tbuckley/cabot-search huggingface dataset:
Uterine transposition before radiation therapy in young female rectal cancer patients: A novel technique aimed at preserving fertiliy.
Authors: D. Querleu, M. Rives, m. Chand, G. Ferron
Journal: Journal of Clinical Oncology (2010)

e19592 Background: Neoadjuvant radiation therapy is standard in the management of locally advanced ano-rectal cancer. Laparoscopic ovarian tranposition is routinely proposed to preserve endocrine function in young patients. However, direct external irradiation of the uterus usually alters endometrial and myometrial funcion, impairing the development and outcome of pregnancy. The only recourse is then surrogacy, that raises unsolved ethical issues and is not legal in many countries. Methods: We report the first attempts at surgical uterine transposition before irradition for rectal cancer in three patients between October and December 2009. The rationale of this operation is to elevate the uterine corpus outside the pelvis thus moving the endometrium away from the irradiation field. Ventrofixation of the uterus has long been described using an open approach in the management of uterine prolapse. As this operation can be performed laparoscopically at the time of ovarian tranposition, it does not delay the initation of definitive therapy. Results: Although modern high precision radiation techniques may reduce the amount of radiation delivered to the uterus, it is clear that moving the endometrium away from the main irradiation field provides a much better protection. Preliminary data show that radiation dose does not exceed 12 grays after uterine transposition. No surgical complication was observed. Menses spontaneously resumed in the first two patients with over one month follow-up. Follow-up is too short to provide obstetrical data but it is clear that uterine transpositon is a novel technique that can be proposed to young patients presenting with rectal cancer. Conclusions: Whenever applicable, the concept can be extended to other pelvic malignancies in children and young female patients. For cured patients, avoiding the burden of definitive infertility or high-risk pregnancy is a substantial improvement in quality of life. No significant financial relationships to disclose.
Phase III trial comparing 4-cycle doxorubicin plus cyclophosphamide followed by 4-cycle taxan with 8-cycle taxan as adjuvant therapy for node-positive breast cancer: Results of N-SAS-BC02 trial
Authors: T. Watanabe, M. Kuranami, K. Inoue, N. Masuda, K. Aogi, H. Iwata, H. Mukai, S. Tanaka, T. Yamaguchi, Y. Ohashi
Journal: Journal of Clinical Oncology (2009)

516 Background: Anthracyclines are the key agents in postoperative regimens for breast cancer (BC). However, relatively rare but life threatening toxicity such as cardiac failure and secondary leukemia are the major concern with anthracycline containing regimens. Retrospective analyses suggested that anthracyclines can be excluded in some pts. Methods: Eligibility included node positive BC age less than 70 yo. Pts were randomized to receive either AC (doxorubicin 60 mg/m 2 + cyclophosphamide 600 mg/m 2 ) every(q) 3 weeks(wks) x 4 -&gt; P (paclitaxel) 175 mg/m 2 q3 wks x 4 (ACP), the same AC -&gt; D(docetaxel) 75 mg/m 2 q3 wks x 4 (ACD), P 175 mg/m 2 q3 wks x 8 (PTX) or D 75 mg/m 2 q3 wks x 8(DTX). Comparison included P vs.D (ACP+PTX vs. ACD+DTX) and with AC or without AC (ACP+ACD vs. PTX+DTX). The primary endpoint was disease free survival (DFS) and the secondary endpoints included overall survival, adverse events (AE) and quality of life (QOL). The trial was powered to prove the non-inferiority of regimens without AC to those with AC (threshold hazard ratio [HR] 1.321) in terms of DFS. Results: 1,060 pts were accrued between Dec. 2000 and Mar.2006. 270 DFS events and 106 deaths after a median follow-up of 46.5 months were observed. In all randomised patients, 8 cycles taxane is not inferior to 4 cycles AC -&gt; 4 cycles taxane in terms of DFS (HR:1.26, 95% CI; 0.99–1.60, p = 0.67). In the subset of HER-2 positive patients, 4 cycles AC -&gt; 4 cycles taxane produced superior DFS to 8 cycles taxane (HR:1.63, 95% CI:1.05 - 2.54) but this is not observed in patients with HER-2 negative patients (HR:1.13, 95% CI: 0.85 - 1.50). D 75 mg/m 2 tends to show superior DFS to P 175 mg/m 2 (HR: 0.81, 95% CI; 0.64–1.03, p = 0.08). Nausea and vomiting was more frequent with AC -&gt; a taxane than 8 cycles taxane. Edema and febrile neutropenia was more frequently observed with D 75 mg/m 2 than P 175 mg/m 2 . The incidence of sensory neuropathy was higher with P 175 mg/m 2 than D 75 mg/m 2 . Conclusions: AC improved DFS in the subset of pts with HER-2 overexpressing BC but not in non-selected population. DFS was better in the arms containing D than in the arms with P. Higher incidence of severe AEs was observed in the arms containing D than in arms with P. No significant financial relationships to disclose.
Dissecting The Effects Of Isoprenoid Pathway Inhibition On Hemostasis and Thrombosis: Differential Effects Of Atorvastatin and Digeranyl Bisphosphonate In Hypercholesterolemic Mice
Authors: Neha Bhasin, Jeff Stevens, Masaru Niki, Huaxiang Tong, Craig Kuder, Raymond J. Hohl, Steven R Lentz
Journal: Blood (2013)
Amphetamine use: return of an old scourge in a consultation psychiatry setting
Authors: H T Baberg, R A Nelesen, J E Dimsdale
Journal: American Journal of Psychiatry (1996)

Recreational use of amphetamine and its analogues has increased considerably during the last decade. The aim of this study was to determine possible demographic characteristics of amphetamine users and nonusers who were seen in psychiatric consultations on inpatient medical and surgery wards.The authors examined data from 2,983 patients admitted to the University of California, San Diego, Medical Center and seen by consultation-liaison psychiatrists from January 1989 to June 1995. Amphetamine use was identified by the results of toxicological screening or patients' self-reports.Throughout the interval covered by the analysis, 8.7% of the patients with consultations were current amphetamine users. The percentage of users decreased from 9.1% in 1989 to 4.5% in 1992 but increased after that to reach 15.6% in the first half of 1995. The users were generally younger than the nonusers; they were typically male, white, single, uninsured, and unemployed. In comparison with nonusers, the users were more likely to have a past psychiatric history (outpatient treatment or inpatient admission) and a family history of psychiatric disorder. The users were more often admitted because of suicide attempts, had a higher probability of being HIV-positive, and were overrepresented in the psychiatric consultations requested by the departments of infectious diseases, obstetrics/gynecology, and trauma surgery.The high prevalence of amphetamine-using patients referred for psychiatric consultation is striking. Although young white men were especially likely to be users, there were users in all age groups, in nearly all hospital wards, and with a variety of psychiatric symptoms.
The effects of changing the world health organization definition of bronchioloalveolar carcinoma
Authors: J. M. Varlotto, A. Recht, M. Nikolov, J. C. Flickinger, M. M. DeCamp
Journal: Journal of Clinical Oncology (2007)

7632 Background: In 1999 the World Health Organization (WHO) changed its definition of bronchioloalveolar carcinoma (BAC). We examined the effects of this change. Methods: Patients included in the Surveillance, Epidemiology, and End Results program from 1992–2002 with Stages I-IIIB non-small cell lung carcinoma (NSCLC) who underwent a definitive surgical procedure were divided into a Cohort A (1,348 patients with BAC diagnosed from 2000–2002), Cohort B (2,955 patients diagnosed with BAC from 1992–1998), and Cohort C (36,861 patients with other NSCLC from the entire period). Overall survival (OS) and disease-free survival (DFS) rates were compared according to potential prognostic factors, including use of a matched-pair analysis. We also compared the demographic, histopathologic, and treatment factors associated with the three groups. Results: The proportion of BAC increased both as a percentage of NSCLC and as a percentage of adenocarcinoma for cohort A(12.5%, 22%) as compared to Cohort B(10.9%, 20%). The proportions of patients with smaller tumor size, female sex, non-black or non-white race, resections less than a pneumonectomy, no radiotherapy, Stage I disease, and well- differentiated tumor grade were similar between Cohorts A and B and statistically different between them and Cohort C. Cohorts A and B also had very similar OS/DFS to each other. Matched patients with Stage I cancer in Cohort A had better OS than in Cohort C; OS was similar for other stages. DFS was improved for all stages in Cohort A as compared to Cohort C (except for Stage II). Conclusions: Patients with BAC diagnosed before or after 1999 have similar outcomes to each other and better outcomes than patients with other NSCLCs. Furthermore, both BAC groups had analogous patient demographic, histopathologic and treatment factors, but differed from those of non-BAC NSCLC during this time period. Surgically-resected BAC defined using the 1999 WHO criteria remains distinctly different than non-BAC NSCLC. Therefore recommendations for adjuvant therapy may need to be different for this patient population. No significant financial relationships to disclose.
Needs in breast cancer patients (pts) during chemotherapy: Customer satisfaction evaluation
Authors: V. D. Ferrari, L. Ferrari, S. Grisanti, F. Consoli, F. Valcamonico, V. Amoroso, G. Rangoni, L. Vassalli, P. Marpicati, G. Marini
Journal: Journal of Clinical Oncology (2009)

e20679 Background: Satisfied patients demonstrate higher levels of compliance for the course of their treatment and the probability of successful treatment completion thus considerably increases. Analysis of pts needs is the base of pts satisfaction. The present analysis aims to identify the needs of our in-outpatients who received chemotherapy. Methods: 134 pts with breast cancer who underwent chemotherapy during 3 months (from 15 September to 30 November) were eligible for study. We administered the “Need Evaluation Questionnaire” (NED) validated by U.O. Psiconcologia Istituto Nazionale Tumori Mi) to 125 pts after consent, 9 pts (7%) refused to answer items. NED was built on 23 items in 7 domains of necessity: 1) information on diagnoses, prognoses, diagnostics tests and treatments (items 1–4); 2) relationship between pts and physicians or nurses (items 5–8), 3) nursing and supportive care (items 9 -13) 4) Hospital service (item 14); 5) economical aspects (items 15–16); 6) psychological, ethical, spiritual care (items 17,18,19,23); 7) relationship with relative. NED makes a quantitative evaluation of necessity with simple questions. Eligibility criteria required age ≥ 18 yrs (median age of pts was 55 yrs), histologically proven breast cancer; at lest 1 completed cycles of neoadjuvant or adjuvant or palliative chemotherapy. 96 (77%) pts completed questionnaire by their self, and 29 pts (23%) were helped because of practical problems (infusional therapy, no glasses at so on ). We choose a descriptive quantitative statistical evaluation for every item. Results: 93 % of pts completed NED questionnaire. More significant data were reported afterward and answers were allocated among the 7 domains: 1) more information about prognosis was required by 52 % of pts; 2) 90 % of pts thought that physicians embroiled them in therapeutic choices, but 36% of pts required information about future and quality of life 3) 96% of pts considered very good nursing care; 4) positive for all pts 5) 26% of pts required more informations about insurance, tickets 6) 13 and 14 % of pts required psychological or spiritual relationship; 7) women generally had support by relatives. Conclusions: this analysis shows that needs of our pts generally received responses, but answers also emphasized assurances on pts’ future. No significant financial relationships to disclose.
Screening for gynecologic cancers among women in HNPCC families
Authors: S. K. Peterson, B. G. Watts, M. Daniels, M. Dinh, P. M. Lynch, K. H. Lu
Journal: Journal of Clinical Oncology (2004)

1023 Background: Hereditary non-polyposis colon cancer (HNPCC) syndrome confers 60% and 12% lifetime risks of endometrial cancer (EC) and ovarian cancer (OC), respectively, and EC is the second most commonly diagnosed cancer in this syndrome. Women at risk for HNPCC-related cancers are advised to begin annual EC and OC screening between ages 25–35 years. We evaluated EC and OC screening behaviors among women from HNPCC families, their attitudes toward screening, and communication with their physicians and family members about EC and OC risk and screening needs. Methods: Women age ≥ 25 years with an HNPCC-predisposing mutation and/or who met Amsterdam I or II criteria completed a study questionnaire. Those with prior hysterectomy and oophorectomy were excluded. Results: Twenty three women (median age=41 years) enrolled, and accrual is ongoing. Seventy four percent had an HNPCC-predisposing mutation, and all but one had received genetic counseling about their risk for HNPCC. Forty five percent or more had never undergone screening by endometrial biopsy, transvaginal ultrasound, or CA-125 serum testing. All respondents generally endorsed the importance and benefits of EC and OC screening; however, 43% were not aware of the recommended age range to begin screening. No participants recalled receiving advice from their gynecologists or other primary care physicians about EC or OC screening. Colonoscopy screening was discussed in all families more frequently compared with EC or OC screening. Although 61% had a family history of EC or OC, only 17% reported that their relatives had ever discussed EC or OC risk with them. Conclusions: HNPCC-affected families and their primary care physicians may lack accurate knowledge of EC and OC risks. Among HNPCC-affected families, there may be greater awareness of the need for screening colonoscopy than the need for gynecologic cancer screening. Nonetheless, women in these families may be receptive to advice and support from their families and physicians for adherence to these screening tests. No significant financial relationships to disclose.
Pharmacodynamic effects of MLN4924, a novel NAE inhibitor, on blood and skin
Authors: J. S. Kauh, R. Cohen, J. W. Clarke, R. Harvey, G. Mulligan, K. Venkatakrishnan, A. Berger, P. G. Smith, L. Petruzelli, J. Sarantopoulos
Journal: Journal of Clinical Oncology (2009)

2562 Background: MLN4924 is a first-in-class, small molecule inhibitor of NEDD8 Activating Enzyme (NAE) with potent antitumor activity in animal models. Inhibition of NAE by MLN4924 leads to decreased neddylation and inhibition of cullin-RING ubiquitin ligase (CRL) activity. CRLs are enzyme complexes that control the ubiquitination and degradation of proteins with important roles in cell cycle and survival. Potent antitumor activity in animal models correlates with accumulation of substrates of the CRLs associated with DNA replication (e.g.Cdt-1), stress response (e.g.Nrf-2), and signal transduction (e.g. pIκB). Methods: A primary objective of this phase I trial in patients (pts) with advanced non-hematologic malignancies was to evaluate the pharmacodynamic (PD) effects of MLN4924 as measured by accumulation of pIκB in peripheral blood mononuclear cells (PBMCs) and Cdt-1 and Nrf-2 in skin. Pts were treated with a daily infusion of MLN4924 for 5 days of a 21-day cycle. PBMCs were isolated for analysis of pIκB levels at screening, baseline, and at selected time points following its administration. Skin biopsies for assay of Cdt-1 and Nrf-2 were performed at baseline and following the second dose of MLN4924. Results: 10 pts have been treated at 3 dose levels. Treatment emergent adverse events include elevations in transaminases, bilirubin and alkaline phosphatase. PK analysis indicated approximately dose-proportional increases in MLN4924 exposure with an estimated half life of 5 to 15 hours and no readily apparent drug accumulation. Analysis of pIκB levels in PBMCs demonstrated accumulation from baseline levels following administration of MLN4924. Cdt-1 and Nrf-2 levels in skin rose above baseline following the second dose of MLN4924. Conclusions: Treatment of pts with MLN4924 results in accumulation of substrates associated with inhibition of NAE in both peripheral blood and skin. Inhibition occurs at exposure levels that are comparable to those resulting in pharmacodynamic activity and in vivo tumor activity in xenograft models. Evidence of PD modulation of NAE activity through the accumulation of CRL substrates has been established in this early analysis, and dose escalation is ongoing to establish the MTD of this agent. [Table: see text]
Molecular mechanisms of HIV latency
Authors: Daniele C. Cary, Koh Fujinaga, B. Matija Peterlin
Journal: Journal of Clinical Investigation (2016)

HIV seeds reservoirs of latent proviruses in the earliest phases of infection. These reservoirs are found in many sites, including circulating cells, the lymphoid system, the brain, and other tissues. The "shock and kill" strategy, where HIV transcription is reactivated so that antiretroviral therapy and the immune system clear the infection, has been proposed as one approach to curing AIDS. In addition to many defective viruses, resting hematopoietic cells harbor transcriptionally latent HIV. Understanding basic mechanisms of HIV gene expression provides a road map for this strategy, allowing for manipulation of critical cellular and viral transcription factors in such a way as to maximize HIV gene expression while avoiding global T cell activation. These transcription factors include NF-κB and the HIV transactivator of transcription (Tat) as well as the cyclin-dependent kinases CDK13 and CDK11 and positive transcription elongation factor b (P-TEFb). Possible therapies involve agents that activate these proteins or release P-TEFb from the inactive 7SK small nuclear ribonucleoprotein (snRNP). These proposed therapies include PKC and MAPK agonists as well as histone deacetylase inhibitors (HDACis) and bromodomain and extraterminal (BET) bromodomain inhibitors (BETis), which act synergistically to reactivate HIV in latently infected cells.
Pseudoprogression after treatment with the TGF-beta 2 inhibitor trabedersen in high-grade glioma patients.
Authors: U. Bogdahn, G. Stockhammer, A. K. Mahapatra, N. K. Venkataramana, V. E. Oliushine, V. E. Parfenov, I. E. Poverennova, P. Jachimczak, H. Heinrichs, K. Schlingensiepen
Journal: Journal of Clinical Oncology (2010)

2054 Background: Pseudoprogression (psPD) has frequently been described in high-grade glioma (HGG) patients after chemoradiotherapy with temozolomide (TMZ). Trabedersen (AP 12009), a TGF-beta 2 specific inhibitor, was successfully tested in three phase I/II studies and one phase IIb study in recurrent/refractory HGG. Methods: The phase IIb study was an open-label, randomized, active-controlled dose-finding study. 134 patients (pts) with recurrent/refractory anaplastic astrocytoma (WHO grade 3, AA) or glioblastoma multiforme (WHO grade 4, GBM) were treated. Main objectives were to compare response rate, survival, and safety of two doses of trabedersen vs. standard chemotherapy (TMZ/PCV). The occurrence of psPD was assessed retrospectively. Data from pre- and posttreatment central MRI assessments, clinical symptoms, steroid use, and survival were analyzed. Results: PsPD was found in 9 of 89 pts (10%) of the trabedersen group and 4 of 45 pts (9%) of the chemotherapy group. PsPD occurred in GBM and AA patients. The psPD was observed approx. 30 days after treatment start in all treatment groups. Pts with psPD had a significantly longer survival than pts without psPD (p = 0.01). The median survival in pts with psPD was 36.1 months (95%CI 18.1-ND) compared to 11.0 months (95%CI 9.0-13.2) in pts without psPD regardless of treatment. Conclusions: Our results extend previous findings of observed psPD after chemoradiotherapy. PsPD was also observed in pts treated with trabedersen, which has a completely different, immunomodulatory mechanism of antitumour activity. PsPD was associated with a prolonged survival after treatment with trabedersen. As psPD and true progression are difficult to distinguish, MRI results should be interpreted cautiously and in the context of the clinical status of the patient to avoid premature discontinuation of a possibly effective treatment. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Antisense Pharma GmbH Antisense Pharma GmbH Antisense Pharma GmbH
Abstract 18444: Constitutive Expression of a Dominant Negative TGF-{beta} Type II Receptor in the Posterior Left Atrium Interrupts Heart Failure Induced Conduction Changes, with a Resulting Decrease in Atrial Fibrillation
Authors: Jason Ng, Haitham al-Angari, D Gordon, G L Aistrop, S Browne, A Kunamalla, Alan V Sahakian, B Knight, R S Passman, Alan H Kadish, J J Goldberger, Rishi Arora
Journal: Circulation (2012)
Netrin‐1 Regulates Fibrocyte Accumulation in the Decellularized Fibrotic Sclerodermatous Lung Microenvironment and in Bleomycin‐Induced Pulmonary Fibrosis
Authors: Huanxing Sun, Yangyang Zhu, Hongyi Pan, Xiaosong Chen, Jenna L. Balestrini, TuKiet T. Lam, Jean E. Kanyo, Anne Eichmann, Mridu Gulati, Wassim H. Fares, Hanwen Bai, Carol A. Feghali‐Bostwick, Ye Gan, Xueyan Peng, Meagan W. Moore, Eric S. White, Parid Sava, Anjelica L. Gonzalez, Yuwei Cheng, Laura E. Niklason, Erica L. Herzog
Journal: Arthritis & Rheumatology (2016)

Fibrocytes are collagen-producing leukocytes that accumulate in patients with systemic sclerosis (SSc; scleroderma)-related interstitial lung disease (ILD) via unknown mechanisms that have been associated with altered expression of neuroimmune proteins. The extracellular matrix (ECM) influences cellular phenotypes. However, a relationship between the lung ECM and fibrocytes in SSc has not been explored. The aim of this study was to use a novel translational platform based on decellularized human lungs to determine whether the lung ECM of patients with scleroderma controls the development of fibrocytes from peripheral blood mononuclear cells.We performed biomechanical evaluation of decellularized scaffolds prepared from lung explants from healthy control subjects and patients with scleroderma, using tensile testing and biochemical and proteomic analysis. Cells obtained from healthy controls and patients with SSc-related ILD were cultured on these scaffolds, and CD45+pro-ColIα1+ cells meeting the criteria for fibrocytes were quantified. The contribution of the neuromolecule netrin-1 to fibrosis was assessed using neutralizing antibodies in this system and by administering bleomycin via inhalation to netrin-1(+/-) mice.Compared with control lung scaffolds, lung scaffolds from patients with SSc-related ILD showed aberrant anatomy, enhanced stiffness, and abnormal ECM composition. Culture of control cells in lung scaffolds from patients with SSc-related ILD increased production of pro-ColIα1+ cells, which was stimulated by enhanced stiffness and abnormal ECM composition. Cells from patients with SSc-related ILD demonstrated increased pro-ColIα1 responsiveness to lung scaffolds from scleroderma patients but not enhanced stiffness. Enhanced detection of netrin-1-expressing CD14(low) cells in patients with SSc-related ILD was observed, and antibody-mediated netrin-1 neutralization attenuated detection of CD45+pro-ColIα1+ cells in all settings. Netrin-1(+/-) mice were protected against bleomycin-induced lung fibrosis and fibrocyte accumulation.Factors present in the lung matrices of patients with scleroderma regulate fibrocyte accumulation via a netrin-1-dependent pathway. Netrin-1 regulates bleomycin-induced pulmonary fibrosis in mice. Netrin-1 might be a novel therapeutic target in SSc-related ILD.