tbuckley/cabot-search huggingface dataset:
Abstract 4231: Immunohistochemical analysis of claudins expression in penile squamous cell carcinoma
Authors: Adriana Bulgarelli, Silvia Vanessa Lourenço, Cláudia Malheiros Coutinho-Camillo, Gustavo Cardoso Guimarães, Fernando Augusto Soares, José Vassallo
Journal: Cancer Research (2012)

Abstract Background: Claudins are tight junction proteins that are critical for the sealing of cellular sheets and controlling paracellular ion flux. Members of the claudin family have been demonstrated to play an important role in carcinogenesis and tumor progression. Penile squamous cell carcinoma (SCC) is a major health problem in Brazil, corresponding to 2,1% of all brazilian men tumors and 5-year survival rate drops dramatically in patients with lymph node metastasis. Objective: The aim of this study was to determine the protein expression pattern of claudins in penile SCC and correlate it with the clinicopathological features of penile cancer. Method: Tissue microarray (TMA) comprising 101 cases of penile SCC were immunohistochemically stained for claudin-1, -3, -4, -5 and -7, with which TMA core showing more than 10% of positive membranous staining cells. Results: Claudin-1, -3, -5 and -7 were downregulated in 55%, 68%, 62% and 88% of penile SCC samples, respectively. Claudin-4 was overexpressed in 58% of the tumor samples. Strong correlation was found between downregulation of claudin-1 and -3 (p&amp;lt; 0.001). Absence of claudin-1, -3 and -5 was associated with urethral infiltration (p=0.03 and p=0.02 and p=0.019, respectively). Loss of claudin -1 and -3 was also associated with perineural invasion (p=0.05 and p=0.02, respectively). Conclusion: Our data provides the first evidence that claudins expression was decreased in areas of invasion and infiltration and could be related to evolution and prognosis of these tumours. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4231. doi:1538-7445.AM2012-4231
Abstract 4611: Cancer reversal by dual strategy: A new molecular target?
Authors: Mario G. Gosalvez
Journal: Cancer Research (2012)

Abstract Haste is a bad counselor when one is striving to address important issues. The new technique, which I draw your attention to, was first started in the 1980's and was completed in 2010 (Gosalvez, M. Thioproline and the reversal of cancer. The Lancet, p. 1108, May 14 1983. M Gosalvez. Mitochondrial Filamentation. AACR 101 Meeting. April 2010. Washington, USA). Throughout these 30 years several molecular targets for a cancer cure have been developed. The last hope, despite countless efforts, malignant neoplasia genetic therapy, has not yet consolidated itself. We trust that our colleagues, dedicated to therapeutic experimentation on human beings, will now address this new possibility, either alone, or in combination with other efforts. Better agents than Quelamycin (Cortes-Funes H, Brugarolas A and Gosalvez M. Quelamycin: A summary of Phase I Clinical Trials. Recent Results in Cancer Research, 74, 200-206, 1980. Eds. G Mathe and FM Muggia, Springer-Verlag. Germany) and Thioproline (Brugarolas A and Gosalvez M. Preliminary clinical results with Norgamem (thioproline) and Revercan (2-amino-2- thiazoline): The first inducers of reverse transformation. In: “Adjuvant Therapies of Cancer”. Mathe, Bonnadona and Salmon Eds.Springer-Verlag, Germany.1982, 346) can be gathered, with the precise cronotherapeutic emphasis, by correctly measuring the mobility (Gosalvez M, Blanco M, Bueno M and Balaguer R. Treatment of Leukaemia 1210 intravenous transplants with tumour modifiers, redoubt cytotoxics and minor tranquilizers, Lubec G and Rosenthal GA Eds. In: “Aminoacids. Chemistry, Biology and Medicine”. Escom Sciences Publishers, 704-711, 1990. Gosalvez, M. Reversal of Cancer by Dual Strategy. Madrid. Editorial Gober. 1992) of the patients under study. Now, after sufficient time has elapsed for the consideration of previous propositions, which have only had partial success, perhaps now the right moment has arrived for our proposal. We believe that, after a few years, the light at last will be seen at the end of the tunnel of suffering for patients and their families. If this proves to be the case, we could now, with the collaboration of everyone, tackle the possibility of using cancer as a therapeutic agent. All the sciences around our problem demand a great commitment for all involved. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4611. doi:1538-7445.AM2012-4611
Stat Bite: Americans' Beliefs About Fruit and Vegetable Consumption
Authors: T. Reynolds
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Stat Bite : Americans' Beliefs About Fruit and Vegetable Consumption Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 14, 15 July 1992, Page 1063, https://doi.org/10.1093/jnci/84.14.1063 Published: 15 July 1992
S47 Enhanced Il-6/ccl3 Signalling In The Plasma Of Patients With Copd
Authors: A. Ravi, S. Khurana, A. Banyard, J. Plumb, G. Booth, M. Catley, L. Healy, E. Smith, J. Vestbo, D. Singh
Journal: Thorax (2014)

<h3>Rationale</h3> IL-6 is a pro-inflammatory cytokine that signals through soluble (sIL-6R/sgp80) and membrane bound (gp80) receptors to promote recruitment of mononuclear cells. IL-6 induces expression of CCL3, a monocytic chemokine. Monocytes are precursors of macrophages and dendritic cells. They can be classified into three subtypes according to surface expression of CD14 (LPS receptor) and CD16 (FcgammaRIII): CD14++CD16-, CD14+CD16+, CD14-CD16++. We measured plasma levels of IL-6, sIL-6R and CCL3 and determined the chemokine receptor expression profile of circulating monocytes in COPD. <h3>Methods</h3> 70 COPD patients and 30 healthy controls comprising 15 smokers (S) and 15 healthy non-smokers (HNS) underwent plasma sampling. Levels of IL-6, sIL-6R and CCL3 were determined by multiplex analysis (MSD) of plasma. Multi-colour flow cytometry was performed on whole blood obtained from 32 COPD patients, 8 S and 8 HNS to measure surface expression levels of chemokine receptors CCR1, CCR2, CCR7, CXCR1 and CX3CR1 on CD14++CD16-, CD14+CD16+ and CD14-CD16++ monocytes. <h3>Results</h3> COPD patients had the greatest levels of IL-6 and sIL-6R. CCL3 was not detected in any controls, but was present in a subset of COPD patients.% surface expression of the CCL3 receptor CCR1 measured on CD14++CD16- monocytes of COPD patients was greater than those of HNS (p = 0.04). There were no significant differences in expression levels of other chemokine receptors. <h3>Conclusion</h3> We report evidence of enhanced IL-6 signalling in the plasma of COPD patients and increased plasma CCL3 in a subset of individuals from this disease group. Furthermore, there was increased CCR1 expression on COPD monocytes. Enhanced IL-6 may co-ordinate the mononuclear component of the inflammatory response in COPD.
Serial interferon-gamma release assay in children younger than 5 years with latent tuberculosis infection
Authors: Natasa Nenadic, Branka Kristic-Kirin, Ivan Pavic, Renata Zrinski Topic, Ivka Zoricic-Letoja, Slavica Dodig
Journal: European Respiratory Journal (2011)

Background:  Interferon gamma release assays (IGRAs) play an important role in diagnosis of latent tuberculosis infection (LTBI), but there is paucity of data about IGRA dynamic values, especially in children younger than 5 years.   Aim:  To evaluate the performance of serial IGRA and tuberculin skin testing (TST) in children younger than 5 years with LTBI.   Methods:  We included 11 BCG vaccinated children younger than 5 years with LTBI. The commercial IGRA (QuantiFERON TB Gold In-Tube®, QFT-GIT), Cellestis Ltd, Carnegie, Australia) was performed two times, before and at the end of 6-month chemoprophylaxis. The cut-off value for positive findings of IGRA was ≥ 0.35 kIU/L. The TST was performed using 2 IU (0.1 mL) of purified protein derivative Tuberkulin PPD RT 23 SSI (Statens Serum Institut, Denmark) according to the Mantoux method and transverse diameter of the induration was measured after 72 hours.   Results:  IGRA values were 8.87±2.01 kIU/L and 8.02±1.99 kIU/L, before and after chemoprophylaxis, respectively, which suggests a slight, insignificant decrease (p=0.89). There was no significant difference in PPD values before (12±2 mm) and after (14±2 mm) the treatment, p=0.50.   Conclusions:  Although the prophylaxis was used, both IGRA and PPD values, remained elevated during the period of 6 months in children with LTBI. Further research is needed to clarify the role of serial IGRA in children up to 5 years.
Abstract LB-248: IRF4 as a critical regulator and potential therapeutic target in ABC type diffuse large B-cell lymphoma
Authors: N. C. Tolga Emre, Arthur L. Shaffer, George W. Wright, Holger Kohlhammer, Louis M. Staudt
Journal: Cancer Research (2011)

Abstract Interferon regulatory factor 4 (IRF4) is a transcriptional regulator with crucial roles in the development of lymphocytes and implicated in malignant transformation. Recently, we have demonstrated that cell lines derived from cancers of plasma cell origin (i.e., multiple myeloma) are addicted to an anomalous gene expression program driven by the wild-type IRF4. Here, we show that an aggressive malignancy of mature B-cells, the activated B-cell-like type of diffuse large B-cell lymphoma (ABC-DLBCL), also requires IRF4 for survival. With an integrative analysis of genome-wide IRF4 localization (ChIP-Seq) assays and gene expression profiling, we identify IRF4 target genes in ABC-DLBCL as members of diverse pathways related to B-cell biology and oncogenesis, largely distinct from the IRF4 targets in multiple myeloma cells. For instance, we identify CARD11, an adaptor in the NF-κB pathway, as a target of IRF4 in ABC-DLBCL, and confirm this by cell-based reporter assays. This novel regulatory mechanism complements the established aspects of ABC-DLBCL pathobiology, where NF-κB pathway is constitutively active and indispensable, and drives IRF4 expression. Furthermore, we find enrichment for a composite ETS-IRF DNA motif in IRF4 binding regions in ABC-DLBCL, suggesting cooperative activity between IRF4 and ETS transcription factor(s). Supporting this, we demonstrate through complementation assays that critical amino acids on IRF4 and the ETS factor SPIB, notably those residues important for their interaction, are essential for the survival of ABC-DLBCL, but not multiple myeloma cells. Taken together we show that ABC-DLBCL cells are addicted to the transcription factor IRF4, in part through a positive feedback mechanism involving CARD11, NF-κB, and IRF4. In addition, our results suggest therapeutic potential for targeting the IRF4-ETS interaction interface in ABC-DLBCL. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-248. doi:10.1158/1538-7445.AM2011-LB-248
Malignant pleural effusion.
Authors: D W Moores
Journal: BMJ (1968)

Malignancy is the most common cause of exudative pleural effusion in patients over the age of 60 years. Control of the effusion significantly reduces morbidity and improves quality of life. Tube thoracostomy with subsequent chemical pleurodesis is the treatment of choice for patients with tumors that are relatively insensitive to systemic chemotherapy. The agents most commonly used for chemical pleurodesis are tetracycline and bleomycin. A 13-center randomized trial compared tetracycline 1 g and bleomycin 60 U. Median time to recurrence or progression of the malignant effusion was 32 days for tetracycline and more than 46 days for bleomycin (P = .037). The recurrence rate within 30 days of instillation was 36% for bleomycin (10 of 28 patients) and 67% (18 of 27 patients) for tetracycline (P = .023). At 90 days, the recurrence rate was 30% (11 of 37) for bleomycin, and 53% (19 of 36) for tetracycline (P = .047). From this study, the authors concluded that intrapleural bleomycin appears superior to tetracycline for controlling malignant pleural effusions. Selected patients who fail tube thoracostomy and chemical pleurodesis should be considered for pleuroperitoneal shunting or pleurectomy.
EPID-09IMPROVED SURVIVAL OF LOW-GRADE GLIOMA PATIENTS (1999-2010) DESPITE DECREASED UTILIZATION OF RADIATION THERAPY: A SEER-BASED ANALYSIS.
Authors: Xuezhi Dong, Abraham Noorbakhsh, Brian Hirshman, Tianzan Zhou, Jessica Tang, David Chang, Bob Carter, Clark Chen
Journal: Neuro-Oncology (2015)

BACKGROUND: The survival trends and the patterns of clinical practice pertaining to radiation therapy and surgical resection for WHO grade I, II, and III astrocytoma patients remain poorly characterized. METHODS: Using the Surveillance, Epidemiology and End Results (SEER) database, we identified 2497 grade I, 4113 grade II and 2755 grade III astrocytomas during the period of 1999-2010. Time-trend analyses were performed for overall survival (OS), radiation treatment (RT), and the extent of surgical resection (EOR). RESULTS: While overall survival of grade I astrocytomas remain unchanged during the study period, we observed improved overall survival for grade II and III astrocytoma patients (Tarone-Ware p < 0.05). The median survival increased from 44 to 57 months and from 15 to 24 months for grade II and III astrocytoma patients, respectively. The differences in survival remained significant after adjusting for pertinent variables including age, ethnicity, marital status, sex, tumor size, tumor location, EOR, and RT status. The pattern of clinical practice in terms of EOR for grade II and III astrocytoma patients did not change significantly during this study period. However, there was decreased RT utilization as treatment for grade II astrocytoma patients after 2005. CONCLUSION: Results from the SEER database indicate that there were improvements in the overall survival of grade II and III astrocytoma patients over the past decade. Notably, the improved survival for grade II astrocytoma was achieved despite an overall decrease in up-front radiation therapy. These results bear significant implications in terms of neuro-cognitive preservation in terms of delaying radiation therapy for grade II glioma patients.
Milk scare hits New Zealand
Authors: S. Catherall
Journal: BMJ (1997)

The New Zealand dairy industry was already poised for action when news broke that a New Zealand medical researcher had discovered a link between milk and insulin dependent diabetes. Within hours of the first wave of media reports, the Dairy Board, which promotes the dairy industry in New Zealand and overseas, had set up a free 0800 telephone information line. Over about six hours 200 callers rang the hotline.

Surprisingly, it was the Dairy Board, which funded the research, that gave Professor Bob Elliott, of the Auckland Medical School, permission to break the story in the first place. Two years ago it agreed to back the professor's research after he observed that a protein, s casein A1, produced by about 20% of New Zealand's dairy herd, could trigger insulin dependent diabetes in those prone to the condition. The story …
SP0127 IL23: A Signal to the Enthesis?
Authors: J. P. Sherlock
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> This lecture will explore the central importance of the powerful, pro-inflammatory cytokine interleukin(IL)-23 in spondyloarthropathy. Although the pathogenesis of these conditions has been highly enigmatic for decades, numerous lines of investigation have recently independently converged upon IL-23, demonstrating it to be fundamental to the biology of spondyloarthropathy. Thus the bowel inflammation which is associated with spondyloarthropathy results in production of IL-23 and HLA-B27, which itself is very strongly associated with these conditions, has also been shown to misfold and trigger production of IL-23. Moreover genetic studies have demonstrated that polymorphisms in the receptor for IL-23 are associated with the risk of developing spondyloarthropathy. We have recently explored the direct mechanism of IL-23 action in this context to show that IL-23 acts directly on the hallmark anatomical sites affected in spondyloarthropathy, such as the entheseal attachments of tendons and ligaments to bone and the aortic root. These findings not only clarify the pathogenesis of these conditions but open exciting new therapeutic approaches for their treatment. <h3>Disclosure of Interest</h3> J. Sherlock Employee of: Work presented in this seminar was conducted wtihin Merck
Abstract P6-11-03: Follow up of breast cancer patients who underwent gamma knife radiosurgery for a diagnosis of brain metastases: A single institutional experience
Authors: MM Abu-Khalaf, C Hatzis, G Chung, M DiGiovanna, S Tara, H Erin, P Lajos, YB James, CL Veronica
Journal: Cancer Research (2013)

Abstract Background: Breast cancer (BC) is the second most common cause of brain metastases in the United States. We performed a retrospective analysis of BC patients (pts) in the Yale Gamma Knife Radiosurgery (GKRS) database treated for brain metastases (mets) to report overall survival (OS) from time of GKRS, and to identify factors that predict improved survival outcomes. Methods: We performed retrospective review of the Yale database of BC pts treated with standard GKRS technique for brain mets from 2000 to May 2013. Treatment doses typically ranged from 16 to 24 Gy prescribed to the 40-85% isodose surfaces. Overall survival (OS) for each patient was calculated from the date of first GKRS treatment of brain metastases. Variables included age, Karnofsky Performance Status (KPS), pre/post whole-brain radiation treatment (WBRT) and/or surgical resection, and # of brain mets treated (1-4 vs ≥5). Results: A total of 80 BC pts were identified, with a mean age of 56.2 yrs; KPS 40-60 in 8pts (10%), 70-80 in 13 (16%), 90-100 in 41 (51%), unknown in 18 (23%); ER+ in 38 (48%), ER- in 38 (48%), unknown in 4 (5%); HER2 + in 38 (48%), HER2- in 33 (41%), indeterminate in 3 (4%) and unknown in 6 (8%). BC subtypes are Luminal A (ER+/HER2-) in 16 (20%), Luminal B (ER+/HER2+) in 19 (24%), HER-2(ER-/HER2+) in 17 (21%), Basal (ER-/HER2-) in 17 (21%), unknown in 11 (14%). Number of brain mets at time of first GKRS ≥5 in 32 (40%); prior WBRT in 30 (38%); WBRT post GKRS in 9 (11%); surgical resection for brain mets in 13 (16%) prior to GKRS and post GKRS in 9 (11%); 16% had ≥3 GKRS. Median time from primary BC dx to brain mets is 62.8 months (m) (range 46.2-81.6); with no significant difference among subtypes. Median OS from GKRS is 13.1 m (7.6-21.9); median OS from brain mets is 18.8 m (11.7-23.9). On univariate analysis, factors associated with significant improved OS from time of GKRS included HER-2 subtype (p = 0.005), KPS 90-100 (p = 0.008), good control of systemic disease (p = 0.017), pre (p = 0.041) and post GKRS surgical resection (p = 0.02). Age, pre or post WBRT, # of brain mets (1-4 vs. 5) were not significant predictors of OS from time of GKRS. In a multivariate Cox analysis (46 cases), HER-2 subtype remained a significant predictor of improved OS from time of GKRS; (HR) 0.26, 95%CI 0.08 to 0.8, p-value = 0.02. There was a trend in favor of surgical resection of brain mets pre GKRS (HR 0.14, 95% CI 0.02 to 1.15, p-value = 0.067 Conclusion: GKRS offers good local control for BC pts with brain mets, and is a reasonable option for pts with ≥5 brain mets. Our results show no associated survival benefit for administration of WBRT pre/post GKRS. HER-2 subtype is a significant predictor of improved survival in BC pts undergoing GKRS for brain mets. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-11-03.
Mitogen Activated Protein Kinase Kinase 3 is up-regulated in cancer, drives the invasive phenotype, and predicts short survival.
Authors: Tim Demuth, Linsey Reavie, Jessica Rennert, Mitsutoshi Nakada, Satoko Nakada, Christian Beaudry, Dominique Hoelzinger, Armanda Henrichs, Erich Anderson, Wendy McDonough, Michael Berens
Journal: Cancer Research (2007)

2147   The early and pervasive tendency of cancer cells to invade into peritumoral normal tissue and to metastasize underlies the patient’s poor prognosis. This malignant spread of tumor cells prevents complete surgical resection and sequesters tumor cells outside the fields of focal radiation; each of these leads to heightened tumor recurrence.  A three dimensional spheroid invasion assay was employed to model the invasive behavior of human glioma cells in vitro. Laser capture microdissection in conjunction with whole genome expression profiling resulted in the differentiation of the invasive cell transcriptome as compared to that of stationary cognates. Mitogen activated protein Kinase Kinase 3 (MKK3) was found to be significantly up-regulated in invasive cells. Immunoblotting on a panel of glioma specimens revealed that MKK3 activation is a marker for tumor progression. Analysis of two comprehensive expression data sets of over 200 glial tumors, revealed MKK3 as a predictor of poor patient survival.  Further clinical validation was performed on tissue microarrays of breast, lung and pancreatic cancer, in which there was evidence of strong activation of MKK3 as compared to normal tissue. MKK3 was identified to be an important driver of tumor invasion that strongly predicts patient survival. (supported by CA085138 and NS42262)