tbuckley/cabot-search huggingface dataset:
Abstract 4814: Inferring liver cancer evolution from spatial and temporal genomic heterogeneity
Authors: Qiang Gao, Zhi-Chao Wang, Rui-Bin Xi, Jia Fan
Journal: Cancer Research (2015)

Abstract Background &amp; Aims: The molecular pathogenesis of primary liver cancer is extremely complex and heterogeneous, which was further complicated by multiple carcinogenesis. We aimed to elucidate the pathogenesis of multifocal primary liver cancer by genomic profiling. Methods: A patient with synchronous hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) who underwent resection and experienced post-operative intrahepatic metastases (IMs) was enrolled. Multiregion whole-exome sequencing was applied on the three primary tumors and two IMs to infer tumor clonality and evolution. The mutational and expression profiles, clinical relevance (n = 236) and functional implications of the identified potential driver gene FAT4 in HCC were investigated. Results: In total, we identified 12, 184, 126, and 54 of protein coding mutation in the cirrhotic liver, two HCCs (designated as HCC-A and HCC-B) and one ICC respectively. The mutational data of the two HCCs and one ICC showed almost no overlaps, suggesting that they developed through an accumulation of complete different sets of genetic alterations. For each tumor, multiregion sequencing data showed varied intratumoral heterogeneity (18.1% in HCC-A, 15.7% in HCC-B, 45.6% in ICC). The mutational profile of two IMs showed obvious similarity with HCC-A (87.6% and 87.7% shared with HCC-A respectively), rather than HCC-B and ICC tumors, indicating that they originated from HCC-A. Notably, FAT4 was the only gene that mutated in both HCCs and the two IMs, but in different locations (HCC-A and two IMs have the same G to A mutation at the coding position 2530, while HCC-B genomes have the A to C mutation at the coding position 14804). Prevalence screen revealed that FAT4 was mutated in over 15% of HCC patients and also several HCC cell lines. Significant down-regulation of FAT4 mRNA and protein expression was found in HCC, and loss of FAT4 independently correlated with early recurrence in HCC patients. In HCC cell lines, knockdown of FAT4 promoted and re-expression of FAT4 reduced cell growth and invasion. Conclusions: Spatial and temporal dissection of genomic alterations during the progression of liver cancer may help elucidate the basis for its dismal prognosis. FAT4 acts as a putative tumor suppressor that is frequently inactivated in human HCC. Citation Format: Qiang Gao, Zhi-Chao Wang, Rui-Bin Xi, Jia Fan. Inferring liver cancer evolution from spatial and temporal genomic heterogeneity. [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 4814. doi:10.1158/1538-7445.AM2015-4814
CD4(+)/CD56(+) Hematodermic (plasmacytoid dendritic cell) Tumor: a Highly Proliferating Neoplasm with Aberrant Expression of Immunohistochemical Markers and Poor Outcome.
Authors: Marina Siakantaris, George Rassidakis, Flora Kontopidou, Aglaia Dimitrakopoulou, Theodoros Vassilakopoulos, Maria K. Angelopoulou, Styliani Kokkoris, Nikolaos Evangelatos, Konstantinos Anargyrou, Othon Michail, Penelope Korkolopoulou, G.A. Pangalis
Journal: Blood (2009)
BIRM, an Andean plant extract, down regulates androgen receptor and shows anti-tumor activity in prostate cancer
Authors: Shinako Araki, Dominic Lyn, Balakrishna L. Lokeshwar
Journal: Cancer Research (2006)

3816  Background: BIRM is a root extract of an Andean plant, Solanum dulcamara. Previously we reported the potent antiproliferative and anti-tumor activities of BIRM against prostate tumor models. The glycosaminoglycan-rich oligosaccharides make up the most active components of BIRM. Our preliminary data suggested that BIRM caused ablation of androgen receptor (AR). Thus, activity of BIRM against prostate cancer (CaP) cells was investigated to uncover the molecular basis of its antitumor activity. Methods: Anti-proliferative activity of BIRM on AR-positive and negative cell lines (LAPC-4, LNCaP, C4-2 and PC-3ML) was investigated by [3H]-thymidine incorporation assay and flow cytometry. Effect of BIRM against AR expression and activity was investigated by immunoblotting, luciferase assay and PSA ELISA. Results: BIRM caused a dose and time-dependent down regulation of total AR and phospho-AR levels in androgen-sensitive LAPC-4 and LNCaP cells as well as androgen-resistant C4-2 cells, suggesting its potential activity in both androgen-responsive and unresponsive prostate cancer. AR down regulation was due to increased proteosome-mediated degradation and was independent of PI-3 kinase/Akt pathway. AR degradation by BIRM was followed by suppression of PSA promoter activity (70.2±3.4%) and decreased PSA production (86±2.7%). BIRM inhibited DNA synthesis in all examined CaP cells (IC 50: 1.0 μl/ml). BIRM induced cell-cycle arrest with increases in G2M (80-112% increase) with a concomitant decrease in S-Phase (23-38%). Further more, BIRM treatment showed cytotoxicity in CaP cells, confirmed by PARP cleavage and MTT assay (IC 50: 28μl/ml). Lower concentration of BIRM caused AR degradation and cell growth arrest, while much higher concentration of BIRM was required for its cytotoxicity. BIRM decreased tumor growth in both LNCaP and PC-3ML tumor xenografts by 71% and 72.2%. Starting the treatment immediately following tumor implantation was more effective in preventing tumor incidence (25% in treated versus 90% in saline control) than starting the treatment after tumors are palpable (100% incidence in either cases), thus implicating potential chemopreventive potential of BIRM against prostate cancer. Discussion: The plant extract BIRM has significant anti-proliferative activity, contributed by its ability to induce cell-cycle arrest and AR down regulation. Studies with AR-positive LAPC-4, LNCaP, C4-2 as well as AR-negative PC-3 tumor models suggest a potential chemopreventive function of BIRM on both AR sensitive and AR resistant prostate cancer. [Supported by NIH Grant 2R01 CA 61038 (to BLL)].
Abstract 3353: Surgical Treatment Versus Percutaneous Mitral Valvuloplasty in Mitral Stenosis With Severe Tricuspid Regurgitation
Authors: Duk-Hyun Kang, Jeong Hoon Kim, Mi-Jeong Kim, Jon Suh, In Hyun Jung, Hyun Song, Jong-Min Song, Myeong-Ki Hong, Jae-Kwan Song, Seong-Wook Park, Seung-Jung Park
Journal: Circulation (2006)

The persistence of significant tricuspid regurgitation (TR) after percutaneous mitral valvulo-plasty (PMV) is known as an independent predictor of adverse outcome in mitral stenosis (MS). However, it has been unclear whether mitral valve (MV) surgery combined with surgical correction of TR would be the better treatment option than PMV in patients with severe MS and severe functional TR.

Methods: We included a total of 92 consecutive patients (18 men, age; 49 ± 13 yrs) with severe MS and severe functional TR, who were potential candidates for PMV from 1997 to 2005, and the exclusion criteria were defined as the presence of left atrial thrombi, mitral regurgitation ≥ grade 3, echo score > 10, and ejection fraction (EF) <35%. PMV was performed in 48 patients (PMV group), and MV surgery combined with tricuspid valve repair (TVP) was performed in 44 patients (TVP group). Echocardiographic evaluation was performed before and after the procedure, and yearly during follow-up. The TR was defined as improved when TR was trace or mild on the 1 year follow-up echocardiography. The clinical events were defined as death, repeat surgery or PMV, and readmission due to heart failure.

Results: Baseline characteristics and clinical results were compared between two groups as shown in table[⇓][1]. There were 2 deaths, 5 MV surgery combined with TVP, 2 heart failure in PMV group, and 2 deaths in TVP group during follow-up, and the event rate of TVP group was significantly lower than PMV group despite its worse baseline characteristics (p < 0.05). The probability of event-free survival in TVP group was 98 ± 2% at 1 year and 95 ± 4% at 5 years and in PMV group 96 ± 3% at 1 year and 77 ± 8% at 5 years, respectively. On multiple Cox stepwise regression analysis, PMV group (p < 0.01) and lower EF (p < 0.05) were independently related with the clinical events.

Conclusions: Compared with PMV, MV surgery combined with TVP can improve TR more effectively and might be a preferable treatment option for severe MS associated with severe TR.



![Table][2]  [1]: #T1
 [2]: pending:yes
A phase II trial of tetrathiomolybdate (TM) in metastatic head &amp; neck cancer (MHNC) patients (pts) after treatment with platinum &amp; 5-fluorouracil (P&amp;5FU)
Authors: F. P. Worden, T. Teknos, J. Lee, S. G. Urba, C. R. Bradford, T. Carey, D. Chepeha, G. T. Wolf, M. Prince, S. Mukherji, S. D. Merajver
Journal: Journal of Clinical Oncology (2008)

6080 Background: The use of antiangiogenesis agents to promote disease stabilization following maximal response to chemotherapy in HNC is not well studied. TM is an oral copper (Cu) depleting agent that inhibits angiogenesis & decreases levels of VEGF when ceruloplasmin (Cp) is reduced to 5–15 mg/dl. We hypothesize that treatment of MHNC with P&5FU followed by continuous TM can delay disease progression by > 2 months (mo) by keeping maximally treated disease in a dormant state. Methods: Eligible pts were treated with 2–4 (21 day) cycles of cisplatin (100 mg/m2) or carboplatin (AUC 6) + 5FU (1000 mg/m2/day over 5 days). Pts who attained complete response (CR), partial response (PR), or stable disease (SD) were given TM (180 mg/day). Cp levels were drawn weekly & TM doses were adjusted to maintain a Cp level of 5–15 mg/dl. Neck/chest CTs were performed every 8 weeks. TM was continued until disease progression (PD). Results: From November 2002 to March 2004, 24 pts were enrolled; 23 were eligible (19 men; 4 women). 13 (58%) had metastatic disease & 10 (42%) had locoregional tumors. 21 had squamous cell carcinoma (SCC) & 2 had high grade mucoepidermoid carcinoma of the parotid gland (MEC). 3 pts received 1 cycle (cy) of P+5FU; 7 pts:2 cycles; 1 pt:3 cy; 12 pts:4 cy. Responses: 1 CR, 6 PR, 8 SD, 7 PD, 1 taken off study. TM was then given to 14 pts. 12 pts achieved a therapeutic Cp level (TCL); the median time to reach TCL was 18.5 days. All pts developed PD & all but 1 are dead. 10 pts (71%) developed PD < 2 months following the start of TM. 1 pt had SD for 39 mo & is alive. The median number of days on TM was 47 (range 17–273). The most common Grade 3 toxicity of TM was anemia: 3 pts. Conclusions: Cu deficiency was safely induced in these pts with advanced disease & TM was reasonably well tolerated. Insufficient numbers of pts were Cu depleted for 2 mo prior to PD to draw definitive conclusions, given that 71% had PD within 2 mo but Cu deficiency took an average of 18 days to be reached. A larger study with more innovative 4 endpoints is required to evaluate the potential usefulness of TM as maintenance therapy. Further study is needed to determine if TM may be useful in the adjuvant setting, following surgical resection of primary SCCHN, or in the treatment of other histological subtypes of HNC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Attenuoun LLC Attenuoun LLC
A 51-Year-Old Man With Exercise-Induced Syncope
Authors: Stuart B. Prenner, Daniel R. Schimmel, Alexandru B. Chicos
Journal: JAMA Cardiology (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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Cardiology journal
Identification of a Neoplastic Stem Cell in Human Mast Cell Leukemia
Authors: Gregor Eisenwort, Barbara Peter, Katharina Blatt, Sabine Cerny-Reiterer, Gregor Hoermann, Irina Sadovnik, Martin Bilban, Thomas Rülicke, Michael Willmann, Juliana Schwaab, Andreas Reiter, Wolfgang R Sperr, Christine Mannhalter, Peter Valent
Journal: Blood (2014)
DEPTOR Is a Regulator of Response to mTOR Kinase Inhibitors in Multiple Myeloma
Authors: Diana Cirstea, Teru Hideshima, Loredana Santo, Homare Eda, Miriam Canavese, Tyler A. Scullen, Anuj K. Mahindra, Gullu Gorgun, Yiguo Hu, Naoya Mimura, Claire Fabre, Jiro Minami, Hiroto Ohguchi, Kenneth C. Anderson, Sylvie M Guichard, Noopur S. Raje
Journal: Blood (2011)
A Multi-Center, Open-Label Study To Evaluate the Safety and Efficacy of Pentostatin, Cytoxan, and Rituxan (PCR) in the Treatment of Previously Untreated or Treated, Stage II, III or IV Chronic Lymphocytic Leukemia (CLL).
Authors: Raul R. Mena, Mehdi M. Moezi, Robert L. Robles, Maureen Cooper
Journal: Blood (2007)
18F-FDG PET/CT of Seminal Vesicle Metastasis From Ascending Colon Adenocarcinoma
Authors: Yu-Ling Hsu, I-Chen Lin, Chun-Liang Tung
Journal: Clinical Nuclear Medicine (2016)

The most common metastatic sites of colorectal cancer are the regional lymph nodes, liver, lungs, and peritoneum. Seminal vesicle metastasis from colon adenocarcinoma is not reported yet; the diagnosis could be challenging. We report a case of seminal vesicle metastasis from a primary ascending colon adenocarcinoma in a 49-year-old man, with elevating carcinoembryonic antigen as the only clinical sign. This also highlights the role of 18F-FDG PET/CT to detect metastatic adenocarcinoma from colon in the genitourinary system.
Abstract 2738: Mechanisms of cadmium carcinogenesis
Authors: Raghu G. Nath, BR Sonawane, SV Vulimiri, YS Lin
Journal: Cancer Research (2015)

Abstract Cadmium is a transition metal and an ubiquitous environmental and industrial pollutant. Laboratory animal studies and epidemiological studies have shown that exposure to cadmium is associated with various organ toxicities and carcinogenic effects. Several national and international regulatory agencies have classified cadmium compounds as carcinogenic to humans. In 2012, International Agency for Research on Cancer (IARC) reviewed the relevant information on cadmium exposure and concluded that there is sufficient evidence in humans for the carcinogenicity of cadmium and its compounds. However, the underlying molecular mechanism(s), especially for the carcinogenicity, are unknown. The mechanisms proposed for carcinogenicity include aberrant gene expression, induction of oxidative DNA damage, stimulation of cell proliferation, malignant cell transformation, inhibition of DNA damage repair, inhibition of apoptosis and epigenetic mechanisms including alteration of DNA methylation. Studies have shown that due to the slow elimination, cadmium is a cumulative toxicant and past exposures could result in toxic effect of the residual metal. To better understand the mechanisms of cadmium carcinogenicity we have reviewed in vitro experimental and in vivo animal studies focused on the proposed mechanisms of carcinogenicity as well as epidemiological evidence on carcinogenicity in lung and kidney following cadmium exposure. Disclaimer: The views expressed are those of the authors and do not necessarily represent the views and/or policies of the U.S. EPA Citation Format: Raghu G. Nath, BR Sonawane, SV Vulimiri, YS Lin. Mechanisms of cadmium carcinogenesis. [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 2738. doi:10.1158/1538-7445.AM2015-2738
90 y-Ibritumomab Tiuxetan or Purine Analogues Severely Affect Peripheral Blood Stem Cell Mobilization: An Analysis On 248 Patients.
Authors: Anna Vanazzi, Alessandra Alietti, Alberto Agazzi, Mara Negri, Maria Teresa Lionetti, Aleksandra Babic, Davide Radice, Luca Nassi, Simona Sammassimo, Cristina Rabascio, Pierluigi Antoniotti, Lara Roveda, Bruno Lucchetti, Tiziana Suardi, Alessio Piredda, Liliana Calabrese, Giovanni Martinelli, Daniele Laszlo
Journal: Blood (2009)
OC-020 Web-based learning in gastroenterology: real-life learning outcomes from a training and assessment module in lesion recognition at capsule endoscopy
Authors: A Haycock, A Postgate, E Despott, S Thomas-Gibson, A Fitzpatrick, S Preston, C H Fraser
Journal: Gut (2010)

<h3>Introduction</h3> Capsule endoscopy (CE) is now the standard investigation for suspected small bowel disease, yet training opportunities remain limited. Unlike flexible endoscopy training, the lesion recognition skills required for CE are ideally suited to web-based e-learning, and with the advent of the e-learning for Health (Elf-H) endoscopy module, could be made available to a wide audience. We have previously developed an e-learning module for lesion recognition skills and validated them under research conditions. A topic-based teaching module provides multimedia learning on normal anatomy, anatomical variations/incidental findings, and pathological abnormalities. An assessment module consists of 50 de-identified video clips with multiple choice questions that can be used as a formative assessment. The aim of this study was to investigate the training efficacy of these modules in a real-life web-based learning environment. <h3>Methods</h3> The assessment module questions that had previously demonstrated construct validity were stratified into two 22 question papers (A and B) which were used in a pre/post test design, with the programme randomly allocating the order of completion (AB or BA) to each individual. The programme automatically records and emails the results from the assessments. Both the training and assessment modules were developed into a downloadable package and placed on the Wolfson Unit website. Invitations to test the module were sent to all gastroenterology trainees in England and placed on several training-related websites. Participants expressing an interest were given access to download the package and could complete the module in their own time. <h3>Results</h3> 99 individuals have so far expressed an interest in completing the module, with full results available for 27. Logistic regression analysis was used to compare the difference between the pre and post training performances on the test modules. There was a significant improvement in test performance after training (p=0.037), although this improvement was slightly smaller than in our previous validation study (8.9% vs 14.9%). Feedback was extremely positive regarding both the training and test modules, with median (range) scores out of 10 for their usefulness of 8.4 (6–10) and 7.2 (4–10), respectively. Trainees found it enjoyable, comprehensive, interactive and easy to use. <h3>Conclusion</h3> Validated web-based e-learning is an effective tool for improving CE lesion recognition skills under “real-life” learning conditions. It can allow rapid dissemination of quality training material and best practice to a wide audience. This approach could help address the current issues surrounding provision of CE training in the UK and elsewhere.
Abstract 238: Citrullination of miRNA regulators by PADs: A potential mechanism for the promotion of colitis and colitis-associated colorectal cancer
Authors: Erin E. Witalison, Xiangli Cui, Corey P. Causey, Paul R. Thompson, Lorne J. Hofseth
Journal: Cancer Research (2015)

Abstract Ulcerative Colitis (UC) is a chronic, relapsing inflammatory bowel disease that affects millions of people worldwide. As a result of DNA damage caused by the chronic inflammatory state of UC, people suffering from UC are at a higher risk of developing colorectal cancer (CRC). Although the cause of UC is still unknown, the protein arginine deiminase (PAD) family of enzymes has been found to be a key component in many human inflammatory diseases and cancer, including UC and CRC. PADs are calcium-dependent enzymes that post-translationally convert positively charged peptidyl-Arginine to neutral peptidyl-Citrulline through a process called ‘citrullination’. In hopes of treating UC and preventing CRC, we developed Chlor-amidine (Cl-amidine), a novel small molecule inhibitor of PADs. Previous results from our group have shown that miR-16, which is often downregulated in cancers, had increased expression levels in mice treated with Cl-amidine. MiR-16 targets (i.e. Cyclin D1 and E1) and colon carcinogenesis were also suppressed in mice treated with Cl-amidine. Our goal is to determine the mechanism(s) by which Cl-amidine targets miR-16 and other tumor suppressor miRNAs. One hypothesis is that Cl-amidine is preventing the citrullination of DNA methyltransferases (DNMTs). Citrullinated DNMTs show hyperactivity, resulting in hypermethylation and subsequent silencing of miRNAs. Evidence suggests that PADs can citrullinate DNMT3A, resulting in ‘methylation-mediated gene silencing’. We predict that this silencing negatively regulates tumor suppressor miRNAs and Cl-amidine treatment will restore these miRNA levels. Initial results suggest citrullination of DNMT3A in our in vitro colon cancer cell line model. Experiments are ongoing to confirm the ability of Cl-amidine to prevent citrullination-induced activation of upstream miRNA regulators. Results from our study will elaborate on the mechanism of action of Cl-amidine and provide further insight into using Cl-amidine as an anti-cancer therapy. Citation Format: Erin E. Witalison, Xiangli Cui, Corey P. Causey, Paul R. Thompson, Lorne J. Hofseth. Citrullination of miRNA regulators by PADs: A potential mechanism for the promotion of colitis and colitis-associated colorectal 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 238. doi:10.1158/1538-7445.AM2015-238