tbuckley/cabot-search huggingface dataset:
Variability in Pathologists' Interpretations of Individual Breast Biopsy Slides: A Population Perspective
Authors: Joann G. Elmore, Heidi D. Nelson, Margaret S. Pepe, Gary M. Longton, Anna N.A. Tosteson, Berta Geller, Tracy Onega, Patricia A. Carney, Sara L. Jackson, Kimberly H. Allison, Donald L. Weaver
Journal: Annals of Internal Medicine (2016)

The effect of physician diagnostic variability on accuracy at a population level depends on the prevalence of diagnoses.To estimate how diagnostic variability affects accuracy from the perspective of a U.S. woman aged 50 to 59 years having a breast biopsy.Applied probability using Bayes' theorem.B-Path (Breast Pathology) Study comparing pathologists' interpretations of a single biopsy slide versus a reference consensus interpretation from 3 experts.115 practicing pathologists (6900 total interpretations from 240 distinct cases).A single representative slide from each of the 240 cases was used to estimate the proportion of biopsies with a diagnosis that would be verified if the same slide were interpreted by a reference group of 3 expert pathologists. Probabilities of confirmation (predictive values) were estimated using B-Path Study results and prevalence of biopsy diagnoses for women aged 50 to 59 years in the Breast Cancer Surveillance Consortium.Overall, if 1 representative slide were used per case, 92.3% (95% CI, 91.4% to 93.1%) of breast biopsy diagnoses would be verified by reference consensus diagnoses, with 4.6% (CI, 3.9% to 5.3%) overinterpreted and 3.2% (CI, 2.7% to 3.6%) underinterpreted. Verification of invasive breast cancer and benign without atypia diagnoses is highly probable; estimated predictive values were 97.7% (CI, 96.5% to 98.7%) and 97.1% (CI, 96.7% to 97.4%), respectively. Verification is less probable for atypia (53.6% overinterpreted and 8.6% underinterpreted) and ductal carcinoma in situ (DCIS) (18.5% overinterpreted and 11.8% underinterpreted).Estimates are based on a testing situation with 1 slide used per case and without access to second opinions. Population-adjusted estimates may differ for women from other age groups, unscreened women, or women in different practice settings.This analysis, based on interpretation of a single breast biopsy slide per case, predicts a low likelihood that a diagnosis of atypia or DCIS would be verified by a reference consensus diagnosis. This diagnostic grey zone should be considered in clinical management decisions in patients with these diagnoses.National Cancer Institute.
Abstract 3075: miRNA-10a* enhances invasiveness via suppression of HDAC5 in lung cancer
Authors: Pin-Yen Hsu, Bing-Ching Ho, Chiou-Ling Cheng, Hsuan-Yu Chen, Sung-Liang Yu, Guan-Tarn Huang
Journal: Cancer Research (2015)

Abstract Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Metastasis, the spread process of cancer cells from a primary tumor to seed secondary tumors in distant sites, is one of the big challenges in cancer treatment today. For most patients, when the cancer is detected, metastasis has already occurred. The growing evidences implied that miRNAs play an important role in developmental lineage and different states of cancers as well as cancer invasion. In this study, we would like to establish a metastasis-based prognostic miRNA signature. First, 16 lung adenocarcinoma cells were divided into the high or low-invasive group. The miRNAs whose expression correlated with invasion were identified. Next, we investigated whether the expressions of identified miRNAs are correlated to patients’ survival. Quantitative RT-PCR results showed that the expression of miR-10a* is significantly correlated to the five-year survival in 98 lung adenocarcinoma patients. The inhibition of miR-10a* attenuated the invasion abilities of the highly invasive lung cancer cells. Moreover, we investigated the underlying regulation of miR-10a*. We found that miR-10a* negatively regulated Histone deacetylase 5 (HDAC5) was assayed by Western Blot, RT-PCR and luciferase reporter assay. These evidences suggested that HDAC5 is a direct target of miR-10a*. Besides, inhibition of HDAC5 promoted invasive ability. RNAs derived from two paired groups (pre-miR-10a* and pre-NC; sh-HDAC5 and sh-LacZ) were assayed by microarray and pathway analysis. The analysis result of MetaCore implied that miR-10a* trigger TGF-beta signalings. RT-PCR and Western Blot were utilized to validate the differentially altered expression of certain genes in miR-10a*-mediated pathways. The rescue effect of HDAC5 expression on miR-10a*-mediated phenotypic changes is also evaluated to elucidate the importance of HDAC5 in miR-10a*-mediated invasive ability. Our findings indicated that miR-10a* may play an oncogenic miRNA role in lung cancer. Citation Format: Pin-Yen Hsu, Bing-Ching Ho, Chiou-Ling Cheng, Hsuan-Yu Chen, Sung-Liang Yu, Guan-Tarn Huang. miRNA-10a* enhances invasiveness via suppression of HDAC5 in lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3075. doi:10.1158/1538-7445.AM2015-3075
Open-label phase II trial of everolimus monotherapy in treatment-naive patients with advanced papillary renal cell carcinoma.
Authors: S. Caglio, K. Slimane, C. May, B. Escudier
Journal: Journal of Clinical Oncology (2010)

TPS234 Background: Papillary renal cell carcinoma (RCC) is genetically and morphologically distinct from other RCCs, and accounts for up to 10% of RCC diagnoses. All RCC histologies are generally resistant to chemotherapy. Newer targeted treatment approaches have demonstrated clinical benefit in patients with clear cell RCC, but options for the treatment of papillary RCC remain limited. Everolimus, an oral mTOR inhibitor, has demonstrated efficacy in the pivotal RECORD-1 study in patients with mRCC with a “clear cell component” histology that progressed on vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy, and everolimus is now indicated for use in this patient population. Because mTOR is also aberrantly activated in papillary RCC, mTOR inhibition presents a novel means for targeted therapy in papillary RCC. The ongoing RAPTOR (RAD001 in Advanced Papillary Tumor Program in Europe) trial is evaluating the efficacy and safety of everolimus monotherapy in treatment-naive patients with advanced papillary RCC. Methods: RAPTOR is an open-label, single-arm, non-randomized, single-stage, multicenter phase II trial currently recruiting participants. Up to 60 patients ≥18 years of age with a centrally confirmed histologic diagnosis of advanced type I or II metastatic papillary RCC, ≥1 measurable baseline lesion as per RECIST criteria, ECOG performance status of 0 or 1, and adequate liver, renal, and bone marrow function will be enrolled. Patients who have received prior systemic RCC therapy (ie, sorafenib, sunitinib, bevacizumab) are excluded. Patients will receive everolimus 10 mg/d orally until disease progression, unacceptable toxicity, death, or study discontinuation for any other reason. The primary study endpoint is PFS rate at 6 months. Disease control rate, objective response rate, duration of response, median PFS, overall survival, and safety will also be assessed. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Bayer Pharma, Pfizer, Roche Bayer, Genentech, Novartis, Pfizer, Roche
The SELECT trial: A multicenter phase II trial of adjuvant erlotinib (E) in patients with resected, early-stage non-small cell lung cancer (NSCLC) and confirmed mutations in the epidermal growth factor receptor (EGFR).
Authors: N. A. Pennell, J. W. Neal, R. Govindan, P. A. Janne, T. L. Evans, D. B. Costa, R. P. G. Rosovsky, M. Lanuti, C. G. Azzoli, L. V. Sequist
Journal: Journal of Clinical Oncology (2011)

TPS209 Background: Adjuvant chemotherapy after resection for early-stage NSCLC has been shown to improve long-term survival. However, the benefit is modest (4-15%) and many pts will still relapse due to the intrinsic chemoresistance of most lung cancers. Cancers with activating EGFR mutations represent a unique subset that is exquisitely sensitive to EGFR tyrosine kinase inhibitors (TKIs) such as E, and TKIs have become the standard of care treatment for advanced NSCLC pts with these mutations. Adjuvant TKIs have not been studied in a genotype-specific population. We hypothesize that genotype-directed adjuvant TKI therapy may be effective in reducing recurrence rates among EGFR-mutant early-stage NSCLC patients. Methods: This is an open-label, single arm phase II study of adjuvant E in pts with resected, early-stage NSCLC with EGFR mutations (NCT00567359). Eligible pts have surgically resected stage IA-IIIA NSCLC and confirmed activating EGFR mutations, must be within 6 mos of surgery, and may have completed routine adjuvant treatment. Pts are treated with 150 mg/day of E for a total of 2 years, with surveillance scans every 3 months. The primary endpoint is disease-free survival (DFS) at 2 years. The planned sample size of 100 patients will provide 90% power to observe an improvement in DFS at 2 years from a historical control of 76% (estimated from a large single institution cohort of mutant NSCLC pts) to 86% for patients treated with adjuvant E. Secondary endpoints include safety and tolerability of adjuvant E, median DFS, and overall survival. When possible, biopsies will be obtained at the time of recurrence to document the mechanism of resistance to E. To date 69 of 100 patients have been enrolled at 6 institutions. Funding for this trial is provided by Genentech.
Sex hormones and systemic inflammation are modulators of the obese‐asthma phenotype
Authors: H. A. Scott, P. G. Gibson, M. L. Garg, J. W. Upham, L. G. Wood
Journal: Allergy (2016)

Abstract Background Both systemic inflammation and sex hormones have been proposed as potential mediators of the obese‐asthma phenotype. The aim of this study was to examine the associations between sex hormones, oral contraceptive pill ( OCP ) use, systemic inflammation and airway inflammation in adults with asthma. Methods Obese ( n = 39) and nonobese ( n = 42) females and obese ( n = 24) and nonobese ( n = 25) males with asthma were recruited. Females were further categorized as reproductive‐aged (&lt;50 years old; n = 36) or older (&gt;50 years old; n = 45). Thirteen (36.1%) reproductive‐aged females were using the OCP . Participants had induced sputum cell counts measured and blood analysed for sex hormones and inflammatory markers. Results Obese reproductive‐aged females had higher sputum %neutrophils than nonobese reproductive‐aged females (45.4 ± 24.3% vs 27.5 ± 17.5%, P = 0.016); however, there was no difference in sputum neutrophils in obese compared with nonobese males ( P = 0.620) or older females ( P = 0.087). Multiple linear regression analysis found testosterone and OCP use to be negative predictors of sputum %neutrophils, while C‐reactive protein and IL ‐6 were positive predictors of sputum %neutrophils. BMI and age were not significant predictors in the multivariate model. Reproductive‐aged females using the OCP had significantly lower sputum %neutrophils than those not using the OCP (23.2 ± 12.6% vs 42.1 ± 23.8%, P = 0.015). Conclusions This study suggests that sex hormones and systemic inflammation may be mediating the obese‐asthma phenotype. The observation that OCP use was associated with lower sputum %neutrophils in reproductive‐aged females warrants further investigation.
Inhibition of Murine Osteogenic Sarcomas by Treatment With Type I or Type II Interferon&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: John L. Crane, Jr., Lowell A. Glasgow
 4, Earl R. Kern, Julius S. Youngner
Journal: JNCI Journal of the National Cancer Institute (1978)

Interferon was used to treat C57BL/6 female mice inoculated with a continuous line of murine osteogenic sarcoma cells. A short 7-day course of 30,000–60,000 U/day of type I interferon either completely inhibited or delayed the appearance of tumors in experimental animals. The therapeutic efficacy of type I interferon was compared with murine serum that contained type II interferon as well as other lymphokine activity. Tumor development was strikingly inhibited in animals treated for 7 days with serum containing only 600 U of type II interferon. Inhibition of tumor development was thus achieved with 100-fold less interferon than that required with type I preparation.
Performance status, global quality of life, fatigue, and appetite loss are correlated with serum TGFa and IL-6 in patients with metastatic colorectal cancer (MCC)
Authors: T. A. Rich, P. Innominato, M. C. Mormont, J. Boerner, S. Iacobelli, C. Jasmin, B. Boran, F. Levi
Journal: Journal of Clinical Oncology (2004)

8024 Background: The predictive power of pre-treatment performance status (PS), quality of life (QOL) and behavioural indices are well known, but the physiologic and molecular mechanisms are unknown. Reported here is an association between circulating levels of growth factors and cytokines (involved with circadian signaling and the hypothalamic-pituitary-adrenal axis) and with performance status and QOL indices. Methods: TGF-a, TNF-a, and IL-6 levels were determined retrospectively with ELISA in sera of 80 MCC patients prospectively treated (Mormont M.C., et al. Clin. Cancer Res, 2000). PS, EORTC QLQ-C30, fatigue, appetite, and HADS indices were assessed prior to treatment. Groups were compared by Kruskal-Wallis rank. Results: TGF-a and IL-6 levels are significantly higher in patients scored PS >1 vs. PS = 0, and in those patients with appetite loss vs. normal appetite; Global QOL scores are significantly lower in those with elevated IL-6. Fatigue is significantly worse in those with elevated TGF-a. Median serum level (pg/ml) HADS scores are not correlated with any factor. TNF-a does not correlate with any behavioural parameter. Conclusions: MCC patients with relatively higher levels of circulating TGF-a and IL-6 have worse performance status and appetite. High fatigue and poor global QOL are associated with higher circulating levels of TGF-a and IL-6, respectively. These preliminary data suggest that circulating growth factors and cytokines, produced either directly or indirectly by metastatic colorectal cancer, may be mechanistically responsible for behaviour changes. Supported by: J W Sieg Fund No significant financial relationships to disclose.
Diabetic Ketoacidosis With Canagliflozin, a Sodium–Glucose Cotransporter 2 Inhibitor, in Patients With Type 1 Diabetes
Authors: Anne L. Peters, Robert R. Henry, Payal Thakkar, Cindy Tong, Maria Alba
Journal: Diabetes Care (2016)

OBJECTIVE To assess the incidence of serious adverse events (AEs) of diabetic ketoacidosis (DKA) with canagliflozin, a sodium–glucose cotransporter 2 inhibitor, as an add-on to insulin in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS In this 18-week, randomized, double-blind, phase 2 study, patients (N = 351; HbA1c 7.0–9.0% [53–75 mmol/mol]) on multiple daily insulin injections or continuous subcutaneous insulin infusion received canagliflozin 100 or 300 mg or placebo once daily. The incidence of ketone-related AEs, defined as any event from a prespecified list of preferred terms (i.e., acidosis, blood ketone body increased, blood ketone body present, DKA, diabetic ketoacidotic hyperglycemic coma, ketoacidosis, ketonemia, ketonuria, ketosis, metabolic acidosis, urine ketone body present), including serious AEs of DKA, was assessed based on AE reports. RESULTS At week 18, the incidence of any ketone-related AE with canagliflozin 100 and 300 mg was 5.1% (n = 6 of 117) and 9.4% (n = 11 of 117), respectively; no patients in the placebo group experienced a ketone-related AE. The incidence of serious AEs of DKA was 4.3% (n = 5 of 117) with canagliflozin 100 mg and 6.0% (n = 7 of 117) with canagliflozin 300 mg; all serious events occurred in the presence of circumstances that are known to potentially precipitate DKA (e.g., infection, insulin pump failure). Among the 12 patients with a serious AE of DKA, blood glucose levels ranged from 9.4 to &amp;gt;44.4 mmol/L (170 to &amp;gt;800 mg/dL). Baseline characteristics were generally similar in patients with and without a ketone-related AE. CONCLUSIONS Canagliflozin was associated with an increased incidence of serious AEs of DKA in patients with type 1 diabetes inadequately controlled with insulin. Mitigation strategies are needed for use in future clinical trials to reduce the risk of DKA with canagliflozin treatment in patients with type 1 diabetes.
CBFβ-SMMHC, Expressed in M4eo Acute Myeloid Leukemia, Reduces p53 Induction and Slows Apoptosis in Hematopoietic Cells Exposed to DNA-Damaging Agents
Authors: Martin Britos-Bray, Manuel Ramirez, Wangsen Cao, Xinping Wang, P. Paul Liu, Curt I. Civin, Alan D. Friedman
Journal: Blood (1998)
Epigenetic Silencing of the Pro-Apoptotic Bim Gene in Glucocorticoid Poor-Responsive Pediatric Acute Lymphoblastic Leukemia, and Its Reversal by Histone Deacetylase Inhibition.
Authors: Richard B Lock, Petra S Bachmann, Rocco G Piazza, Carwyn Davies, Mary James, Nicholas C Wong, Vivek A Bhadri, Angela Mogavero, Vera Magistroni, Carlo Gambacorti-Passerini, Richard Saffery, Jeffrey M Craig, John E Pimanda, Glenn M Marshall
Journal: Blood (2009)
Prevalence of Hoxb13G84E Germline Mutation in Uk Prostate Cancer Cases; Correlation with Tumour Characteristics and Outcomes
Authors: C. Mikropoulos, T. Dadaev, M. Tymrakiewicz, D. Leongamornlert, E. Saunders, S.J. Little, K. Govindasami, M. Guy, R. Wilkinson, A. Morgan, J. Donovan, D. Neal, F. Hamdy, A. Antoniou, R. Eeles, Z. Kote-Jarai
Journal: Annals of Oncology (2014)
Neoadjuvant Treatment of Rectal Cancer: Short-Course Vs Long-Course Radiotherapy?
Authors: I. Shchepotin, O.O. Kolesnik, V.I. Ivankova, O.Y. Stolyarova, A.P. Beznosenko, D. Mahmudov, V.V. Zvirich
Journal: Annals of Oncology (2014)
Results of the Extension Trial of Optim, a Multicenter, Randomized Phase 3 Trial of Talimogene Laherparepvec (T-Vec) Vs Gm-Csf for Unresected Stage Iiib-Iv Melanoma
Authors: J.J. Nemunaitis, R.H. Andtbacka, M. Ross, T. Amatruda, J. Chesney, F.A. Collichio, K.J. Harrington, N.M. Steven, S. Fourie, L. Dreosti, A. Li, K. Liu, M. Shilkrut, R. Coffin, H. Kaufman
Journal: Annals of Oncology (2014)
Endoscopic detachable snare ligation: a new treatment method for colonic diverticular hemorrhage
Authors: Daisuke Akutsu, Toshiaki Narasaka, Mariko Wakayama, Masahiko Terasaki, Tsuyoshi Kaneko, Hirofumi Matsui, Hideo Suzuki, Ichinosuke Hyodo, Yuji Mizokami
Journal: Endoscopy (2015)

<b>Background and study aims:</b> Colonic diverticular hemorrhage is the most common cause of lower intestinal bleeding. We tried to develop a convenient and reliable hemostatic method, endoscopic detachable snare ligation (EDSL), to treat diverticular hemorrhage and retrospectively explored its safety and efficacy. <b>Patients and methods:</b> The definitive bleeding diverticulum was ligated with a detachable snare, instead of a rubber band, in a procedure similar to endoscopic band ligation. Removal of the scope to attach a ligation device and reinsertion for treatment are not needed in this method. <b>Results: </b>From November 2013 to September 2014, EDSL was used to treat 8 patients with colonic diverticular hemorrhage. The mean procedure time required for hemostasis after identification of the bleeding diverticulum was 5 ± 2 minutes. Sustained hemostasis was achieved in 7 patients (88 %), and early rebleeding occurred in 1 patient, in whom the applied suction seemed inadequate. No complications occurred in any patient. <b>Conclusions:</b> EDSL may be a safe and effective treatment for colonic diverticular hemorrhage. However, additional studies are warranted to confirm these initial exploratory data.
Outcome Assessments and Cost Avoidance of an Oral Chemotherapy Management Clinic
Authors: Siu-Fun Wong, Mark Bounthavong, Cham P Nguyen, Timothy Chen
Journal: Journal of the National Comprehensive Cancer Network (2016)

Increasing use of oral chemotherapy drugs increases the challenges for drug and patient management. An oral chemotherapy management clinic was developed to provide patients with oral chemotherapy management, concurrent medication (CM) education, and symptom management services. This evaluation aims to measure the need and effectiveness of this practice model due to scarce published data.This is a case series report of all patients referred to the oral chemotherapy management clinic. Data collected included patient demographics, depression scores, CMs, and types of intervention, including detection and management outcomes collected at baseline, 3-day, 7-day, and 3-month follow-ups. Persistence rate was monitored. Secondary analysis assessed potential cost avoidance.A total of 86 evaluated patients (32 men and 54 women, mean age of 63.4 years) did not show a high risk for medication nonadherence. The 3 most common cancer diagnoses were rectal, pancreatic, and breast, with capecitabine most prescribed. Patients had an average of 13.7 CMs. A total of 125 interventions (detection and management of adverse drug event detection, compliance, drug interactions, medication error, and symptom management) occurred in 201 visits, with more than 75% of interventions occurring within the first 14 days. A persistence rate was observed in 78% of 41 evaluable patients. The total estimated annual cost avoidance per 1.0 full time employee (FTE) was $125,761.93.This evaluation demonstrated the need for additional support for patients receiving oral chemotherapy within standard of care medical service. A comprehensive oral chemotherapy management referral service can optimize patient care delivery via early interventions for adverse drug events, drug interactions, and medication errors up to 3 months after initiation of treatment.
Next Generation Sequencing (Ngs) Reveals Qualitative and Quantitative Molecular Heterogeneity Within Egfr-Mutant Advanced Lung Adenocarcinoma (Ala) Patients (Pts) Receiving Gefitinib (G)
Authors: E. Bria, S. Pilotto, E. Amato, M. Fassan, S. Novello, U. Peretti, T. Vavala, S. Kinspergher, L. Righi, A. Santo, I. Sperduti, M. Milella, A. Scarpa, G. Tortora
Journal: Annals of Oncology (2014)
Recent Trends in PSA Testing and Prostate Cancer Incidence
Authors: Ruth Etzioni, Roman Gulati
Journal: JAMA Oncology (2016)

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