tbuckley/cabot-search huggingface dataset:
The Head to Head trial: Letrozole vs anastrozole as adjuvant treatment of postmenopausal patients with node positive breast cancer
Authors: R. De Boer, H. A. Burris, A. Monnier, H. Mouridsen, J. A. O’Shaughnessy, K. McIntyre, K. I. Pritchard, I. Smith, D. Yardley
Journal: Journal of Clinical Oncology (2006)

10672 Introduction: Aromatase Inhibitors (AIs) have demonstrated both efficacy and safety advantages over tamoxifen (T) in all treatment settings in breast cancer (BC) and are becoming the new standard of care as endocrine therapy for postmenopausal patients (PM) with BC. Rationale: Cumulative evidence suggests that all AIs may not be the same, raising the question of whether there is a superior AI, and whether any specific patient populations derive differing degrees of benefit from a particular AI. In the ATAC trial, evaluating anastrozole (A) in PM patients with early breast cancer (EBC), at 33 months median follow up the risk of recurrence in the hormone receptor positive (HR+) population was reduced by 22%.The BIG 1–98 Trial, evaluating letrozole (L) in PM women with EBC, showed a significant benefit in favor of L over T at a median follow up of 26 months, with a 19% reduction in the risk of recurrence; in subgroup analyses, L significantly decreased the risk of recurrence in LN+ patients and in patients who received adjuvant chemotherapy. This study is a head to head comparison of L and A in HR+, LN+ PM patients with EBC and aims to compare L vs A in the adjuvant treatment of these patients. Design and Methods: This is a Phase IIIb open-label, randomized, multicentre study including 4000 PM patients from up to 250 international sites. PM patients with HR+, LN+ BC who have recently undergone surgery for primary BC will be randomized to either receive L 2.5 mg or A 1 mg daily. Treatment will commence following completion of standard chemotherapy (if given) and concurrently with radiotherapy (if given)Patients will receive treatment until disease recurrence/relapse for up to 5 years. Patients will be stratified by number of LN and HER2 status. The primary objective is disease free survival at 5 years for L and A. Secondary objectives include safety, overall survival, time to distant metastases and time to contralateral breast cancer. Data analysis will be conducted by an independent group of investigators. Summary: Updated patient accrual figures, including any available early safety data, will be presented at the meeting. No significant financial relationships to disclose.
Accidental Carbon Monoxide Poisoning
Authors: F. S. Fiddes
Journal: BMJ (1956)

URETHRO-TRIGONITISMEDBAi Ju-RNsA 697 not showing such a close relationship as that of the cervix to the floor of the bladder, nevertheless shows a ready lymphatic connexion.This is well shown by Rouviere (1932), and there would seem to be no reason why infection should not spread from the lymphatics of one organ to those of the other, which would appear, on clinical grounds, to be the -case.The results of treatment of the bowel condition combined with that of the bladder neck go far to support this theory.Dilatation of the bladder neck and even fulguration of polypi and granulations have not produced very encourag- ing results in such cases, but when the lesion of the bowel is alleviated the urethro-trigonitis responds to treatment very much more readily.Thus the bladder neck was treated in exactly the same way as when the infection came from the cervix, care being taken not to irritate the urethra by too frequent dilatation-that is, not more than once every six weeks and usually at less frequent intervals.Treatment of the bowel depends on the type of lesion and its extent.In the less extensive lesions, in which surgery is not called for, the institution of a low residual diet which does not irritate the mucosa of the bowel and limits fermen- tation, combined with regulation of bowel action by '-petrolagar" with or without phenolphthalein, alone may give much improved results, but infection can be further limited by the administration of phthalylsulphathiazole in an initial dose of six 0.5-g.tablets followed by two tablets every six hours for fourteen days.This course can be repeated at fortnightly intervals until the infection has been greatly diminished. (In the more resistant cases an initial course of streptomycin and sulphaguanidine followed by phthalyl- sulphathiazole may be necessary.)As a result of this routine the symptoms of urethro-trigonitis were improved in each of the cases treated. SummarySymptoms of urethro-trigonitis were present in 25 to 30% of female patients attending an out-patient clinic, and this condition was verified by urethroscopy in which characteristic changes were found present at the bladder neck.These changes have been proved to arise from lesions of the cervix and genital tract, and were found in 66% of these cases.Of the remaining 34%, a third were found to have radiologically demonstrable lesions of the large intestine.Treatment of the intestinal infection, combined with dilatation and, where necessary, fulguration of the bladder neck, gives excellent results as compared with dilatation and fulguration alone.
Transmission of hepatitis C virus infection among younger and older people who inject drugs in Vancouver, Canada
Authors: Brendan Jacka, Tanya Applegate, Art F. Poon, Jayna Raghwani, P. Richard Harrigan, Kora DeBeck, M.-J. Milloy, Mel Krajden, Andrea Olmstead, Jeffrey B. Joy, Brandon D.L. Marshall, Kanna Hayashi, Oliver G. Pybus, Viviane Dias Lima, Gkikas Magiorkinis, Julio Montaner, Francois Lamoury, Gregory J. Dore, Evan Wood, Jason Grebely
Journal: Journal of Hepatology (2016)
Re-Examining the Role of Radiation Therapy for Diffuse Large B-Cell Lymphoma in the Modern Era
Authors: Andrea K. Ng, Bouthaina Shbib Dabaja, Richard T. Hoppe, Timothy Illidge, Joachim Yahalom
Journal: Journal of Clinical Oncology (2016)

Andrea K. Ng, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA Bouthaina Shbib Dabaja, The University of Texas MD Anderson Cancer Center, Houston, TX Richard T. Hoppe, Stanford University School of Medicine, Stanford, CA Timothy Illidge, University of Manchester, Manchester Academic Health Sciences Centre, The Christie National Health Service Foundation Trust, Manchester, United Kingdom Joachim Yahalom, Memorial Sloan Kettering Cancer Center, New York, NY
The actin-bundling motility protein fascin and vascular endothelial growth factor (VEGF) are universally over-expressed in human angiosarcoma
Authors: D. Dim, V. Ravi, J. Tan, D. Hicks, M. Wong
Journal: Journal of Clinical Oncology (2007)

10068 Background: Angiosarcoma is a highly aggressive soft tissue malignancy with a dismal progression-free survival (PFS). Treatment options for disseminated disease are limited and present systemic therapies have not shown evidence of prolonging overall survival. In this regard, a greater understanding of the molecular and cellular basis of the tumor phenotype of this uncommon malignancy and how these features correlate to clinical behavior would be an important step towards identifying potential new molecular targets for therapy. Our previous work show that acquisition of the chemotherapy-resistant phenotype by angiosarcoma cells occurs concomitantly with a marked increase in cell motility and VEGF expression. Increased expression of the angiogenic factor VEGF and the motility protein fascin have been associated with more aggressive clinical course in a number of other tumor types and may play a direct role in the biologic behavior of these malignancies. Therefore, in the current study, we sought to characterize angiosarcoma by immunohistochemistry for the expression of VEGF and fascin, and compared the staining pattern to benign vascular tumors. Methods: 20 cases of angiosarcoma, and 5 cases of hemangioma were stained for tumor cell expression of VEGF and fascin using anti-VEGF polyclonal antibody (clone A-20, 1:50, Santa Cruz Biotechnology, Santa Cruz, CA) and antibody to fascin (clone 55K-2, 1:500, DakoCytomation, Carpinteria, CA). Results: Surprisingly, every case of angiosarcoma showed high expression for both VEGF and fascin with moderate to strong staining intensity in 75 to 100% of the tumor cells for each case. By comparison, both proteins were either absent or only weakly positive in hemangiomas. Conclusions: In the current study we found high levels of VEGF and fascin universally expressed in angiosarcomas, which was not the case for benign vascular tumors. These factors maybe part of the malignant phenotype for these tumors and contribute to an aggressive clinical course through enhanced cell motility and autocrine/paracrine signaling. Additional study will be needed to better define a role for these proteins in angiosarcoma and to determine if they might represent potential new molecular targets for therapy. No significant financial relationships to disclose.
Physiopathology, Clinical Manifestations, and Treatment of Gout: Part 2. Clinical and Therapeutic Studies
Authors: S. de Seze, A. Ryckewaert, J. Levernieux, R. Marteau
Journal: Annals of the Rheumatic Diseases (1958)

Less than 10 years in 20 patients More than 10 or less than 20 years in 28 patients 20 years or more in 52 patientsThe patients' ages were distributed as follows: From 30 to 39 years: I case From 40 to 49 years: 20 cases From 50 to 59 years: 45 cases From 60 to 69 years: 27 cases Over 70 years: 7 cases I. AETIOLOGY Sex Ratio.-Ourseries of one hundred patients.included only four women.Family History.-37patients knew of at least one on July 18,
The TCA cycle transferase DLST is important for MYC-mediated leukemogenesis
Authors: N M Anderson, D Li, H L Peng, F J F Laroche, M R Mansour, E Gjini, M Aioub, D J Helman, J E Roderick, T Cheng, I Harrold, Y Samaha, L Meng, A Amsterdam, D S Neuberg, T T Denton, T Sanda, M A Kelliher, A Singh, A T Look, H Feng
Journal: Leukemia (2016)
Storage of semen. (Letter to the editor)
Authors: Silbert Ja
Journal: JAMA (1973)

Concern is expressed about the widely reported study by Smith and Steinberger that gives the impression that the storage potential of human semen is limited to about 3 years.  The author cites a study by J.K. Sherman in which conceptions from human semen stored 10 years were reported.  This study and a study by R. Foote on bull semen indicate that the limitations found by Smith and Steinberger were brought on by their particular method of handling and storage of semen.  When samples are stored under the surface of liquid nitrogen the storage time seems to be indefinite.
The Src Inhibitor AZD0530 Prevents the Development of Osteolytic Bone Disease in Multiple Myeloma
Authors: Roy Heusschen, Joséphine Muller, Marilène Binsfeld, Erwan Plougonven, Nadia Mahli, Geert Carmeliet, Angélique Léonard, Martine Cohen-Solal, Karin Vanderkerken, Yves Beguin, Eline Menu, Jo Caers
Journal: Blood (2015)
What price for a year of life? A survey of U.S. and Canadian oncologists
Authors: S. R. Berry, P. J. Neumann, C. Bell, E. Nadler, W. C. Evans, J. Palmer, E. Strevel, P. A. Ubel
Journal: Journal of Clinical Oncology (2009)

6565 Background: New cancer drugs are increasingly expensive and raise difficult questions about the magnitude of therapeutic benefit needed to justify their incremental cost. In this context, it is unclear whether oncologists endorse standard thresholds of $50,000 to $100,000 per year of life. Methods: We surveyed 1,379 U.S. and 356 Canadian (Cdn) oncologists and asked how much longer a patient would need to survive metastatic cancer to justify the expense of a new treatment. To determine the stability of attitudes towards cost-effectiveness (CE) we randomized oncologists to receive two different versions of the scenario in which the price of the new treatment was varied (higher versus lower drug cost). In the U.S. survey, oncologists were also randomized to receive surveys in which we varied the provision of contextual information about the CE of several familiar interventions. Both U.S. and Cdn oncologists were asked to indicate what they “thought was ‘good value for money’ expressed as cost per life-year gained (LYG).” Results: Response rate was 57% in the U.S. and 48% in Canada. CE ratios implied by oncologists’ responses differed significantly between the groups randomized to the higher versus lower price of the hypothetical treatment (p &lt; 0.001 U.S., p &lt; 0.0001 Canada), but were independent of randomization to varying contextual information (p &gt; 0.1). The median willingness to pay for a quality-adjusted year of life ranged from $150,000 (for oncologists considering the lower priced drug) to $250,000 (for those considering the more expensive drug) in both countries. Among those who considered the more expensive drug, 25% of respondents implicitly endorsed a CE ratio greater than $600,000 (U.S.) and $500,000 (Canada). In contrast, when asked directly to indicate CE ratios that were good value for the money outside of the clinical scenario, 70% (U.S.) and 64% (Canada) of respondents indicated values of less than $100,000 per LYG. Conclusions: Oncologists responding to our survey provided inconsistent views on how much benefit expensive new drugs should provide to be worthwhile. This suggests that means of eliciting input from physicians that reflect more stable attitudes need to be developed to appropriately inform decision-makers. No significant financial relationships to disclose.
5α-reductase from radical prostatectomy tissue and utilization of testosterone and androstenedione to produce DHT: A dual isotope method and preliminary results.
Authors: Evan Kovac, Kai-Hsiung Chang, Eric A. Klein, Nima Sharifi
Journal: Journal of Clinical Oncology (2015)

58 Background: Previous work has shown that 5α-reductase prefers androstenedione (AD) in favor of testosterone (T) for dihydrotestosterone (DHT) synthesis in castration-resistant prostate cancer. Yet, 5α-reductase substrate preference in the setting of localized prostate tissue has yet to be fully elucidated. We propose a novel ex-vivo method for tracking steroid handling by the prostate and report our preliminary findings. Methods: Prostate tissue from the peripheral and transitional zones of patients who underwent radical prostatectomy (RP) for localized prostate cancer were incubated in media, along with ( 3 H)-labeled AD and ( 14 C)-labeled T. Media was collected after 7, 24 and 48 hours of incubation, treated with glucuronidase and high performance liquid chromatography (HPLC) was used to identify steroids tagged with either 3 H or 14 C. Results: In total, 11 patients were consented for tissue procurement at the time of RP. Qualitatively, both AD and T are utilized by the prostate to produce DHT. Over time, concentrations of tritiated AD decreased, while concentrations of tritiated T, 5α-androstanedione and DHT rose. Similarly, concentrations of 14 C-T decreased over a 48-hour period, while AD, 5α-androstanedione and DHT increased. Conclusions: We describe a dual isotope method for characterizing androgen handling by prostate tissue from patients with localized prostate cancer, using 2-channel radiolabel detection. Preliminary results show that both AD and T can be utilized by localized prostate cancer tissue. Future work will focus on determining if different phenotypes of androgen handling exist among various patient genotypes and cancer risk groups.
Aldo-keto reductase (AKR) 1C3 as an androgen receptor coactivator.
Authors: Ramesh Narayanan, Muralimohan Yepuru, Zhongzhi Wu, Christina Barrett, Juhyun Kim, Trevor M. Penning, Mitchell S. Steiner, Duane D. Miller, James T. Dalton
Journal: Journal of Clinical Oncology (2013)

100 Background: Castration resistant prostate cancer (CRPC) may occur by several mechanisms including up-regulation of the androgen receptor (AR), coactivators, and steroidogenic enzymes, including AKR1C3. AKR1C3 (type 5 17b-hydroxysteroid dehydrogenase) converts weaker 17-keto androgenic precursors to more potent 17-hydroxy androgens and is consistently a major up-regulated gene in CRPC. The objective is to examine the role of AKR1C3 in AR function and CRPC. Methods: AR transactivation studies were performed with GRE-LUC in the presence or absence of AKR1C3 in HEK-293 cells. Gene expression patterns and prostate cancer cell and tumor growth were evaluated in LNCaP and VCaP cells. Molecular studies, including co-immunoprecipitation, chromatin immunoprecipitation and others, were performed to determine AKR1C3 localization and interaction with the AR. Novel small molecule AKR1C3 selective-inhibitors were synthesized and characterized in prostate cancer models. Results: We identified unique AR selective coactivator- and prostate cancer growth-promoting-roles for AKR1C3. AKR1C3 over-expression promotes the growth of both androgen-dependent prostate cancer and CRPC xenografts, with concomitant reactivation of androgen signaling. AKR1C3 interacted with AR in prostate cancer cells and in a human CRPC sample and was recruited to the promoter of an androgen responsive gene, PSA. The coactivator and growth promoting functions of AKR1C3 were inhibited by an AKR1C3-selective competitive inhibitor. Conclusions: AKR1C3 is a novel AR selective coactivator and may represent the first nuclear hormone receptor coactivator that can be pharmacologically targeted.
Erythema nodosum and oral contraceptives. (Letter)
Authors: Taaffe A, Finlay Ay, Marks R
Journal: BMJ (1977)

A case of erythema nodosum in a 26-year-old woman who took Minilyn for 3 years is reported.  The occurrence of erythema nodosum corresponded to the periods of use and discontinuation of Minilyn;  it was assumed that Minilyn was responsible for the condition.  After a challenge with 4 unknown types of pills 1 of which was Minilyn the erythema nodosum did not recur.  It is possible that desensitization to Minilyn had occurred in the meantime.
Pegylated liposomal doxorubicin (PLD) as an alternative treatment of cutaneous T-cell lymphoma
Authors: G. Quereux, A. Khammari, J. M. Nguyen, M. Benmiloud, B. Dreno
Journal: Journal of Clinical Oncology (2007)

8096 Background: Therapy of cutaneous T-cell lymphoma (CTCL) at early stages consists of various modalities. The advanced or transformed stage of CTCL is treated by the CHOP regimen as standard chemotherapy; has a 40% response rate and relapses within 6 months in &gt; 60% of pts. Methods: A prospective open multicentre Phase II study to evaluate the use of PLD as a CTCL therapeutic agent, with 25 pts, (59±12 years). Eligibility criteria: Pts with histologic proof of CTCL stage II to IV, unresponsive to at least 2 lines of therapy; transformed CTCL or non epidermotropic lymphoma CD30 + or CD30. PLD was administered i.v., 40 mg/m 2 every 4 wks for 8 cycles. Objective of study was overall response rate (ORR); secondary objectives were safety, disease-free survival (DFS) and overall survival (OS). Results: Phase II study of 14pts with CTCL stage IIb/III, and 11pts with transformed CTCL, at baseline. Treatment duration was 8 cycles in 13 pts, 2–6 cycles in 10pts, and 2 pts were withdrawn during cycle 1 due to anaphylactic-like reactions. Among 23 treated pts, 5pts (22%) achieved a complete response (CR), 9pts (39%) a partial response (PR), with 61% ORR. DFS was 18 ± 4.5 mos; longest treatment duration was 24 mos. Median OS was 28 ± 3 mos. In general, PLD treatment was well tolerated. The main adverse events were grade 3 neutropenia (4%); grade 3 septicemia (8%) and 1 case of bilateral grade 3 pneumopathy. There were only 3 cases of grade 1 palmoplantar erythrodysesthesia. Conclusions: This is the first prospective multicentric study investigating activity and tolerance of 40 mg/m 2 q28days of PLD in CTCL. The current study confirmed effectiveness of PLD(∼61%) in CTCL treatment, but did not show improved efficacy with dose increases (Wollina, Cancer, 2003). This data combined with Wollina’s data, support the use of PLD as a promising therapy in advanced stages of CTCL. The duration of response is superior to that achieved with CHOP. This has been confirmed in a small, trial, and needs to be confirmed in a larger trial. No significant financial relationships to disclose.
Combined chemoradiation (CRT) with high dose rate brachytherapy (HDR) for locally advanced cervical cancer: A regional experience
Authors: A. Lin, J. Ryu, D. Harvey, S. Scudder, S. Lee, G. Leiserowitz, L. Smith, J. Dalrymple, J. Skilling, W. Kinney, A. Russell
Journal: Journal of Clinical Oncology (2005)

5162 Background: CRT with HDR has become standard practice for patients (pts) with locally advanced cervical cancer. However, the clinical outcome data remains sparse in patients treated with CRT-HDR compared to CRT-low dose rate brachytherapy (LDR). This is a report of Sacramento regional experience utilizing CRT-HDR over a 10-year period. Methods: 232 pts with locally advanced cervical carcinoma (FIGO Stage IB2/IIA: 15%, IIB: 53%, III: 28%, IVA: 3%) who were treated with concurrent chemotherapy (5FU ± CDDP every 4 weeks or CDDP weekly), external beam RT and HDR with a curative intent from 3/91 to 10/01 were analyzed retrospectively. 74 pts had lymph node (LN) involvement pathologically or radiographically, of whom 30 had positive paraaortic LN. 100 pts (43%) received an extended field RT. 175 pts completed treatment within 8 weeks. The survival analysis and the association of independent variables (e.g. age, stage, tumor size, LN status, treatment duration) with overall (OS) and disease-free survival (DFS) were performed using the Kaplan-Meier method and Cox proportional hazards model, respectively. Results: Median follow-up of 139 surviving pts was 4 years with 20 lost to follow-up within a year. The estimated 5-year OS and DFS rates for all pts were 58% and 63%. 21 pts had documented in-field failure and 57 had distant metastases. Advanced stage and LN involvement predicted for worse DFS (p<0.001, p<0.015 respectively). In a multivariate analysis, only the stage predicted for worse OS and DFS (p<0.015) and treatment duration predicted for worse OS (e.g. increase of 1 treatment day was associated with 1% increased hazard of death). Grade 3/4 late effects were observed in small bowel (6%), rectum (4%), and bladder (8%). Conclusions: Aggressive CRT integrating HDR is feasible in this high-risk population. The late effects were comparable to CRT-LDR data reported in RTOG 90–01. This experience included many patients ineligible for RTOG 90–01 due to worse prognoses (e.g., hydronephrosis/renal dysfunction, paraaortic LN involvement). Nevertheless, the OS and DFS were favorable. Comparison of survival data of our cohort to those of RTOG 90–01 will be presented. No significant financial relationships to disclose.