tbuckley/cabot-search huggingface dataset:
Abstract A35: Integration of melanoma genotyping in clinical care
Authors: Amel Salhi, Ines Pires Da Silva, Kevin P. Lui, Naima Ismaili, Chaowei Wu, Eleazar C. Vega-Saenz de Miera, Richard L. Shapiro, Russell S. Berman, Anna C. Pavlick, Judy Zhong, Adriana Heguy, Iman Osman
Journal: Cancer Research (2015)

Abstract Background: Molecularly targeted therapy is improving response rates and overall survival in subsets of melanoma patients. However, targeted therapy for triple negative patients (BRAF, NRAS and c-KIT wild type) is not yet defined. In addition, new evidence suggests that germline variants may have an impact in melanoma progression and response to therapy. In this study, we attempt to define the utility of a recently developed clinical assay that encompasses targeted sequencing of 50 genes with known impact on cancer progression. Methods: We used the AmpliSeq Cancer Panel HotSpot.V2 from Ion Torrent. The panel targets sequencing of Hotspot regions including 2,800 COSMIC mutations within 50 oncogenes and tumor suppressor genes. Tumor and blood germline DNAs were studied. All identified mutations were independently validated by Sanger sequencing. We then linked the molecular profile to extensive clinicopathological information including treatment and prospective clinical follow-up. Results: We examined 35 tumor samples from 35 melanoma patients (2 patients had 2 specimens). 14/35 (40%) had BRAF mutations, 15/35 (34%) had NRAS, KRAS or HRAS mutations and 1 had c-KIT mutant tumor. Eight patients were triple negative and presented with mutations in TP53, ERBB4, PIK3CA, NOTCH, EZH2 and VHL. We detected germline variants in TP53 (49%), KDR (VEGFR2 - 34%), APC (31%), KIT (23%) and PIK3CA (14%) genes. Notably, KDR Q472H has been shown to affect VEGFR2 function. Patients with KDR Q742H had higher microvessels density and higher VEGF production. In addition, melanoma cell lines with KDR Q472H variant proliferate and invade more when compared with WT cell lines. More important, only cell lines with that variant respond to anti-VEGFR2 treatment. Finally, the presence of the KDR Q472H variant is associated with a higher prevalence of brain metastases and with a shorter survival (15.1 months compared to 54.6 months). Conclusions: Sequencing using a validated clinical assay was informative of several targetable mutations in triple negative melanoma. Inhibitors targeting some of these mutations are already FDA approved for non-melanoma and others are currently tested in clinical trials. Our data also revealed a role of germline variant KDR Q472H in melanoma progression, that was not reported before, suggesting that further functional studies are warranted. Citation Format: Amel Salhi, Ines Pires Da Silva, Kevin P. Lui, Naima Ismaili, Chaowei Wu, Eleazar C. Vega-Saenz de Miera, Richard L. Shapiro, Russell S. Berman, Anna C. Pavlick, Judy Zhong, Adriana Heguy, Iman Osman. Integration of melanoma genotyping in clinical care. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr A35.
Reflectance confocal microscopy as a new tool in the<i>in vivo</i>evaluation of desquamative gingivitis: patterns in mucous membrane pemphigoid, pemphigus vulgaris and oral lichen planus
Authors: S.S. Alessi, M.M.S. Nico, J.D. Fernandes, S.V. Lourenço
Journal: British Journal of Dermatology (2012)

Desquamative gingivitis refers to a clinical manifestation associated with several mucocutaneous disorders. The most common are mucous membrane pemphigoid, pemphigus vulgaris and lichen planus. Their specific diagnosis is better established by histopathological and immunofluorescence evaluation.To examine cases of desquamative gingivitis using reflectance confocal microscopy (RCM) and compare the findings with those of normal gingiva. To compare RCM findings in desquamative gingivitis with conventional histopathology of the biopsied lesions, in order to establish criteria for this noninvasive diagnostic technique.A total of 25 cases of suspected mucous membrane pemphigoid, pemphigus vulgaris and lichen planus were included. RCM was performed on the gingiva of a healthy person and on gingival lesions. All lesions were biopsied in order to perform a RCM-histopathological correlation.Reflectance confocal microscopy examination of the gingival lesions suspected to be mucous membrane pemphigoid revealed a separation at the level of the dermal-epidermal junction, filled with small, bright structures interpreted as blood cells. Histopathological and immunofluorescence findings confirmed the diagnosis. For pemphigus vulgaris, RCM features were intraepithelial clefts with round, detached cells interpreted as acantholytic keratinocytes, similar to the histopathological features. Hyperkeratosis and spongiosis associated with infiltration of inflammatory cells, seen as small, bright cells intermingling with the honeycomb keratinocyte epithelial structure, were seen in lichen planus. Mildly bright, round structures interpreted as necrotic keratinocytes and mildly bright, stellate structures, interpreted as melanophages, were also seen in the dermis. These features were present on histopathology, confirming the diagnosis of lichen planus.We propose that RCM is a useful tool to help distinguish between the three most common causes of desquamative gingivitis.
Abstract 28: The influence of PDGF and VEGF on tumor proliferation in colon cancer
Authors: Romana Mönch, Tanja Grimmig, Vinicius Kannen, Christoph T. Germer, Ana Maria Waaga-Gasser, Martin Gasser
Journal: Cancer Research (2014)

Abstract Background: The platelet derived growth factor (PDGF) and Vascular Endothelial Growth Factor (VEGF) are known to play a crucial role in different tumor entities. Involved in cell migration and proliferation of stromal cells and tumor cells they represent key targets in cancer therapy. The aim of the study was to analyse the specific role of PDGF and VEGF stimulation on tumor cell proliferation and metabolism in colorectal cancer (CRC). Methods: The human colon cancer cell line HT-29 and Caco-2 were cultured and stimulated with PDGF and VEGF in a time-dependent manner. Whole cell extracts and RNA extracts were analyzed by Western Blot and RT-q-PCR for PDGF- and VEGF receptors and for components of cellular metabolism. To discover effects of PDGF and VEGF on proliferation MTS proliferation assays were performed. Results: Western Blot analysis and RT-qPCR showed no relevant PDGF-receptor α and β expression in HT-29 cells but varying expression in Caco-2 cells. Stimulation with PDGF or VEGF resulted in increased proliferation compared to untreated controls while simultaneous stimulation with both growth factors did not result in intensified proliferation. Additionally, under stimulation altered expression of various metabolic components was detected. Conclusion: Our results demonstrate a promoting effect on tumor cell proliferation of both growth factors VEGF and PDGF. Simultaneous stimulation did not show synergistic effects. PDGF in HT-29 cells resulted in proliferation in the absence of PDGF receptors with changes in tumor cell metabolism after stimulation. Moreover in HT-29 cells glucose metabolism changed during stimulation. In conclusion, our data give evidence for direct receptor/ligand signalling of PDGF not only on stromal cells but also on colon cancer cells even in the absence of the PDGF receptor. Citation Format: Romana Mönch, Tanja Grimmig, Vinicius Kannen, Christoph T. Germer, Ana Maria Waaga-Gasser, Martin Gasser. The influence of PDGF and VEGF on tumor proliferation in colon cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 28. doi:10.1158/1538-7445.AM2014-28
Abstract 18178: Cardiac Index Declines During Long-term LVAD Support
Authors: Rohan J Kalathiya, Jordan M Chaisson, Gerin R Stevens, Christopher M Sciortino, Ashish S Shah, Glenn J Whitman, Stuart D Russell, Ryan J Tedford
Journal: Circulation (2014)

Background: It is increasingly common for patients to be supported by left ventricular assist devices (LVADs) for an extended period of time. At our institution, we have anecdotally noticed a decline in functional status during the course of prolonged LVAD therapy. Our objective was to analyze hemodynamic and echocardiographic data of patients with at least 2 years of ongoing LVAD support. Methods: We retrospectively reviewed all patients who underwent HeartMate II implantation between 2005 and 2012. Of the 131 patients reviewed, we identified 20 patients who were supported by LVADs for at least 2 years and had right heart catheterization (RHC) in both the initial postoperative period and at 2-3 year follow-up. No patients were on inotropic therapy at the time of RHC. Results: The mean times of initial and follow-up post-LVAD RHCs were 59 ± 41 days and 889 ± 160 days, respectively. Cardiac index (CI) declined by an average of 0.4 L/min/m2 over the study period (p=0.04). Other than a reduction in transpulmonary gradient, no other hemodynamic differences were observed. There was a statistically significant worsening of aortic insufficiency (AI) at follow-up. However, when dichotomized by the median change in CI (-0.4 L/min/m2), there is no difference in AI between groups (p =0.60). In fact, 2 of the 3 patients with moderate AI had an increase in CI. There were no differences in pump speed, mean pressure, aortic valve opening, or lactate dehydrogenase between initial and follow up periods (Table 1). Conclusion: In the first study to report long term hemodynamic follow up in patients supported by HeartMate II LVADs, cardiac index significantly declined over time. The decline was not the result of worsening right ventricular function or valvular regurgitation nor a difference in pump speed or blood pressure. This is a potentially worrisome finding, especially for destination therapy patients. Further studies are needed to understand what factors may contribute to this decline.
Abstract 3844: Venous thromboembolism in patients with pancreatic cancer
Authors: Seug Yun Yoon, Namsu Lee, Sook-Ja Kim, Hee-Jeong Cheong, Kyoung Ha Kim, Jong-Ho Won, Hee Sook Park
Journal: Cancer Research (2014)

Abstract Background: Venous thromboembolism (VTE) is a critical complication of malignant disease. Pancreatic cancer is one of the cancers most commonly associated VTE. In general, the VTE incidence rate of Asians is lower than that of Caucasians. In 2007, a Korean study reported that only four cases of VTE (5.3%) occurred in Seventy five patients with advanced pancreatic adenocarcinoma. We evaluated VTE incidence in pancreatic cancer and characteristics of pancreatic cancer patients with VTE. Method: We retrospectively reviewed the medical records of patients with histopathologically proven pancreatic cancer from January 2006 to December 2012 at Soonchunhyang university hospital. We detected VTE through CT (chest CT, pulmonary embolism CT) and low extremity ultrasoundgraphy. Results Five hundred and fourteen patients with pancreatic adenocarcinoma were enrolled. (M: F, 300:214, localized: locally advanced: metastatic=31:230:253, mean age: 66.7 years). Ninety six of 514 patients (18.6%, symptomatic: aymptomatic=38:58, PE: DVT: PE+DVT: visceral thrombosis=20:19:19:38) were diagnosed as VTE. At the time of DVT diagnosis, cancer status of 50 patients cancer was progression, and that of 15 was stable. Thirty one patients were diagnosed with the pancreatic cancer and VTE, at the same time. They all had metastatic lesions. Fifty VTE patients were treated with antithrombotic therapy. Ninety three of 96 patients died, and three of them have probability that cause of death was VTE. The others died of pancreatic cancer progression. From pancreatic cancer diagnosis to VTE diagnosis, the period is 1.7month. (95%CI 1.1-2.3 month). Median overall survival (OS) was not significantly different between pancreatic cancer with VTE or without VTE. OS was significantly longer VTE patients after pancreatic cancer diagnosis than VTE patients with pancreatic cancer at the same time (10.73m vs. 1.7, p=0.00). Conclusion The incidence of VTE (18.6%) in Soonchunhyang university hospital with pancreatic cancer was not lower than that in western groups. Citation Format: Seug Yun Yoon, Namsu Lee, Sook-Ja Kim, Hee-Jeong Cheong, Kyoung Ha Kim, Jong-Ho Won, Hee Sook Park. Venous thromboembolism in patients with pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3844. doi:10.1158/1538-7445.AM2014-3844
Mucosal tissue polyclonal IgE is functional in response to allergen and SEB
Authors: N. Zhang, G. Holtappels, P. Gevaert, J. Patou, B. Dhaliwal, H. Gould, C. Bachert
Journal: Allergy (2010)

Staphylococcus aureus may modify airway disease by inducing local formation of polyclonal IgE antibodies (abs), the role of which is unknown.Nasal mucosal tissue and serum was obtained from 12 allergic rhinitis (AR) and 14 nasal polyp (NP) subjects. Skin prick tests were performed, and total and specific IgE abs to inhalant allergens and enterotoxin B were determined in serum and tissue. Tissue fragments were stimulated with anti-IgE, enterotoxin B, or grass and house dust mite allergens in different concentrations for 30 min. RBL SX38 cells were sensitized with NP homogenates containing IgE and stimulated with grass pollen extracts.In AR patients, degranulation of tissue mast cells upon allergen exposure and presence of specific IgE to inhalant allergens corresponded in almost all cases. Total IgE concentrations in serum and mucosal tissue homogenates highly correlated. In contrast, in NP patients, reactivity of tissue mast cells upon allergen exposure and presence of specific IgE to inhalant allergens or Staphylococcus aureus enterotoxin B corresponded for tissue, but not for serum. Total IgE was significantly higher in tissue compared to serum and failed to show correlation. Tissue IgE to grass pollen was functional to degranulate RBL cells.We here demonstrate that mucosal IgE abs in NP tissue are functional and able to activate mast cells; specific IgE abs in NP tissue can be found independently of their presence in serum. We postulate that superantigen-induced polyclonal IgE in airway disease contributes to chronic inflammation by continuously activating mast cells.
Abstract 17107: Induced Vascular Progenitor Cells Derived from Endothelial Cells Stimulate Coronary Collateral Growth
Authors: Liya Yin, Vahagn Ohanyan, Yuh Fen Pung, Angelo L Delucia, Erin Bailey, Molly Enrick, Kelly Stevanov, Christopher L Kolz, Giacinta Guarini, William Chilian
Journal: Circulation (2011)

Liya Yin, 2011 Finalist and Presenting Author
Inheritance of porphyria cutanea tarda*.
Authors: GIANCARLO TOPI, LUCIANA D'ALESSANDRO GANDOLFO
Journal: British Journal of Dermatology (1977)

The existence of hereditary porphyria cutanea tarda must be supported by chemical and clinical investigations capable of discriminating this porphyria from porphyria variegata, because the clinical symptoms may overlap. On the basis of such investigations (normal urinary excretion of deltaALA and of porphobilinogen; urinary excretion of large amounts of 8- and 7-carboxyl porphyrins; faecal coproporphyrin and X porphyrin fractions may be increased) we have been able to classify 14 cases, out of 200 cases of PCT that we have observed in the last 7 years, as hereditary PCT. The 14 patients belong to 5 different families: two members in each of the first three families, 3 members in the fourth, and 5 members in the fifth. In this last family heredity is bilateral.
Some Mother's Daughter: the Hidden Movement of Prostitute Women Against Violence
Authors: Jenny Kitzinger
Journal: BMJ (2001)

International Prostitutes Collective (ed Nina Lopez-Jones) 

Crossroads Books, £8, pp 180

ISBN 0 951 7775 8 X

Rating: ![Graphic][1] ![Graphic][2] ![Graphic][3] 

Vice girl, social pariah, the victim who “asks for it”—these are some of the stereotypes about prostitutes. Rape, beatings, and abuse are often seen as inevitable, almost justified, hazards of “the lifestyle.” The murder of at least six prostitutes in Glasgow over the past nine years has been met with a resounding silence. Their deaths are not deemed worthy of major news coverage. Only when “ordinary” women are attacked does such violence become noteworthy.

This is not new. When the Yorkshire Ripper, an English serial killer, was terrorising women in northern England the media distinguished between prostitutes and “innocent” victims. The attorney general …

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HISTOCHEMICAL STUDIES ON CUTANEOUS LEIOMYOMATOSIS..
Authors: K. K. MUSTAKALLIO, E. LEVONEN, M. NIEMI
Journal: British Journal of Dermatology (1963)

Journal Article HISTOCHEMICAL STUDIES ON CUTANEOUS LEIOMYOMATOSIS.: I: INNERVATION OF NORMAL ARRECTOR PILI MUSCLES AND PILOMYOMAS. Get access K. K. MUSTAKALLIO, K. K. MUSTAKALLIO Department of Dermatology, University of Helsinki, Snellmanink 14, Helsinki, Finland Search for other works by this author on: Oxford Academic Google Scholar E. LEVONEN, E. LEVONEN Department of Forensic, Medicine, University of Helsinki Search for other works by this author on: Oxford Academic Google Scholar M. NIEMI M. NIEMI Department of pathology, section II, University of Helsinki Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 75, Issue 2, 1 February 1963, Pages 60–70, https://doi.org/10.1111/j.1365-2133.1963.tb13939.x Published: 01 February 1963
Abstract 3907: Human pancreatic cancer stem cells utilized to generate an in-vivo mouse/rat model system for screening potential drug candidates for treatment of pancreatic cancer patients
Authors: Cristian Sharma, Patrick Cleary, Esteban Gomez, Shruthi Satish, Michael Sharma, Michael Perez, Natalee Amecuza, Jitesh Jani, Rubio Punzalan, Jay P. Sharma
Journal: Cancer Research (2014)

Abstract Cancer stem cells (CSCs) are critical for engraftment and long-term growth of many tumors, including pancreatic cancer. The Cancer Stem cells are less sensitive to conventional chemotherapies and radiation therapies, and treatments that can target CSCs are critically needed. Human Pancreatic Cancer is a heterogeneous tumor composed of tumor cells and small fraction of cancer stem cells, with high tumorigenic potential. Pancreatic cancer stem cells are phenotypically similar to the normal stem cells, they express CD133 gene and other genes characteristic of neural stem cells (Nestin) and posses self-renewal potential. The CD133+ Pancreatic CSCs have been isolated with Celprogen Media and ECM and characterized as chemo-/radio-resistant tumor-initiating cells which are responsible as one of the major factors involved in post-treatment recurrence. In order to explore the molecular properties of tumorigenic CD133+ Pancreatic CSCs that resist treatment, we isolated CD133+ Pancreatic CSCs from tumors that are recurrent and have previously received chemo-/radio-therapy. We found that the purified CD133+ Pancreatic CSCs sorted from the CD133+ Pancreatic CSC spheres express SOX2 ,CD44, Nestin and are capable of clonal self-renewal. We generated in-vivo model systems in mice and rats with these cells to screen potential drug agents for the treatment of Pancreatic Cancer patients. We were capable of generating Pancreatic tumors in mice and rats within 20 days by subcutaneously injecting 1000 Pancreatic CSCs at the hind limbs of the rodents. Within day 5 the Pancreatic CSCs were already present in the rodent's pancreas. At days 10, 15 &amp; 20 the Pancreatic CSCs labeled with GFP were located in the rodent's pancreas. We tested various compound candidates in this model system and we were able to show decrease in Pancreatic tumor when the treatment was started at day 10. We were able to demonstrate gene signatures associated with Pancreatic CSCs in this model system. We do see a down regulation of certain cancer promoter genes in the treatment group when compared to non-treatment groups. Citation Format: Cristian Sharma, Patrick Cleary, Esteban Gomez, Shruthi Satish, Michael Sharma, Michael Perez, Natalee Amecuza, Jitesh Jani, Rubio Punzalan, Jay P. Sharma. Human pancreatic cancer stem cells utilized to generate an in-vivo mouse/rat model system for screening potential drug candidates for treatment of pancreatic cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3907. doi:10.1158/1538-7445.AM2014-3907
CRMP-2 induces axons in cultured hippocampal neurons
Authors: Naoyuki Inagaki, Kazuyasu Chihara, Nariko Arimura, Céline Ménager, Yoji Kawano, Naruhiro Matsuo, Takashi Nishimura, Mutsuki Amano, Kozo Kaibuchi
Journal: Nature Neuroscience (2001)
Impact of worsening renal function related to medication in heart failure
Authors: Hans‐Peter Brunner‐La Rocca, Christian Knackstedt, Luc Eurlings, Vinzent Rolny, Friedemann Krause, Matthias E. Pfisterer, Daniel Tobler, Peter Rickenbacher, Micha T. Maeder
Journal: European Journal of Heart Failure (2014)
Abstract 13249: European and American Blood Cholesterol Guidelines Result in Similar Rates of Statin Recommendations when Applied to a Country with High Cardiovascular Disease Risk
Authors: Ann M Navar-Boggan, Tomasz Zdrojewski,, Adam Wyszomirski, Mateusz Lachacz, Grzegorz Opolski, Piotr Bandosz, Marcin Rutkowski, Zbigniew Gaciong, Bogdan Wyrzykowski, Michael J Pencina
Journal: Circulation (2014)

Introduction: The American Heart Association and American College of Cardiology (AHA/ACC) recently released updated guidelines for management of blood cholesterol, which differ from current European Society of Cardiology and European Atherosclerosis Society (ESC/EAS) guidelines. How these differences affect the overall number of individuals recommended for statin therapy in a country with high cardiovascular disease (CVD) risk remains unclear. Hypothesis: Due to the lower threshold for statin recommendations for primary prevention based on 10-year CVD risk under the AHA/ACC guidelines, more adults overall would be recommended for statin therapy under American compared to European guidelines. Methods: Using 2011 data from a nationwide cross-sectional survey in Poland (NATPOL), we estimated the number and characteristics of adults aged 40-65 recommended for lipid lowering therapy under the ESC/EAS and AHA/ACC guidelines. The survey sample of 1060 adults represented 13.5 million adults in Poland aged 40-65. Results: Under ESC/EAS guidelines, 47.6% of adults (44.6-50.7%) aged 40-65 were recommended for immediate statin therapy, compared to 49.9% (46.9-52.9%) under AHA/ACC guidelines. Among adults free of cardiovascular disease (CVD), 10.5% had discordant recommendations between guidelines. Individuals recommended for statin therapy under ACC/AHA but not ESC/EAS guidelines had less chronic kidney disease, higher HDL cholesterol, higher 10-year (AHA/ACC calculator) risk, and higher 30-year (Framingham) risk than adults recommended under ESC/EAS but not under ACC/AHA guidelines. Ten-year CVD mortality risk estimated by the SCORE algorithm was similar between the two groups. Conclusions: In spite of differences between current European and American cholesterol guidelines, when applied to a nationwide representative sample from a country with high CVD risk, the number of adults aged 40-65 recommended for cholesterol lowering therapy under each guideline was nearly identical. Although more adults met criteria for primary prevention based on 10-year CVD risk under new American guidelines, the impact of this is offset by additional criteria for statin therapy in current European guidelines.