tbuckley/cabot-search huggingface dataset:
Final results of XRP6976D: Preoperative TAC (docetaxel, doxorubicin, cyclophsophamide) in conjunction with the development of a standard protocol for the management of locally advanced breast cancer
Authors: A. Chan, D. Hastrich, D. Ingram, J. Anderson, T. Barham, A. van der Schaaf, D. Joseph, A. Redfern, A. Provis, P. Willsher
Journal: Journal of Clinical Oncology (2008)

628 Background: In Australia, there is no consistent management approach for locally advanced breast cancer (LABC). Our aim was to assess the feasibility of a standardized multidisciplinary protocol for the management of LABC. In addition, MRI and PET accuracy in predicting extent of residual disease following 6 cycles of TAC was evaluated. Methods: Patients with LABC, (T3/4, N2/3, M0); ECOG 0/1, received preoperative chemotherapy (docetaxel 75mg/m2, doxorubicin 50mg/m2, cyclophosphamide 500mg/m2 (TAC) q21 days for 6 cycles, unless progression or intolerable toxicity). Breast and regional nodes were monitored clinically and by ultrasound. MRI and PET performed at baseline and after cycle 6. Mastectomy or local excision with axillary clearance was done and post-surgery radiotherapy given according to the predetermined protocol. Adjuvant trastuzumab and endocrine therapy given as appropriate. Results: 50 patients were included from three institutions in Perth, Western Australia, April 2005 to October 2006. Median age 49 yrs (34–78), pre/postmenopausal 25/25, mean tumor diameter 70mm (25–105), T4d 9 (18%), regional nodal metastases 31 (62%). 46 (92%) completed all planned treatments in accordance with protocol. Chemotherapy commenced within 35 days of diagnosis in 90% of patients. Surgery performed within 42 days of last chemotherapy in 82%, radiotherapy commenced within 42 days of surgery in 50%. Clinical response: CR 20%, PR 52%, SD 16%, PD 12%. Twenty-two SAE occurred in 13 patients with 55% of episodes related to neutropenic sepsis. Pathological CR breast 24%, node negative 34%. Pre- and post-chemotherapy MRI and PET scanning were performed in 42 and 38 pts, respectively. MRI was most accurate in assessing the extent of residual cancer. Correlation of clinical, pathological MRI and PET will be presented. Conclusions: The majority of patients with LABC can complete this standardized management protocol. Adopting such an approach is likely to improve outcomes since patients are more likely to receive optimal multimodality treatments. MRI is the most accurate method for assessing residual disease and could be the most useful method for choosing breast-conserving surgery. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Aventis Aventis
Abstract 18375: Cardioprotection by Cardiosphere-Derived Cells Administered 20 Min After Reperfusion in Rats: Reductions of Infarct Size, Apoptosis, and Macrophage Infiltration, Accompanied by Improved Function
Authors: Geoffrey de Couto, Eleni Tseliou, Hideaki Kanazawa, Linda Marbán, Eduardo Marbán
Journal: Circulation (2013)

Introduction: Cardiosphere-Derived Cells (CDCs) have been shown to reduce scar size following an established myocardial infarction (CADUCEUS Trial). It is currently unknown whether CDCs confer acute cardioprotection following ischemic injury. Here we test the hypothesis that intracoronary infusion of CDCs following ischemia/reperfusion (I/R) injury reduces cardiomyocyte stress, and protects against cardiac dysfunction and infarct expansion. Methods &amp; Results: Wistar-Kyoto rats (aged 8-12 weeks) underwent 45 minutes of ischemia and 20 minutes of reperfusion. Animals were then randomly allocated to either CDC or placebo groups and treated with 5x105 CDCs or PBS, respectively. Two days following I-R injury, CDC-treated rats revealed a reduction in percent infarct mass relative to PBS-treated controls (6.3% vs. 13.6%, p&lt;0.01 n=5/group). These findings were accompanied with reduced programmed cell death within the infarct zone at day 2 (cleaved caspase 3, TUNEL positivity; p&lt;0.05), and improved cardiac function at day 14 (EF: 45% vs. 62% p&lt;0.01). While no difference was observed in peripherally circulating inflammatory cells, a reduction in CD68+ macrophages (Mϕ) was found within the myocardium of CDC-treated animals (23% vs. 18%, p&lt;0.05; n=4/group). In vitro co-culture of CDCs with TNF-α-stimulated Mϕ cells attenuated the expression of IL-6, while concomitantly elevating IL-10, Tgfb1, and Arg1, gene expression profile within Mϕ cells (p&lt;0.05). Conclusions: Collectively, these data demonstrate that intracoronary infusion of CDCs following I/R produce acute cardioprotection, and confer prolonged myocardial integrity. Furthermore, CDCs reduce infarct expansion at 2 days and improve cardiac function at 14 days. The cardioprotective effects of CDCs involve a reduction in infiltrating, cytotoxic Mϕ cells.
A combination phase I study of topotecan with carboplatin for relapsed small cell lung cancer: Results of West Japan Thoracic Oncology Group trial (WJTOG0202)
Authors: T. Kashii, T. Kurata, K. Takeda, N. Seki, M. Tsuboi, T. Miwa, R. Morinaga, M. Kobayashi, T. Satoh, M. Fukuoka
Journal: Journal of Clinical Oncology (2007)

18126 Background: Topotecan is an active agent for relapsed or recurrent SCLC. Combination chemotherapy of topotecan and carboplatin for relapsed SCLC has not been fully evaluated. To determine the maximum-tolerated dose (MTD), a phase I study was conducted. Method: Patients with measurable disease and one prior chemotherapy regimen excluding topotecan were enrolled in this study. Topotecan was administered through days 1 to 5, whereas carboplatin was administered on day 5. Courses were repeated every 3 weeks. The starting doses of topotecan and carboplatin were 0.50 mg/m 2 /day and AUC=5, respectively. The dose levels examined are shown in the table below. Results: A total of 32 patients with relapsed SCLC have been enrolled. Patient characteristics are as follows: median age, 64 yrs (range 43–74); male/female, 23/9; ECOG PS 0/1, 15/17 patients. Dose-limiting toxicities (DLTs) were observed in 1 patient at dose level 1 (infection), level 3 (diarrhea), and level 5 (thrombocytopenia), respectively. Three of 6 patients have experienced DLTs at dose level 6 (thrombocytopenia). MTD of topotecan and carboplatin were determined to be 0.85 mg/m 2 and AUC=5, respectively. Five of 29 (17 %) assessable patients have responded to treatment with a partial response (PR), and 13 (45 %) patients have had stable disease (SD) at best response. Conclusions: The recommended doses are 0.75 mg/m 2 of topotecan and AUC=5 of carboplatin. The combination of topotecan and carboplatin shows an acceptable activity and toxicity profile in relapsed SCLC patients. Further study in the phase III setting is warranted. [Table: see text] No significant financial relationships to disclose.
Reasons to Conserve Nature
Authors: Richard G. Pearson
Journal: Trends in Ecology & Evolution (2016)

Is it sufficient to base arguments for conservation on the intrinsic value of nature, regardless of the services and economic benefits that biodiversity provides for humans? This question underlies much recent debate that has been at times acrimonious and has led to calls for a more inclusive approach to conservation. Yet melding different ideologies within a unified conceptual framework has proven difficult. Here I describe an approach that recognizes the importance of the level of biological organization and spatial extent in determining the strength of alternative arguments for why we should conserve nature. I argue that the framework helps reconcile contrasting viewpoints and brings clarity to when different conservation management approaches (for instance, regulation versus monetary valuation) are most appropriate.
New Virus Associated With Merkel Cell Carcinoma Development
Authors: Dana E Rollison, Anna R Giuliano, Jürgen C Becker
Journal: Journal of the National Comprehensive Cancer Network (2010)

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine malignancy of the skin with an annual incidence in the United States of 0.34 and 0.17 per 100,000 men and women, respectively. MCC incidence increases with age, is higher among men and whites, and positively correlates with solar ultraviolet (UV) index, suggesting UV radiation exposure may play a role in the development of MCC. MCC incidence rates are also higher among severely immunosuppressed populations, including people who have undergone organ transplantation, have lymphoma, and are HIV-infected. Given the increased risk for MCC observed with immunosuppression and the established associations between viral infections and other cancers that occur more often in immunosuppressed populations, MCC was a prime cancer candidate for a viral cause. Subsequent investigation discovered a genome encompassing 5387 base pairs of a new polyomavirus, subsequently named the Merkel cell polyomavirus.
Reference values for the incremental shuttle-walking test in Japanese adults
Authors: Masatoshi Itaki, Tsuyoshi Nishinakagawa, Masaharu Asai, Kazuaki Suyama, Kenichiro Tanaka, Takako Tanaka, Ryo Kozu, Hideaki Senjyu
Journal: European Respiratory Journal (2014)

Introduction : Exercise intolerance is a typical feature in a number of chronic diseases. The Incremental Shuttle Walking Test (ISWT) is typically used to assess the degree of intolerance. A predictive expression of the walk distance in the ISWT (ISWD) is reported for South American healthy subjects. However, these reference values are not available for Japanese subjects, who exhibit a difference in build. Thus, assessing the degree of exercise intolerance compared with a healthy subject in the Japanese population remains problematic.

Aims : To establish a reference equation for ISWD prediction.

Methods : We evaluated ISWT, age, weight, height, and body mass index (BMI) in 399 healthy Japanese subjects ( 20–80 years old; 134 male), according to the protocol of Singh (Singh et al 1992).

Results : The subjects walked 580m [IQR25–75%: 480–730m] in the ISWT. There were significant correlations between ISWD and age, gender, weight, and height (p<0.001 for all). A model of stepwise multiple regression showed that age (b=-0.408), gender (b=-0.356), and height (b=0.163) were independent contributors to the ISWT in 53.3% of healthy subjects. The derived reference equation was: ISWT pred = 544.495 – 4.793 × age – 142.445 × gender + 3.332 × height (cm), where male gender =0 and female gender =1.

Conclusions : In healthy Japanese subjects, we developed a reference equation of ISWD that incorporated age, gender, and height. The prediction accuracy was high. Thus, in clinical practice, ISWD can be predicted based on subject age, gender, and height, which can be used to evaluate the extent of exercise capacity versus the measured value.
Phase II trial of vaccination with WT1 peptide, GM-CSF, and KLH in patients with acute myeloid leukemia and myelodysplasia: Final immunological, molecular, and clinical results
Authors: A. Letsch, C. Scheibenbogen, A. Busse, A. M. Asemissen, A. Schmittel, W. K. Hofmann, L. Uharek, I. W. Blau, E. Thiel, U. Keilholz
Journal: Journal of Clinical Oncology (2007)

3008 Purpose: A phase II trial of vaccination with the HLA-A2-restricted WT1.126–134 peptide was performed in patients (pts) with AML and MDS and overexpression of WT1 to determine toxicity, immunogenicity, and molecular and clinical activity. Methods: Patients received intra/subcut. vaccinations of 0.2 mg WT1.126–134 peptide (day 3), 62.5 mcg GM-CSF (days 1–4) as DC-stimulant and 1 mg keyhole limpet hemocyanin (day 3) as T helper protein. Vaccination was biweekly x 4 followed by 4-weekly in the first 13 patients and continuously biweekly in the subsequent 13. Early disease progression until vaccine # 6 was allowed, if not requiring chemotherapy. WT1-specific T cell responses were measured by tetramer and cytokine flow cytometry. WT1 levels were assessed by qRT-PCR. Clinical response assessment followed IWG-MDS criteria, capturing stable disease and hematologic improvement. Statistical analysis was performed by frequency tables and exploratory comparisons using Fishers test. Results: Of 29 pts enrolled 25 were evaluable, 23 with AML and 2 with RAEB. 15 AML pts had &gt;5% marrow blasts and 8 had high-risk CR with detectable WT1 mRNA. A median of 11 (range 3 - 25) vaccinations was administered, 3 pts are ongoing. No relevant toxicity occurred. There were no obvious differences in outcome parameters between the 2 vaccination schedules. The percentage of patients with WT1 tetramer response increased from 28% prior to vaccination to 80% at week 10 (p=0.003), while the WT1 peptide specific cytokine response increased from 20% to 57% (p=0.012) of patients. WT1 mRNA-levels increased in 22% of patients, were stable in 26%, and decreased in 52% (2 to&gt;50-fold). One CR (514 days) and 13 SD (99 to 339 days) were observed, 5 SD with &gt;50% blast reduction and 3 with hematologic improvement. The CR and 3 SD occurred after initial PD. The median time to treatment failure (TTF) was 143 days. There was a significant association between decrease in WT1 mRNA levels and TTF (p=0.026). Conclusions: This study proves immunological, molecular and clinical efficacy of WT1 peptide vaccination in AML. Further investigations are indicated in WT1 expressing carcinomas and in combination with agents targeting CTLA4 or PD1. No significant financial relationships to disclose.
Stimulation of nonclonal hematopoiesis and suppression of the neoplastic clone after treatment with recombinant human granulocyte- macrophage colony-stimulating factor in a patient with therapy-related myelodysplastic syndrome
Authors: S Vadhan-Raj, HE Broxmeyer, G Spitzer, A LeMaistre, S Hultman, G Ventura, JD Tigaud, MA Cork, JM Trujillo, JU Gutterman
Journal: Blood (1989)
Prevalence of Antibody to Lymphadenopathy-Associated Virus among Drug-Detoxification Patients in New York
Authors: T J Spira, D C Des Jarlais, M Marmor, S Yancovitz, S Friedman, J Garber, H Cohen, C Cabradilla, V C Kalyanaraman
Journal: New England Journal of Medicine (1984)

This letter reports the seroprevalence of antibody to human T-lymphotropic virus type III (HTLV-III) among New York City drug detoxification patients without acquired immunodeficiency syndrome (AIDS).  Serum specimens were collected from 86 intravenous drug users in May-June 1984 84% of whom reported daily drug use.  In addition serum from 17 intravenous drug users who had been diagnosed as having AIDS was collected.  Controls were 70 healthy employees from the Centers for Disease Control.  The prevalence of anti-HTLV-III among drug abusers without AIDS was 87% (75 subjects) when the enzyme-linked immunosorbent assay (ELISA) was used and 58% (50 subjects) according to radioimmunoprecipitation assay (RIPA).  Among drug abusers with AIDS seroprevalence was noted in 65% (11 subjects) by the ELISA method and in 29% (5 subjects) by RIPA.  Finally only 2 controls (3%) were seropositive according to the ELISA test; no controls showed reactivity by RIPA.  Seropositive non-AIDS intravenous drug abusers from this series are being followed to determine which will acquire immunosuppression-related disease.  It is noted that drug users in detoxification programs are not representative of all intravenous drug users.  Such a sample is biased toward recent intensive care and possibly toward the presence of other health problems.  However this is not a small subpopulation; over 4000 persons/year enter inpatient detoxification programs in New York City.
Sixty seconds on . . . vaginal seeding
Authors: Gareth Iacobucci
Journal: BMJ (2016)

The term describes the use of a gauze swab to transfer maternal vaginal fluid (and therefore vaginal microbiota) onto infants born by caesarean section.

It might rank alongside faecal transplants in the Top Trumps of new, distasteful sounding medical procedures. But just as faecal transplantation has become a common treatment for Clostridium difficile infection, …
Axitinib versus sorafenib as second‑line therapy in Asian patients with metastatic renal cell carcinoma (mRCC): Results from a registrational study.
Authors: Shukui Qin, Feng Bi, Ying Cheng, Jun Guo, Xiu Bao Ren, Yiran Huang, Jinwan Wang, Yong Ben, Sinil Kim, Jie Tang, Dingwei Ye
Journal: Journal of Clinical Oncology (2012)

LBA4537 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Saturday, June 2, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
NCCN Oncology Research Program's Investigator Steering Committee and NCCN Best Practices Committee Molecular Profiling Surveys
Authors: Razelle Kurzrock, A. Dimitrios Colevas, Anthony Olszanski, Wallace Akerley, Carlos L. Arteaga, William E. Carson, Jeffrey W. Clark, John F. DiPersio, David S. Ettinger, Robert J. Morgan, Lee S. Schwartzberg, Alan P. Venook, Christopher D. Gocke, Jonathan Tait, F. Marc Stewart
Journal: Journal of the National Comprehensive Cancer Network (2015)

Background: With advances such as next-generation sequencing (NGS) increasing understanding of the basis of cancer and its response to treatment, NCCN believes it is important to understand how molecular profiling/diagnostic testing is being performed and used at NCCN Member Institutions and their community affiliates. Methods: The NCCN Oncology Research Program's Investigator Steering Committee and the NCCN Best Practices Committee gathered baseline information on the use of cancer-related molecular testing at NCCN Member Institutions and community members of the NCCN Affiliate Research Consortium through 2 separate surveys distributed in December 2013 and September 2014, respectively. Results: A total of 24 NCCN Member Institutions and 8 affiliate sites provided quantitative and qualitative data. In the context of these surveys, "molecular profiling/diagnostics" was defined as a panel of at least 10 genes examined as a diagnostic DNA test in a Clinical Laboratory Improvement Amendments (CLIA)–certified laboratory. Conclusions: Results indicated that molecular profiling/diagnostics are used at 100% of survey respondents' institutions to make patient care decisions. However, challenges relating to reimbursement, lack of data regarding actionable targets and targeted therapies, and access to drugs on or off clinical trials were cited as barriers to integration of molecular profiling into patient care. Frameworks for using molecular diagnostic results based on levels of evidence, alongside continued research into the predictive value of biomarkers and targeted therapies, are recommended to advance understanding of the role of genomic biomarkers. Greater evidence and consensus regarding the clinical and cost-effectiveness of molecular profiling may lead to broader insurance coverage and increased integration into patient care.
Can adjuvant homeopathy improve the control of post-chemotherapy emesis in breast cancer patients? Results of a randomized placebo-controlled trial
Authors: I. L. Ray-Coquard, J. Provençal, A. C. Hardy-Bessard, T. Bachelot, D. Coeffic, J. P. Jacquin, J. P. Guastalla, C. Agostini, X. Pivot, A. Bajard, D. Pérol
Journal: Journal of Clinical Oncology (2009)

e20566 Background: Homeopathy used as an adjunct in the treatment of chemotherapy (CT)-induced emesis has rarely been evaluated. Methods: Patients with non-metastatic breast cancer treated with 6 courses of FAC 50, FEC 100 or TAC chemotherapy were randomized to Cocculus/nux vomica/tabacum/petroleum extract (Cocculine, C) or Placebo (P) in a multicentric comparative double-blind phase III study. Anti-emetic treatment was standardized (corticoids + ondansetron). Patients were evaluated after each course. The primary endpoint was nausea measured after the 1 st CT course using the FLIE (Functional Living Index for Emesis) with 5-day recall. The planned sample size was 396 evaluable patients based on a minimum expected difference in mean of 0.5 ± 1.6 on a scale from 1 (a lot) to 7 (not at all) with 5% two-sided α error and 85% power. An intent-to-treat analysis was planned. Secondary evaluation criteria were: vomiting measured by the FLIE score, patient self-evaluation (EVA) and investigator recording (NCI-CTC) of nausea and vomiting intensities, and compliance. Results: From September 05 to January 08, 431 patients were randomized (217 to P and 214 to C). Patient characteristics were well balanced between groups. Median age was 53 years, 35% of the patients experienced nausea or vomiting. In total, 403 patients (93.5%) were assessable for the primary endpoint, with few nausea episodes (FLIE nausea scores after the 1 st CT course were 6.02 and 6.07 for P and C, respectively) and very good compliance (81% patients complied with the protocol). Adverse events related to nausea occurred in 51% vs. 47% of the patients treated with P and C, respectively (p = 0.48). FLIE and NCI-CTC vomiting scores were similar between the 2 arms (6.91 vs. 6.88, p = 0.47, and 20% vs. 21%, p = 0.73, for P and C, respectively). Grade II-III nausea occurred in 17.6% and 15.7% of patients receiving P and C (p = 0.62). Conclusions: No benefit of homeopathy over standard treatment was noted in this study. But surprisingly we observed lower rates of nausea and vomiting measured by patients and by investigators, than in other studies using identical chemotherapy regimens. The observation and management of emesis could modify the perception and rate of such adverse events. No significant financial relationships to disclose.
Phase I trial of anti-PSMA designer T-cell autografting in prostate cancer
Authors: M. Abedi, Q. Ma, A. Bais, E. Gomes, E. Beaudoin, L. Lu, P. Davol, S. I. Cohen, R. Junghans
Journal: Journal of Clinical Oncology (2009)

e16132 Background: We created chimeric immunoglobulin-T cell receptors (IgTCR) specific for prostate specific membrane antigen (PSMA). When expressed in patient T cells, these “designer T cells” specifically kill prostate cancer cells in vitro and in vivo in animal models, with 5/9 (55%) of xenografted mice experiencing complete remissions (Ma et al. Prostate 2004:61:12–25). A Phase I clinical trial was approved by the FDA in metastatic prostate cancers. Methods: Patient T cells are retrovirally transduced and expanded ex vivo to span dose levels of 10^9 to 10^11 T cells. Adapting methods of Dudley, Rosenberg and colleagues, patients undergo prior non-myeloablative (NMA) conditioning to create a “hematologic space” into which the infused designer T cells will stably engraft for prolonged in vivo efficacy. Patients are co-administered continuous infusion IL2. Outcomes will include Phase Ia goals of safety and toxicity and Phase Ib goals of establishing an optimal biologic dose in terms of designer T cell engraftment and tumor response. Results: For the first two patients, excellent T cell modifications of 50–60% were obtained. After NMA conditioning, T cells were infused and stable engraftments of 1–5% were observed post recovery, even at this lowest 10^9 T cell dose level, thus affirming one of the study end-points. The patients had PSA reductions of 50 and 70% in the two months following treatment. Patients experienced neutropenia and lymphopenia after conditioning, but no designer T cell-related toxicities. Results with additional patients will be described in terms of safety, engraftment efficiency and tumor responses. Conclusions: A new approach to adoptive immune therapy in metastatic prostate cancer has been devised. This clinical trial is funded by the US Army/DOD. No significant financial relationships to disclose.