tbuckley/cabot-search huggingface dataset:
Proteomics of the ascitic fluid for the differentiation of advanced ovarian cancer.
Authors: Gururao Hariprasad, Roopa Hariprasad, Lalit Kumar, Amit Kaushik, Alagiri Srinivasan
Journal: Journal of Clinical Oncology (2012)

e15510 Background: Ovarian cancers are classified as primary, if it arises in the ovary and secondary or metastatic, if the origin is from other parts of the body. The clinical manifestations of these cancers in the advanced stage are very similar making it difficult to distinguish clinically, hiostopathologically and radiologicaly. The therapeutics and management of the primary and secondary malignancies are completely different. While, the advanced primary malignancies are treated by cytoreduction followed by chemotherapy, the metastatic tumors are treated mainly with palliative chemotherapy. The prognosis is better for primary than secondary ovarian cancer making their diagnosis very crucial for patient care. Methods: 1D and 2D-gel based proteomic approaches were used to study the differentially expressed proteins in the ascitic fluid of patients (10 primary and 4 secondary) with advanced ovarian cancer. The relative ratios of the protein expression were estimated by densitometric analysis. The bands/spots with more than three fold difference were subjected to in-gel trypsin digestion and identified by mass spectrometric analysis. The differential expression of one of the proteins was further validated by western blot experiments and ELISA. Results: Programmed Cell Death 1-Ligand 2 and apolipoprotein A1 were seen to be up regulated in the advanced primary ovarian cancer while apolipoprotein A4, and chain L, humanized version of the anti-human fas antibody Hfe7a were seen to be up regulated in the metastatic variant. Validation for the expression of apolipoprotein A1 shows that a 61.8ng/ml cut off is ideal to differentiate the primary and secondary advanced ovarian cancers. The assay has 100% sensitivity, 75% specificity, positive predictive value of 90.9%, negative predictive value of 100%, accuracy of 92.85% and a pre-test odds positive of 2.5. Conclusions: Proteomics of ascitic fluid is useful for the differentiation of advanced ovarian cancers. There are proteins which are differentially expressed in the ascitic fluid of patients with primary and secondary ovarian cancer. Apolipoprotein A1 is a potential biomarker that can be used to differentiate the closely mimicking clinical scenarios of advanced ovarian cancer.
Extraskeletal osteosarcoma: Clinicopathologic features and results of multimodal management.
Authors: N. Fabbri, A. Tiwari, M. Umer, D. Vanel, M. Alberghini, P. Ruggieri, S. Ferrari, P. Picci, M. Mercuri
Journal: Journal of Clinical Oncology (2010)

10093 Background: Extraskeletal osteosarcoma (OGS) is a rare malignant tumor of the soft tissues usually associated with worse outcome than its skeletal counterpart despite multimodal approach. Purpose of this study was to review a single Institution experience and results of management, with emphasis on the role of combined treatment consisting of surgery and adjuvant chemotherapy. Methods: Retrospective study of 48 patients observed 1966-2007 was undertaken: 36 patients were admitted and managed at our Institution while 12 cases were consultations and not included in this study. Clinicopathologic features and details of treatment of all 36 patients were correlated with outcome. Updated follow-up was available in all patients. Results: There were 21 males and 15 females, mean age was 53.6±19.3 years (range 14-84 yrs); 23 patients (63.9%) presented with localised disease while distant metastases were detected in 13 patients (36.1%). Primary tumor involved the extremities in 25 patients (69.4%) and the girdles or trunk in 11 (30.6%). Surgery consisted of a limb-salvage procedure in 25 cases (69.4%) and amputation in 9 (25%) while 2 patients were considered inoperable (5.6%). Multiagent chemotherapy was administered in 19 patients (52.8%). At mean follow-up of 5.8 years, 23 patients had died of disease, expected 5 and 10 year overall survival rates were 41% and 31%. Tumour volume (p=0.01) and age at presentation (p=0.07) were the most important predictors of survival. Disease-specific survival rate was 43.5% for patients with localised disease and 23% in patients with metastasis at presentation even though the difference did not reach statistical significance. Addition of adjuvant chemotherapy to local management was associated with improved disease-free survival in patients with localised disease (60% vs. 31%, p=0.09). Conclusions: Extraskeletal OGS was associated with overall worse prognosis than skeletal OGS despite multimodal management. Incidence of metastasis at diagnosis (36.1%) was higher than usually observed in bone OGS. Tumour volume and age were significant factors affecting the outcome while adjuvant chemotherapy showed a trend towards improved survival in patients with localized disease. No significant financial relationships to disclose.
Single Nucleotide Polymorphisms in ABCB1 and CBR1 Predict Toxicity to R-CHOP Type Regimens in Patients with Diffuse Non Hodgkin's Lymphoma
Authors: Lars-Petter Jordheim, Vincent Ribrag, Herve Ghesquieres, Sophie Pallardy, Richard Delarue, Herve Tilly, Corinne Haioun, Fabrice Jardin, Gilles Salles, Charles Dumontet
Journal: Blood (2012)
Abstract 18019: Impact Of Diabetes on Survival after Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction
Authors: Matthew Kahn, Richard Cubbon, Ben Mercer, Guy Gherardi, Alison Wheatcroft, Kathryn Somers, Alan Liu, Jonathan Blaxill, Jim McLenachan, Mohan Sivananthan, Dan Blackman, John Greenwood, Stephen Wheatcroft
Journal: Circulation (2010)
Firearm access and risk of suicide: reply (letter)
Authors: Jeffrey W. Swanson, Richard J. Bonnie, Paul S. Appelbaum
Journal: JAMA (2016)

Mr Kels highlights a confusing aspect of federal and state laws that disqualify certain people from accessing firearms. What types of involuntary mental health interventions result in a gun-prohibiting record that is reportable to the NICS? The question is difficult to answer because commitment practices vary substantially by state and locality. Under federal law, individuals lose their firearm rights if they have been committed to a mental institution. In many states, commitment proceedings have 2 stages. The initial stage is a short period (eg, 3-5 days) of hospitalization for the purposes of providing emergency treatment and evaluation of whether patients meet commitment criteria; the second stage is a formal commitment hearing. These admissions are often authorized by an emergency medicine physician or mental health professional and in some states are ratified ex parte by a magistrate. These patients are discharged quite often before a formal hearing is required, so hospitalization never results in a commitment order. Language: en
Bone Marrow Stroma Protects Myeloma Cells from Cytotoxic Damage Via Induction of the Oncoprotein MUC1
Authors: Michal Bar-Natan, Katarina Luptakova, Maxwell Douglas Coll, Dina Stroopinsky, Hasan Rajabi, Athalia Rachel Pyzer, Kristen A Palmer, Michaela R. Reagan, Poorvi Somaiya, Salvia Jain, Jon Arnason, Irene M. Ghobrial, Jacalyn Rosenblatt, Kenneth C. Anderson, Donald Kufe, David Avigan
Journal: Blood (2014)
Updates on Acute Coronary Syndrome
Authors: Alon Eisen, Robert P. Giugliano, Eugene Braunwald
Journal: JAMA Cardiology (2016)

Acute coronary syndrome (ACS), the acute manifestation of ischemic heart disease, remains a major cause of morbidity and mortality worldwide and is responsible for more than 1 million hospital admissions in the United States annually. Considerable research is being conducted in the field. This review provides a contemporary overview of key new findings on the pathophysiology, diagnosis, treatment, and prognosis of ACS.While plaque rupture is the most frequent cause of coronary thrombosis, studies with optical coherence tomography demonstrate that superficial plaque erosion is more common than previously thought. High-sensitivity troponin assays (not yet available in the United States) and cardiac computed tomographic angiography are being increasingly used in diagnosis and risk stratification of patients with suspected ACS. New data from long-term dual antiplatelet therapy studies and investigations of anticoagulants provide important insights into the balance between ischemic and bleeding risks. The added benefit of percutaneous coronary intervention in non-infarct-related arteries in patients with ST-segment elevation myocardial infarction has been demonstrated in randomized trials, and the radial approach has become the standard of care in patients with ACS undergoing angiography. Promising old and new adjunctive therapies, such as pretreatment with β-blockers, ezetimibe, and proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors, are discussed. New guidelines on the management of non-ST-segment elevation ACS were published in the last 2 years, as well as scientific documents on ACS in understudied populations, such as women and patients with renal dysfunction.Substantial progress in the prevention, diagnosis, and management of patients with ACS has been accomplished in recent years. Despite optimal pharmacological and invasive therapies, the burden of recurrent ischemic events and mortality remains high, and future research is ongoing to prevent and improve the outcome of patients with ACS.
Abstract 3470: Obesity and metformin alter progression of triple negative breast cancer
Authors: Laura Camacho, Lei Xue, Lacey Dobrolecki, Susan G. Hilsenbeck, Chandandeep Nagi, Nagireddy Putluri, Michael T. Lewis, Arun Sreekumar, Sao Jiralerspong
Journal: Cancer Research (2016)

Abstract Background: Epidemiological studies from us and others have reported an association of obesity with more aggressive breast tumors and &amp;gt;30% higher risk of recurrence and mortality compared to normal weight patients. This includes poorer outcomes for triple negative breast cancer (TNBC), an aggressive subtype with early recurrence and shorter survival. Metformin is a leading frontline therapy for type 2 diabetes and its safety profile is well documented. Laboratory and clinical studies including ours suggest that metformin may have anti-tumor effects in breast cancer. However, the nature and molecular mechanisms of these correlations are poorly understood. Experimental design and methods: We used a PDX (patient-derived xenograft) breast cancer model in diet-induced obese mice to study how obesity promotes breast cancer growth and how metformin antagonizes these effects. After feeding the mice with a high-fat diet (HFD) vs. a control diet (CD), we transplanted a TNBC PDX into the mammary fat pads. When tumors reached about 50 mm3, mice in HFD and CD groups were randomly assigned to metformin treatment or no treatment. Tumor volumes were measured bi-weekly, and blood, tumors, and organs were collected after 4 weeks of treatment. Histological and immunohistochemical staining, serum adipokines array and metabolomics and lipidomics analyses were performed to examine potential mechanisms. Results: HFD (obese) group compared to CD (lean) group was associated with larger tumors, whereas metformin compared to no treatment was associated with smaller tumors. A panel of adipokines and metabolites was identified to be differentially expressed between the groups. Conclusion: Our results suggest a growth promoting effect of obesity in TNBC, while metformin appears to have the opposite effect. The identification of adipokines and metabolites involved in these effects will help us understand the mechanisms by which obesity and metformin alter the progression of TNBC. Citation Format: Laura Camacho, Lei Xue, Lacey Dobrolecki, Susan G. Hilsenbeck, Chandandeep Nagi, Nagireddy Putluri, Michael T. Lewis, Arun Sreekumar, Sao Jiralerspong. Obesity and metformin alter progression of triple negative breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3470.
Abstract 3921: A screen of breast and colon cancers with HER2 antibody clone UMAB36 does not exhibit the cross-reactivity of clone 4B5 with HER4 protein
Authors: Lixin Zhou, Kehu Yuan, Fangfang Ren, Lili Ki, Min Zhou, Wei Fu, Xiaozheng Huang, Rachel M. Gonzalez, Youmin Shu, Yi Shen, Guangli Wang, Donghui Ma, Wei-Wu He, Jian Chen
Journal: Cancer Research (2016)

Abstract Increased sensitivity and specificity of immunohistochemical (IHC) detection of HER2 expression is crucial as the role of Trastuzumab have expanded in the treatment of HER2 positive non-breast cancer patients such as gastric cancer patients. Non-specific nuclear and cytoplasmic staining of the HER2 antibody clone 4B5 has been reported by other labs. In this study, we evaluated the specificity of HER2 clone 4B5 and a new HER2 antibody clone UMAB36 using a suite of methods including protein lysate arrays, western blots, FISH and IHC correlation screens on 129 breast and 158 colon cancer cases for HER2 expression. The protein lysate array and western results revealed that clone 4B5 recognizes three proteins: HER2, HER4, and ZSCAN18, a nuclear transcription protein. In comparison, clone UMAB36 recognized only HER2 protein in the same protein lysate array and western screen as clone 4B5. False negative results, based on correlation of IHC with FISH HER2 positives, were generated using clone 4B5 in 1 breast and 5 gastric of the total 287 cancer cases screened. Comparatively, no false negative results were observed using clone UMAB36 in which there was a 100% correlation between IHC and FISH screen. In this study, areas of normal gastric tissue often stained positive by HER2 clone 4B5, so we performed further analysis of 470 normal gastric cases using Ventana's BenchMark instrument. The results show that 278 normal gastric cases had positive stain with clone 4B5 compared to 3 cases with clone UMAB36. The high background by clone 4B5 may be due HER4 being upregulated in adjacent normal gastric tissue. Our results indicate clone UMAB36 has higher specificity and sensitivity than clone 4B5 in screening gastric tumors. Citation Format: Lixin Zhou, Kehu Yuan, Fangfang Ren, Lili Ki, Min Zhou, Wei Fu, Xiaozheng Huang, Rachel M. Gonzalez, Youmin Shu, Yi Shen, Guangli Wang, Donghui Ma, Wei-Wu He, Jian Chen. A screen of breast and colon cancers with HER2 antibody clone UMAB36 does not exhibit the cross-reactivity of clone 4B5 with HER4 protein. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3921.
Cervical Radiculopathy
Authors: Simon Carette, Michael G. Fehlings
Journal: New England Journal of Medicine (2005)

A 37-year-old woman presents with a two-week history of severe neck pain radiating to her left shoulder girdle and extending to the arm, forearm, and dorsum of the hand. Physical examination reveals weakness of her left triceps, finger extensors, and wrist flexors, as well as hypoesthesia of the third digit and a diminished triceps reflex. How should her case be managed?
Are Chronic Myeloproliferative Neoplasms Associated with Age-Related Macular Degeneration?
Authors: Marie Bak, Torben Lykke Sørensen, Esben Meulengracht Flachs, Ann-Dorthe Olsen Zwisler, Knud Juel, Henrik Frederiksen, Hans Hasselbalch
Journal: Blood (2015)
Abstract 891: Dual defects of MDM2/MDMX-p53 pathways cause global metabolic disruption and enhance tumorigenesis
Authors: Hua Lu, Yi-wei zhang, Peng Liao, Wenjuan Liao, Jiaxiang Chen, Shelya X. Zeng
Journal: Cancer Research (2016)

Abstract Although recent discoveries have linked the tumor suppressing functions of p53 to its regulation on cellular metabolism, the exact signaling pathways underlying how p53 is activated in response to various metabolism stresses, and how p53 coordinates the systemic metabolism homeostasis and further blocks tumorigenesis remain largely unclear. Previous studies have shown that the mice containing a single knock-in at cysteine residue 305 of MDM2 (MDM2C305F) is defective in ribosomal stress (RS) induced p53 activation and display severe nutrient shortage-induced hepatosteatosis. And very recently we found that in response to metabolic stress (MeS), AMPK directly phosphorylates serine 342 of MDMX, leading to p53 activation, which is defective in MDMX3SA mice harboring a mutant MDMX with S341A, S367A and S402A mutations. In the current study, we want to determine if the dual defects in the MDM2/MDMX-p53 pathways might thoroughly impair p53's ability to regulate metabolic homeostasis and thus favor metabolism-related tumorigenesis, by generating a double knock-in (DKI) MDMX3SA/MDM2C305F mouse line. Our results indicate that DKI mice on normal chow diet exhibit mild, but significant, metabolism abnormalities, including increased body weight, higher fasting-glucose level and impaired glucose tolerance, which is exacerbated by high-fat-diet feeding. Consistently, MEFs isolated from DKI mice possess higher capacity of differentiation into adipocytes, and less beige fat is induced in the subcutaneous white adipose tissue of DKI mice after chronic cold exposure. Furthermore, we observe that the survival rate of DKI mice is significantly lower compared to either control or single knock-in groups, which may be due to the higher morbidity of cancers in DKI mice, including hepatoma, lymphoma and lung carcinoma. Because of these observations, we further specifically investigate if dual defects of these p53 activation pathways will accelerate hepatocellular carcinogenesis or not. We indeed find that treatment of carcinogen DEN causes more and bigger tumor nodules in the liver of DKI mice. These results suggest that both RS-MDM2-p53 and MeS-MDMX-p53 pathways play important roles in regulation of global metabolism, and dual defects of these pathways benefit metabolism-related tumor formation and growth. Further study is required to establish the direct effect of the p53 pathway defects-mediated metabolic disruption on tumorigenesis, and determine the underlying mechanisms. Citation Format: Hua Lu, Yi-wei zhang, Peng Liao, Wenjuan Liao, Jiaxiang Chen, Shelya X. Zeng. Dual defects of MDM2/MDMX-p53 pathways cause global metabolic disruption and enhance tumorigenesis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 891.
Should genetic testing for <i>BRCA1/2</i> be permitted for minors? Opinions of parents who completed <i>BRCA1/2</i> testing
Authors: A. R. Bradbury, L. Patrick-Miller, M. Feigon, K. Pawlowski, B. Egleston, C. Ibe, C. B. Sands, S. Cummings, O. I. Olopade, C. K. Daugherty
Journal: Journal of Clinical Oncology (2008)

1511 Background: ASCO recommends against the genetic testing of minors for hereditary cancer syndromes that present in adulthood. To better understand the opinions of those most affected by these issues, we interviewed parents who had undergone BRCA1/2 testing and had children <25 years old at the time of BRCA testing. Methods: 153 parents completed semi-structured interviews (52 BRCA1/2 mutation carriers (MC), 77 with uninformative negative results (UN), 6 with true negative results (TN) and 18 with a variant of uncertain significance (VUS). Multiple logistic regressions evaluated the associations among biomedical factors, demographic factors and support of testing minors. Wald tests and likelihood ratio tests assessed statistical significance for binary covariates and nominal covariates. Results: 63 (41%) of participants supported testing minors for BRCA1/2 in response to a dichotomous (Y/N) question. In a multivariable analysis, support was greatest among participants with TN (83%) and UN (45%) results and lower among MC (35%) and participants with a VUS (28%, p=0.03). Support was also associated with minority race (other>black>white, p=0.04) and a younger mean offspring age (p=0.004). Responses to open-ended questions suggest that 27% parents unconditionally support testing of minors and 25% support testing only in certain situations (i.e. perceived medical indication or a mature child). Psychological risks, a lack of medical necessity and the insufficient maturity of minors were frequent concerns of those opposed. The potential to positively impact minors’ health behaviors was the most reported reason for supporting testing. Conclusions: A significant minority of parents support the genetic testing of minors in some or all circumstances. Further research is necessary to evaluate the risks and benefits of providing genetic testing to minors for adult-onset hereditary cancer syndromes in order to inform clinical practice and public policy that will ensure optimal psychosocial and medical outcomes for all members of families at risk for hereditary cancer. No significant financial relationships to disclose.
Long-Term Trends in Newly Diagnosed Brugada Syndrome
Authors: Ruben Casado-Arroyo, Paola Berne, Jayakeerthi Yoganarasimha Rao, Moisés Rodriguez-Mañero, Moisés Levinstein, Giulio Conte, Juan Sieira, Mehdi Namdar, Danilo Ricciardi, Gian-Battista Chierchia, Carlo de Asmundis, Gudrun Pappaert, Mark La Meir, Francis Wellens, Josep Brugada, Pedro Brugada
Journal: Journal of the American College of Cardiology (2016)