tbuckley/cabot-search huggingface dataset:
Abstract LB-78: A randomized trial on folic acid supplementation and risk of recurrent colorectal adenoma
Authors: Kana Wu, Elizabeth A Platz, Walter C Willett, Jacob Selhub, Charles S Fuchs, Edward Giovannucci
Journal: Cancer Research (2008)

Abstract Results from two recently published randomized trials (Logan et al., 2008 and Cole et al., 2007) found little evidence for a protective effect of folic acid supplementation on the recurrence of colorectal adenomas. In one trial (Cole et al., 2007) folic acid supplementation even appeared to be non-significantly associated with higher risk of advanced adenoma. This following paper reports on results from another randomized controlled trial of folic acid (1000 micrograms/day) versus placebo among participants of two large prospective cohorts, the Health Professionals Follow-up Study (HPFS) and the Nurses’ Health Study (NHS), who had a previous diagnosis of colorectal adenoma. The primary endpoint of interest was any new diagnosis of adenoma during the study period (May, 1996 to March, 2003). 346 subjects were randomized to folic acid and 346 subjects to placebo for a period of three to up to 6 1/2 years. The incidence of at least one recurrent adenoma was not associated with folic acid supplementation (RR=0.86, 95% CI=0.64-1.16, p=0.32). There was some suggestion of an inverse association between folic acid supplementation and recurrent distal adenoma (multivariate adjusted relative risk (RR) =0.67, 95% confidence interval (CI)=0.39-1.15, p=0.14), and early stage adenoma (small and tubular) (RR=0.74, 95% CI=0.48-1.15, p=0.19), but none of the associations reached statistical significance. Advanced adenoma (large or adenomas with villous component) was not associated with folic acid supplementation, but the number of advanced cases was low (16 cases folate group, 18 cases placebo group; RR=0.96 95% CI=0.50-1.84, p=0.90). However, when associations were examined by folate blood concentrations drawn prior to time of randomization (&amp;lt;=7.5 ng/mL vs. &amp;gt;7.5 ng/mL) significant inverse associations were found for total recurrent adenoma (43 cases placebo, 32 cases folate, RR=0.64 (95% CI=0.43-0.96, p=0.03), distal adenoma (20 cases placebo, 9 cases folate, RR=0.36 (95% CI=0.14-0.61, p=0.001), early adenoma (22 cases placebo, 10 cases folate, RR=0.36 (95% CI=0.17-0.76, p=0.007), advanced adenoma (14 cases placebo, 9 cases folate, RR=0.48 (95% CI= 0.22-1.06, p=0.07) among those with low folate levels. No associations were found for participants with higher folate levels at baseline (at least one adenoma: 30 cases placebo, 30 cases folate, RR=1.30 (95% C=0.83-2.03, p=0.25). Occurrence of deaths, cancer and cardiovascular disease did not differ by treatment status. Our results do not support a protective effect of folic acid supplementation on the recurrence of colorectal adenomas; however, there may be some benefit on adenoma recurrence among those with a lower folate levels at baseline. The role of additional folic acid supplementation as a potential preventive measure for colorectal adenomas/cancer needs to be reevaluated especially with regard to dose and timing.
Abstract P3-08-24: Mutational characterization of HER2-positive breast cancer
Authors: A Velasco Sánchez, A Gasol Cudos, S Morales, J Veas Rodriguez, A Serrate López, J Mele Olivé, C Canosa Morales
Journal: Cancer Research (2019)

Abstract Background: Studies of mutational analysis have been widely reported in various global series of breast cancer. However, in the era of different phenotypes of breast cancer, these analyses should be more specific in order to find differences in each phenotype that could predict response to treatment. Particularly HER2 positive is a special subtype with different connotations that make the analysis of its genotype very interesting. Methods: Cohorts of 47 consecutive samples of HER2 positive breast cancer, treated in our institution were analyzed. It was conducted a mutational study with NGS technique of the most common genes involved in breast cancer. Results: 10 patients were metastatic at diagnostic, 17 with negative estrogen receptor expression, the median value of Ki67 was 45 (20-95) and the median initial tumor size was 33.5 mm (18-111). Inmunohistochemical expression of HER2 was +3 in 31 tumors and +2 in 15 with a median ratio by FISH of 3,2 (1,18-8,3). We also analyzed the expression of HER by PCR of mRNA in 35 samples with a median expression of 2,49 (0,26-33,15). 38 patients underwent surgical excision of the tumor with a pathologic complete response observed in 19. We found a total of 38 significant mutations and the genes with more frequent mutations were MCPH1 (100%), HNF1 (98%), p53 (96%), somatic BRCA1 (62%), TSC1 (30%), PIK3CA (23%), ATM (21%), ALK (15%) and somatic BRCA2 (13%). Although the aim of the study was to find the most frequent mutations in this subtype, we have also analyzed possible correlations of those with pathological response or with more common variables, finding no significance in any of them. Conclusions: In our series, we found a high percentage of mutations in MCPH1, HNF1 and p53 genes with almost 100% of mutations in p53 that are also limited in a very specific area. Also interesting is the 62% of mutations found in BRCA1 and 13% in BRCA2 that could allow more specific treatments in this subgroup. Although the study did not have the power to assess the predictive factor of these mutations, it is very suggestive that in the 7 patients with BRCA mutations, 6 achieved a complete pathological response. Citation Format: Velasco Sánchez A, Gasol Cudos A, Morales S, Veas Rodriguez J, Serrate López A, Mele Olivé J, Canosa Morales C. Mutational characterization of HER2-positive breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-08-24.
Maternal Asthma, Preeclampsia, and Risk for Childhood Asthma at Age Six
Authors: Hooman Mirzakhani, Vincent J. Carey, Thomas F. McElrath, Bruce W. Hollis, George T. O’Connor, Robert S. Zeiger, Leonard Bacharier, Augusto A. Litonjua, Scott T. Weiss
Journal: American Journal of Respiratory and Critical Care Medicine (2019)
Pills, pills, pills
Authors: Isobel Weinberg
Journal: BMJ (2012)

How good is your prescribing? Not very good at all, if statistics are to be believed. Junior doctors make nearly a fifth of prescribing errors; just 35% of medical students have filled in a drug chart more than three times before qualifying. The blame is being laid at the feet of inconsistent and inadequate clinical pharmacology teaching in medical schools. One pharmacology professor described teaching in French medical schools as “insufficient, uncoordinated, and likely to get worse.” (p 10)

The British Pharmacological Society and the Medical Schools …
NHS Reforms: not all bad news
Authors: Gajendiran Thiruchandran
Journal: BMJ (2012)

You don’t need to consult a savvy hedge fund guru to realise that the return on our communal investment in the NHS has been poor. Hospital waiting times have increased, hospital deficits are the norm, beds are in short supply, and superbugs are still a problem.

Patient care should be our priority but given the grim economic climate a less spendthrift and resourceful NHS is needed. Without substantial reform to the NHS, it would seem that “cutting the deficit not the NHS,” an election slogan coined by the conservatives, is a “mission impossible.”

The health secretary Andrew Lansley’s proposed Health and Social Care Bill has received fierce criticism from most quarters, including the BMJ whose scathing attack—beseeching us to “sweep the bill’s …
Abstract P2-08-30: Vitamin D as a prognostic factor in triple negative early breast cancer
Authors: S Morales Murillo, A Gasol Cudos, J Veas Rodriguez, M Santacana, C Canosa Morales, J Mele Olivé
Journal: Cancer Research (2019)

Abstract Background: Triple negative breast cancer is a special phenotype where the pathological complete response (pCR) remains the most important factor but only around a 40% of patients achieve this response. We analyze if the vitamin D receptors (VDR) could be a prognostic factor not related with the histological response. Methods: A series of 160 patients with early or locally advanced triple negative breast cancer that received neoadjuvant chemotherapy were retrospectively reviewed from 2007 to 2017. Clinicopathological and vitamin D receptors analysis were correlated to pCR. Results: Median age was 53, median tumor size 30mm, 48% had nodal involvement, and median ki67 expression was of 70%. Androgen receptor was expressed in 28% of tumors analyzed, EGFR in 89%, CK5/6 in 63%. VDR (cytoplasmatic and nuclear) expression was determined in 56 patients, finding in 45 (80%) an expression that was considered as high. We achieved a total of 73/160 pCR (45%) with a significant median disease free survival of 178 months (log rank p: 0,0001). In the univariate analysis, the initial tumoral size, initial nodal involvement and expression of VDR was significant; and in the mutivariate model the expression of VDR maintains the level of significance ( HR: 0,138 IC 95% 0,039-0,493 p:0,002). Conclusions: The expression of VDR in the initial tumor before starting neoadjuvant chemotherapy is a strong predictor of recurrence independently of histological response with a median disease free survival of 149 months in patients with high expression versus 62 month. Furthermore, in patients without histological response, progression-free median survival is 86 months for patients with high expression versus 35 months. Citation Format: Morales Murillo S, Gasol Cudos A, Veas Rodriguez J, Santacana M, Canosa Morales C, Mele Olivé J. Vitamin D as a prognostic factor in triple negative early breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-30.
Abstract ES8-2: New data on hormones and risk of breast cancer
Authors: S Hankinson
Journal: Cancer Research (2019)

Abstract This session has two primary objectives: (1) to provide a review of recent research findings relating both endogenous and exogenous hormone exposures to later risk of breast cancer in women, and (2) to put these findings into context with what we already knew. For example, circulating levels of anti-Mullerian hormone (AMH), a hormone measureable only in premenopausal women, has recently been associated with increased risk of both premenopausal and postmenopausal breast cancer in a large prospective pooled analysis. Thus, circulating levels of AMH can now be considered along with the plasma estrogens and androgens (where weaker but consistent associations are observed) to be a probable or confirmed breast cancer risk factor. In postmenopausal women, plasma concentrations of sex steroid hormones, factors consistently linked with increased risk of breast cancer, were shown in recent studies to significantly improve breast cancer risk prediction models (such as the Gail Model). From older epidemiologic studies, we knew that recent or current use of oral contraceptives modestly increases risk of breast cancer, and this increase in risk subsides with duration since quitting use. Recent studies of newer contraceptives now add additional insight into this important issue. Citation Format: Hankinson S. New data on hormones and risk of breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES8-2.
Electrical Cell Stimulation: Fabrication of a Biocompatible Liquid Crystal Graphene Oxide–Gold Nanorods Electro‐ and Photoactive Interface for Cell Stimulation (Adv. Healthcare Mater. 9/2019)
Authors: Daniela Duc, Paul R. Stoddart, Sally L. McArthur, Robert M. I. Kapsa, Anita F. Quigley, Mitchell Boyd‐Moss, Simon E. Moulton
Journal: Advanced Healthcare Materials (2019)

Illustration of liquid crystal graphene oxide-gold nanorods (LCGO-AuNR) film used as interface for electrical and near-infrared (NIR) co-stimulation of neurons. In article number 1801321, Simon E. Moulton and co-workers develop an LCGO-AuNR nanocomposite film with promising electroactivity and photoactivity in the NIR. Good biocompatibility with neuronal cell line is also shown. Illustration credit: George Chiramal Davis.
A longitudinal big data approach for precision health
Authors: Sophia Miryam Schüssler-Fiorenza Rose, Kévin Contrepois, Kegan J. Moneghetti, Wenyu Zhou, Tejaswini Mishra, Samson Mataraso, Orit Dagan-Rosenfeld, Ariel B. Ganz, Jessilyn Dunn, Daniel Hornburg, Shannon Rego, Dalia Perelman, Sara Ahadi, M. Reza Sailani, Yanjiao Zhou, Shana R. Leopold, Jieming Chen, Melanie Ashland, Jeffrey W. Christle, Monika Avina, Patricia Limcaoco, Camilo Ruiz, Marilyn Tan, Atul J. Butte, George M. Weinstock, George M. Slavich, Erica Sodergren, Tracey L. McLaughlin, Francois Haddad, Michael P. Snyder
Journal: Nature Medicine (2019)
Gene Expression Profiling of Lung Atypical Carcinoids and Large Cell Neuroendocrine Carcinomas Identifies Three Transcriptomic Subtypes with Specific Genomic Alterations
Authors: Michele Simbolo, Stefano Barbi, Matteo Fassan, Andrea Mafficini, Greta Ali, Caterina Vicentini, Nicola Sperandio, Vincenzo Corbo, Borislav Rusev, Luca Mastracci, Federica Grillo, Sara Pilotto, Giuseppe Pelosi, Serena Pelliccioni, Rita T. Lawlor, Giampaolo Tortora, Gabriella Fontanini, Marco Volante, Aldo Scarpa, Emilio Bria
Journal: Journal of Thoracic Oncology (2019)

DNA mutational profiling showed that atypical carcinoids (ACs) share alterations with large cell neuroendocrine carcinomas (LCNECs). Transcriptomic studies suggested that LCNECs are composed of two subtypes, one of which shares molecular anomalies with SCLC. The missing piece of information is the transcriptomic relationship between ACs and LCNECs, as a direct comparison is lacking in the literature.Transcriptomic and genomic alterations were investigated by next-generation sequencing in a discovery set of 14 ACs and 14 LCNECs and validated on 21 ACs and 18 LCNECs by using custom gene panels and immunohistochemistry for Men1 and Rb1.A 58-gene signature distinguished three transcriptional clusters. Cluster 1 comprised 20 LCNECs and one AC harboring concurrent inactivation of tumor protein p53 gene (TP53) and retinoblastoma 1 gene (RB1) in the absence of menin 1 gene (MEN1) mutations; all cases lacked Rb1 nuclear immunostaining. Cluster 3 included 20 ACs and four LCNECs lacking RB1 alterations and having frequent MEN1 (37.5%) and TP53 mutations (16.7%); menin nuclear immunostaining was lost in 75% of cases. Cluster 2 included 14 ACs and eight LCNECs showing intermediate features: TP53, 40.9%; MEN1, 22.7%; and RB1, 18.2%. Patients in cluster C1 had a shorter cancer-specific survival than did patients in C2 or C3.ACs and LCNECs comprise three different and clinically relevant molecular diseases, one AC-enriched group in which MEN1 inactivation plays a major role, one LCNEC-enriched group whose hallmark is RB1 inactivation, and one mixed group with intermediate molecular features. These data support a progression of malignancy that may be traced by using combined molecular and immunohistochemical analysis.
Abstract P4-06-25: B7-H3 and B7-H4 expression in ductal carcinoma in situ of the breast: Associations with clinicopathologic features and T-cell infiltration
Authors: JS Lee, G-E Kim, MH Park, JH Yoon
Journal: Cancer Research (2019)

Abstract Background: With the clinical success of immune check point blockades in treating malignant tumors, there are intense investigations in identifying new pathways to activate immune system by targeting immunoregulatory molecules. B7-H3 and B7-H4 play an inhibitory role in T cell function by limiting proliferation and cytokine production. Although several studies have investigated the expression of B7-H3 and B7-H4 in invasive breast cancers, the information of the B7-H3 and B7-H4 molecules in ductal carcinoma in situ (DCIS) remains uncertain. The present work was undertaken to evaluate the expression of B7-H3 and B7-H4 in DCIS and its association with clinicopathological features in patients with DCIS. In addition, the association of B7-H3 and B7-H4 expression with the T-cell infiltration was also assessed to investigate its roles in the regulation of tumor immune surveillance. Materials and methods: B7-H3 and B7-H4 expression was examined in 8 pairs of DCIS tissues and matched normal adjacent tissues at mRNA and protein levels by RNAscope in situ hybridization (ISH) and immunohistochemistry. Immunohistochemical staining of B7-H3 and B7-H4 was done in 79 DCIS samples with known hormone receptor (HR) and human epidermal growth factor 2 (HER2) expression using tissue microarray. In addition, immunohistochemical staining was also performed for the T cell lineage markers CD3 and CD8 in DCIS. Results: RNAscope ISH and immunohistochemistry of B7-H3 and B7-H4 confirmed their increases in DCIS tissues compared with their corresponding normal tissues. B7-H3 and B7-H4 mRNA and protein expression appeared to be concentrated mainly in the DCIS carcinoma cells. High B7-H3 and B7-H4 expression was observed in 58 (73.4%) and 62 (78.5%) cases with DCIS, respectively. High B7-H3 expression was significantly associated with high nuclear grade and presence of comedo-type necrosis (P &amp;lt; 0.05 and P &amp;lt; 0.05, respectively). B7-H3 expression was higher in the HR–/HER2+ subtypes than in the HR+/HER2– subtype (P &amp;lt; 0.05). B7-H3 and B7-H4 expression tended to be associated with low stromal tumor infiltrating lymphocytes density and was negatively related to the CD3+ and CD8+ T cell infiltrates density. Conclusions: These results suggest that B7-H3 and B7-H4 may play an important role in immune surveillance mechanisms of DCIS and may be useful targets for immune-based therapy to alter or prevent DCIS progression. Citation Format: Lee JS, Kim G-E, Park MH, Yoon JH. B7-H3 and B7-H4 expression in ductal carcinoma in situ of the breast: Associations with clinicopathologic features and T-cell infiltration [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-06-25.
Inositol-triphosphate 3-kinase B confers cisplatin resistance by regulating NOX4-dependent redox balance
Authors: Chaoyun Pan, Lingtao Jin, Xu Wang, Yuancheng Li, Jaemoo Chun, Austin C. Boese, Dan Li, Hee-Bum Kang, Guojing Zhang, Lu Zhou, Georgia Z. Chen, Nabil F. Saba, Dong M. Shin, Kelly R. Magliocca, Taofeek K. Owonikoko, Hui Mao, Sagar Lonial, Sumin Kang
Journal: Journal of Clinical Investigation (2019)

How altered metabolism contributes to chemotherapy resistance in cancer cells remains unclear. Through a metabolism-related kinome RNAi screen, we identified inositol-trisphosphate 3-kinase B (ITPKB) as a critical enzyme that contributes to cisplatin-resistant tumor growth. We demonstrated that inositol 1,3,4,5-tetrakisphosphate (IP4), the product of ITPKB, plays a critical role in redox homeostasis upon cisplatin exposure by reducing cisplatin-induced ROS through inhibition of a ROS-generating enzyme, NADPH oxidase 4 (NOX4), which promotes cisplatin-resistant tumor growth. Mechanistically, we identified that IP4 competes with the NOX4 cofactor NADPH for binding and consequently inhibits NOX4. Targeting ITPKB with shRNA or its small-molecule inhibitor resulted in attenuation of NOX4 activity, imbalanced redox status, and sensitized cancer cells to cisplatin treatment in patient-derived xenografts. Our findings provide insight into the crosstalk between kinase-mediated metabolic regulation and platinum-based chemotherapy resistance in human cancers. Our study also suggests a distinctive signaling function of IP4 that regulates NOX4. Furthermore, pharmaceutical inhibition of ITPKB displayed synergistic attenuation of tumor growth with cisplatin, suggesting ITPKB as a promising synthetic lethal target for cancer therapeutic intervention to overcome cisplatin resistance.
Drowning in alphabet soup
Authors: Richard Bagshaw
Journal: BMJ (2011)

When I recently flicked through my old hospital notebooks, I discovered the scribblings of a lunatic:

69 y/o Cauc female c/o 2/52 Hx SOBOE + productive cough. ↑To, ohaemoptysis, ochest pain, o↓kg, onight sweats, oPND, oorthopneoa. PMHx STEMI – revascularised PC, ↑BP. SHx Ex-smoker; 30 pack yrs. DHx verapamil, aspirin, simvastatin, NKDA

It will not come as news that medicine is awash with technical terms. The Oxford Handbook contains a list of just under 300 acronyms; not an exhaustive list, but the bare minimum needed to survive as a junior doctor. What alarms me is how easily and eagerly students become inured to this alien …
Effects of multidisciplinary team working on breast cancer survival: retrospective, comparative, interventional cohort study of 13 722 women
Authors: Rej Bhumbra
Journal: BMJ (2013)

The paper

Effects of multidisciplinary team working on breast cancer survival: retrospective, comparative, interventional cohort study of 13 722 women by Eileen Kesson and colleagues ( BMJ 2012;344:e2718)

Abstract

Objectives —To describe the effect of multidisciplinary care on survival in women treated for breast cancer.

Design —Retrospective, comparative, non-randomised, interventional cohort study.

Setting NHS hospitals, health boards in the west of Scotland, UK.

Participants —14 358 patients diagnosed with symptomatic invasive breast cancer between 1990 and 2000, residing in health board areas in the west of Scotland. 13 722 (95.6%) patients were eligible (excluding 16 diagnoses of inflammatory cancers and 620 diagnoses of breast cancer at death).

Intervention —In 1995, multidisciplinary team working was introduced in hospitals throughout one health board area (Greater Glasgow; intervention area), but not in other health board areas in the west of Scotland (non-intervention area).

Main outcome measures —Breast cancer specific mortality and all cause mortality.

Results —Before the introduction of multidisciplinary care (analysed time period January 1990 to September 1995), breast cancer mortality was 11% higher in the intervention area than in the non-intervention area (hazard ratio adjusted for year of incidence, age at diagnosis, and deprivation, 1.11; 95% confidence interval 1.00 to 1.20). After multidisciplinary care was introduced (time period October 1995 to December 2000), breast cancer mortality was 18% lower in the intervention area than in the non-intervention area (0.82, 0.74 to 0.91). All cause mortality did not differ significantly between populations in the earlier period, but was 11% lower in the intervention area than in the non-interventional area in the later period (0.89, 0.82 to 0.97). Interrupted time series analyses showed a significant improvement in breast cancer survival in the intervention area in 1996, compared with the expected survival in the same year had the pre-intervention trend continued (P=0.004). This improvement was maintained after the …