tbuckley/cabot-search huggingface dataset:
BAY 43-9006 in patients with advanced melanoma: The Royal Marsden experience
Authors: T. Ahmad, R. Marais, L. Pyle, M. James, B. Schwartz, M. Gore, T. Eisen
Journal: Journal of Clinical Oncology (2004)

7506 Background: Approximately 70% of melanomas have an activating mutation in BRAF, leading to elevated RAF kinase activity and cellular proliferation. BAY 43-9006 is a potent RAF kinase inhibitor that retards the growth of human melanoma xenografts. This phase II study aims to determine the clinical benefit and toxicity of BAY 43-9006 in advanced melanoma and to correlate these findings with BRAF status of the patients and their tumours. Methods: Patients with stage IV refractory melanoma were recruited from The Royal Marsden Melanoma Unit and treated with BAY 43-9006 400mg BD orally for 12 weeks after baseline imaging and tumour biopsy. At the 12 week reassessment, patients with objective tumour responses continued BAY 43-9006 until disease progression or unacceptable toxicity. Patients with stable disease were randomised in a double-blind manner between BAY 43-9006 or placebo and followed for on-going response.In the event of disease progression in this cohort, the code was broken and those receiving placebo were re-challenged with BAY 43-9006.Tumour responses were evaluated by CT/MRI at 12 weeks and every 6 weeks thereafter. Tumour biopsies were performed at weeks 0,4 and 12 for sequencing BRAF and identification of downstream activity of RAF kinase. Results: Twenty patients were enrolled between October 2002 and April 2003,the median age was 52 (range 18–69) years. At week 12,1 partial response and 3 stable disease were seen. Fifteen patients had progressive disease before or at 12 weeks. Grade 3 skin toxicity was observed in 5 patients and 2 patients developed hypertension requiring intervention. There was no haematological toxicity and all toxicity was reversible. Laboratory analysis of tumour samples to determine BRAF status will be presented. Conclusions: BAY 43-9006 has very modest activity as a single agent. Preliminary data from combination studies are promising and trials are ongoing. The drug is generally well-tolerated and the determination of BRAF status in patients may allow correlation with clinical behaviour of tumours and efficacy of BAY 43-9006 Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Pharmaceutical Corp. Bayer Bayer Bayer Bayer
Genitourinary small cell carcinoma: Analysis of clinical and treatment factors associated with survival among patients in the Veterans Affairs Health System.
Authors: M. Kalaiah, W. Gonsalves, P. Townley, T. Tashi, I. Aldoss, N. Didwaniya, A. Ganta, R. Thota, I. AL-Howaidi, S. Subbiah
Journal: Journal of Clinical Oncology (2010)

e15073 Background: Primary small cell carcinomas of the genitourinary tract (SCC-GUT) are rare, aggressive, and rapidly fatal neoplasms. Hence no prospective studies evaluating the most effective treatment have been done. We aim to characterize the clinicopathologic features and evaluate the treatment outcomes of SCC-GUT in adult patients. Methods: Retrospective analysis of 196 patients diagnosed with small cell carcinoma of the GU tract from 1995 to 2008 was done via the Veteran's Affairs Central Cancer Registry. Demographic, staging, treatment and outcome data was recorded. Staging was classified as limited (confined to true and false pelvis) or extensive disease (metastatic or spread outside pelvis). Results: We found 64 patients with SCC of prostate and 132 patients with SCC of bladder representing 0.06% and 0.45% of all prostate and bladder cancers.The median age of diagnosis was 69.1 years (range: 53-89).109 patients had limited disease, 67 patients had extensive disease and 20 patients were not staged adequately. Patients received variety of treatments (Table) with different survival outcomes. Limited stage bladder SCC have better survival when multimodality therapy combining chemotherapy with radiation or surgery is used whereas in limited stage prostate SCC surgical resection provided the best outcomes. Conclusions: Limited stage appears to have better survival with multimodality therapy involving chemotherapy in bladder SCC and in prostate SCC surgical resection is associated with better outcomes. Prognosis of extensive stage SCC-GUT irrespective of site is dismal. Targeted therapies are now established for several diseases, randomized trials incorporating novel targeted agents are needed to improve survival. Stage and treatment Median survival (months) Bladder Prostate Limited disease 13.4 (n=90) 16.1 (n=19) No treatment 1.9 (n=4) 9.1 (n=3) Single-modality therapy 8.2 (n=31) 46.5 (n=6) Multimodality therapy 16.4 (n=55) 11.2 (n=10) Extensive disease 4.2 (n=30) 5.7 (n=37) No treatment 1.5 (n=4) 1.1 (n=11) Single-modality therapy 3.6 (n=14) 10.3 (n=15) Multimodality therapy 8.8 (n=12) 12.2 (n=11) No significant financial relationships to disclose.
Results of clinical renal function tests in lithium patients
Authors: R H Gerner, J Psarras, M A Kirschenbaum
Journal: American Journal of Psychiatry (1980)

Because there have been reports suggesting that patients who receive lithium are at risk for renal damage, the authors carried out extensive noninvasive testing of renal function in 43 patients who had been taking lithium for from 1 to 120 months. Their only abnormal finding was that the urine concentrating ability of these patients was moderately but asymptomatically impaired. They suggest that although patients receiving lithium should be carefully evaluated and tested, there is not enough evidence to justify not initiating or continuing lithium use in patients who might benefit from it.
Failure to Induce Tumors in Swiss Mice After Concurrent Administration of Amino Acids and Sodium Nitrite&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M Greenblatt, W Lijinsky
Journal: JNCI Journal of the National Cancer Institute (1972)

The effect of concurrent administration to Swiss mice of sodium nitrite (0.1%) with proline, hydroxyproline, or arginine (0.5%) in drinking water was investigated by use of the rapid quantitative lung-adenoma technique as a screening test. Nitrosoproline (0.05 and 0.1%), nitrosopiperidine (0.01%), and nitrosopyrrolidine (0.01%) were also tested. Lung adenomas did not increase with the amino acid/nitrite combinations or with nitrosoproline. Nitrosopiperidine (65 mg total dose/mouse), the positive control, caused tenfold more lung adenomas. Nitrosopyrrolidine (15 mg total dose/mouse) enhanced the number of lung adenomas, but was severely hepatotoxic. From the results of this screening bioassay, nitrosoproline probably is not carcinogenic. The concurrent administration of hydroxyproline or arginine together with 0.1% NaNO2 in the drinking water did not increase the lung adenoma frequency.
A Randomized Phase II Trial of Short-Course Androgen Deprivation Therapy With or Without Bevacizumab for Patients With Recurrent Prostate Cancer After Definitive Local Therapy
Authors: Rana R. McKay, Amado J. Zurita, Lillian Werner, Justine Y. Bruce, Michael A. Carducci, Mark N. Stein, Elisabeth I. Heath, Arif Hussain, Hai T. Tran, Christopher J. Sweeney, Robert W. Ross, Philip W. Kantoff, Susan F. Slovin, Mary-Ellen Taplin
Journal: Journal of Clinical Oncology (2016)

Patients with recurrent prostate cancer after local treatment make up a heterogeneous population for whom androgen deprivation therapy (ADT) is the usual treatment. The purpose of this randomized phase II trial was to investigate the efficacy and toxicity of short-course ADT with or without bevacizumab in men with hormone-sensitive prostate cancer.Eligible patients had an increasing prostate-specific antigen (PSA) of ≤ 50 ng/mL and PSA doubling time of less than 18 months. Patients had either no metastases or low burden, asymptomatic metastases (lymph nodes < 3 cm and five or fewer bone metastases). Patients were randomly assigned 2:1 to a luteinizing hormone-releasing hormone agonist, bicalutamide and bevacizumab or ADT alone, for 6 months. The primary end point was PSA relapse-free survival (RFS). Relapse was defined as a PSA of more than 0.2 ng/mL for prostatectomy patients or PSA of more than 2.0 ng/mL for primary radiation therapy patients.Sixty-six patients received ADT + bevacizumab and 36 received ADT alone. Patients receiving ADT + bevacizumab had a statistically significant improvement in RFS compared with patients treated with ADT alone (13.3 months for ADT + bevacizumab v 10.2 months for ADT alone; hazard ratio, 0.47; 95% CI, 0.29 to 0.77; log-rank P = .002). Hypertension was the most common adverse event in patients receiving ADT + bevacizumab (36%).ADT combined with bevacizumab resulted in an improved RFS for patients with hormone-sensitive prostate cancer. Long-term follow-up is needed to determine whether some patients have a durable PSA response and are able to remain off ADT for prolonged periods. Our data provide rationale for combining vascular endothelial growth factor-targeting therapy with ADT in hormone-sensitive prostate cancer.
A Bipartite Network-Based Method for Prediction of Long Non-Coding RNA–Protein Interactions
Authors: Mengqu Ge, Ao Li, Minghui Wang
Journal: Genomics Proteomics & Bioinformatics (2016)

As one large class of non-coding RNAs (ncRNAs), long ncRNAs (lncRNAs) have gained considerable attention in recent years. Mutations and dysfunction of lncRNAs have been implicated in human disorders. Many lncRNAs exert their effects through interactions with the corresponding RNA-binding proteins. Several computational approaches have been developed, but only few are able to perform the prediction of these interactions from a network-based point of view. Here, we introduce a computational method named lncRNA-protein bipartite network inference (LPBNI). LPBNI aims to identify potential lncRNA-interacting proteins, by making full use of the known lncRNA-protein interactions. Leave-one-out cross validation (LOOCV) test shows that LPBNI significantly outperforms other network-based methods, including random walk (RWR) and protein-based collaborative filtering (ProCF). Furthermore, a case study was performed to demonstrate the performance of LPBNI using real data in predicting potential lncRNA-interacting proteins.
P-278 A phase II study of cetuximab in combination with irinotecan plus S-1 as first-line treatment in patients with KRAS wild-type metastatic colorectal cancer (CIRIS study): overall survival analysis
Authors: T. Eto, T. Masuishi, T. Matsui, S. Anzai, Y. Suzuki, Y. Fukami, K. Suzuki, F. Kusano, Y. Sakai, J. Tazawa
Journal: Annals of Oncology (2015)
Case 37-1998
Authors: William C. Aird, William M. Kettyle
Journal: New England Journal of Medicine (1998)

Presentation of CaseA 41-year-old woman was admitted to the hospital because of thrombocytopenia and anemia.The patient had been well until a few weeks earlier, when her menses, which had been profuse in recent years, became even heavier. Five days before admission, she again began to menstruate profusely and had orthostatic weakness. Two days later, she entered another hospital, where hematologic studies were performed (Table 1). Blood chemical values were normal. Three units of packed red cells were transfused. On the second hospital day, laboratory studies were repeated (Table 1). Since platelets were needed but unavailable for transfusion, she . . .
Equality Of Access To Transplant For Ethnic Minority Patients Through Use Of Cord Blood and Haploidentical Transplants
Authors: Robert N Lown, Steven GE Marsh, Helen Blake, Sergio Querol, Irina Evseeva, Stephen Mackinnon, Antonio Pagliuca, Michael Potter, Nigel Russell, Charles Craddock, J. Alejandro Madrigal, Bronwen E. Shaw
Journal: Blood (2013)
Importation, Antibiotics, and<i>Clostridium difficile</i>Infection in Veteran Long-Term Care
Authors: Kevin A. Brown, Makoto Jones, Nick Daneman, Frederick R. Adler, Vanessa Stevens, Kevin E. Nechodom, Matthew B. Goetz, Matthew H. Samore, Jeanmarie Mayer
Journal: Annals of Internal Medicine (2016)

Background: Although clinical factors affecting a person's susceptibility to Clostridium difficile infection are well-understood, little is known about what drives differences in incidence across long-term care settings. Objective: To obtain a comprehensive picture of individual and regional factors that affect C difficile incidence. Design: Multilevel longitudinal nested case–control study. Setting: Veterans Health Administration health care regions, from 2006 through 2012. Participants: Long-term care residents. Measurements: Individual-level risk factors included age, number of comorbid conditions, and antibiotic exposure. Regional risk factors included importation of cases of acute care C difficile infection per 10 000 resident-days and antibiotic use per 1000 resident-days. The outcome was defined as a positive result on a long-term care C difficile test without a positive result in the prior 8 weeks. Results: 6012 cases (incidence, 3.7 cases per 10 000 resident-days) were identified in 86 regions. Long-term care C difficile incidence (minimum, 0.6 case per 10 000 resident-days; maximum, 31.0 cases per 10 000 resident-days), antibiotic use (minimum, 61.0 days with therapy per 1000 resident-days; maximum, 370.2 days with therapy per 1000 resident-days), and importation (minimum, 2.9 cases per 10 000 resident-days; maximum, 341.3 cases per 10 000 resident-days) varied substantially across regions. Together, antibiotic use and importation accounted for 75% of the regional variation in C difficile incidence (R 2 = 0.75). Multilevel analyses showed that regional factors affected risk together with individual-level exposures (relative risk of regional antibiotic use, 1.36 per doubling [95% CI, 1.15 to 1.60]; relative risk of importation, 1.23 per doubling [CI, 1.14 to 1.33]). Limitations: Case identification was based on laboratory criteria. Admission of residents with recent C difficile infection from non–Veterans Health Administration acute care sources was not considered. Conclusion: Only 25% of the variation in regional C difficile incidence in long-term care remained unexplained after importation from acute care facilities and antibiotic use were accounted for, which suggests that improved infection control and antimicrobial stewardship may help reduce the incidence of C difficile in long-term care settings. Primary Funding Source: U.S. Department of Veterans Affairs and Centers for Disease Control and Prevention.
Gamma knife stereotactic radio-surgery and BRAF inhibition in metastatic melanoma.
Authors: Melissa Wilson, John Y Lee, Michelle Alonso-Basanta, Wei Xu, Suzanne McGettigan, Lynn Mara Schuchter, Ravi K. Amaravadi, Tara C. Gangadhar
Journal: Journal of Clinical Oncology (2013)

9088 Background: Gamma knife radio-surgery (GK) is an effective approach to treating brain metastases in patients with metastatic melanoma. BRAF inhibition with vemurafenib produces a median progression free survival (PFS) of 7 months, but low central spinal fluid penetration may limit its effectiveness in patients who develop brain metastases. We report long term follow-up of patients with BRAF mutant melanoma treated with vemurafenib and GK. Methods: Demographics and clinical outcomes were characterized for 18 BRAF mutant melanoma patients with brain metastases treated between 2007 and 2012 with GK and with vemurafenib (vem) for &gt;1 month. Results: The median age at starting vem was 51 yrs (range 34-76). 61% of the patients were women. Patients were treated with a median of 1 prior therapy (range 0-3). 7/18 patients (39%) had brain involvement prior to starting vem. 16/18 patients (89%) had stage M1c disease at the time of starting vem. Patients were treated with vem for a median of 8.4 months (range 2.1 to 27 months), had a median survival of 15.7 months after starting vem (range 4.2-29.4), and a median survival after GK of 7.8 months (range 1.2-21.1). Patients underwent GK to a median of 3 lesions (range 1-6). In total, 8/18 patients (44%) were treated with WBRT. 7/18 patients underwent craniotomies, 2 of which were for progression in lesions treated with GK, and 4 of which were also among the patients treated with WBRT. In 7/18 patients treated with GK for new brain progression after starting vem, vem was continued after GK for a median duration of 4.1 months (range 1.3 to 15.8). In these 7 patients that had vem and GK and continued vem, the median overall survival after starting vem was 19.9 months (range 6.7 to 29.3). Of these 7 patients, 4 required whole brain radiation therapy (WBRT); 3 have not required any additional brain directed therapy, including 2 patients who continue on vemurafenib at the time of analysis. 5/18 patients were treated with more than 1 round of GK, 3 of which were subsequently treated with WBRT. Conclusions: Despite the brain being a common site of progression on vemurafenib therapy, long term survival can be achieved in some cases by continuing vem after GK therapy.
Immunomodulation therapy and soluble interleukin-2 receptor (sIL-2R) levels in patients with HIV- myeloma (HIV-M, triclonal gammopathy) treated with biaxin-pentoxifylline-decadron (BPD)
Authors: E. McPherson, E. Mejia, M. Ragasa, J. Babu, E. Hazel, P. Tassy
Journal: Journal of Clinical Oncology (2005)

6739 Background: Levels of serum sIL-2R represents the total amount of activated T lymphocytes in tumor infiltrating lymphocytes of cancer tissues and metastatic organs. In most malignant diseases, elevated levels of serum sIL-2R are present, compare to normal control. Immunomodulatory effect of low dose IL-2 therapy on interferon (IFN), tumor necrosis factor (TNF) production in vivo and in vitro and on the expression of sIL-2R in HIV-M patients with IgM-laden myeloma cells and triclonal is unknown. Methods: We present a 63 year old female with stage II multiple myeloma (HIV-M), referred to our center with epistaxis, hypercoagulabe state, protein S deficiency, lupus anticoagulant and severe gastrointestinal distress (angulated transverse colon) and a serum viscosity of > 3.00 centipoises (cp). She was treated with immunomodulation therapy BPD (Biaxin, Pentoxifylline, Decadron). Prior to admission she was given plasmapheresis once but relapsed soon afterwards with a rising serum viscosity and bleeding. Her paraprotein parameters were reduced by 50% over ten weeks. We measured serum sIL-2R, C-rective protein (CRP), beta-2-microglobulin (B2M), IgG-kappa, IgG-lambda, IgM-kappa, before and throughout immunomodulation therapy. Her CD4+ count: 728/cumm: viral load:>100K. Highly antiretroviral therapy (HAART) was started. Results: The CRP level began decreasing with cessation of epistaxis. Triclonal parameters decreased steadily over 12 -24 weeks. The sIL-2R level was significantly reduced to normal levels after 24 weeks of immunomodlulation therapy but the beta-2- microglobulin levels remained elevated. Conclusions: The suppression with immunomodulation therapy of CRP gene transcription with manipulation of NF-Kb and IK-Kb with BPD and normalization of sIL-2R in HIV-M patients with early stage triclonal myeloma may have a direct independent effect on the prognostic factor in triclonal IgM-laden HIV-M patients. Serum sIL-2R levels may be a useful parameter for evaluating HIV-M disease stage and monitoring the disease progression during and post-treatment follow-up. No significant financial relationships to disclose.
SpreaD3: Interactive Visualization of Spatiotemporal History and Trait Evolutionary Processes
Authors: Filip Bielejec, Guy Baele, Bram Vrancken, Marc A. Suchard, Andrew Rambaut, Philippe Lemey
Journal: Molecular Biology and Evolution (2016)

Model-based phylogenetic reconstructions increasingly consider spatial or phenotypic traits in conjunction with sequence data to study evolutionary processes. Alongside parameter estimation, visualization of ancestral reconstructions represents an integral part of these analyses. Here, we present a complete overhaul of the spatial phylogenetic reconstruction of evolutionary dynamics software, now called SpreaD3 to emphasize the use of data-driven documents, as an analysis and visualization package that primarily complements Bayesian inference in BEAST ( http://beast.bio.ed.ac.uk , last accessed 9 May 2016). The integration of JavaScript D3 libraries ( www.d3.org , last accessed 9 May 2016) offers novel interactive web-based visualization capacities that are not restricted to spatial traits and extend to any discrete or continuously valued trait for any organism of interest.
Axl Represents a Therapeutic Target In T315I-Mutated and WT Chronic Myeloid Leukemia
Authors: Robert Erdmann, Heather Jorgensen, Alexander Schultze, Gunhild von Amsberg, Isabel Ben-Battala, Mark Wroblewski, Miguel Cubas Cordova, Stefanie Sawall, Victoria Witzke, Elaine K Allan, Leena Mukherjee, Heather Morrison, Jennifer Cassels, Philippe Schafhausen, Nicolaus Kroeger, James Lorens, Richard E. Clark, Peter Vandenberghe, Tim H. Brümmendorf, Andreas Hochhaus, Peter Carmeliet, Klaus Pantel, Carsten Bokemeyer, Tessa L. Holyoake, Sonja Loges
Journal: Blood (2013)
Echocardiographic Patterns in Patients with the Syndrome of Systolic Click and Late Systolic Murmur
Authors: Richard E. Kerber, Dale M. Isaeff, E. William Hancock
Journal: New England Journal of Medicine (1971)

Ten patients with systolic clicks and late systolic murmurs, documented phonocardiographically, were studied with the use of reflected ultrasound. In five patients, the anterior leaflet of the mitral valve displayed an abrupt posterior motion in mid-systole, coincident with the systolic click and onset of the systolic murmur. A similar motion of the posterior leaflet of the mitral valve was recorded definitely in one patient and possibly in three others; a visible separation of the mitral-valve leaflets in mid-systole was thus produced. In only one of the 10 patients did the recorded mitral-valve motion appear normal. Eight additional patients with systolic clicks but no murmurs were studied; in none of these could a posterior displacement of either valve leaflet in systole be detected. These findings support the cineangiographic observation that the syndrome of systolic click with late systolic murmur is a result of systolic prolapse of one or both mitral-valve leaflets into the left atrium. The echocardiographic pattern observed appears to be characteristic of this condition.
Immunologic Abnormalities in Melanoma-Prone Families<xref ref-type="fn" rid="FN2">2</xref>
Authors: J H Dean, M H Greene, R R Reimer, F V LeSane, E A McKeen, J J Mulvihill, W A Blattner, R B Herberman, J F Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1979)

Sixty members of 4 families prone to cutaneous malignant melanoma (CMM) and a genetically determined precursor nevus syndrome underwent extensive Immunologic evaluation. The most consistent finding was a diminished In vitro response to pooled alloantlgens In the one-way mixed leukocyte culture (MLC) and a tendency to low T-Iymphocyte and B-Iymphocyte levels. When compared to controls, low B-Iymphocyte levels and reduced MLC responses were found not only In family members with CMM and/or precursor nevi but also In unaffected blood relatives and spouses. The genesis of the Immune dysfunction and Its possible relationship to melanoma pathogenesis remain to be clarlfled
Mitral Insufficiency Due to Ruptured Chordae Tendineae Simulating Aortic Stenosis
Authors: Howard A. Shapiro, Daniel R. Weiss
Journal: New England Journal of Medicine (1959)

THE case reported below illustrates two interesting and unusual phenomena. The first is the production of the physical signs and phonocardiographic evidence of aortic stenosis in a patient with mitral insufficiency but without disease of the aortic valve. A similar case has recently been reported but without phonocardiographic confirmation.1 The second is the production of mitral insufficiency by rupture of un-diseased chordae tendineae attached to a normal valve leaflet, in the absence of a history of direct chest trauma.Case ReportA 39-year-old man entered the San Francisco Veterans Administration Hospital on July 31, 1958, because of increasing signs and . . .