tbuckley/cabot-search huggingface dataset:
Respiratory Failure in a Woman 8 Months After an Allogeneic Stem Cell Transplant
Authors: Jonathan Chou, Erika Wallender, Brian S. Schwartz
Journal: JAMA Oncology (2016)

A 67-year-old woman with peripheral T-cell lymphoma after an allogeneic stem cell transplant on empirical broad-spectrum antibiotics for dyspnea and bilateral CXR opacities develops respiratory failure and diffuse ground-glass opacities on CT scan. What would you do next?
Metabotropic glutamate receptor-1: A new molecular target for the therapy of triple-negative breast cancer.
Authors: D. H. Gorski, C. L. Speyer, J. Smith, M. L. Banda, J. S. Goydos
Journal: Journal of Clinical Oncology (2010)

10619 Background: Metabotropic glutamate receptors (mGluRs) play critical roles in the central nervous system and have been implicated in neurologic diseases, including amyotropic lateral sclerosis and epilepsy. Recently, mGluRs have been found to be important in the pathogenesis of melanoma, and targeting one of them (mGluR1) by an off-label use of an existing drug (Riluzole) inhibited melanoma growth in vitro and in vivo and downregulated MAPK and Akt in human melanoma in a phase 0 clinical trial. Recently, we detected mGluR1 expression in breast cancer cell lines and hypothesized that mGluR1 might also be a molecular target for the treatment of breast cancer. Methods: We analyzed mGluR1 expression in multiple breast cancer cell lines (quantitative real time PCR and Western Blot) and 50 human breast cancer specimens (qRT-PCR). The effect of targeting mGluR1 was determined in cell culture by MTT assay and cell counts in the presence and absence of BAY36-7620 and Riluzole, specific non- competitive inhibitors of mGluR1 signaling. Finally, the effect of Riluzole on breast cancer formation growth in vivo was determined in a triple-negative xenograft model (MDA-MB-231) expressing mGluR1. Results: All breast cancer cell lines tested expressed mGluR1 message and protein. mGluR1 message was expressed at significantly higher levels in clinical breast cancer specimens than in matched specimens of normal breast. mGluR1 message levels strongly correlated with ER(+) status, and more weakly with lymphatic invasion and T-stage. Riluzole and BAY36-720 strongly inhibited breast cancer growth in vitro, and Riluzole strongly inhibited the growth of a triple-negative xenograft (MDA-MB-231). Conclusions: mGluR1 is a potential new molecular target for breast cancer and, because it is an oral drug with low toxicity, Riluzole thus represents a promising approach to treating breast cancer, in particular triple-negative breast cancer. Based on these data, we have recently started a phase 0 trial to test whether treatment with Riluzole results in the downregulation of its downstream targets in breast cancer. No significant financial relationships to disclose.
Time in Therapeutic Range in Warfarin-Treated Patients
Authors: Rod Passman
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Role of Anti–Carbamylated Protein Antibodies Compared to Anti–Citrullinated Protein Antibodies in Indigenous North Americans With Rheumatoid Arthritis, Their First‐Degree Relatives, and Healthy Controls
Authors: H. Koppejan, L. A. Trouw, J. Sokolove, L. J. Lahey, T. J. W. Huizinga, I. A. Smolik, D. B. Robinson, H. S. El‐Gabalawy, R. E. M. Toes, C. A. Hitchon
Journal: Arthritis & Rheumatology (2016)

Objective Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies, including seropositivity for rheumatoid factor (RF) and anti–citrullinated protein antibodies (ACPAs). In addition, antibodies to carbamylated proteins (anti‐CarP) are present in patients with RA and are associated with joint damage. This study was undertaken to assess the presence of anti‐CarP antibodies in indigenous North Americans (First Nations [FN] populations) with RA compared to their at‐risk first‐degree relatives (FDRs) and healthy controls. Methods Anti‐CarP IgG and ACPAs (specifically, anti–cyclic citrullinated peptide [anti‐CCP] antibodies) were measured by enzyme‐linked immunosorbent assay in the sera of FN patients with RA (n = 95), their unaffected FDRs (n = 109), and healthy FN controls (n = 85). Antibodies to additional citrullinated peptides were measured using a multiplex ACPA array, and the number of peptides recognized was reported as an ACPA score. Groups were compared using the chi‐square test and Mann‐Whitney U test. Associations between RA and seropositivity for RF, ACPAs, and anti‐CarP antibodies were determined by logistic regression. Results Anti‐CarP antibodies were more frequent in FN patients with RA (44.3%) compared to FDRs (18.3%) and FN controls (4.7%) (both P &lt; 0.0001 versus RA). Moreover, anti‐CarP antibodies were more frequent in FDRs than in FN controls ( P = 0.008). The ACPA score was higher in anti‐CCP–positive FN patients with RA than in anti‐CCP–positive FN FDRs (median score 7 [interquartile range (IQR) 7] versus median score 1 [IQR 4]; P = 0.04). The association with RA was strongest when all 3 autoantibodies (RF, anti‐CCP, and anti‐CarP) were present in the patients’ serum (odds ratio 194, 95% confidence interval 23–1,609, P &lt; 0.0001). Conclusion Anti‐CarP antibodies are prevalent in FN patients with RA and also more common in their at‐risk FDRs compared to healthy controls. The results indicate an association of RF, ACPAs, and anti‐CarP with RA that is strongest when all 3 autoantibodies are present. These findings may provide new insights into the evolution of autoimmunity in preclinical RA.
Pretreatment with topical glucocorticosteroids to enhance the antitumour efficacy of imiquimod: long-term follow-up in Bowen disease
Authors: A. Okazaki, T. Fukuda, Y. Yamazaki, T. Shiohara
Journal: British Journal of Dermatology (2016)

Despite the initial enthusiasm, the efficacy of imiquimod (IMQ) has been limited to a given disease setting1. Therefore, we need adjunct therapies to improve the anti-tumour efficacy of IMQ. We initially hypothesised that decreasing the recruitment of Foxp3+ regulatory T cells (Tregs) to the tumour site before IMQ therapy could have therapeutic value.

This article is protected by copyright. All rights reserved.
Impact of consultation in a long term follow-up clinic on breast cancer and cardiovascular screening in Hodgkin lymphoma survivors.
Authors: Kathryn Baxstrom, Chung Kyu Kim Lee, Bruce A. Peterson, Rachel Isaksson Vogel, Anne Hudson Blaes
Journal: Journal of Clinical Oncology (2015)

e20607 Background: Women treated with chest radiation for Hodgkin lymphoma (HL) are at significantly increased risk of developing breast cancer and cardiovascular disease. HL survivors are recommended to have screening with mammogram (MMG) and breast magnetic resonance imaging (MRI) annually, as well as echocardiogram (echo) five years after completion of radiation. Our aim was to characterize the women who are and are not getting dual breast cancer screening and baseline echo, and to examine the impact of a long term follow-up (LTFU) clinic consultation on screening. Methods: We conducted a retrospective review of 120 women treated for HL at the University of Minnesota Masonic Cancer Center between 1993 and 2009. Demographics, disease and treatment history (age at diagnosis, stage, radiation dose and field, chemotherapy) were assessed. Screening practices (MMG, MRI, echo), participation in LTFU clinic, and screening recommendations from providers were evaluated. Screening outcomes were compared by participation in the LTFU clinic (y/n) using Chi-squared analysis and Fisher's exact tests. P-values < 0.05 were considered significant. Results: 39 of 120 women met inclusion criteria (chest radiation, follow up) for analysis. Median age at diagnosis was 29 (range 12-58); majority (65.7%) were diagnosed at stage IIa. Median dose of radiation was 3510 cGy (range 2040-4500 cGy); the largest subset had mantle radiation (46.2%), followed by mediastinal (28.2%) and modified mantle (12.8%). 53.8% participated in the LTFU clinic. 20.5% had no breast cancer screening; of those screened 48.4% had dual screening with both MMG and MRI and 51.6% had screening with only MMG. Women were more likely to have dual screening if seen in LTFU clinic versus not seen (70.6% vs 21.4%, p = 0.011). 32.3% were screened with echo; women were not more likely to have screening with echo if seen in LTFU clinic versus not seen (17.7% vs 50.0%, p = 0.121). Conclusions: Many women treated for HL with radiation are not getting proper dual screening for breast cancer despite their increased risk. LTFU clinic consultation did increase dual screening for breast cancer but not echo screening for cardiovascular disease.
99P Predicting no metastases to axillary lymph nodes beyond positive sentinel nodes in patients with breast cancer: a simple rule
Authors: E. Nagai, K. Horiuchi, A. Sakamoto, Y. Omi, Y. Yoshida, H. Tokumitsu, M. Sakurai, K. Haniu, T. Okamoto
Journal: Annals of Oncology (2015)
Mir-125a Confers Multi-Lineage Long-Term Repopulating Stem Cell Activity to Human Hematopoietic Committed Progenitors
Authors: Eric R. Lechman, Karin G. Hermans, Erwin M. Schoof, Aaron Trotman-Grant, Stephanie M Dobson, Gabriela Krivdova, Janneke J. Elzinga, James A. Kennedy, Olga I Gan, John E Dick
Journal: Blood (2015)
Genomic instability in human breast epithelial cells induced by malathion and estrogen
Authors: Gloria Calaf, Carlos Echiburu-Chau, Debasish Roy
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3154 

Breast cancer risk is associated with prolonged exposure to female hormones. Among the hormonal influences a leading role is attributed to estradiol. Environmental chemicals are also involved in such etiology. The development of breast cancer is a complex multi-step process that depends on various exogenous and endogenous factors that modulate the transformation of normal human breast into malignant ones. Organophosphorous compounds are the most widely used pesticides in agriculture, medicine and industry. Using a spontaneously immortalized human breast epithelial cell line, MCF-l0F we have shown previously that radiation, in combination with estrogen, induced neoplastic transformation. Studies have shown high frequency loss of genetic information on the long arm of chromosome 17 and 11 in various primary breast cancers. The aim of this work was to study the susceptibility to transformation of MCF-l0F by the organophosphorous pesticide malathion (M) in the presence or absence of 17 beta estradiol (E). Results indicated that the pesticide in the presence of E increased cell proliferation, induced anchorage independency, invasiveness with increased expression of mutant p53, BRCA1 and c-Ha-ras proteins. To correlate the malignant transformation of MCF-10F cell line with genetic alterations, we investigated the frequency of loss of heterozygosity (LOH) and microsatellite instability (MSI) using several markers for chromosome 17 and 11 by multiplex PCR. Markers for chromosome 17 as p53 and BRCA1 were studied. Results showed that LOH was induced by either M and E alone, and MSI by the combination of both in p53 locus. M alone and combined with E also induced MSI, and E alone and combination with M showed LOH in BRCA1 locus. Markers for chromosome 11 as c-Ha-ras showed MSI induced by M plus E treatment and LOH by M and E alone. Other markers for the same chromosome indicated MSI by treating either with M or E alone and LOH by M plus E. The combination of M plus E induced mutations in BRCA1 as well as in c-Ha-ras in codons 12 and 61. These results strongly suggest the presence of oncogenes and tumor suppressor genes in critical regions of chromosome 17 and 11. Thus, genomic instability was induced in human breast epithelial cells by malathion and estrogen influencing the carcinogenesis process. It also represents the first indication of allele loss at these loci in human breast epithelial cells induced by pesticides and estrogen suggesting a potential interventional target in breast carcinogenesis. Work supported by FONDECYT #1040300.
<i>ALK</i> and <i>ROS1</i> gene rearrangements detected in colorectal cancer (CRC) by fluorescence in situ hybridization (FISH).
Authors: Andrew James Weickhardt, Teresa T. Nguyen, Diego D. Paskulin, Anh T. Le, Dara Aisner, Nathan Schulte, Fiona J.M. Chionh, John Mariadason, Niall C. Tebbutt, Robert Charles Doebele, Marileila Varella-Garcia
Journal: Journal of Clinical Oncology (2013)

3545 Background: Activation of ROS1 and ALK tyrosine kinases through gene fusions lead to unchecked cell proliferation and transformation. ROS1 and ALK gene fusions were found in about 5% and 2% of lung adenocarcinomas and are highly sensitive to specific tyrosine kinase inhibitors. This study aimed at identifying the presence of ROS1 and ALKrearrangements in CRC using FISH technology. Methods: Arrayed specimens of metastatic CRC (mCRC) patients were tested with a 4-target, 4-color break-apart FISH probe set (Abbott Molecular) designed to simultaneously evaluate the genomic status of ROS1 and ALK. Fused 3’/5’ signals of each gene were considered negative for rearrangement; single 3’/single 5’ (for ROS1) and split 3’-5’ or single 3’ (for ALK) were considered positive for rearrangement. Results: Among 236 mCRC patients tested, two were positive for ROS1 (single 3’ROS1 signals in 39% and 61% of tumor cells) and one was positive for ALK rearrangement (single 3’ALK in 41% of tumor cells). The upper cut-off for positive FISH patterns in the negative specimens was identified as &lt;15% both for ROS1 and ALK. Interestingly, the ALK+ patient displayed intra-tumoral heterogeneity, detected in the tissue cores and confirmed in two resection blocks. The fusion partner for ALK was identified as EML4 by PCR-based tests and sequencing. The fusion partner(s) for ROS1 remains to be identified by other technologies. A small fraction of specimens presented duplicated or clustered copies of native ALK and ROS1. Conclusions: The novel FISH probe set was effective to identify the first cases of ROS1 rearrangements in CRC and re-confirm the occurrence of ALK rearrangements. This supports further evaluation of mCRC cases for ROS1 and ALK gene fusions as these may represent new targets for evaluation in clinical trials. Tumor heterogeneity in the ALK rearrangement must be addressed for screening tests. (Partially supported by research grant from Abbott Molecular and the Colorado CCSG P30CA046934).
Long-term event-free and overall survival after risk-adapted melphalan and SCT for systemic light chain amyloidosis
Authors: H Landau, M Smith, C Landry, J F Chou, S M Devlin, H Hassoun, C Bello, S Giralt, R L Comenzo
Journal: Leukemia (2016)

Stem cell transplantation (SCT), an effective therapy for amyloid light chain (AL) amyloidosis patients, is associated with low treatment-related mortality (TRM) with appropriate patient selection and risk-adapted dosing of melphalan (RA-SCT). Consolidation after SCT increases hematologic complete response (CR) rates and may improve overall survival (OS) for patients with <CR. We retrospectively analyzed outcomes for 143 patients who underwent RA-SCT with or without consolidation. Melphalan was administered at 100 (14%), 140 (52%) and 200 (34%) mg/m2. The TRM rate at 100 days was 5%. RA-SCT resulted in CR in 24% (3 months) and 48% (12 months) of patients. The CR rate was particularly high (62%) in patients offered bortezomib consolidation. With a median follow-up among survivors of 7.7 years, median event-free survival (EFS) with RA-SCT was 4.04 years (95% confidence interval (CI): 3.41–5.01 years); median OS was 10.4 years (95% CI: 7.3–not achieved). Patients with CR at 12 months after SCT had significantly longer EFS (P=0.01) and OS (P=0.04). In a multivariate analysis, melphalan dose had no impact on EFS (P=0.26) or OS (P=0.11). For selected patients, RA-SCT was safe and was associated with extended long-term survival. With the availability of novel agents for consolidation, RA-SCT remains a very effective and important backbone treatment for AL amyloidosis.
Abstract 4832: Independent prognostic role of chromosome 12p deletion in prostate cancer
Authors: Sarah Jane Pauline Minner, Ramin Ahray, Martina Kluth, Thorsten Schlomm, Ronald Simon, Guido Sauter, Maria Christina Tsourlakis
Journal: Cancer Research (2015)

Abstract Deletion of chromosome 12p is a recurrent alteration in prostate cancer, but the prevalence and clinical significance of this alteration is unclear. More than 7,000 prostate cancers with clinical follow-up data in a tissue microarray (TMA) format were analyzed by dual labeling fluorescence in situ hybridization (FISH) using probes for 12p13 (CDKN1B; p27) and for centromere 12 as a reference. CDKN1B was selected as a probe because this gene is located in the center of the deletion, which spans &amp;gt;10 Mb and includes &amp;gt;50 genes in 80% of cancers with 12p deletion. In 13.7% of prostate cancers a deletion of 12p was found (13.5% hemizygeous; 0.2% homozygeous deletions). 12p deletions were linked to advanced tumor stage (p&amp;lt;0.0001), high Gleason grade (p&amp;lt;0.0001), lymph node metastasis (p = 0.0004), rapid tumor cell proliferation (p&amp;lt;0.0001), and early biochemical recurrence (BCR) (p = 0.0027). Multivariate analysis including pT stage (p&amp;lt;0.0001), Gleason grade (p&amp;lt;0.0001), pN status (p = 0.0001), preoperative PSA levels (p = 0.0001), and resection margin status (p = 0.0001) revealed an independent prognostic value of 12p deletion (p = 0.0014). There was no association with ERG fusion status. Deletion of 12p deletion was only minimally linked to p27 expression status, which by itself was unrelated to clinical outcome. This argues against p27 as the key target gene of 12p deletions. Since none of the involved 12p genes is recurrently mutated in next generation sequencing studies, simultaneous dosage reduction of multiple genes may exert a relevant biological effect in 12p deleted cancers. In summary, the results of our study demonstrate that 12p deletion is frequent and provides independent prognostic information in prostate cancer. Citation Format: Sarah Jane Pauline Minner, Ramin Ahray, Martina Kluth, Thorsten Schlomm, Ronald Simon, Guido Sauter, Maria Christina Tsourlakis. Independent prognostic role of chromosome 12p deletion in prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4832. doi:10.1158/1538-7445.AM2015-4832
Antitumor Effect Of Sepantronium Bromide (YM155), a Survivin Suppressant, In Combination With Bendamustine and Rituximab In Diffuse Large B-Cell Lymphoma
Authors: Naoki Kaneko, Keisuke Mitsuoka, Nobuaki Amino, Kentaro Yamanaka, Aya Kita, Masamichi Mori, Miyoshi Sosuke, Sadao Kuromitsu
Journal: Blood (2013)
Infographic. Physical activity benefits for adults and older adults
Authors: Hamish Reid, Charlie Foster
Journal: British Journal of Sports Medicine (2016)

Over one third of the UK's adult population fail to meet the Chief Medical Officers' (CMOs') recommended physical activity (PA) guidelines for health.1 Knowledge of the CMOs' PA recommendations is low amongst healthcare workers2 despite physical inactivity being the most prevalent risk factor for non-communicable disease, which accounts for 80% of deaths in the UK. …
The Functional Significance of Paradoxical Low-Gradient Aortic Valve Stenosis
Authors: Candelas Pérez Del Villar, Raquel Yotti, María Ángeles Espinosa, Enrique Gutiérrez-Ibañes, Alicia Barrio, María José Lorenzo, Pedro Luis Sánchez Fernández, Yolanda Benito, Raquel Prieto, Esther Pérez David, Pablo Martínez-Legazpi, Francisco Fernández-Avilés, Javier Bermejo
Journal: JACC. Cardiovascular imaging (2016)
Examining extent of resection and progression-free survival in glioblastoma: A systematic review and meta-analysis.
Authors: Timothy J Brown, Matt Christopher Brennan, Yan Michael Li, Ephraim W Church, Nicholas J Brandmeir, Kevin Rakszawski, Akshal S Patel, Elias B Rizk, Dima Suki, Raymond Sawaya, Michael J. Glantz
Journal: Journal of Clinical Oncology (2016)

e13500 Background: Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The relationship between extent of tumor resection (EOR) and progression-free survival (PFS) is ill-defined notwithstanding many relevant studies. We present the results of a quantitative systematic review addressing the effect EOR on PFS in patients with GBM. Methods: Search engines were systematically reviewed with the guidance of an expert librarian. Additional articles were included after consultation with experts and evaluation of bibliographies. Data were analyzed to assess PFS following gross total resection (GTR), subtotal resection (STR), and biopsy (Bx). The body of evidence was evaluated according to GRADE criteria and PRISMA guidelines. Results: Our search yielded 1055 articles, of which 9 articles were suitable for inclusion. The meta-analysis revealed significantly decreased likelihood of six-month and one-year progression for GTR compared to STR (RR = 0.80, 95% CI = 0.65-0.97 NNT = 14; RR = 0.66, 95% CI = 0.43-0.99, NNT = 26), decreased likelihood of six-month progression for STR compared to biopsy (RR = 0.76, 95% CI = 0.60-0.95, NNT = 8), and decreased likelihood of progression at 6 months with any EOR compared to Bx (RR = 0.71, 95% CI = 0.63-0.81). The quality of the body of evidence by GRADE criteria was moderate to low. Conclusions: Ours represents the largest and only quantitative systematic review to date performed on this subject. GTR substantially improves the likelihood of 6- and 12-month progression-free survival compared to STR, but the quality of the supporting studies is only moderate to low. Further cohort studies will not provide additional useful data, and randomized controlled trials have not proved feasible. An audited, prospective registry of GBM patients represents a valuable alternative source of high-quality evidence, and is a critical priority for the oncology and neurosurgery communities.