tbuckley/cabot-search huggingface dataset:
Role of single nucleotide polymorphisms of gemcitabine metabolic genes in metastatic colorectal cancer patients treated with gemcitabine-based salvage therapy.
Authors: J. Rodriguez, E. Bandres, A. Hernandez, R. Zarate, V. Boni, M. Ponz-Sarvisé, N. Bitarte, J. Garcia-Foncillas
Journal: Journal of Clinical Oncology (2010)

e13579 Background: Gemcitabine (GMB) exerts its antitumor activity through inhibition of ribonucleotide reductase (RRM1) and DNA synthesis. Although GMB monotherapy has minimal activity in mCRC, salvage therapy with gemcitabine- based combinations has proved to be clinically active and manageable in this setting. We aimed to investigate whether single nucleotide polymorphisms (SNPs) in gemcitabine metabolism genes were associated with clinical outcome in mCRC pts treated with GMB-based salvage regimens. Methods: We retrospectively evaluated SNPs of hCNT1, CDA, DCTD and RRM1 genes in 90 mCRC patients treated from January 2005 to October 2009 through a compassionate use program. Polymorphisms were detected using the TaqMan genotyping assays (Applied Biosystems, CA). The association of genotypes with objective response (OR), disease control rate (DCR: PR, CR and SD>6 months), progression-free survival (PFS) and overall survival (OS) were tested by univariate and multivariate analysis (Cox regression). Results: No association was found between hCNT1 (Q237K), DCTD (V116V), RRM1 (R284R, T741T) polymorphisms and clinical outcome. CDA-76C carriers were associated with DCR (71.4% for CC+CA vs 28.6% for AA genotypes, p=0.06). Patients carrying the RRM1-37CC genotype had a significantly longer PFS (6.6 vs. 4.2 months, p=0.03), OS (23 vs. 8.7 months, p=0.03), and a higher OR (p<0.001) than A-carriers. RRM1-524C>T was associated with a higher OR (p=0.03) and a trend towards an improved PFS and OS. Since by multivariate analysis only Köhne risk index remained significant, we evaluated the impact of SNPs among low and intermediate risk groups (n=66). RRM1-37CC and RRM1-524TT (TT) carriers showed a longer PFS (7.5 vs. 5 months, p=0.015 and 7.4 vs. 4.9 months, p=0.06, respectively) and OS (26.5 vs. 10 months, p=0.025 and 26.4 vs. 11.7 months, p=0.03, respectively) than alternative genotypes. CDA-76C carriers showed a trend for improved PFS (7.9 vs. 5.1, p=0.056). Conclusions: Our results suggest that genetic variants of drug metabolic genes may represent biomarkers to select mCRC pts most likely to benefit from GMB-based salvage therapy. No significant financial relationships to disclose.
OUTCOMES OF CADAVERIC SPLIT LIVER TRANSPLANTATION FOR HEPATITIS C INFECTED PATIENTS. A SINGLE CENTRE COHORT
Authors: Mohammad A. Al-Freah, Abid Suddle, Michael A. Heneghan, Matthew J. Bruce, Ivana Carey, John G. O'Grady, Wayel Jassem, Varuna Aluvihare, Andreas Prachalias, Parthi Srinivasan, Hector Vilca-Melendez, Mohamed Rela, Julia Wendon, Kosh Agarwal, Nigel Heaton
Journal: Hepatology (2010)
Urokinase Exerts Antimetastatic Effects by Dissociating Clusters of Circulating Tumor Cells—Letter
Authors: Juan Garona, Daniel F. Alonso
Journal: Cancer Research (2016)

Blood-borne spread is responsible for the vast majority of cancer-related deaths, and it is recognized that clusters of circulating tumor cells (CTC) are much more likely to cause metastasis than single CTCs. In the November issue of Cancer Research , Choi and colleagues utilized an elegant in vivo
Baby doll simulation scheme does not reduce teen pregnancies, study finds
Authors: Susan Mayor
Journal: BMJ (2016)

Girls taking part in a scheme that aims to reduce teenage pregnancies by getting teenagers to look after an electronic doll that cries when it needs feeding or changing were more likely to become pregnant than those not involved in the scheme, a randomised study has found.1

Schemes to tackle teenage pregnancy must look beyond this purported “magic doll,” one commentator has said, and must target girls and boys in infancy rather than adolescents.

Programmes using infant simulators are increasingly used in high income countries to try to reduce teenage …
Child Maltreatment as a Root Cause of Mortality Disparities
Authors: Idan Shalev, Christine M. Heim, Jennie G. Noll
Journal: JAMA Psychiatry (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
D3-03: IALT-Bio: a challenging research to improve adjuvant chemotherapy of completely resected NSCLC
Authors: Robert Pirker, Martin Filipits, Ariane Dunant, Jean-Pierre Pignon, Jean-Charles Soria, Elisabeth Brambilla, Helmut Popper, Fabrice André, Rolf Stahel, Thierry Le Chevalier
Journal: Journal of Thoracic Oncology (2007)
Paediatric study of bedaquiline remains an “open issue”
Authors: Lindsay McKenna, Laia Ruiz Mingote
Journal: European Respiratory Journal (2016)

In their editorial, "Bedaquiline and multidrug-resistant tuberculosis: a systematic and critical analysis of the evidence", Pontali et al . [1] detail and analyse the existing evidence for bedaquiline for multidrug-resistant tuberculosis (MDR-TB). The authors also discuss "open issues" or areas where additional research is required to inform use, including in children. Pontali et al . [1] mention the planned phase II paediatric study of bedaquiline ([www.clinicaltrials.gov][1] identifier number NCT 02354014). This study to evaluate the pharmacokinetics and safety of bedaquiline in children is crucial to guiding treatment in people under 18 years of age, who have previously been excluded from trials of bedaquiline. Paediatric study of bedaquiline is open but several years behind schedule, delaying access for children with MDR-TB <http://ow.ly/4mP8wm> [1]: http://www.clinicaltrials.gov
Recessions are harmful to health
Authors: Ben Barr, David Taylor-Robinson
Journal: BMJ (2016)

A government’s response can be even more damaging

The 2008 economic crisis led to rising unemployment, homelessness, and poverty—all important determinants of health. Government debt increased, as public money was used to prevent the collapse of the financial system, and many governments then cut public services to reduce this debt. But what has been the effect of all of this on health?

In a linked systematic review in The BMJ , Parmar and colleagues1 find that most studies investigating the 2008 recession in Europe show it was associated with adverse health outcomes. These findings were strongest for suicides and mental health problems. They find less evidence that the recession had a negative effect on self reported health, mortality, and health behaviours, and conclude that there was a high risk of bias in most of the studies reviewed.

Assessing the health effects of recessions is challenging. Firstly, the exposure of interest is poorly defined. The 2008 recession involved multiple economic processes, extending over at least 10 years, which could all negatively affect health.2 3 …
MRI and FDG PET/CT Findings of Primary Orbit Leiomyosarcoma
Authors: Weiyan Zhou, Fengchun Hua, Jiang Qian, Yingwen Bi, Yihui Guan
Journal: Clinical Nuclear Medicine (2016)

Primary leiomyosarcoma of the orbit is extremely rare. Here we report the case of a 32-year-old woman who presented with proptosis and diplopia of the left eye. MRI examination showed a solid mass in the left orbit with invasion to adjacent tissue, and the lesion had intense FDG uptake with SUVmax of 18.7 on F-FDG PET/CT. Primary orbit leiomyosarcoma was diagnosed by surgery-pathology. F-FDG PET/CT has an advantage in excluding secondary or metastatic orbit malignancy.
Platelet Activation Rather Than Apoptosis Contributes Most to the Platelet Storage Lesion during Conventional and Extended Storage of Platelet Concentrates
Authors: Valery Leytin, David J. Allen, Asuman Mutlu, Sergiy Mykhaylov, Elena Lyubimov, Armen V. Gyulkhandanyan, John Freedman
Journal: Blood (2008)
Benefits of statins have been underestimated and harms overstated, review finds
Authors: Nigel Hawkes
Journal: BMJ (2016)

People are confused about statins because too much emphasis is placed on observational studies and too little on randomised controlled trials (RCTs), a review published in the Lancet shows. The benefits have been underplayed and the harms exaggerated as a result of this misperception, the authors argue.1

Richard Horton, editor of the Lancet , said that the controversy over statins had probably harmed the health of thousands of people across the United Kingdom and that the review aimed to better inform patients and their doctors. “We hope the impact will be to correct the public record about the safety and efficacy of statins but also to highlight the problems about unreliable evidence and minority opinions,” Horton told a media briefing at the Science Media Centre in London on Wednesday.

Rory Collins of the University of Oxford, the review’s lead author, said that …
Predictors of Antiestrogen Recommendation in Women With Estrogen Receptor–Positive Ductal Carcinoma In Situ
Authors: Rondi M. Kauffmann, Leanne Goldstein, Emily Marcinkowski, George Somlo, Yuan Yuan, Philip H.G. Ituarte, Laura Kruper, Leslie Taylor, Courtney Vito
Journal: Journal of the National Comprehensive Cancer Network (2016)

Background: Antiestrogen (anti-e) use in estrogen receptor–positive (ER+) ductal carcinoma in situ (DCIS) has been shown to reduce the incidence of noninvasive and invasive breast cancer. Few studies have evaluated factors associated with anti-e recommendation in ER+ DCIS. Methods: The California Cancer Registry was queried for female patients diagnosed with ER+ DCIS and treated with lumpectomy or unilateral mastectomy from 2004 to 2011. Patient demographics, comorbidities, and clinical characteristics were analyzed for association with anti-e recommendation. Results: Of 5,527 patients identified, 76.4% patients underwent lumpectomy and 23.6% underwent unilateral mastectomy. Of the total cohort, 31.6% patients were recommended anti-e therapy, 60.4% were not, and the remaining 8.0% were recommended anti-e, but administration was not documented. Performance of lumpectomy predicted anti-e use compared with mastectomy (odds ratio [OR], 2.08; 95% CI, 1.77–2.43). Asian/Pacific Islanders were more often recommended anti-e therapy when compared with whites (OR, 1.28; 95% CI, 1.10–1.49). Patients younger than 70 years were more often recommended anti-e (age, 18–49 years: OR, 1.38; CI, 1.12–1.71; and age, 50–69 years: OR, 1.43; CI, 1.20–1.71). Conclusions: Despite current guidelines to consider the use of anti-e therapy, recommendation of anti-e after surgical treatment of DCIS is low, having been recommended to 40% of patients, and used by fewer than one-third. Significant predictors include lumpectomy compared with unilateral mastectomy, Asian/Pacific Islander race, younger age, and number of comorbidities. Further work is merited to understand patterns of anti-e therapy recommendation by providers in patients with DCIS.
Clinical outcomes and survival in patients with hepatocellular carcinoma and HIV infection.
Authors: M. Berretta, E. Garlassi, P. Ventura, B. Cacopardo, A. Lleshi, S. Cocchi, G. Guaraldi, A. Pietrangelo, U. Tirelli
Journal: Journal of Clinical Oncology (2010)

4132 Background: Hepatocellular carcinoma (HCC) is an emerging problem for HIV patients (pts), particularly if HCV and/or HBV co-infected. At present, few data are available on the effect of HCC treatment receipt in HIV-positive (HIV+) pts. Our data aim to retrospectively compare survival rates in pts with and without HIV infection affected by liver cirrhosis and HCC (HCC-LC). Methods: 65 HIV+ (54 on HAART; 34 A1-A3, 17 B1-B3 and 9 C1-C3 stage; 12 with CD4 lower than 200) and 267 HIV-negative (HIV-) HCC-LC subjects were compared in terms of survival rates considering age, tumor and liver disease characteristics at diagnosis (etiology, BCLC stage, number of lesions, vascular invasion, progression), treatment receipt (no treatment, palliative or curative, treatment at the progression), HIV status. All subjects were male and had at least three-months of disease follow-up. Results: Table resumes median survival rates according to different treatment strategies in the considered groups. Factors independently related to survival (Cox regression) were: HIVab pos (HR=0.567, 95%CI 0.317÷.912, p=0.046), HCC treatment (HR=1.506, 95%CI 1.154÷2.549, p=0.035), tumor size >5 cm (HR=1.257, 95%CI 1.106÷1.636, p=0.025) BCLC 0-1 (HR=1.247, 95%CI 1.100÷1.576, p=0.034), such as HAART therapy (HR=2.25, 95% CI 1.01-5.048, p=0.048) and treatment at progression (TaP) (HR=2.801, 95%CI 1.78- 4.56, p=0.000). HIV pts had a higher frequency of TaP (88.6% vs. 67.3%, p=0.001). Conclusions: Data show that HIV infection negatively influences HCC outcome, even in treated pts. The role of reduced re-treatment rate in case of HCC progression in these pts needs to be evaluated. Further researches are needed to evaluate if the difference in treatment at progression between HIV+ and HIV- pts corresponds to a different survival rate. Median survival (months) p HIV+ HIV− Overall 31.3 ± 4.91 (n = 65) 59.7 ± 7.07 (n = 267) 0.010 Untreated 4.52 ± 1.83 (n = 6) 36.1 ± 15.2 (n = 48) 0.000 Treated (all treatment) 35.0 ± 11.3 (n = 59) 65.0 ± 7.23 (n = 219) 0.042 Treated (curative) 35.1 ± 11.9 (n = 25) 67.8 ± 14.7 (n = 75) 0.000 Treated (palliative) 31.1 ± 10.2 (n = 34) 53.1 ± 11.1 (n = 144) 0.052 No significant financial relationships to disclose.
The angiogenic switch leads to a metabolic shift in human glioblastoma
Authors: Krishna M Talasila, Gro V Røsland, Hanne R Hagland, Eskil Eskilsson, Irene H Flønes, Sabrina Fritah, Francisco Azuaje, Nadia Atai, Patrick N Harter, Michel Mittelbronn, Michael Andersen, Justin V Joseph, Jubayer Al Hossain, Laurent Vallar, Cornelis J F van Noorden, Simone P Niclou, Frits Thorsen, Karl Johan Tronstad, Charalampos Tzoulis, Rolf Bjerkvig, Hrvoje Miletic
Journal: Neuro-Oncology (2016)

Invasion and angiogenesis are major hallmarks of glioblastoma (GBM) growth. While invasive tumor cells grow adjacent to blood vessels in normal brain tissue, tumor cells within neovascularized regions exhibit hypoxic stress and promote angiogenesis. The distinct microenvironments likely differentially affect metabolic processes within the tumor cells.In the present study, we analyzed gene expression and metabolic changes in a human GBM xenograft model that displayed invasive and angiogenic phenotypes. In addition, we used glioma patient biopsies to confirm the results from the xenograft model.We demonstrate that the angiogenic switch in our xenograft model is linked to a proneural-to-mesenchymal transition that is associated with upregulation of the transcription factors BHLHE40, CEBPB, and STAT3. Metabolic analyses revealed that angiogenic xenografts employed higher rates of glycolysis compared with invasive xenografts. Likewise, patient biopsies exhibited higher expression of the glycolytic enzyme lactate dehydrogenase A and glucose transporter 1 in hypoxic areas compared with the invasive edge and lower-grade tumors. Analysis of the mitochondrial respiratory chain showed reduction of complex I in angiogenic xenografts and hypoxic regions of GBM samples compared with invasive xenografts, nonhypoxic GBM regions, and lower-grade tumors. In vitro hypoxia experiments additionally revealed metabolic adaptation of invasive tumor cells, which increased lactate production under long-term hypoxia.The use of glycolysis versus mitochondrial respiration for energy production within human GBM tumors is highly dependent on the specific microenvironment. The metabolic adaptability of GBM cells highlights the difficulty of targeting one specific metabolic pathway for effective therapeutic intervention.
Novel Observation That Mice Lacking the Fifth Complement Cascade Protein Component (C5) Are Very Poor Stem Cell Mobilizers Explained by Defective Egress of Granulocytes: A Novel Role for Bone Marrow Granulocytes to Act as “ice Breaker” Cells in Facilitating Egress of Hematopoietic Stem/Progenitor Cells
Authors: Wan Wu, Hakmoo Lee, Marcin Wysoczynski, Magdalena Kucia, Janina Ratajczak, Mariusz Z Ratajczak
Journal: Blood (2008)
Prostate Cancer Transmitted in an Orthotopic Heart Transplant
Authors: Raymond Pollack
Journal: JAMA (1997)

<h3>To the Editor.</h3> —The case report by Dr Loh et al<sup>1</sup>of a donorderived prostate cancer in a heart transplant recipient and the accompanying Editorial<sup>2</sup>are interesting additions to the literature on this subject. Fortunately, this is a rare occurrence following transplantation, but it may also include the transmission not only of malignant neoplasms, but potentially morbid and sometimes lethal infectious agents (ie, hepatitis viruses, human immunodeficiency virus [HIV], and cytomegaloviruses).<sup>3</sup>Careful predonation evaluation by organ bank personnel, including a detailed social and medical history, thorough physical examination, and a battery of biochemical and serological tests, serves to eliminate those organ donors who might transmit disease.<sup>4</sup>Thereafter, a proper intraoperative assessment to detect occult disease states must be made in a collaborative way by procurement surgeons to further mitigate the transplantation of poor-quality organs or the transmission of disease. Thus, the article by Loh et al certainly does not
DNA mismatch repair status and site of tumor recurrence in stage II and III colon cancers treated in 5-fluorouracil-based adjuvant therapy trials.
Authors: F. Sinicrope, N. R. Foster, D. J. Sargent, S. Gallinger, P. Benatti, S. Marsoni, G. Monges, R. Labianca, M. J. O'Connell, C. J. Allegra
Journal: Journal of Clinical Oncology (2010)

3519 Background: DNA mismatch repair (MMR) status has been shown to confer prognostic and predictive information in colon cancer patients. We analyzed site of recurrence data in relation to MMR status and adjuvant treatment. Methods: TNM stage II and III colon carcinoma patients (n = 2,141) were treated in 13 randomized, 5-FU-based trials conducted by U.S., Canadian, and European groups. Tumors were analyzed for microsatellite instability (MSI) and/or MMR protein expression. Deficient MMR (n = 347; 16.2%) was defined as MSI-H or loss of an MMR protein (IHC). Treatment was categorized as effective (n = 1,382) or none/ineffective (n = 759). Site-of-recurrence (n = 601) was categorized as local, intra-abdominal, and distant sites. An Italian case series (n = 404; 110 MSI-H) was also analyzed. Association of MMR and treatment with survival was analyzed using a Cox model, and with site of recurrence using Chi-square or Fisher's Exact tests. Results: Deficient (vs. proficient) MMR was associated with reduced tumor recurrence (20% vs. 32%; p < 0.0001). However, patients with MMR deficient tumors receiving effective adjuvant therapy had a significant increase in local (12% vs. 8%) and intra-abdominal recurrence rates (31% vs. 17%), and a reduction in distant metastases (overall p = 0.026). Among patients receiving observation/ineffective treatment, MMR status was not associated with site of recurrence. Site of recurrence was prognostic for OS with local having better OS compared to intra-abdominal or distant sites (HR 0.62 [95% CI 0.43-0.90]; p = 0.0275). The impact of 5-FU-based treatment was significantly predictive for DFS and OS in proficient MMR cases, but not in deficient MMR tumors (ASCO 2008; 26: abstr 4008). In a separate case series, deficient (vs. proficient) MMR was associated with reduced rates of recurrence (16 vs. 33%; p = 0.001), higher local vs. distant spread (p = 0.0549), and more favorable OS (p = 0.0016). Conclusions: Colon cancers with deficient MMR have significantly reduced rates of recurrence and show higher rates of local and intra-abdominal recurrence after 5-FU-based adjuvant therapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genomic Health
Evidence-Based Medicine on Trial
Authors: Clark Watts
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal