tbuckley/cabot-search huggingface dataset:
Comparison of the tolerance and efficacy of LV5FU2-CPT11 and FOLFIRI regimens in front-line treatment of advanced colorectal cancer –A pooled analysis of 254 patients included in 2 randomised trials
Authors: E. Mitry, C. Tournigand, T. Andre, J. Y. Y. Douillard, C. Louvet, D. Cunningham, E. Magherini, D. Mery-Mignard, A. De Gramont, P. Rougier
Journal: Journal of Clinical Oncology (2004)

3576 Background: With only one 5FU bolus injection and an increased dose of 5FU by continuous infusion, the simplified LV5FU2 regimen is considered as effective as but less toxic and more convenient than the original LV5FU2 de Gramont regimen [Tournigand ASCO 1998 #1052]. LV5FU2-CPT11 and FOLFIRI are safe and active in the front-line treatment of metastatic colorectal cancer [Douillard Lancet 2000 –V303 trial, Tournigand JCO 2004 –V308 trial]. In both regimens, CPT11 is given at a dose of 180 mg/m2 combined with the LV5FU2 regimen for LV5FU2-CPT11 or with the simplified LV5FU2 regimen for FOLFIRI. Methods: We performed a comparison based on the individual data from the V303 and V308 trials to assess the safety profile and efficacy of LV5FU2-CPT11 and FOLFIRI. Main severe adverse events (NCI grade 3–4) possibly and probably related to treatment as well as the objective response rate (ORR) and progression-free survival (PFS) were compared by treatment group. Results: 145 pts received the LV5FU2-CPT11 combination in the V303 trial and 109 pts received the FOLFIRI regimen in the V308 trial. Pre-treatment characteristics appeared to be similar in the two groups except for the sex-ratio (F: LV5FU2-CPT11: 29.0%, FOLFIRI: 43.1%) and number of metastatic sites (≥3 sites: LV5FU2-CPT11: 14.5%, FOLFIRI: 4.6%). Severe neutropenia (24% vs. 45%, p=0.001) and asthenia (4% vs. 9%, ns) were less frequent whereas mucositis (10% vs. 4%, ns), nausea and vomiting (10% vs. 3%; ns) were more frequent with the FOLFIRI regimen. The frequency of severe diarrhea was 14% in both groups. ORR: LV5FU2-CPT11: 33.1% [95CI: 25.5–41.4], FOLFIRI: 56.0% [95CI: 46.1–65.5] (p<0.01, HR= 1.2 [1.1–1.3]. PFS: LV5FU2-CPT11: 5.7 months [95CI: 4.1–6.7], FOLFIRI: 8.5 months [95CI: 7.0–9.5] (ns). Conclusions: This non-randomized retrospective comparison suggests that the FOLFIRI regimen has a different toxicity profile and may have higher efficacy than the LV5FU2-CPT11 regimen. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis
Body Size and Lung-Tumor Susceptibility in Outbred Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Joyce L. Bloom
Journal: JNCI Journal of the National Cancer Institute (1964)

During a series of experiments on the genetic control of susceptibility to induced lung tumors involving normal mice from two outbred stocks, information was collected on the weights at various ages and on the tail length of each mouse. This paper gives the results of statistical analysis of these data, thus providing information on the relationship of weight and growth with induced lung-tumor susceptibility in a large number of normal outbred mice. The outbred stocks JC and LX were chosen because of their difference in size. The larger LX mice were considerably more susceptible to urethan-induced lung tumors than the JC mice. However, the simple hypothesis that the LX mice were more susceptible because they were bigger was not borne out. Within a stock, the only statistically significant relationship between weight and susceptibility was at 3 weeks of age and this correlation was negative, i.e., the smaller the mouse at this age the greater its susceptibility. Possible explanations of this finding are discussed in relation to the work of other authors.
High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with vitamin K antagonists
Authors: V De Stefano, M Ruggeri, F Cervantes, A Alvarez-Larrán, A Iurlo, M L Randi, E Elli, M C Finazzi, G Finazzi, E Zetterberg, N Vianelli, G Gaidano, E Rossi, S Betti, I Nichele, D Cattaneo, M Palova, M H Ellis, R Cacciola, A Tieghi, J C Hernandez-Boluda, E Pungolino, G Specchia, D Rapezzi, A Forcina, C Musolino, A Carobbio, M Griesshammer, E Sant’Antonio, A M Vannucchi, T Barbui
Journal: Leukemia (2016)
A Short-Term Clinical Evaluation of L-697,661, a Non-Nucleoside Inhibitor of HIV-1 Reverse Transcriptase
Authors: Michael S. Saag, Emilio A. Emini, Oscar L. Laskin, Jeffrey Douglas, William I. Lapidus, William A. Schleif, Richard J. Whitley, Carol Hildebrand, Vera W. Byrnes, John C. Kappes, Kevin W. Anderson, Ferdinand E. Massari, George M. Shaw
Journal: New England Journal of Medicine (1993)

The non-nucleoside reverse transcriptase inhibitors are novel antiretroviral agents with selective activity in vitro against human immunodeficiency virus type 1 (HIV-1). They act through direct inhibition of reverse transcriptase and are not incorporated into DNA.
Transfusion-associated graft-versus-host disease.
Authors: K Anderson
Journal: Journal of Clinical Oncology (1991)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1991.9.10.1727 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 1919623 Transfusion-associated graft-versus-host disease. K AndersonxK AndersonSearch for articles by this author https://doi.org/10.1200/JCO.1991.9.10.1727 First Page PDF © 1991 by American Society of Clinical Oncology
Fine Needle Biopsies are Feasible As a Minimally Invasive Means for Targeted Next Generation Sequencing in Advanced Solid Tumors
Authors: A. Hansen, W. Geddie, S. Boerner, S. Ghai, H. Berman, S. Serra, M. Roehrl, A.M. Joshua, A.M. Oza, M. Moore, E. Amir, T. Usmani, A. Giesler, N. Amin, T. Zhang, M. Sukhai, T. Stockley, S. Kamel-Reid, L.L. Siu, P. Bedard
Journal: Annals of Oncology (2014)
Neonatal Herpes Simplex Infection
Authors: Veronique E J van Ham-Borawitz, Edo D Stam, Kathleen M Welborn, Theo C J Sas
Journal: New England Journal of Medicine (1988)

Neonatal encephalitis caused by herpes simplex virus (HSV) is a familiar disease with a high mortality and morbidity rate. Isolated skin-eye-mouth infection is less familiar among professionals. In this article we present two neonates with an isolated skin lesion caused by an HSV infection. Of the neonates infected with HSV, 40-45% show isolated skin-eye-mouth disease. With correct treatment, the risk of spread to the central nervous system will decrease from 50-60% to 5-10%. Typical HSV skin lesions may present at a late stage of the disease or may be masked by a secondary bacterial infection. When a neonate presents with atypical skin lesions starting 7-12 days after the birth, immediate testing for HSV and immediate treatment are required, to decrease the risk of further progression of the disease.
Neurocognitive performance in breast cancer survivors (BCS): Exploring the relationship with adjuvant treatment, psychological and reproductive factors
Authors: S. A. Castellon, P. A. Ganz, L. Petersen, J. E. Bower, G. A. Greendale
Journal: Journal of Clinical Oncology (2004)

8028 Background: Decreased neurocognitive test performance has been associated with adjuvant chemotherapy treatments and self-reported cognitive complaints have been associated with mood alterations. In a cross-sectional study of mood and neurocognitive performance in 53 BCS and 19 healthy age-matched controls, we found that chemotherapy treated BCS had significantly poorer performance on tests of visual memory and visuo-spatial performance (J Clin Exp Neur, in press). In this study we examine the contributing role of psychological and reproductive health factors to neuropsychological performance. Methods: BCS for this study were recruited from a cohort study focused on cancer and menopause (JCO 21:4184, 2003). Multiple linear regression was used to examine the association of breast cancer treatments (chemotherapy, tamoxifen), menopausal status (pre- or postmenopausal), treatment-induced menopause, chemotherapy/treatment-induced menopause interaction, and anxiety, with performance on neurocognitive tests of visual memory and visuo-spatial performance. Results: Complete data on all predictors were available in 48 BCS, who were on average 47 yrs old (range 32–56) and were a mean of 4.5 yrs since diagnosis (range 2.7–6.4 years). 20 were premenopausal and 14 had received no adjuvant therapy. For visual memory, the model found that chemotherapy treatment (p=.008) and increased anxiety (p=.005) were significant predictors of poorer performance (model adjusted R2=0.22, p=.01). For visuo-spatial performance, the model found that chemotherapy and tamoxifen treatments were significant predictors (p=.04 and p=.05, respectively) of poorer performance, (model adjusted R2 =0.18, p=.03). Conclusions: These data support the important independent role of chemotherapy in predicting poorer neurocognitive performance in these 2 domains, and also implicate anxiety and tamoxifen therapy as additional significant predictors of poorer neurocognitive performance. The contribution of these factors to neurocognitive performance in BCS warrants further evaluation in prospective studies. No significant financial relationships to disclose.
Molecular Insights of Pathways Resulting from Two Common PIK3CA Mutations in Breast Cancer
Authors: Poornima Bhat-Nakshatri, Chirayu P. Goswami, Sunil Badve, Luca Magnani, Mathieu Lupien, Harikrishna Nakshatri
Journal: Cancer Research (2016)

Abstract The PI3K pathway is activated in approximately 70% of breast cancers. PIK3CA gene mutations or amplifications that affect the PI3K p110α subunit account for activation of this pathway in 20% to 40% of cases, particularly in estrogen receptor alpha (ERα)-positive breast cancers. AKT family of kinases, AKT1–3, are the downstream targets of PI3K and these kinases activate ERα. Although several inhibitors of PI3K have been developed, none has proven effective in the clinic, partly due to an incomplete understanding of the selective routing of PI3K signaling to specific AKT isoforms. Accordingly, we investigated in this study the contribution of specific AKT isoforms in connecting PI3K activation to ERα signaling, and we also assessed the utility of using the components of PI3K–AKT isoform–ERα signaling axis as predictive biomarkers of response to PI3K inhibitors. Using a variety of physiologically relevant model systems with defined natural or knock-in PIK3CA mutations and/or PI3K hyperactivation, we show that PIK3CA-E545K mutations (found in ∼20% of PIK3CA-mutant breast cancers), but not PIK3CA-H1047R mutations (found in 55% of PIK3CA-mutant breast cancers), preferentially activate AKT1. Our findings argue that AKT1 signaling is needed to respond to estrogen and PI3K inhibitors in breast cancer cells with PIK3CA-E545K mutation, but not in breast cancer cells with other PIK3CA mutations. This study offers evidence that personalizing treatment of ER-positive breast cancers to PI3K inhibitor therapy may benefit from an analysis of PIK3CA–E545K–AKT1–estrogen signaling pathways. Cancer Res; 76(13); 3989–4001. ©2016 AACR.
Abstract P3-12-10: Overall survival in triple-negative breast cancers - Prognostic influence of type of surgery and adjuvant radiotherapy: A systematic review and meta-analysis
Authors: MA O'Rorke, LJ Murray, N Bhoo Pathy
Journal: Cancer Research (2016)

Abstract BACKGROUND: Triple negative breast cancers (TNBC) are an aggressive, poorer prognostic tumour subtype which are negative for oestrogen, progesterone and human epidermal growth factor receptor 2 (HER-2) expression. Whilst the role of radiotherapy (RT) following breast conserving therapy (BCT) is widely accepted, there is no agreed consensus on the use of post-mastectomy RT, particularly in early-stage TNBC patients. METHODS: Four electronic databases were searched from their inception to April 2015 including PubMed, MEDLINE, EMBASE and web of science. Observational studies investigating overall survival and locoregional/distant recurrence outcomes in women with TNBC according to type of surgery and radiotherapy receipt were included. Authors were contacted directly for further data. A random effects model was used to pool study effect estimates using mastectomy (MT) only patients as the reference group. RESULTS: 8 studies including data from 3,456 patients were included. The median age and duration of follow-up was 54 years and 3.6 years respectively. The adjusted pooled hazard ratio (HR) and 95% confidence interval (CI) for overall survival comparing BCT and MT+RT to MT only was 0.52 (95% CI 0.31, 0.87; I2= 70.9%) and HR 0.60 (95% CI 0.38, 0.96; I2=41.5%) respectively. In subgroup analysis of MT+RT vs. MT alone, there was no significant interaction with early (T1-2, N0-1) vs. late stage (T3-4, N2-3) disease p=0.773 or age at diagnosis (&amp;lt;40, 40-64, ≥65 years) p=0.320. 5 studies evaluated local regional recurrence. Comparing BCT and MT+RT to MT only, the pooled HR was 0.61 (95% CI 0.41, 0.92) and HR 0.83 (95% CI 0.55, 1.26) respectively, with low heterogeneity detected (I2 0.0%). 4 studies assessed distant metastases. The pooled HR comparing BCT and MT+RT to MT only was 0.88 (95% CI 0.62, 1.23; I2= 0.0%) and HR 1.95 (95% CI 0.85, 4.49; I2= 75.1%) respectively. CONCLUSIONS: The addition of adjuvant radiotherapy appears to favourably impact overall survival, irrespective of the type of surgery received. BCT may reduce the risk of locoregional recurrence in comparison to MT only. The small number of contributing studies and often high study heterogeneity suggest cautious interpretation of the findings. Further epidemiological studies or pooled analyses of individual patient data are warranted. Citation Format: O'Rorke MA, Murray LJ, Bhoo Pathy N. Overall survival in triple-negative breast cancers - Prognostic influence of type of surgery and adjuvant radiotherapy: A systematic review and meta-analysis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-10.
Re-Examination of Histocompatibility Antigens Found in Patients with Juvenile Rheumatoid Arthritis
Authors: David J. Gibson, Charles B. Carpenter, J. Sydney Stillman, Peter H. Schur
Journal: New England Journal of Medicine (1975)

One hundred and twenty-three patients with juvenile rheumatoid arthritis and a similar number of controls were tissue typed for 30 HL-A antigens to determine if there were any associations between particular HL-A antigens and the disease. None were found. However, HL-A7 was found more frequently in patients with juvenile rheumatoid arthritis demonstrating tenosynovitis than in the population with juvenile rheumatoid arthritis as a whole. These observations fail to support the contention of others that HL-A-W27 is found more frequently than expected in such patients. (N Engl J Med 293:636–638, 1975)
Prevention of falls in older people living in the community
Authors: Edgar R Vieira, Richard C Palmer, Paulo H M Chaves
Journal: BMJ (2016)

The number of people living into older age (≥65 years) is rising rapidly. Older people are more likely to fall and this has adverse consequences for their quality of life and that of their families. Falls also pose a substantial financial burden on healthcare systems . Extensive research from systematic reviews and meta-analyses has established effective approaches for reducing falls among older people, although uncertainties and controversy remain. The evidence suggests that exercise based and tailored interventions are the most effective way to reduce falls and associated healthcare costs among older people in the community. This review integrates current knowledge on assessment and management strategies to prevent falls in older people living in the community. It summarizes known risk factors for falls in this population and presents assessment strategies that can be used to assess the risk of falls. It discusses the management of risks and interventions to reduce falls among older people in the community, as well as future directions and promising approaches.

A fall is an event during which a person inadvertently comes to rest on the ground or other lower level.1 According to the World Health Organization, 28-35% of older people (≥65 years) fall each year globally and prevalence increases with age.1 Falls are the main cause of injury, injury related disability, and death in older people.2 The severity of resulting injuries varies, and 40-60% of falls result in major lacerations, fractures, or traumatic brain injuries.3 A longitudinal study found that 68% of people who fell reported some injury; healthcare was needed in 24% of cases, functional decline was reported by 35%, and social and physical activities were impaired for more than 15%.4 Close to 95% of all hip fractures are caused by falls; 95% of patients with a hip fracture are …
Anti–factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study
Authors: Andreas Tiede, Christoph J. Hofbauer, Sonja Werwitzke, Paul Knöbl, Saskia Gottstein, Rüdiger E. Scharf, Jürgen Heinz, Jürgen Groß, Katharina Holstein, Christiane Dobbelstein, Fritz Scheiflinger, Armin Koch, Birgit M. Reipert
Journal: Blood (2016)
A phase II trial of cetuximab as therapy for recurrent non-small cell lung cancer (NSCLC)
Authors: T. J. Lynch, R. Lilenbaum, P. Bonomi, R. Ansari, R. Govindan, P. A. Janne, N. Hanna
Journal: Journal of Clinical Oncology (2004)

7084 Background: The addition of cetuximab (Erbitux™), an IgG1 monoclonal antibody, to chemotherapy has produced encouraging results in advanced non-small cell lung cancer (NSCLC) in doublet (ASCO 2002: A1168; ASCO 2003: 2581) as well as triplet therapy (ASCO 2003: A2587; ASCO 2003: A2582). Since single agent activity of cetuximab in NSCLC is not known, a phase II trial was undertaken. Methods: Eligible pts with stage IIIB/IV NSCLC who have recurrent or metastatic disease following ≥ 1 prior regimen, including a prior platinum, are eligible to participate in the study. Patients must have an ECOG PS of 0 or 1, and tumors can be EGFR positive or negative. Patients receive an initial cetuximab dose of 400 mg/m2 on Day 1 of Cycle 1, followed by weekly cetuximab doses of 250 mg/m2. One cycle equals four weeks. Weekly treatment with cetuximab continues until disease progression or unacceptable toxicity develops. The response rate with cetuximab will be determined for EGFR (+) positive pts, EGFR (-) negative pts, and for the total study population. Patients will also be assessed for time to disease progression, survival, and toxicity. Results: At a planned interim analysis of the first 29 EGFR + patients, there were 2 confirmed partial responses and 5 pts with stable disease. Preliminary demographic and safety data includes: 29 EGFR + pts, M/F 20/10, 23 pts with stage IV, 6 pts who never smoked and a mean age of 64 years (range 40–78). The mean number of cycles received was 3 (range 1–6). Reported grade 3/4 adverse events deemed possibly related to cetuximab included rash, cellulitis, fatigue, nausea and vomiting (1 pt each). Conclusions: The study is currently ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis; Bristol-Myers Squibb; GlaxoSmithKline GlaxoSmithKline AstraZeneca; Aventis; Bristol-Myers Squibb Bristol-Myers Squibb Aventis
Abstract 3537: Stem-cell based selective delivery of alpha keto reductases for therapeutic targeting of residual androgens in prostate cancer
Authors: Manish Ranjan, Zakaria Abd Elmageed, Hogyoung Kim, Amrita Datta, Nobel Bhasin, Steven E. Braun, Debasis Mondal, Asim B. Abdel-Mageed
Journal: Cancer Research (2015)

Abstract The twice as high incidence and mortality among African Americans (AA) compared to Caucasian Americans and other ethnic minorities remains elusive. The de novo synthesis of androgens by prostate tumors provides a significant survival advantage leading to outgrowth of castration resistant tumors. The “intracrine” production of androgens in the tumor microenvironment is greatly influenced by the synthesis of androgen metabolizing enzymes (AMEs) and the level of circulating hormones. Currently, targeting de novo synthesis of androgens in tumor microenvironment is singularly the toughest challenge presented to oncologists. Our present research attempts to identify and exploit the key players among the AMEs for targeting the backdoor pathway of DHT synthesis in castration resistant prostate cancer (CRPC). Comparative analysis of gene expression of AMEs in microdissected cells versus the adjacent normal tissue revealed AKR1C4 to be the most promising candidate for targeting the backdoor pathway in DHT synthesis. Existing literature supports this view since Type 1 3a-HSD enzyme has been shown to readily oxidize testosterone to Δ4-androstene-3, 17-dione in a substrate dependent reaction. Our analysis using recombinant AKR1C4 induced cytotoxicity and apoptosis in androgen dependent PC cells in vitro. Next, using a lentivirus construct, we genetically engineered tumor-tropic adipose-derived stem cells (ASCs) to express and secreted AKR1C14 (mouse homolog of AKR1C4). The results showed that ASCs are capable of expressing the enzyme, which can catabolize DHT in vitro and induce apoptosis in androgen dependent prostate cancer cells as shown by DHT Elisa, psPSA reporter assays and cytotoxicity and survival assays. Our current research plan is to examine the efficacy of tumor-tropic AKR1C14-expressing ASCs in targeting and inhibiting prostate metastatic growth in an animal model system. Citation Format: Manish Ranjan, Zakaria Abd Elmageed, Hogyoung Kim, Amrita Datta, Nobel Bhasin, Steven E. Braun, Debasis Mondal, Asim B. Abdel-Mageed. Stem-cell based selective delivery of alpha keto reductases for therapeutic targeting of residual androgens in prostate 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 3537. doi:10.1158/1538-7445.AM2015-3537
Utility of recorded guided imagery and relaxing music in reducing patient pain and anxiety, and surgeon anxiety, during cutaneous surgical procedures: A single-blinded randomized controlled trial
Authors: Murad Alam, Wanjarus Roongpisuthipong, Natalie A. Kim, Amita Goyal, Jillian H. Swary, Renata T. Brindise, Sanjana Iyengar, Natalie Pace, Dennis P. West, Mahesh Polavarapu, Simon Yoo
Journal: Journal of the American Academy of Dermatology (2016)