tbuckley/cabot-search huggingface dataset:
Novel, double-lumen removable stent to treat caustic esophageal stenosis
Authors: Marek Woynarowski, Maciej Dądalski, Violetta Wojno, Mikołaj Teisseyre, Leszek Hurkała, Emil Płowiecki
Journal: Endoscopy (2014)

Recurrent esophageal stenosis following caustic injury may be difficult to treat. A tube stent developed at our institution [1] can be used as an alternative to repetitive endoscopic esophageal stricture dilation. The case of a boy with severe larynx and esophageal caustic injury at the age of 2 years is reported here.
DIAGNOSIS OF PRIMARY BILIARY CIRRHOSIS (PBC), SCLEROSING CHOLANGITIS (SC), AND ISOLATED COMMON BILE DUCT OBSTRUCTION (ICBDO) BY Tc-99m-IDA SCINTIGRAPHY
Authors: Shakuntala Krishnamurthy, Gerbail T. Krishnamurthy, David A. Lieberman, Emmet B. Keeffe, Susan Gilbert
Journal: Clinical Nuclear Medicine (1986)

Krishnamurthy, Shakuntala; Krishnamurthy, Gerbail T.; Lieberman, David A.; Keeffe, Emmet B.; Gilbert, Susan Author Information
Radioiodine Uptake in an Ovarian Mature Teratoma Detected With SPECT/CT
Authors: Bulent Yazici, Aylin Oral, Ozgur Omur, Ayse Yazici
Journal: Clinical Nuclear Medicine (2014)

A 28-year-old woman underwent a near-total thyroidectomy for papillary carcinoma. Before radioiodine therapy, the serum thyroid-stimulating hormone level was 50 μIU/mL, the thyroglobulin level was 1 μg/L, and the antithyroglobulin was negative. She received 100 mCi of 131I for ablation of residual thyroid tissue. After therapy, 131I whole-body scan demonstrated focal uptake in the right pelvic area, which localized to the right ovary on SPECT/CT fusion images. The ovarian cyst was resected, and histopathological examination revealed a mature teratoma without thyroid tissue component. At 6-month follow-up, the whole-body radioiodine scan was normal, and serum thyroglobulin was undetectable.
Analysis of the rate of missing data, the rate of discordance between readers, and the rate of site versus central discordance in clinical studies of recently approved breast cancer agents that have used blinded independent central review.
Authors: K Borradaile, K Cadogan, S Somers, R Ford
Journal: Cancer Research (2009)

Abstract Abstract #2081 Background: The United States Food and Drug Administration (USFDA) recommends blinded independent central review (BICR) for oncology registration studies when the primary study endpoint is based on tumor measurements, such as progression-free survival (PFS) or objective response rate (ORR). However, there is no published guidance regarding acceptable metrics during the BICR.&amp;#x2028; Method: The USFDA Summary Basis of Approvals and Oncologic Drugs Advisory Committee (ODAC) transcripts for the following recently approved breast cancer therapies: Gemzar, Abraxane, Tykerb, Ixempra, and Avastin, were reviewed with attention to metrics referable to the BICR. The findings are summarized.&amp;#x2028; Results: Up to 13% of subjects were reported as unevaluable at the BICR based on missing data, with missing data defined as missing radiographic evaluations. The rates of discordance between two readers during the BICR were reportedly between 34-51% depending on the number of adjudication variables. The rates of discordance between the site and BICR were reportedly between 34-49% for the date of progression and 24-29% for the progression status. Up to 9% of subjects enrolled with measurable disease at baseline did not have this confirmed by the BICR. The causes of discordance were reportedly related to differences in the methodologies used to perform the reviews, and clinical or image data that was missing at the time of the BICR. Additional reported causes included imaging requirements not detailed in the protocol, the BICR charter containing more stringent requirements for determining response and progression than was indicated in the protocol, protocol amendments issued midway through the study which changed the imaging eligibility criteria for the sites while the BICR used the same requirements throughout the study, differences in the choice and classification of lesions, radiographic exams only repeated at subsequent time points if deemed positive by the investigator resulting in missing data and unevaluable assessments at the BICR, variability in measurement of small lesions, and discordance in the determination of new lesions. Inter- and intra-reader variability was reported in a small population of subjects; 8% resulted in 1-step response discrepancies for inter-reader variability and 31% for intra-reader variability.&amp;#x2028; Conclusion: Based on FDA approvals, metrics as described above may prove to be valuable benchmarks when using BICR data to determine endpoints in future breast cancer studies. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2081.
Targetless T cells in cancer immunotherapy
Authors: Per thor Straten, Federico Garrido
Journal: Journal for ImmunoTherapy of Cancer (2016)

Attention has recently focused on new cancer immunotherapy protocols aiming to activate T cell mediated anti-tumor responses. To this end, administration of antibodies that target inhibitory molecules regulating T-cell cytotoxicity has achieved impressive clinical responses, as has adoptive cell transfer (ACT) using expanded tumor infiltrating lymphocytes (TIL) or genetically modified cytotoxic T cells. However, despite clear clinical responses, only a fraction of patients respond to treatment and there is an urgent call for characterization of predictive biomarkers. CD8 positive T cells can infiltrate tumor tissues and destroy HLA class I positive tumor cells expressing the specific antigen. In fact, current progress in the field of cancer immune therapy is based on the capacity of T cells to kill cancer cells that present tumor antigen in the context on an HLA class I molecule. However, it is also well established that cancer cells are often characterized by loss or down regulation of HLA class I molecules, documented in a variety of human tumors. Consequently, immune therapy building on CD8 T cells will be futile in patients harboring HLA class-I negative or deficient cancer cells. It is therefore mandatory to explore if these important molecules for T cell cytotoxicity are expressed by cancer target cells. We have indications that different types of immunotherapy can modify the tumor microenvironment and up-regulate reduced HLA class I expression in cancer cells but only if the associated molecular mechanisms is reversible (soft). However, in case of structural (hard) aberrations causing HLA class I loss, tumor cells will not be able to recover HLA class I expression and as a consequence will escape T-cell lysis and continue to growth. Characterization of the molecular mechanism underlying the lack or downregulation of HLA class I expression, seems to be a crucial step predicting clinical responses to T cell mediated immunotherapy, and possibly aid the selection of strategies that could condition patients for response. Thus, characterization of HLA expression by cancer cells could therefore represent an important predictive marker for immunotherapy of cancer.
University of Wisconsin experience treating adult ALL with the BFM regimen
Authors: S. C. Medlin, B. Kahl, W. Longo, E. Williams, J. Lionberger, J. Kim, K. Kim, M. Juckett
Journal: Journal of Clinical Oncology (2006)

16501 Background: Berlin-Frankfurt-Munster therapy (BFM) is an effective regimen for acute lymphoblastic leukemia (ALL) in children and young adults (Lancet 2:921–924,1988). Treating children and young adults at higher risk for relapse with an augmented BFM was shown to increase both event free and overall survival (NEJM 338:23,1663–1671,1998). Outcomes using standard BFM or augmented BFM in adults are unknown. Methods: This is a case-series of 29 adult patients treated with the BFM regimen. Patients were stratified into low, intermediate and high-risk groups based upon the following characteristics: age, white blood cell count, adverse cytogenetics and absence of CD 10. Low risk patients received the standard BFM regimen. Intermediate risk patients were given augmented BFM if less than 50 years old, standard BFM if older than age 50. High-risk patients received augmented BFM. Cranial irradiation was omitted in most patients (25/29). Events were defined as relapse, death from any cause, and stopping treatment for any reason. Results: Fifteen patients (median age 38, range 19–70) were treated with standard BFM and 14 patients (median age 37, range 21–72) with augmented BFM. Complete remission at day 28 was 93% (27/29). For the entire group, the 3-year overall survival was 60% with a 3-year event free survival of 45%. Patients treated with augmented BFM experienced a 3-year EFS, PFS, OS of 26%, 43%, and 48% respectively. Patients treated with standard BFM had a 3-year EFS, PFS, OS of 60%, 78%, and 78% respectively. Toxicity was common with significant neuropathy and neutropenic fever occurring in 83% and 48% respectively. Septic shock occurred in 17% of patients. Severe toxicity resulted in 1 death and discontinuation of BFM in 3 patients. The entire regimen was completed in 33 % of those treated with augmented BFM and 71% of those treated with standard BFM. Conclusion: Standard BFM is an effective and tolerable regimen for treatment of adult ALL. Augmented BFM is a difficult regimen for adult patients to complete. For both regimens, the 3-year PFS and OS compare favorably to other published regimens. No significant financial relationships to disclose.
Abstract 2331: Select epidithiodiketopiperazine (ETP) compounds disrupt the HIF-1α/p300 interaction and HIF-mediated transcription
Authors: Emily D. Richardson, Kelie M. Reece, Tessa J. Campbell, Heather Pressler, Stephen T. Pisle, William D. Figg
Journal: Cancer Research (2012)

Abstract As solid tumors grow, regions in the tumor become hypoxic because of increased metabolism, heterogeneous and abnormal vasculature delivering oxygen within the tumor, and greater size. In order for the tumor to continue to grow, it depends on survival mechanisms to overcome this hypoxic state, including up-regulation in glycolysis, invasion and metastasis, and angiogenesis, or the growth of new blood vessels. The hypoxia-inducible factor (HIF) transcription factor complex is a major mediator of the cell's response to a hypoxic state and a tumor's survival mechanism under hypoxia. The complex is composed of the hypoxia-dependent HIF-1α subunit and a constitutively expressed HIF-1α subunit, and it requires the co-activator protein p300 to function. In the presence of oxygen, HIF-1α is rapidly degraded. Under hypoxia, HIF-1α forms a complex with HIF-1α and p300 in the nucleus to up-regulate transcription of pro-survival and angiogenic genes. Targeting this transcription factor complex in tumors could circumvent the tumor's hypoxia survival mechanism and lead to growth arrest and cell death. The compounds chetomin, chaetocin, and gliotoxin, members of the epidithiodiketopiperazine (ETP) family of fungal metabolites, have been shown to disrupt the HIF-1α/p300 interaction in an over-expression system. In the following experiments, we sought to validate the disruption of the HIF-1α /p300 transcription factor complex in cells, and to determine the associated downstream cellular effects. By co-immunoprecipitation of the complex from prostate cancer cells, we were able to show that treatment with those select ETPs under hypoxic conditions disrupted the HIF-1α/p300 complex. We performed an enzyme-linked immunosorbent assay (ELISA) to determine the effect of ETPs on levels of secreted vascular endothelial growth factor (VEGF), a major target of HIF transcription. We observed a decrease in VEGF concentration that correlated with ETP treatment under hypoxia. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the transcription levels of other HIF target genes to validate that disruption of the HIF-1α/p300 complex by select ETP treatments indeed affects HIF-mediated transcription. In order to determine the antiangiogenic effects of these agents in vivo, ongoing animal studies in our lab are testing the efficacy of these ETPs in reducing tumor growth and determining feasibility of pre-clinical development. Targeting the HIF complex could circumvent a tumor's survival mechanism under hypoxia, and would be a new treatment strategy in solid tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2331. doi:1538-7445.AM2012-2331
Unusual cause of constipation: sunflower seeds bezoar
Authors: R. Lim, A. Rawlings, S. Schultz, L. Bradley, H. Hammad, M. Bechtold
Journal: Endoscopy (2013)

Bezoars are accumulated foreign material that forms concretions in the gastrointestinal tract, inducing abdominal pain, constipation, obstruction, and even peritonitis. This case report describes a rare rectal bezoar in a healthy young woman who had recently consumed large quantities of sunflower seeds.
ASSOCIATION OF BASELINE RENAL DYSFUNCTION WITH OUTCOMES IN PATIENTS UNDERGOING POPLITEAL AND INFRA-POPLITEAL PERCUTANEOUS PERIPHERAL ARTERIAL INTERVENTIONS
Authors: Kesav C. Parvataneni, Chatchawan Piyaskulkaew, Susan Szpunar, Tarun Sharma, Vishal Patel, Patel Saurabhkumar, Thomas Davis, Hiroshi Yamasaki, Howard Rosman, Rajendra Mehta
Journal: Journal of the American College of Cardiology (2016)
Abstract P3-06-18: Increase of serum androgen and its metabolites in postmenopausal primary breast cancer patients with disease progression during neo-adjuvant exemestane treatment; JFMC 34–0601 TR
Authors: M Takada, S Saji, N Honma, N Masuda, Y Yamamoto, K Kuroi, H Yamashita, S Ohno, K Aogi, T Ueno, M Toi
Journal: Cancer Research (2012)

Abstract BACKGROUND: We reported a positive correlation between body mass index (BMI) and clinical response to neo-adjuvant hormonal therapy (NAH) with steroidal aromatase inhibitor, exemestane, in post-menopausal breast cancer patients (Takada M et al. Breast 2012). Here, we examined the relationship between serum concentrations of sex steroids and BMI, and explored their predictive value for clinical response. PATIENTS AND METHODS: Among the 116 post-menopausal patients enrolled in the JFMC 34–0601 clinical trial of 24 weeks (wks) of NAH with exemestane, serums from 60 patients at pre-treatment, at 4wks and end of the treatment (24wks) were subjected to this study. Estradiol (E2), estrone (E1), dehydroepiandrosterone (DHEA), androstenedione (A-dione), 5-androstene-3β, 17β-diol (Aenediol), 5α-androstane-3β, 17β-diol (Aanediol) were measured using LC-MS/MS analysis and E1- sulfate (E1S) was by RIA. RESULTS: There were no significant correlations between pre-treatment concentrations of sex steroids and BMI, except for moderate correlation of E2 and BMI (p = 0.004). In multivariate analysis, E1 was an independent predictive factor for objective response [odds 6.0, 95% confidence interval (CI) 1.5 — 34.6, p = 0.011], as well as BMI. All of the estrogens decreased to under-detection levels (0.5 for E1 and E2, 5 pg/assay for E1S) at 4 wks of treatment, and maintained through to the end of treatment in almost all patients independently of clinical response. The geometric mean percentage changes in androgens after NAH were: DHEA −0.2% (95%CI −15.3% — +17.6%) for patients without progressive disease (non-PD) and +44.8% (95%CI +22.1% — +71.8%) for patients with progressive disease (PD); A-dione −2.3% (95%CI −17.3% — +15.4%) for non-PD and +45.6% (95%CI +28.3% — +65.3%) for PD; Aenediol −11.5% (95%CI −20.6% — −1.4%) for non-PD and +24.9% (95%CI +1.9% — +53.0%) for PD; Aanediol +21.3% (95%CI −5.5% — +55.8%) for non-PD and +56.3% (95%CI +5.3% — +132.0%) for PD, respectively. The changes in the concentrations of both DHEA and A-dione in patients with PD were statistically significant (p = 0.008 and p = 0.002, respectively). In all of the PD patients, the serum concentrations of DHEA and A-dione were increased after NAH. CONCLUSION: Pretreatment serum concentration of E1 was an independent predictive factor for clinical response to NAH with exemestane. Measurement of dynamics of the serum androgen concentrations might be helpful for monitoring treatment response, and mechanism of increase of androgens has a value for further investigation. Our results should be validated using a larger dataset. (UMIN ID; C000000345) Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-18.
αvβ3 Integrin-Mediated Adenoviral Transfer of Interleukin-12 at the Periphery of Hepatic Colon Cancer Metastases Induces VCAM-1 Expression and T-Cell Recruitment
Authors: Guillermo Mazzolini, Iñigo Narvaiza, Matilde Bustos, Marina Duarte, Iñigo Tirapu, Roberto Bilbao, Cheng Qian, Jesús Prieto, Ignacio Melero
Journal: Molecular Therapy (2001)

We previously reported that systemic injection of recombinant adenovirus resulted in a rim of gene transduction around experimental liver tumor nodules. This zone of higher infection is dependent on the αvβ3 integrin, acting as an adenovirus internalization receptor, which is overexpressed in tissues surrounding liver metastases. When a recombinant adenovirus encoding interleukin-12 (AdCMVIL-12) is given into a subcutaneous tumor nodule in mice also bearing concomitant liver tumors, a fraction of AdCMVIL-12 reaches the systemic circulation and infects liver tissue, especially at the malignant/healthy tissue interface. As a result of the expression at this location of the interleukin-12 transgenes, VCAM-1 is induced on vessel cells and mediates the recruitment of adoptively transferred anti-tumor cytolytic T-lymphocytes. These studies provide mechanistic explanations for the potent therapeutic synergy observed between interleukin-12 gene transfer and adoptive T-cell therapy. We previously reported that systemic injection of recombinant adenovirus resulted in a rim of gene transduction around experimental liver tumor nodules. This zone of higher infection is dependent on the αvβ3 integrin, acting as an adenovirus internalization receptor, which is overexpressed in tissues surrounding liver metastases. When a recombinant adenovirus encoding interleukin-12 (AdCMVIL-12) is given into a subcutaneous tumor nodule in mice also bearing concomitant liver tumors, a fraction of AdCMVIL-12 reaches the systemic circulation and infects liver tissue, especially at the malignant/healthy tissue interface. As a result of the expression at this location of the interleukin-12 transgenes, VCAM-1 is induced on vessel cells and mediates the recruitment of adoptively transferred anti-tumor cytolytic T-lymphocytes. These studies provide mechanistic explanations for the potent therapeutic synergy observed between interleukin-12 gene transfer and adoptive T-cell therapy.
Indications of the Thymus-Derived Nature of the Proliferating Cells in Six Patients with Sézary's Syndrome
Authors: Jean-Claude Brouet, Georges Flandrin, Maxime Seligmann
Journal: New England Journal of Medicine (1973)

The Sézary syndrome consists of erythroderma, lymphadenopathy and abnormal mononuclear leukocytes. In four of six patients with this syndrome, the abnormal cells were smaller than the classic large Sézary cell. The membrane properties of circulating abnormal cells, studied by conventional stains, electron microscopy, cytogenetic analysis, immunofluorescence, and rosette formation, manifested similar ultrastructural and chromosomal characteristics whether the cells were large or small. The abnormal cells were devoid of membrane-bound immunoglobulin detectable by immunofluorescence, did not bind aggregated human IgG, were able to form spontaneous rosettes with sheep erythrocytes and, in the three patients studied, were killed by a specific rabbit antihuman T-cell antiserum. These findings indicate that these cells are related to thymus-derived lymphocytes. (N Engl J Med 289:341–344, 1973)
THE ASSESSMENT OF LEFT ATRIAL FUNCTION DURING CATECHOLAMINE STRESS TEST IN PATIENTS AFTER SURGICAL REPAIR OF TOTAL ANOMALOUS PULMONARY VENOUS CONNECTION USING 3D ECHOCARDIOGRAPHY
Authors: Atsuya Shimabukuro, Kiyohiro Takigiku, Kouta Takei, Seiichi Tazawa, Manabu Nitta, Koudai Momoki, Masafumi Utsumi, Satoshi Yasukouchi
Journal: Journal of the American College of Cardiology (2016)
Abstract 5116: p70 S6 kinase regulates the actin cytoskeleton in ovarian cancer cell motility by binding and cross-linking actin filaments
Authors: Carman Ka Man Ip, Alice S. T. Wong
Journal: Cancer Research (2010)

Abstract p70 S6 kinase (p70S6K) is a downstream effector of phosphatidylinositol 3-kinase and is frequently activated in human ovarian cancer. Here we show for the first time that p70S6K functions in actin cytoskeleton reorganization responsible for the acquisition of invasiveness during tumor progression. Ectopic expression of active p70S6K in ovarian cancer cells induced dramatic reorganization of the actin cytoskeleton and promoted cell migration. Inhibition of p70S6K by siRNA or small molecule inhibitor resulted in diminished cell migration and actin cytoskeleton reorganization, confirming that these effects were p70S6K specific. By using cosedimentation and differential sedimentation assays, p70S6K was found to bind actin filaments, and was more effective in the presence than in the absence of phosphorylation. Importantly, purified p70S6K could be cosedimented with purified filamentous actin, indicating a direct association between p70S6K and actin. The response to p70S6K could be blocked with cytochalasin D, indicating that the binding of p70S6K to the cytoskeleton is mediated by actin. In addition, our results suggest that this is a functional interaction, because p70S6K was capable of generating specialized, actin-based cell morphologies via direct cross-linking activity. This bundling activity was confirmed by light scattering and electron microscopy. These results, in conjunction with our prior evidence that p70S6K regulates Rac and Cdc42 GTPases, suggest that p70S6K serves as an important regulator of the actin cytoskeleton, highlighting a role for p70S6K in the regulation of tumor progression and metastasis in ovarian cancer (This work is supported by Hong Kong Research Grants Council Grant HKU7599/05M to A.S.T.W.). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5116.