tbuckley/cabot-search huggingface dataset:
Abstract LB-125: Germline mutations in BAP1 predispose to melanocytic nevi and melanoma
Authors: Thomas Wiesner, Anna Obenauf, Rajmohan Murali, Isabella Fried, Klaus Griewank, Peter Ulz, Christian Windpassinger, Shea Loy, Werner Wackernagel, Ingrid Wolf, Juergen Becker, Agnes Viale, Alex Lash, Mono Pirun, Nick Socci, Arno Ruetten, Gabrielle Palmedo, Arthur Ott, David Abramson, Kenneth Offit, Lorenzo Cerroni, Heinz Kutzner, Boris Bastian, Michael Speicher
Journal: Cancer Research (2011)

Abstract We describe an autosomal-dominant syndrome characterized by multiple non-pigmented, exophytic melanocytic nevi and an increased susceptibility for melanoma, caused by germline mutations in the histone deubiquitinase BAP1. To identify the causative alterations, we performed comprehensive genomic analyses in two unrelated families with numerous dermal nevi composed largely of large, epithelioid melanocytes with abundant amphophilic cytoplasm and large, pleomorphic, vesicular nuclei with prominent nucleoli. Both families each had one proband with uveal melanoma, and three probands in one family had cutaneous melanoma. Array-based comparative genomic hybridization (aCGH) revealed losses of parts of or the entire chromosome 3 in 11 of 22 neoplasms studied. Genotypic analyses revealed that the deletions invariably affected the chromosome from the unaffected parent. Genome partitioning of the minimally deleted region on chromosome 3p21 followed by massively parallel sequencing revealed two different inactivating germline mutations of the BAP1 tumor suppressor gene that in both families segregated with the phenotype. In almost all tumors the remaining wild type BAP1 allele was eliminated by deletion, separate inactivating mutations, or loss of heterozygosity. 35 of 40 nevi (88%) showed mutations in BRAF, while the uveal melanomas had mutations in GNAQ. Our data identify BAP1 as a highly penetrant susceptibility gene for melanocytic neoplasia. Somatic BAP1 mutations have recently been reported in uveal melanoma and linked to the metastatic phenotype. Our observation of frequent bi-allelic inactivation of BAP1 in nevi indicates that the role of BAP1 in melanocytic neoplasia is more complex, and may differ depending on other factors such as the type of melanocyte (uveal or cutaneous) and the co-existing oncogenic mutation. 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-125. doi:10.1158/1538-7445.AM2011-LB-125
P1210 PREDICTORS OF SVR24 FOR 1078 PATIENTS WITH SEVERE FIBROSIS OR COMPENSATED CIRRHOSIS: THE INTERNATIONAL TELAPREVIR ACCESS PROGRAM
Authors: M. Colombo, S.I. Strasser, C. Moreno, P.A. Ferreira, P. Urbanek, I. Fernández, D. Abdurakhmanov, A. Streinu-Cercel, A. Verheyen, W. Iraqi, R. Demasi, A. Hill, I. Lonjon-Domanec, H. Wedemeyer
Journal: Journal of Hepatology (2014)
P5-08-04: Mammographic Microcalcifications and Breast Cancer Tumorigenesis: A Radiologic-Pathologic Analysis.
Authors: M Naseem, J Murray, JF Hilton, D Han, S Hogeveen, RL Heersink, D Muradali, C Simmons, D Bell, R Haq, C Brezden-Masley
Journal: Cancer Research (2011)

Abstract Background Microcalcifications (MCs) are tiny deposits of calcium in breast soft tissue. They serve as key diagnostic radiological features for localization of malignancy. Approximately 30% of early invasive breast cancers have fine, granular MCs detectable on mammography; however, their role in breast cancer tumorigenesis is currently unknown. The purpose of this study was to investigate the relationship between mammographic MCs and breast cancer pathology. Methods: A retrospective chart review was performed for 882 women treated for breast cancer between 2000–2010 at St. Michael's Hospital. Demographic information (age and menopausal status), tumor pathology (size, histology, grade, nodal status and lymphovascular invasion), hormonal status (ER and PR), HER-2 overexpression and presence of MCs were collected for breast cancer patients. Chi-square tests were performed for categorical variables and t-tests were performed for continuous variables. All tests were two-sided and p-values less than 0.05 were considered statistically significant. Results: A total of 826 patient charts were included; 56 (6.4%) patients had metastatic carcinoma and were excluded from analysis. Only 37.0% (326/882) of the patients presented with mammographic MCs. Patients were more likely to have MCs if they were HER-2 positive (51%) as opposed to being HER-2 negative (33.4%) (p=0.001). There was a significant association between MCs and being perimenopausal with a mean age of 50 (65.2%) (p=0.012). Patients with invasive ductal carcinomas (39.7%) were more likely to present with MCs than were patients with other tumor histology (p=0.001). There was a positive correlation between MCs and tumor grade (p=0.051), with grade III tumors (41.85%) presenting with the most MCs, followed by grade II (37.95%) and grade I (29.8%). There was no significant association between mean age, mean tumor size, ER and PR status with the presence of MCs. Conclusion: This is the largest study that suggests the appearance of MCs on mammograms is strongly associated with HER-2 overexpression, invasive ductal carcinoma and perimenopausal status. Since HER-2 is implicated in mediating aggressive tumor growth and metastasis, future studies should investigate the molecular pathways underlying HER-2 overexpression and MC development. This would help better understand the role of MCs in breast cancer tumorigenesis. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-08-04.
MB-20 * EVALUATING THE ONCOGENIC POTENTIAL OF TSC1/2 MUTATIONS AND EFFICACY OF MTOR INHIBITORS IN HIGH RISK PEDIATRIC MEDULLOBLASTOMA
Authors: J. Henderson, J. Wagner, M. Davare
Journal: Neuro-Oncology (2015)

Medulloblastoma is the most common malignant pediatric brain tumor. Molecular profiling recently enabled the classification of medulloblastoma into four distinct subgroups, of which Group 3 patients have the worst prognosis. To identify targetable molecular vulnerabilities in Group 3 medulloblastoma, we utilized a high-throughput kinase inhibitor screening assay against the Group 3-like medulloblastoma cell line D341. Comparing inhibitor sensitivities of D341 to other medulloblastoma cell lines, >400 primary leukemia samples and >100 established human cancer cell lines, we found pronounced susceptibility to inhibitors of the PI3K/AKT/MTOR pathway as reflected by nanomolar IC50 values. We found this sensitivity to be biochemically correlated with increased phospho-MTOR as well as phosphorylation of MTOR effectors in the D341 cells when compared to the medulloblastoma cell lines exhibiting weaker or no MTOR inhibitor sensitivity. Exposure of D341 cells to the FDA-approved MTOR inhibitor everolimus resulted in a dose-dependent decrease in MTOR pathway activation and increase in cell death markers. Exome sequencing of D341 revealed a TSC2 A415V point mutation, which we found has significantly diminished TSC1-interaction potential in a heterologous expression system. Loss-of-function of the TSC1:TSC2 A415V complex concomitantly increased activation of the MTOR pathway. In silico mining of previously published exome sequencing data from primary patient samples unveils a subset of medulloblastoma tumors harboring TSC1 and TSC2 mutations in regions predicted to result in loss of function. We tested the functional consequence of these mutations using a heterologous model system and found they resulted in loss of the TSC1:TSC2 complex. Taken together, these findings corroborate that a subset of high risk medulloblastoma patients may have functionally relevant mutations in the MTOR pathway leading to oncogenic addiction to the pathway and susceptibility to MTOR inhibitors. In vitro response to an FDA-approved MTOR inhibitor may suggest a potentially promising adjunct treatment for a subgroup of medulloblastoma patients.
Abstract LB-90: DUPA-99mTc localizes to prostate cancer in men with locally advanced and metastatic disease.
Authors: Thomas A. Gardner, James W. Fletcher, Song-Chu Ko, Philip S. Low, Timothy L. Ratliff
Journal: Cancer Research (2013)

Abstract Objectives: Currently, the absence of an effective prostate cancer targeted imaging agent limits the ability to correctly clinically stage prostate cancer. The conjugation of a high affinity PSMA-targeting ligand, 2-[3-(1, 3-dicarboxy propyl)-ureido] pentanedioic acid (DUPA) to technetium 99m (99mTc) has generated a new prostate cancer imaging agent termed DUPA-99mTc. The objective of this phase 0 clinical trial was to confirm the preclinical data demonstrating high affinity localization to human prostate cancer cells and tissues. Methods: Nine men with advanced and metastatic prostate cancer confirmed by CT scan and/or bone scan were enrolled in the Phase 0 trial to investigate both the biologic efficacy and toxicity of the DUPA-99mTc agent. Dosimetry studies of images, blood and urine at 5 and 20 mCi doses were obtained at baseline, 5 min, 1, 2, 4, 8 and 24 hours. Results: Nine men with documented prostate cancer were enrolled. Seven of the nine subjects were evaluable. One patient did not receive a full iv dose and another received poorly labeled DUPA-99mTc (70%). The remaining seven patients, who received DUPA-99mTc in excess of 95% labeled product, demonstrated localization to all cancerous areas seen on pre-enrollment images (CT and Bone Scans) plus additional lesions in several of the patients. Two men who had biopsy-confirmed locally recurrent prostate cancer had scans prior to resection, and tissue was monitored intra-operatively and ex-vivo to confirm the higher 99mTc counts in malignant tissue compared to normal tissue. No significant toxicity was demonstrated with administration of the DUPA-99mTc in any subject. Conclusions: DUPA-99mTc compound can be reliably administered to men with prostate cancer without toxicities and with equal or superior imaging compared to conventional CT and bone scans. A Phase I/II trial will be conducted to confirm the performance of this imaging agent in a larger patient population. Citation Format: Thomas A. Gardner, James W. Fletcher, Song-Chu Ko, Philip S. Low, Timothy L. Ratliff. DUPA-99mTc localizes to prostate cancer in men with locally advanced and metastatic disease. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-90. doi:10.1158/1538-7445.AM2013-LB-90
PWE-142 Endoscopic stenting for malignant biliary obstruction: a 3-year review
Authors: R Mahmood, N C Fisher
Journal: Gut (2012)

<h3>Introduction</h3> Placement of biliary stents in malignant biliary obstruction is an area of controversy as ERCP and stent placement may cause morbidity in patients with operable disease. We review here our experience in a cohort of relevant patients. <h3>Methods</h3> A 3-year database review to identify all relevant cases for case note review. Principal outcome measures were: success of stent placement; need for further endoscopic intervention; surgical resection rates and documented complications. <h3>Results</h3> 124 cases were identified. 100 patients underwent ERCP; stent placement was successful at first ERCP in 82% of cases. A further 5% were stented at a second ERCP and 10% required percutaneous drainage. Plastic biliary stents were used in most cases (75/87, 86%); remaining patients had metal stents. Of plastic stents, 31/75 (41%) required unscheduled re-intervention for stent occlusion, after a median interval of 90 days. 66 patients were referred for a surgical opinion; remaining patients had inoperable disease or co-morbidity. Of the referred patients, 28 (23% of whole cohort) underwent resection surgery and of these 8/28 (29%) needed pre-operative revision of their biliary stents. The median post-operative stay was 11 days and serious complications including one death occurred in three cases (11%). <h3>Conclusion</h3> In this review only 23% of patients with malignant biliary obstruction were suitable for surgical resection. However where prior plastic biliary stents were used, a high proportion required re-intervention and this practice may have contributed to post-operative complications. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Sewnath ME</b>, Karsten TM, Prins MH, <i>et al.</i> A meta-analysis on the efficacy of preoperative biliary drainage for tumors causing obstructive jaundice. <i>Ann Surg</i> 2002;<b>236</b>:17–27. 2. <b>Wang Q</b>, Gurusamy KS, Lin H, <i>et al.</i> Preoperative biliary drainage for obstructive jaundice. <i>Cochrane Database Syst Rev</i> 2008;(3):CD005444. 3. <b>van der Gaag NA</b>, Rauws EA, van Eijck CH, <i>et al.</i> Preoperative biliary drainage for cancer of the head of the pancreas. <i>N Engl J Med</i> 2010;<b>362</b>:129–37.
Abstract LB-422: Photodynamic ablation of lymphatic vessels and intralymphatic cancer cells prevents metastasis
Authors: Tuomas Tammela, Anne Saaristo, Tanja Holopainen, Seppo Ylä-Herttuala, Leif C. Andersson, Susanna Virolainen, Ilkka Immonen, Kari Alitalo
Journal: Cancer Research (2011)

Abstract The dissemination of tumor cells (metastasis) from the primary tumor is the principal cause of death in cancer patients. The lymphatic vessels serve as a key conduit for metastasizing tumor cells, which often colonize the lymph nodes first. Although the primary tumor and lymph nodes invaded by tumor cells are removed during surgery, tumor cells inside lymphatic vessels are not removed. Here, we demonstrate tumor cell growth inside lymphatic vessels in mice bearing mouse melanoma tumors or human lung tumors and in a human melanoma patient, suggesting that these in-transit tumor cells give rise to metastases. We selectively destroyed lymphatic vessels using photodynamic therapy with the benzoporphyrin derivative verteporfin in mice and pigs. Destruction of tumor-draining lymphatic vessels also eradicated intralymphatic tumor cells, and prevented in-transit metastasis of mouse melanoma cells and subsequent relapse. Photodynamic therapy, when combined with anti-lymphangiogenic therapy, prevented further tumor invasion of lymphatic vessels and may provide a way to eradicate in-transit tumor cells in patients. 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-422. doi:10.1158/1538-7445.AM2011-LB-422
Abstract 4821: Somatic variation scoring and validation for large-scale cancer genome sequencing
Authors: Krishna P. Pant, Steve Lincoln, Jonathan Baccash, Aaron L. Halpern, Igor Nazarenko, Paolo Carnevali, Dennis G. Ballinger
Journal: Cancer Research (2011)

Abstract Complete Genomics has sequenced the genomes of over 100 tumor-normal sample pairs from a variety of cancers (e.g. Lee, et al., Nature 465: 473-477, 2010) using a unique high throughput sequencing platform (Drmanac, et al., Science 327:78-81, 2010). We have assembled a tool set to investigate somatic mutations in these samples, including small variations (SNVs, deletions, insertions and substitutions), as well as larger structural variations, copy number variations and regions of LOH (Loss of Heterozygosity). Included in this sample set are 12 cancer cell lines and matched normal cell lines obtained from the American Type Tissue Culture collection (ATCC), comprising 10 breast cancers and 2 lung cancers. We have developed and characterized somatic variation scoring methods for each variant class that can be tuned for particular applications and sample types. Comparative analyses with previously published data show high specificity and sensitivity of somatic variation detection. We will discuss the application of these methods for somatic variation analysis in larger cancer genome studies. 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 4821. doi:10.1158/1538-7445.AM2011-4821
Some HMOs Embrace Clinical Trials
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Some HMOs Embrace Clinical Trials Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 15, 2 August 1995, Pages 1104–1106, https://doi.org/10.1093/jnci/87.15.1104 Published: 02 August 1995
SP0076 What is New in SLE and APS
Authors: R. F. Van Vollenhoven
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> What is new in SLE and APS Over the past year, some important developments have taken place for the clinical approach to SLE. A multi-year large international initiative by the SLICC group resulted in the publication of a new set of classification criteria for SLE which, while not necessarily ‘better’ than the established ACR criteria, appear to have gained in face validity and seem to reflect some specific features of the diagnostic challenges surrounding this disease. In SLE therapeutics new analyses of the two phase III clinical trials with belimumab provided some guidance for clinicians as to which patients have the highest likelihood to benefit from this biologic. A large randomized trial of abatacept for lupus nephritis was reported as negative, but a post-hoc analysis demonstrated that the choice of endpoint in such trials can have a critical role in determining success or failure. Other biologics are currently in clinical trials, some with encouraging results. While progress in APS has not been as dramatic, some developments of interest have occurred. In this lecture I will review the past year’s literature on SLE and APS with a primary focus on new findings that have immediate bearing on clinical practice when caring for such patients. <h3>Disclosure of Interest</h3> R. Van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, MSD, Pfizer, Roche, UCB, Consultant for: AbbVie, BMS, GSK, Lilly, MSD, Pfizer, Roche, UCB
Profound Cytopenia Secondary to Azidothymidine
Authors: Gary Forester
Journal: New England Journal of Medicine (1987)

To the Editor: A 38-year-old black male homosexual in an advanced stage of the acquired immunodeficiency syndrome had fever, diarrhea, and thrush from 1983 to 1986; in April 1986, pneumocystis pneumonia developed. The patient recovered from that, then had recurrent salmonellosis with diarrhea and abdominal pain. This was later accompanied by progressive anemia (hemoglobin, 7.0 g per deciliter). Mycobacterium avium–intracellulare was isolated from the bone marrow in January 1987. The patient's course included episodes of salmonella sepsis and a perianal abscess requiring drainage. On April 1, after transfusion increased the hemoglobin level to 11 g per deciliter, azidothymidine (AZT) was . . .
P190 Long-term outcome of bronchial artery embolisation (BAE) for massive haemoptysis
Authors: A. Adlakha, R. Rupta, A. Sebastian, P. Tait, J. Jackson, P. Ind
Journal: Thorax (2011)

<h3>Background</h3> BAE for massive haemoptysis is potentially life-saving with low short-to-medium term failure rates in previous studies. We aimed to characterise patients referred for BAE, to examine long-term treatment success and identify risk factors for requiring repeat BAE. <h3>Methods</h3> We retrospectively identified all patients undergoing BAE from 1994 to 2007. We collated data from hospital databases and primary care on demographics, respiratory diagnoses and procedure with follow-up of up to 16 years. Outcomes were all-cause mortality and recurrence of haemoptysis requiring repeat BAE. <h3>Results</h3> 158 patients were embolised on 208 occasions. 85 (54%) patients were male and median age was 54 (IQR: 41–67) y. The most common underlying diagnoses were aspergilloma (n=38; 24% of patients), bronchiectasis (n=24; 15%), unidentified cause (n=17; 11%) chronic tuberculosis (n=14; 9%), active tuberculosis (n=12; 8%) and cystic fibrosis (n=11; 7%). All-cause mortality at 1 month and 3 years was 5.3% and 29.7%, and need for repeat BAE was 4.7% and 30.7% respectively. Repeat BAE at 3 years was most common with aspergilloma (50%) and least common with active TB (0%). 3-year mortality was highest in cystic fibrosis (40%) and least with unknown cause (7.7%) Neither number nor location of vessels embolised predicted mortality or need for repeat BAE. No major procedural complications were noted. <h3>Conclusions</h3> BAE by experienced operators is a safe, minimally invasive procedure for massive haemoptysis with excellent short-term success. It does not prevent late recurrence of haemoptysis nor obviate the need for repeat BAE, the risk of which is related to the underlying disease rather than to technical aspects of the procedure.
A Clinical Trial of Beta Carotene to Prevent Basal-Cell and Squamous-Cell Cancers of the Skin
Authors: E. Robert Greenberg, John A. Baron, Thérèse A. Stukel, Marguerite M. Stevens, Jack S. Mandel, Steven K. Spencer, Peter M. Elias, Nicholas Lowe, David W. Nierenberg, Garrett Bayrd, J. Corwin Vance, Daniel H. Freeman, William E. Clendenning, Theodore Kwan
Journal: New England Journal of Medicine (1990)

Beta carotene has been associated with a decreased risk of human cancer in many studies employing dietary questionnaires or blood measurements, and it has had protective effects in some animal models of carcinogenesis.We tested the possible cancer-preventing effects of beta carotene by randomly assigning 1805 patients who had had a recent nonmelanoma skin cancer to receive either 50 mg of beta carotene or placebo per day and by conducting annual skin examinations to determine the occurrence of new nonmelanoma skin cancer.Adherence to the prescribed treatment was good, and after one year the actively treated group's median plasma beta carotene level (3021 nmol per liter) was much higher than that of the control group (354 nmol per liter). After five years of follow-up, however, there was no difference between the groups in the rate of occurrence of the first new nonmelanoma skin cancer (relative rate, 1.05; 95 percent confidence interval, 0.91 to 1.22). In subgroup analyses, active treatment showed no efficacy either in the patients whose initial plasma beta carotene level was in the lowest quartile or in those who currently smoked. There was also no significant difference between treated and control groups in the mean number of new nonmelanoma skin cancers per patient-year.In persons with a previous nonmelanoma skin cancer, treatment with beta carotene does not reduce the occurrence of new skin cancers over a five-year period of treatment and observation.
Delayed Postoperative Stenosis of a Right Hepatic Choledochojejunostomy
Authors: GARY R. CONRAD, PARTHA SINHA
Journal: Clinical Nuclear Medicine (2002)

From the Department of Radiology, The University of Kentucky Chandler Medical Center, Lexington, Kentucky Received for publication December 3, 2001. Accepted January 8, 2002. Reprint requests: Gary R. Conrad, Department of Radiology, 800 Rose Street, Lexington, Kentucky 40536-0293. E-mail: [email protected]
Traitement endoscopique du carcinome épidermoïde superficiel de l'œsophage: suivi à long terme
Authors: JM Canard, G Rahmi, T Maniere, L Palazzo, C Cellier, R Jian
Journal: Endoscopy (2008)

Introduction: La mucosectomie endoscopique est un des traitements curatifs du carcinome épidermoïde superficiel de l'œsophage. Il a effectivement été montré que le taux de résécabilité complète est important et que le taux de récidive précoce est faible. L'objectif de cette étude est d'évaluer l'efficacité de la mucosectomie à plus long terme.