, Jian Ding, Aijun Shen, Meiyu Geng
Journal: Theranostics (2018)

Over the past decade, therapies targeting the VEGF/VEGFR and mTOR pathways have served as the standard of care for the clinical management of renal cell carcinoma (RCC) patients.Albeit promising, these targeted drugs have attained only modest clinical benefits with limited prolonged progression-free survival.Therefore, alternative reasonable and applicable therapeutic approaches should be introduced to improve the clinical outcome of RCC patients.Methods: FDA approved kinase inhibitors were screened to evaluate their abilities to suppress the proliferation of RCC cells.Then, the downstream effector, therapeutic target and signaling pathway of the selected drug were identified by gene expression array, RNAi, kinase profile and rescue verification.Finally, the in vivo effectiveness of the drug was assessed in cell line-based xenograft models and patient-derived xenograft models.Results: In this study, we discovered that dasatinib is a potent agent that can impair RCC cell viability in vitro and decrease tumor growth in vivo.Mechanistically, we improved the understanding of the precise mechanistic role of YAP as a pivotal effector of dasatinib-induced anti-proliferation through Src-JNK-LIMD1-LATS signaling cascade in RCC cells.Meanwhile, our results indicated that the alteration of p-YAP is closely correlated to the growth inhibition caused by dasatinib in sensitive RCC models.Conclusion: Our findings provide evidence that dasatinib may serve as a powerful drug candidate to treat subgroups of RCC patients with hyper-activated Src-YAP signaling axis, and the alteration of p-YAP could serve as a functional response biomarker of dasatinib in RCC.