tbuckley/cabot-search huggingface dataset:
Abstract 3449: Placental characteristics and risk of cryptorchidism among populations at high and low risk of testicular germ cell tumors
Authors: Armen A. Ghazarian, Britton Trabert, Barry Graubard, Matthew Longnecker, Mark Klebanoff, Katherine McGlynn
Journal: Cancer Research (2016)

Abstract Background: Testicular germ cell tumors, which are significantly more common among white men than black men in the U.S., are thought to be part of a Testicular Dysgenesis Syndrome (TDS) that also includes impaired fertility, hypospadias and cryptorchidism. The etiology of the TDS conditions is not well understood, but the in-utero milieu is likely to be a significant factor. As the placenta is a critically important determinant of the in-utero milieu, placental characteristics may play a role in determining risk of the TDS conditions. Prior evidence suggests that placental weight, in particular, may be associated with cryptorchidism. Methods: We examined placental characteristics (weight, thickness, placental weight/birth weight ratio, infarct size, disorders of membrane development, presence of macrophages in the amniotic fluid) and cryptorchidism in a nested case-control study within the Collaborative Perinatal Project (CPP). The CPP was a maternal-child cohort study conducted in 12 medical centers in the U.S. between 1959 and 1965. Diagnoses of cryptorchidism made during the first year of life were included in the case group. The analysis contrasted 413 (232 white, 181 black) boys with cryptorchidism to 23,799 (12,092 white, 11,707 black) boys without cryptorchidism. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression, stratified by race. Results: Among white boys, cryptorchidism was significantly associated with circummarginate placenta (OR: 1.7, 95% CI: 1.1-2.7) or a combination of circummarginate/circumvallate (OR: 1.3, 95% CI: 1.0-1.8) placenta. Among black boys, cryptorchidism was significantly associated with having at least one placental infarct greater than 3 cm (OR: 2.3, 95% CI: 1.1-4.8) and with placental weight in the lower (OR: 1.7, 95% CI: 1.1-2.6) or higher (OR: 1.5, 95% CI: 1.0-2.3) tertile compared with the middle tertile. No significant associations were found between cryptorchidism and the other placental characteristics in either white or black boys. Conclusion: These results suggest that there may be associations between cryptorchidism and certain placental characteristics which differ between white and black births. The race-specific findings suggest an area where future research may prove fruitful. Citation Format: Armen A. Ghazarian, Britton Trabert, Barry Graubard, Matthew Longnecker, Mark Klebanoff, Katherine McGlynn. Placental characteristics and risk of cryptorchidism among populations at high and low risk of testicular germ cell tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3449.
XBP-1 a Selective and Specific Target for Immunotherapy in Myeloma.
Authors: Jooeun Bae, Ruben Carrasco, Kumar Sukhdeo, Pierfrancesco Tassone, Paola Neri, Tai Yu-Tzu, Xianfeng Li, Rory Coffey, Rao Prabhala, Kenneth Anderson, Nikhil Munshi
Journal: Blood (2005)
Insights Into Diagnosis and Etiology of Diamond Blackfan Anemia by Analysis of Pre-rRNA Processing
Authors: Ross Fisher, Adrianna Henson, Paola Quarello, Anna Aspesi, Jason E Farrar, Robert J. Arceci, David M. Bodine, Irma Dianzani, Jeffrey M. Lipton, Ugo Ramenghi, Adrianna Vlachos, Steven R Ellis
Journal: Blood (2012)
Abstract 2764: Detection of early gastric cancer with Sox17 DNA methylation analysis of gastric washes
Authors: Yoshiyuki Watanabe, Ritsuko Oikawa, Hiroyuki Yamamoto, Fumio Itoh
Journal: Cancer Research (2016)

Abstract Aim: Although minimal invasive treatment is widely accepted for early stage of gastric cancer (EGC), we still do not have any appropriate risk markers to detect residual neoplasia and some potential of recurrence. We previously reported that aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of gastric neoplasia (Gastroenterology 2009, Tumor Biology 2011). Our goal is to verify the potency of our three selected candidate genes (Sox17, MINT25, miR34) as a treatment marker for EGC. Method: We conducted a multicenter, prospective study using selected three candidate genes (Sox17, MINT25 and miR34) by Methylated CpG Island Amplification Microarray (MACAM) based analysis and analyzed the DNA methylation levels before and after endoscopic resection (ER) for EGC using gastric washes. We statistically analyzed sensitivity, specificity and AUC with DNA methylation levels of before / after ER and information of recurrent cases in 2 years. Results: 352 EGC cases were registered and endoscopically removed. 182 cases could followed endoscopically for 2 years (51.7%). Sensitivity, specificity and AUC were as follows. Sox17 (70.0%, 48.1%, 0.646), MINT25 (70.0%, 35.2% 0.555), miR34 (65.0%, 49.4%, 0.578). Conclusion: We have developed a new methodology for gastric cancer detection by DNA methylation in gastric washes. It is easy and useful for early detection of recurrence after endoscopic treatment in GCa patients. Citation Format: Yoshiyuki Watanabe, Ritsuko Oikawa, Hiroyuki Yamamoto, Fumio Itoh. Detection of early gastric cancer with Sox17 DNA methylation analysis of gastric washes. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2764.
Racial Distribution of Aneurysms in Zimbabwe
Authors: N D Kitchen
Journal: Journal of the Royal Society of Medicine (1989)

The distribution of aneurysms amongst African and Caucasian patients in two hospitals in Zimbabwe was surveyed in a retrospective study. Aneurysms were more common amongst the Caucasian patients and abdominal aortic aneurysms predominated (85%). Amongst the African patients there was a high incidence of thoracic aortic aneurysms (42%). Possible roles of atherosclerosis and syphilis in explaining these results are discussed.
Phase II study of Yale modified FOLFIRINOX (mFOLFIRINOX) in locally advanced pancreatic cancer (LAPC).
Authors: Stacey Stein, Xiangyu Cong, Xiaopan Yao, Carol Hahn, Jia Li, Jeremy S. Kortmansky, Bryan William Chang, Charles Cha, Ronald R Salem, Howard S. Hochster, Jill Lacy
Journal: Journal of Clinical Oncology (2015)

e15274 Background: There is no standard management of LAPC. Although FOLFIRINOX is superior to gemcitabine in metastatic pancreatic cancer (MPC) (Conroy et al. N Engl J Med 2011;364:1817), this regimen has not been evaluated prospectively in LAPC. To examine efficacy and tolerability of dose-attenuated FOLFIRINOX in LAPC, we conducted a multi-institutional prospective phase II open label study of mFOLFIRNOX in pts with both LAPC and MPC, and we report the efficacy in the LAPC cohort here. We previously reported entire cohort toxicities and MPC cohort efficacy (James et al, J Clin Oncol 33, 2015, Supp3, abst395). Methods: Previously untreated pts with LAPC (LA unresectable and borderline resectable) received mFOLFIRINOX (25% dose reductions of irinotecan & bolus 5FU) every 2 weeks. For pts who achieved max response after ≥ 8 cycles, continuation on mFOLFIRINOX or discontinuation to pursue radiation or surgery was at the discretion of the treating physician. CAT scans were obtained every 4 cycles for response assessment by RECIST. Pt characteristics, response rate (RR) and surgical outcomes in the LAPC cohort were determined. Results: 31 LAPC pts were enrolled from 11/11 to 02/14 with characteristics: med age, 63.4 yrs (range 46-86); male, 21; ECOG PS 0/1 = 15/16; head of pancreas involvement 22; biliary stent 17; LA unresectable 21; borderline resectable 10; med # of cycles 8 (range 2-21). Toxicity data was previously presented with the MPC cohort. RR (n) as follows: PR 16.1% (5); SD 77.4% (24) including minor response 29% (9); PD 0% (0); Ineval 6.5% (2). 17 pts received RT. 13 pts (41.9%) underwent resection (8 borderline, 5 unresectable at diagnosis); 6/13 pts received RT prior to resection. All 13 pts had R0 resections and12/13 were node-negative including one pathologic CR. 19 patients are alive. At 9 mo, 83.3% of evaluable pts (25/30) remained progression-free. 29 pts have been followed for ≥ 12 mo, and survival at 12 mo was 79.3% (23/29). PFS and OS have not been reached. Conclusions: In this prospective phase II trial, mFOLFIRINOX in pts with LAPC is well tolerated and associated with favorable disease control rate (100% in evaluable pts) and R0 resection rate (41.9% in intent-to-treat pts). Updated PFS and OS data will be presented. Clinical trial information: NCT01523457.
DNA polymerase ι functions in the generation of tandem mutations during somatic hypermutation of antibody genes
Authors: Robert W. Maul, Thomas MacCarthy, Ekaterina G. Frank, Katherine A. Donigan, Mary P. McLenigan, William Yang, Huseyin Saribasak, Donald E. Huston, Sabine S. Lange, Roger Woodgate, Patricia J. Gearhart
Journal: The Journal of Experimental Medicine (2016)

DNA polymerase ι (Pol ι) is an attractive candidate for somatic hypermutation in antibody genes because of its low fidelity. To identify a role for Pol ι, we analyzed mutations in two strains of mice with deficiencies in the enzyme: 129 mice with negligible expression of truncated Pol ι, and knock-in mice that express full-length Pol ι that is catalytically inactive. Both strains had normal frequencies and spectra of mutations in the variable region, indicating that loss of Pol ι did not change overall mutagenesis. We next examined if Pol ι affected tandem mutations generated by another error-prone polymerase, Pol ζ. The frequency of contiguous mutations was analyzed using a novel computational model to determine if they occur during a single DNA transaction or during two independent events. Analyses of 2,000 mutations from both strains indicated that Pol ι–compromised mice lost the tandem signature, whereas C57BL/6 mice accumulated significant amounts of double mutations. The results support a model where Pol ι occasionally accesses the replication fork to generate a first mutation, and Pol ζ extends the mismatch with a second mutation.
Part 7.3: Management of Symptomatic Bradycardia and Tachycardia
Journal: Circulation (2005)

Part 7.3: Management of Symptomatic Bradycardia and TachycardiaC ardiac arrhythmias are a common cause of sudden death.ECG monitoring should be established as soon as possible for all patients who collapse suddenly or have symptoms of coronary ischemia or infarction.To avoid delay, apply adhesive electrodes with a conventional or automated external defibrillator (AED) or use the "quick-look" paddles feature on conventional defibrillators.For patients with acute coronary ischemia, the greatest risk for serious arrhythmias occurs during the first 4 hours after the onset of symptoms (see Part 8: "Stabilization of the Patient With Acute Coronary Syndromes"). 1
A combined microRNA-based targeted therapeutic approach to eradicate glioblastoma stem-like cells
Authors: Carla L. Esposito, Silvia Nuzzo, Swati A. Kumar, Anna Rienzo, Clare L. Lawrence, Roberto Pallini, Lisa Shaw, Jane E. Alder, Lucia Ricci-Vitiani, Silvia Catuogno, Vittorio de Franciscis
Journal: Journal of Controlled Release (2016)
A selective estrogen receptor alpha agonist (ORG 37663) suppresses inflammation and arthritis in mouse models
Authors: J. Dulos, C. L. Hofstra, L. A. B. Joosten, D. H. Veening-Griffioen, M. A. Lucassen, C. M. Doorn, J. H. Graaf, A. M. M. Miltenburg, F. A. Dijcks, T. H. Ederveen, Annemieke Boots
Journal: Annals of the Rheumatic Diseases (2006)
Abstract 2148: MM-151 elicits broad and unique inhibition of cells harboring EGFR extracellular domain mutations — results of multiscale experiments with genome-edited cell lines
Authors: Hongfang Wang, Shawn P. Carey, Olga Burenkova, Jian Tang, Nastaran Gerami-Moayed, Sabrina Arena, Alberto Bardelli, Rachel Nering, Jeffrey D. Kearns
Journal: Cancer Research (2016)

Abstract Mutations in the extracellular domain (ECD) of EGFR have been reported in colorectal (CRC) patients as a mechanism of acquired resistance to the EGFR-directed antibodies cetuximab and panitumumab. Similar to EGFR intracellular domain mutations observed in patients treated with EGFR kinase inhibitors, these EGFR-ECD mutations inhibit the binding of the antibodies while maintaining EGFR signaling activity. MM-151, an investigational agent consisting of three anti-EGFR IgG1 antibodies, has been recently reported to overcome these mutations in over-expression and patient-derived cell line models. Here, we extend these studies to characterize the mechanisms of action that enable MM-151 to provide robust inhibition of EGFR-ECD mutations beyond that achievable by other monoclonal and oligoclonal EGFR antibodies. First, utilizing a cell-free binding assay with recombinant EGFR-ECD mutants, we found that MM-151, but not the Sym004 combination of two antibodies, maintained oligoclonal binding to all mutants. Second, we performed a panel of 2D and 3D in vitro experiments with over-expression and genome-edited (CRISPR-Cas9) cell lines harboring EGFR-ECD mutations to characterize target engagement, cell signaling, proliferation, and the impact of hetero- versus homozygous expression of EGFR wild type or mutant alleles. We observed that the three mechanisms of action for MM-151- antagonism of both low- and high-affinity EGFR ligands, EGFR down-regulation, and immune-effector activity— were preserved in these models. Third, we performed xenograft experiments to evaluate the behavior of MM-151 and found that MM-151 maintained inhibitory activity in an in vivo context. The results of our multiscale experiments identified the impact of combining three antibodies to overcome the high plasticity of the EGFR extracellular domain and thus reveal the potential for clinical evaluation of MM-151 in both EGFR-naïve and EGFR-refractory CRC populations. Citation Format: Hongfang Wang, Shawn P. Carey, Olga Burenkova, Jian Tang, Nastaran Gerami-Moayed, Sabrina Arena, Alberto Bardelli, Rachel Nering, Jeffrey D. Kearns. MM-151 elicits broad and unique inhibition of cells harboring EGFR extracellular domain mutations — results of multiscale experiments with genome-edited cell lines. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2148.
Marqibo®, Vincristine Sulfate Liposome Injection, for the Treatment of Advanced, Relapsed or Refractory Philadelphia Chromosome-Negative (Ph-) Acute Lymphoblastic Leukemia (ALL) in an Adolescent Young Adult (AYA) Population
Authors: Gary J Schiller, Lloyd E. Damon, Wendy Stock, Steven E Coutre, Pamela Hsu, Lucy Prasad, Dan Douer
Journal: Blood (2015)
Abstract 3682: Phosphorylation mediated conformational changes defines nuclear role of phosphatase and tensin homology (PTEN) in tumor suppression
Authors: Prerna Malaney, Jonathan Semidey-Hurtado, Jamaal Hardee, Deepal Patel, Daniel Hennessey, Kate Stanford, Emily Palumbo, Zhi Tian, Diane Allen-Gipson, Vrushank Davé.
Journal: Cancer Research (2016)

Abstract Loss of function of tumor suppressor PTEN (Phosphatase and tensin homolog) causes cancer in various tissues. PTEN C-terminal phosphorylation (pPTEN) inactivates PTEN, leading to multiple malignancies with increased severity. However, little is known about the molecular mechanisms underlying such inactivation. Therefore, the objective of our work is to ascertain the molecular mechanisms by which PTEN phosphorylation drives lung cancer. PTEN C-terminal phosphorylation at a serine-threonine cluster (Ser380, Thr382, Thr383 and Ser385) conformationally inactivates PTEN, abrogating its tumor suppressor function. Replacement of these serine/threonine residues with alanine generated an artificial phosphorylation-deficient mutant of PTEN (PTEN-4A), which is constitutively active. PTEN-4A suppressed cell proliferation and migration to a greater extent as compared to PTEN-WT. PTEN-4A preferentially localized to the nucleus and suppressed the E2F-mediated transcription of cell cycle genes. The nuclear localization sequence and phosphatase activity of PTEN-4A is critical for this transcriptional suppression. Immuno-precipitation assays show that PTEN physically associates with the transcription factor E2F1, a likely mechanism for its suppressive effect on E2F1 related genes. Further, deletion analysis of PTEN-4A protein revealed that the C2 domain is indispensable for suppression of E2F-related genes. Systematic transcriptional assays identify disease-associated C2 domain mutations that lose their ability to suppress E2F-mediated transcription, supporting the concept that these mutations are oncogenic in patients. Taken together, we reveal nuclear functions of PTEN-4A in tumor suppression that can be therapeutically leveraged for developing adjunctive cancer therapies. Small molecule inhibitors that hinder PTEN phosphorylation maybe utilized to activate PTEN nuclear function in tumors. Such adjunctive therapy has a high likelihood to reduce toxic doses of chemotherapeutic agents and targeted inhibitors, including kinase inhibitors that are being used in clinical settings. Citation Format: Prerna Malaney, Jonathan Semidey-Hurtado, Jamaal Hardee, Deepal Patel, Daniel Hennessey, Kate Stanford, Emily Palumbo, Zhi Tian, Diane Allen-Gipson, Vrushank Davé. Phosphorylation mediated conformational changes defines nuclear role of phosphatase and tensin homology (PTEN) in tumor suppression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3682.
Psat1-Dependent Fluctuations in α-Ketoglutarate Affect the Timing of ESC Differentiation
Authors: In-Young Hwang, Sojung Kwak, Sangho Lee, Hyunsoo Kim, Sang Eun Lee, Jae-Hwan Kim, Young Ah Kim, Yoon Kyung Jeon, Doo Hyun Chung, Xing Jin, Sunghyouk Park, Hyonchol Jang, Eun-Jung Cho, Hong-Duk Youn
Journal: Cell Metabolism (2016)
Abstract 3125: KCNQ1 expression is a strong prognostic biomarker for disease recurrence in stage II and III colon cancer
Authors: Sjoerd H. den Uil, Veerle M.H. Coupe, Janneke F. Linnekamp, Evert van den Broek, Jeroen A.C.M. Goos, Pien M. Delis-van Diemen, Eric J.T. Belt, Nicole C.T. van Grieken, Patricia M. Scott, Louis Vermeulen, Jan Paul Medema, Herman Bril, Hein B.A.C. Stockmann, Robert T. Cormier, Gerrit A. Meijer, Remond J. Fijneman
Journal: Cancer Research (2016)

Abstract Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Accurately identifying stage II CRC patients at high risk of recurrence and stage III patients at low risk of recurrence are key unmet clinical needs. We previously identified KCNQ1 as a tumour suppressor gene of which loss of expression was associated with poor survival in patients with CRC liver metastases. The present study aimed to examine the prognostic value of KCNQ1 in stage II and III colon cancer patients. Methods: KCNQ1 mRNA expression was assessed in 90 stage II colon cancer patients (AMC-AJCCII-90) using microarray gene expression data. KCNQ1 protein expression was evaluated by immuno-histochemistry on tissue microarrays of 386 stage II and III colon cancer patients. Results: Low KCNQ1 mRNA expression in microsatellite stable (MSS) stage II colon cancers was associated with poor disease free survival (DFS) (HR 3.35; 95% CI 1.16-9.66; p&amp;lt;0.05). Loss of KCNQ1 protein expression from epithelial cells was strongly associated with poor DFS in MSS stage II (HR 3.82; 95% CI 2.04-7.14; p&amp;lt;0.0001), MSS stage III (HR 2.93; 95% CI 1.70-5.02; p = 0.0001) and MSI stage III colon cancers (HR 5.06; 95% CI 1.07-23.89; p&amp;lt;0.05). Multivariate analysis demonstrated KCNQ1 to have independent prognostic value in addition to established clinicopathological parameters such as angioinvasion, nodal stage en MSI-status. Conclusion: We conclude that KCNQ1 is a strong prognostic biomarker for prediction of disease recurrence (HR∼4) and may aid stratification of patients with stage II MSS colon cancer and stage III MSI CRC for adjuvant chemotherapy. Because KCNQ1 protein expression is determined by immuno-histochemistry, this biomarker can be implemented in standard clinical care using existing workflows. Citation Format: Sjoerd H. den Uil, Veerle M.H. Coupe, Janneke F. Linnekamp, Evert van den Broek, Jeroen A.C.M. Goos, Pien M. Delis-van Diemen, Eric J.T. Belt, Nicole C.T. van Grieken, Patricia M. Scott, Louis Vermeulen, Jan Paul Medema, Herman Bril, Hein B.A.C. Stockmann, Robert T. Cormier, Gerrit A. Meijer, Remond J. Fijneman. KCNQ1 expression is a strong prognostic biomarker for disease recurrence in stage II and III colon cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3125.