tbuckley/cabot-search huggingface dataset:
Lymphedema Precautions: Time to Abandon Old Practices?
Authors: Soojin Ahn, Elisa R. Port
Journal: Journal of Clinical Oncology (2015)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.A 46-year-old premenopausal woman with a body mass index of 21 was found on screening mammography to have a new, approximately 1-cm spiculated mass with associated calcifications in the upper outer quadrant of the left breast. Stereotactic core biopsy showed a focus of invasive duct carcinoma, strongly positive for estrogen and progesterone receptors and negative for human epidermal growth factor receptor 2, with associated ductal carcinoma in situ. Clinical examination revealed no palpable mass or axillary lymphadenopathy. She underwent a left lumpectomy with seed localization and sentinel lymph node biopsy. Final pathology revealed an 8-mm well-differentiated invasive carcinoma without lymphovascular invasion and intermediate grade ductal carcinoma in situ. The margins were clear, and three sentinel lymph nodes were negative for metastasis. The 21-gene recurrence score was 10, suggesting a 7% risk of 10-year distant recurrence with adjuvant endocrine treatment. After the completion of adjuvant radiotherapy (42.50 Gy in 16 fractions to the breast), the patient has returned for a follow-up visit. She is a professional violinist and would like to know what she can do to prevent lymphedema on her upcoming flight to Vienna.
Chitosan thermogels for local T lymphocyte delivery for cancer immunotherapy
Authors: Anne Monette, Caroline Ceccaldi, Sophie Lerouge, Réjean Lapointe
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The success of systemic adoptive T cell transfer lies in the capacity of the antigen-experienced cytotoxic T lymphocytes to access and persist within the tumour microenvironment. The mimicking of tertiary lymphoid structures that promote a protective immune response against cancer
Metastatic breast cancer detection and therapy monitoring using folate-targeting flow cytometry.
Authors: B. Hong, M. Mace, R. Crowder, T. Coleman, W. He, F. Szczepanski, J. Feczko, J. Lyzak
Journal: Journal of Clinical Oncology (2011)

23 Background: Circulating tumor cell (CTC) has emerged as a valuable surrogate tumor marker for cancer diagnosis, prognosis, therapy personalization, and drug discovery. To identify CTCs, EpCAM and/or cytokeratin have been commonly used; however, their expression may diminish for subgroups of breast cancers or during epithelial-mesenchymal transition. A unique approach by targeting folate receptor (FR) on CTCs overcomes the limitation. Cancer cells overexpress FR with high affinity (K D =0.1 nM) to internalize high levels of folate for rapid growth. FR is also found upregulated in most cancers, while at very low levels in normal tissues. Methods: A flow cytometry based in-vitro CTC assay kit (OncoIVDx) was developed by IV Diagnostics Inc to specifically enumerate CTCs which overexpress FRs. 20 mL of 9 metastatic breast cancer (MBC) patients' peripheral blood was collected using CellSave tube before and after the treatment in midst of therapy. CTCs were tagged by fluorescently labeled folate conjugate, while leukocytes were counterstained by anti-CD45. To absolutely count the rare CTCs, a fluorescent bead was added serving internal control. Results: Table. Conclusions: No obvious shift in dot plots was found for patients' leucocytes compared to those in normal sample. Tumor size, histologic grade, nodal involvement and lymphovascular invasion (LVI) did not display a significant association with CTC presence, although more positive nodes with identified LVI might indicate an unfavorable increase in CTC counts. CTC presence was found associated with serum marker CA27.29. A score of 30 and less correlated with CTC response to the treatment. Chemotherapy alone or in combination with hormone therapy did not correlate with the change in CTC counts after treatment, except for hormone therapy alone. Unfavorable progression of cancers could be predicated for the patients with approximately 25 and more CTCs. We would like to thank NIH/NCI for SBIR phase I grant (1R43CA13789301A1). [Table: see text]
Acute Cholecystitis Occurs More Commonly Than Expected Following Allogeneic Hematopoietic Stem Cell Transplantation and Is Ineffectively Diagnosed Using Abdominal Ultrasound
Authors: Stephen J. Bagley, Alison R. Sehgal, Noelle V. Frey, Saar Gill, Elizabeth Hexner, Alison W. Loren, James K. Mangan, David L. Porter, Ran Reshef, Edward A. Stadtmauer, Selina Luger
Journal: Blood (2013)
Testin knock-out mice reveal a tumor suppressor function in chemically-induced forestomach carcinogenesis
Authors: Alessandra Drusco, Nicola Zanesi, Jean Letofsky, John L. Farber, Louise Y. Fong, Carlo M. Croce
Journal: Cancer Research (2005)

1983   Loss of Hetherozygosity (LOH) at a given chromosomal fragile site is associated with the loss of tumor suppressor genes (TSG). One of these regions is located on the long arm of chromosome 7 and it is deleted in epithelial cancers as well as in hematopoietic malignancy. At 7q31.2 we have identified the Testin (Tes) gene as a putative TSG for this region. Tes encodes for a LIM domain protein that plays a role in cell adhesion. The protein is mainly localized to the tip of actin stress fibers at focal adhesion plaques and cell-cell-contact areas: its overexpression seems to affect cell growth, cell spreading and cell motility. To test whether Testin displays a tumor suppressor role in vivo we have generated a Tes knock-out mouse and we have assessed its role in a well established gastric carcinogenic model. In mice a zinc deficient diet (ZD) enhances cellular proliferation in forestomach and susceptibility to N-nitrosomethylbenzylamine (NMBA) induced carcinogenesis. Five week old Tes wild type (+/+), heterozygous (+/−) and homozygous (−/−) mice have been homogenously distributed into four groups: zinc sufficient diet fed mice (ZS), zinc deficient diet fed mice (ZD), zinc sufficient fed+NMBA treated mice (ZS+NMBA), zinc deficient fed+NMBA treated mice (ZD+NMBA). After four weeks from the beginning of the study, the ZS+NMBA and ZD+NMBA groups were treated with three intragastric doses of NMBA (2 mg/kg body weight, twice a week). Animals were all sacrificed eight weeks after NMBA administration to assess the tumor incidence in each group for each genotype. In the ZS+NMBA group we have found mostly a mild proliferative epithelium and small papillomas in 8/14 cases (57.1%) of the +/+ mice, large papillomas and dysplasia in 19/21 cases (90.4%) of the +/− mice and large papillomas, adenomas and carcinomas in 20/21 cases (95.2%) of the −/− mice. The ZD+NMBA group has shown only benign lesions in 8/15 cases (53.3%) of +/+ mice, multiple very large papillomas, atypical glandular metaplasia and carcinomas in 29/30 cases (96.6%) of +/− mice, very large papillomas, squamous cell carcinomas and invasive carcinomas in 16/16 cases (100%) of −/− mice. A statististical significant difference was found in the ZS+NMBA group between +/+ versus +/− (P=0,038) and +/+ versus −/− (P=0,01) mice as well as in the ZD+NMBA group between +/+ versus +/− (P=0,006) and +/+ versus −/− (P=0,0009) mice. We are still studying the spontaneous tumor phenotype in the Tes +/+, +/− and −/− mice. Our results provide the the first evidence that Testin functions as a tumor suppressor gene in vivo.
Clinical and Biomarker Changes in Dominantly Inherited Alzheimer's Disease
Authors: Wilfried Schroyens, Casey O'connell, David Sykes
Journal: New England Journal of Medicine (2012)

as the completely reversible nature of the symptoms, suggests that the abnormal plasma-cell clone and monoclonal gammopathy are the likely cause of the TEMPI syndrome.Efforts to identify the antigenic target of the paraprotein are under way.We suspect that there exist other patients with the TEMPI syndrome -as well as patients with other disorders -whose symptoms might be explained by a plasma-cell dyscrasia or underlying monoclonal gammopathy.We welcome any reader insights into this unusual syndrome.
Pleural fluid proGRP in the diagnosis of neuroendocrine – Related lung carcinomas
Authors: Leila Antonangelo, Ernesto Terreri, Lisete Teixeira, Debora Rosolen, Leslie Kulikowski, Vanessa Alvarenga, Roberta Sales, Francisco Vargas
Journal: European Respiratory Journal (2011)

Pro-gastrin-releasing peptide (ProGRP) is a neuropeptide associated with tumors of neuroendocrine lineage which has been used to differentiate small cells from non small cells lung carcinomas.

Objective: To evaluate the ProGRP in pleural fluid (PF) of patients with malignant pleural effusion (MPE).

Methods: ProGRP was quantified by chemiluminescence immunoassay with microparticles (CMIA, Architect, Abbott) in PF (collected in EDTA tubes) from 49 patients with MPE (45) and benign effusions (4). Malignant samples corresponded to pleural metastasis of: neuroendocrine lung carcinoma (3), breast (7), lung adenocarcinoma (20), lung poorly differentiated carcinoma (4), bronchioloalveolar adenocarcinoma (1), and others (10). Benign cases corresponded to parapneumonic (3) and lupus-related effusions (1).

Results: Considering 4 levels, we obtained: 0 to 46 pg/mL: 37 (75%); 47 to 100 pg/mL: 4 (8.2%); 101 to 200 pg/mL: 2 (4.1%) and > 200 pg/mL: 6 (12.2%) of cases. The benign cases and most of the metastatic effusions were in level 1. All cases in level 2 corresponded to lung adenocarcinoma. In level 3, one case corresponded to a poorly differentiated lung carcinoma and one to bronchioloalveolar adenocarcinoma. In level 4, two cases were poorly differentiated lung adenocarcinoma, and one was a sarcoma of the omentum with pleural metastasis; the remaining 3 cases corresponded to tumors of neuroendocrine lineage. In these cases, the concentration of ProGRP was higher than 30,000 pg/mL.

Conclusion: PF ProGRP can be useful in identifying pleural metastasis of undifferentiated tumors. Although a greater number of cases should be studied, it seems unequivocal its importance in recognizing neuroendocrine lineage tumors.
Orthovoltage radiotherapy for nonmelanoma skin cancer (NMSC): Comparison between 2 different schedules
Authors: Riccardo Pampena, Tamara Palmieri, Athanassios Kyrgidis, Dafne Ramundo, Cinzia Iotti, Aimilios Lallas, Elvira Moscarella, Stefania Borsari, Giuseppe Argenziano, Caterina Longo
Journal: Journal of the American Academy of Dermatology (2015)
Multiple Trigger Points for Quantifying Heat-Health Impacts: New Evidence from a Hot Climate
Authors: Diana B. Petitti, David M. Hondula, Shuo Yang, Sharon L. Harlan, Gerardo Chowell
Journal: Environmental Health Perspectives (2015)

BackgroundExtreme heat is a public health challenge. The scarcity of directly comparable studies on the association of heat with morbidity and mortality and the inconsistent identification of threshold temperatures for severe impacts hampers the development of comprehensive strategies aimed at reducing adverse heat-health events.ObjectivesThis quantitative study was designed to link temperature with mortality and morbidity events in Maricopa County, Arizona, USA, with a focus on the summer season.MethodsUsing Poisson regression models that controlled for temporal confounders, we assessed daily temperature–health associations for a suite of mortality and morbidity events, diagnoses, and temperature metrics. Minimum risk temperatures, increasing risk temperatures, and excess risk temperatures were statistically identified to represent different "trigger points" at which heat-health intervention measures might be activated.ResultsWe found significant and consistent associations of high environmental temperature with all-cause mortality, cardiovascular mortality, heat-related mortality, and mortality resulting from conditions that are consequences of heat and dehydration. Hospitalizations and emergency department visits due to heat-related conditions and conditions associated with consequences of heat and dehydration were also strongly associated with high temperatures, and there were several times more of those events than there were deaths. For each temperature metric, we observed large contrasts in trigger points (up to 22°C) across multiple health events and diagnoses.ConclusionConsideration of multiple health events and diagnoses together with a comprehensive approach to identifying threshold temperatures revealed large differences in trigger points for possible interventions related to heat. Providing an array of heat trigger points applicable for different end-users may improve the public health response to a problem that is projected to worsen in the coming decades.CitationPetitti DB, Hondula DM, Yang S, Harlan SL, Chowell G. 2016. Multiple trigger points for quantifying heat-health impacts: new evidence from a hot climate. Environ Health Perspect 124:176–183; http://dx.doi.org/10.1289/ehp.1409119
Critical Amplification by Gas6 of the Epo-Dependent Erythropoietic Response to Anemia: Novel Opportunities for Anemia Treatment.
Authors: Anne Angelillo-Scherrer, Laurent Burnier, Richard Fish, Stéphane Plaisance, Eduardo Martinez-Soria, Patrick Maxwell, Désiré Collen, Shozo Izui, Edward M. Conway, Peter Carmeliet
Journal: Blood (2004)
Abstract #5539: Increased HuR expression in pancreatic cancer cells dramatically optimizes gemcitabine efficacy
Authors: Christina Costantino, Agnieszka Witkiewicz, Yuki Kuwano, Joseph Cozzitorto, Charles Yeo, Myriam Gorospe, Jonathan Brody
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

The Hu/ELAV mRNA binding protein HuR has functionally been linked to the tumorigenesis process. HuR binds U- or AU-rich sequences embedded in the 3' untranslated regions (UTRs) of target mRNAs, translocating and stabilizing transcripts in the cytoplasm. Here we surveyed for the first time the expression and cellular distribution of HuR in clinical specimens of pancreatic ductal adenocarcinomas (PDA). We observed predominantly cytoplasmic HuR in the most aggressive forms of PDAs, poorly differentiated PDAs (7 of 9 cases) and moderately differentiated PDAs (7 of 20), as compared to well-differentiated PDAs (0 of 6) and normal pancreatic tissue where HuR expression was almost exclusively nuclear. Thus, the cytoplasmic localization of HuR, which is linked to its mRNA stabilizing influence, correlated with clinicopathologic parameters including differentiation status and tumor size. Similarly, by immunofluorescence, we detected an increase in cytoplasmic HuR levels in cultured pancreatic cancer cells treated with apoptotic stimuli such as staurosporine, tamoxifen, and gemcitabine. Stable overexpression of HuR in 3 different pancreatic cancer cell lines renders them strikingly and selectively hypersensitive to gemcitabine (up to 50-fold in some instances), the reference drug used to treat pancreatic cancer patients. This hypersensitivity is accompanied with an enrichment in S-phase cells and a significant increase in apoptosis within 48 hours post treatment. We also discovered that HuR binds to a transcript that encodes the enzyme deoxycytidine kinase (dCK), which functions as the rate-limiting and activating enzyme of gemcitabine cellular metabolism. HuR is computationally predicted to bind to several segments of the dCK 3\#8217;-UTR, likely contributing to the stabilization of the dCK mRNA. Accordingly, HuR overexpression dramatically increased dCK protein expression in pancreatic cancer cells. Further confirmation that HuR sensitization to gemcitabine was elicited via dCK was obtained from experiments showing that the chemotherapeutic cytarabine (Ara-C), which also utilizes dCK as an activating enzyme, was preferentially cytotoxic in cells expressing high HuR levels. Taken together, these data support the hypothesis that HuR is a key mediator of gemcitabine efficacy in cancer cells by stabilizing the dCK mRNA. In summary, HuR-mediated stabilization of specific target transcripts such as dCK may dictate the therapeutic efficacy of gemcitabine, and thus may be a favorable target to enhance the clinical utility of this commonly used chemotherapeutic agent against multiple tumor types.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5539.
18F-FDG PET/CT Metabolic Activity in a Patient With Solitary Extramedullary Plasmacytoma of the Lung
Authors: Linqi Zhang, Xu Zhang, Rusen Zhang, Wei Fan
Journal: Clinical Nuclear Medicine (2015)

Extramedullary plasmacytoma is a rare variant of plasmacytoma that is frequently observed in the head and neck. Primary plasmacytoma of the lung is quite rare. A 92-year-old woman presented with chest distress for 6 months with a mass detected in the right posterior thoracic cavity. Enhanced T1-weighted image showed marked enhancement of the mass. 18F-FDG PET/CT showed strong FDG uptake of the lesion with SUVmax of 21.9. Thoracentesis of the tumor was subsequently performed, and pathologic analysis confirmed the diagnosis of primary pulmonary plasmacytoma.
Detection of pepsin in sputum: a rapid and objective measure of airways reflux
Authors: Vicki Strugala, Andrew D. Woodcock, Peter W. Dettmar, Shoaib Faruqi, Alyn H. Morice
Journal: European Respiratory Journal (2015)

The diagnostic test, Peptest (RD Biomed Ltd, Cottingham, UK), detects pepsin in expectorated saliva and is established as a simple, noninvasive measure of reflux of gastric contents. It has been used to detect pepsin A in patients with both gastro-oesophageal reflux disease (GORD) and extra-oesophageal reflux into the laryngopharynx and airways [1–5]. Detection of salivary pepsin (Peptest) may be a useful adjunct in the diagnosis of airway reflux <http://ow.ly/T7B0l> We gratefully acknowledge the RD Biomed Ltd technical assistance of Jeanine Fisher (Cottingham, UK), the NHS patient management of Karen Welburn and the NHS secretarial assistance of Hanka Remblance (both Centre for Cardiovascular and Metabloic Research, Hull York Medical School, University of Hull, Castle Hill Hospital, Cottingham).
International Committee on Mental Health in Cystic Fibrosis: Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus statements for screening and treating depression and anxiety
Authors: Alexandra L Quittner, Janice Abbott, Anna M Georgiopoulos, Lutz Goldbeck, Beth Smith, Sarah E Hempstead, Bruce Marshall, Kathryn A Sabadosa, Stuart Elborn
Journal: Thorax (2015)

Studies measuring psychological distress in individuals with cystic fibrosis (CF) have found high rates of both depression and anxiety. Psychological symptoms in both individuals with CF and parent caregivers have been associated with decreased lung function, lower body mass index, worse adherence, worse health-related quality of life, more frequent hospitalisations and increased healthcare costs. To identify and treat depression and anxiety in CF, the CF Foundation and the European CF Society invited a panel of experts, including physicians, psychologists, psychiatrists, nurses, social workers, a pharmacist, parents and an individual with CF, to develop consensus recommendations for clinical care. Over 18 months, this 22-member committee was divided into four workgroups: Screening; Psychological Interventions; Pharmacological Treatments and Implementation and Future Research, and used the Population, Intervention, Comparison, Outcome methodology to develop questions for literature search and review. Searches were conducted in PubMed, PsychINFO, ScienceDirect, Google Scholar, Psychiatry online and ABDATA by a methodologist at Dartmouth. The committee reviewed 344 articles, drafted statements and set an 80% acceptance for each recommendation statement as a consensus threshold prior to an anonymous voting process. Fifteen guideline recommendation statements for screening and treatment of depression and anxiety in individuals with CF and parent caregivers were finalised by vote. As these recommendations are implemented in CF centres internationally, the process of dissemination, implementation and resource provision should be closely monitored to assess barriers and concerns, validity and use.
Cross-sectional Associations between Exposure to Persistent Organic Pollutants and Leukocyte Telomere Length among U.S. Adults in NHANES, 2001–2002
Authors: Susanna D. Mitro, Linda S. Birnbaum, Belinda L. Needham, Ami R. Zota
Journal: Environmental Health Perspectives (2015)

Exposure to persistent organic pollutants (POPs) such as dioxins, furans, and polychlorinated biphenyls (PCBs) may influence leukocyte telomere length (LTL), a biomarker associated with chronic disease. In vitro research suggests dioxins may bind to the aryl hydrocarbon receptor (AhR) and induce telomerase activity, which elongates LTL. However, few epidemiologic studies have investigated associations between POPs and LTL.We examined the association between 18 PCBs, 7 dioxins, and 9 furans and LTL among 1,330 U.S. adults from NHANES 2001-2002.We created three summed POP metrics based on toxic equivalency factor (TEF), a potency measure including affinity for the AhR: a) non-dioxin-like PCBs (composed of 10 non-dioxin-like PCBs; no AhR affinity and no TEF); b) non-ortho PCBs (composed of 2 non-ortho-substituted PCBs with high TEFs); and c) toxic equivalency (TEQ) (composed of 7 dioxins, 9 furans, 2 non-ortho-substituted PCBs, and 6 mono-ortho-substituted PCBs; weighted by TEF). We tested the association between each metric and LTL using linear regression, adjusting for demographics, blood cell count and distribution, and another metric with a different TEF (i.e., non-ortho PCBs and TEQ adjusted for non-dioxin-like PCBs; non-dioxin-like PCBs adjusted for non-ortho PCBs).In adjusted models, each doubling of serum concentrations of non-ortho PCBs and TEQ was associated with 3.74% (95% CI: 2.10, 5.40) and 5.29% (95% CI: 1.66, 9.05) longer LTLs, respectively. Compared with the lowest quartile, the highest quartile of exposure was associated with 9.16% (95% CI: 2.96, 15.73) and 7.84% (95% CI: -0.53, 16.92) longer LTLs, respectively. Non-dioxin-like PCBs were not associated with LTL.POPs with high TEFs and AhR affinity were associated with longer LTL. Because many dioxin-associated cancers are also associated with longer LTL, these results may provide insight into the mechanisms underlying PCB- and dioxin-related carcinogenesis.Mitro SD, Birnbaum LS, Needham BL, Zota AR. 2016. Cross-sectional associations between exposure to persistent organic pollutants and leukocyte telomere length among U.S. adults in NHANES, 2001-2002. Environ Health Perspect 124:651-658; http://dx.doi.org/10.1289/ehp.1510187.
Prevalence of Ideal Cardiovascular Health Among Adults in the United States
Authors: Adnan Younus, Ehimen C. Aneni, Erica S. Spatz, Chukwuemeka U. Osondu, Sameer Shaharyar, Lara Roberson, Shozab S. Ali, Oluseye Ogunmoroti, Rameez Ahmad, Janisse Post, Theodore Feldman, Wasim Maziak, Arthur S. Agatston, Emir Veledar, Khurram Nasir
Journal: Journal of the American College of Cardiology (2015)