tbuckley/cabot-search huggingface dataset:
MicroRNA regulation in mantle cell lymphoma
Authors: R. Chen, S. Patel, L. Bemis, W. Robinson, H. Myint
Journal: Journal of Clinical Oncology (2007)

8056 Mantle Cell Lymphoma (MCL) represents only 5–10% of all non-Hodgkins lymphomas, making it an uncommon but difficult form of lymphoma to treat. It has the worst prognosis among the B cell lymphomas with median survival of three years. The genetic hallmark of MCL is a t(11;14) q32 translocation which results in ectopic and dysregulated expression of cyclin D1. Recent comparative genomic hybridization studies have identied Syk as another gene important in the pathogenesis of MCL. Previous studies have suggested that post transcriptional regulation of Cyclin D1 and Syk may be important the pathogenesis of in MCL. MicroRNAs are a new class of abundant small RNAs that play important regulatory roles at the post transcriptional level by binding to the 3’ untranslated region (UTR) of mRNAs blocking either their translation or initiating their degradation. There have been numerous reports of misregulation of microRNAs and their targets in human cancers. We hypothesized that altered microRNA regulation of cyclin D1 and/or Syk may be present in MCL. Based on bioinformatics, we identified 8 microRNAs and their putative docking sites in either Cyclin D1 and Syk. We then examined their integrity in MCL cell lines, and identified a mutation in the 3’UTR of Syk at the docking site of 1 mir-452* and a SNP in mir-458. Using a GFP reporter construct with the mutated Syk 3’UTR we demonstrated that this mutation resulted in altered microRNA function. We also show that mimics of the microRNA leads to down regulation of Syk protein. This data suggests that microRNA regulation of important genes in MCL may be compromised and play a role in the development and progression of this disease. No significant financial relationships to disclose.
Identification of a novel breast cancer molecular subgroup associated with a deficiency in DNA-damage response.
Authors: J. M. Mulligan, L. A. Hill, S. Deharo, F. A. McDyer, T. S. Davison, M. Bylesjo, N. M. Lindor, L. Galligan, T. Delaney, I. A. Halfpenny, V. Farztdinov, N. Goffard, V. Proutski, K. E. Keating, P. B. Mullan, J. E. Quinn, P. G. Johnston, F. J. Couch, D. P. Harkin, R. D. Kennedy
Journal: Journal of Clinical Oncology (2011)

10511 Background: Loss of a functional DNA-damage response (DDR) sensitizes tumors to DNA-damaging as well as targeted therapeutics such as PARP-1 inhibitors. However, there is no assay to detect DDR proficiency and guide therapeutic choice. Although abrogation of the DDR can result from multiple mechanisms, including loss of components of the BRCA/Fanconi anemia pathway, the resultant DNA-damage may activate common molecular pathways. We hypothesized that these pathways could define a molecular subgroup and form the basis of a diagnostic test for sensitivity to DNA-damaging and targeted therapies. Methods: Using DNA-microarray technology, we profiled a cohort of BRCA mutant enriched and thus DDR-deficient (DDRD) primary breast tumor samples. Hierarchical agglomerative clustering analysis was performed and identified a molecular subtype in breast cancer characterized by activation of pathways known to respond to DNA damage. Computational classification was performed resulting in the generation of a gene signature that could identify this DDRD molecular subgroup. Results: A subset of tumors was identified as displaying biology associated with DDRD. Computational classification was performed based upon expression of this DDRD-related biology resulting in the generation of a 44-gene signature. Retrospective validation in independent breast cancer datasets indicated that the DDRD signature was predictive of response to anthracycline-based chemotherapy with an odds ratio of 15.02 (CI 3.51 – 63.49). In addition, the signature could accurately identify non-responding patients with a negative predictive value of 0.96 (CI 0.88-0.99). Conclusions: We report the identification of a novel molecular subgroup associated with a deficiency in DDR that can be identified in both ER-positive and ER-negative breast cancer using a 44-gene signature. This subgroup is enriched for BRCA1/2 mutant tumors and demonstrates sensitivity to DNA-damaging agents. We propose that the DDRD signature could be used as a patient stratification tool for existing chemotherapy or as a clinical trial enrichment tool for DNA-damaging or repair targeted drugs in development.
Abstract 12423: Adoption of Radial Access and Comparison of Outcomes to Femoral Approach in Percutaneous Coronary Intervention: An Updated Report From the NCDR(R) (2007-2011)
Authors: Dmitriy N Feldman, Rajesh V Swaminathan, Lisa Kaltenbach, Dmitri Baklanov, Luke K Kim, S. Chiu Wong, Robert M Minutello, John Messenger, Issam Moussa, Kirk Garratt, Robert N Piana, William B Hillegass, Mauricio Cohen, Ian C Gilchrist, Sunil V Rao
Journal: Circulation (2012)

Background: Prior reports have shown slow uptake of transradial percutaneous coronary intervention (r-PCI) in the US despite its widespread dissemination outside the US and association with lower r...
Association Between Change in Body Mass Index, Unified Parkinson’s Disease Rating Scale Scores, and Survival Among Persons With Parkinson Disease
Authors: Anne-Marie A. Wills, Adriana Pérez, Jue Wang, Xiao Su, John Morgan, Suja S. Rajan, Maureen A. Leehey, Gregory M. Pontone, Kelvin L. Chou, Chizoba Umeh, Zoltan Mari, James Boyd
Journal: JAMA Neurology (2016)

Greater body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) is associated with improved survival among persons with Huntington disease or amyotrophic lateral sclerosis. Weight loss is common among persons with Parkinson disease (PD) and is associated with worse quality of life.
Abstract 176: Saxagliptin and Tadalafil Differentially Alter Global and Cellular Cardiac Function in a Translational Miniature Swine Model of Left Ventricle Hypertrophy
Authors: Jessica A Hiemstra, Anne K Gibson, Jan R Ivey, Melissa S Cobb, Christopher P Baines, Maike Krenz, Timothy L Domeier, Craig A Emter
Journal: Circulation Research (2014)

Left ventricular (LV) hypertrophy is a common characteristic of heart failure with preserved ejection fraction (HFpEF). Our lab recently characterized a mini-swine model of LV hypertrophy induced by aortic banding (AB) that displays clinical features associated with HFpEF including LV hypertrophy, diastolic dysfunction, and depressed contractile reserve. Disrupted cGMP signaling, a result of impaired production or enhanced catabolism, may play a role in development of HFpEF. We hypothesized preservation of cGMP signaling would attenuate pathological remodeling and improve cardiac function. The purpose of this study was to promote cGMP signaling via two mechanisms: 1) the DPP4 inhibitor saxagliptin; and 2) the PDE5 inhibitor tadalafil. We assessed whole heart and individual cardiomyocyte function 6 months post-AB in: control non-banded (CON; n=6), AB-control (AB; n=7), AB saxagliptin-treated (AB-SAX; n=7), and AB tadalafil-treated (AB-TAD; n=8) swine. Heart weight:body weight ratio increased to a similar extent in all AB groups. However, changes in cardiomyocyte morphology were variable. Cardiomyocyte length was increased only in the AB-TAD group, while cell width increased in both AB and AB-TAD animals. Cardiomyocyte length:width ratio decreased in the AB and AB-TAD groups, commensurate with decreased LV end diastolic (ED) and end systolic (ES) volumes. These changes were prevented in AB-SAX animals, as LV volumes and cell morphology were similar to CON. Pressure-volume analysis showed resting LV wall stiffness (ED pressure volume relationship [EDPVR] slope) was increased similarly in all AB groups. Increased resting LV contractility (ESPVR and preload recruitable stroke work) was observed in AB and AB-TAD animals. Interestingly, cardiomyocyte shortening was reduced in the AB-TAD group contrasting findings observed at the whole heart level. Saxaglitpin attenuated hypercontractile LV function at rest and preserved normal cardiomyocyte shortening. In conclusion, LV and cardiomyocyte function was distinctly altered in response to separate methods of pharmacological cGMP regulation. Our data suggest different pharmacological approaches to augment cGMP signaling promote distinct LV functional adaptations to developing HF.
The Iowa 500: suicide in mania , depression, and schizophrenia
Authors: G Winokur, M Tsuang
Journal: American Journal of Psychiatry (1975)

Long-term (30-to 40-year) follow-up data for 76 manic patients, 182 depressives. 170 schizophrenics, and 109 controls showed that 10 per cent of the schizophrenics, 8.5 percent of the manics, and 10.6 percent of the depressives who were decreased had died by suicide. None of the controls had committed suicide. The authors suggest that suicide is a significant outcome factor in all three of these illnesses and is likely to occur at an earlier age in schizophrenia than in the other illnesses.
A randomized comparison of standard chemotherapy versus alternating chemotherapy and maintenance versus no maintenance therapy for extensive-stage small-cell lung cancer: a phase III study of the Eastern Cooperative Oncology Group.
Authors: D S Ettinger, D M Finkelstein, M D Abeloff, J C Ruckdeschel, S C Aisner, J C Eggleston
Journal: Journal of Clinical Oncology (1990)

The present randomized, prospective study was designed to assess whether alternating induction cyclophosphamide, doxorubicin, vincristine-altretamine (hexamethylmelamine), etoposide, and methotrexate (CAV-HEM) chemotherapy is better than standard chemotherapy (CAV) in improving response, survival, and remission time in 577 evaluable patients having extensive-disease small-cell lung cancer (SCLC). In addition, the study was designed to assess the impact of maintenance chemotherapy following a complete response (CR) on the time to progression and survival. The response rates (CR plus partial response [PR]) for CAV-HEM and CAV were 64% and 61%, respectively, but 23% of the patients on CAV-HEM achieved a CR compared with 16% for CAV alone (P = .03). Among complete responders, the continuation of therapy significantly increased the remission time for patients on CAV, while maintenance therapy for patients on CAV-HEM had no significant impact on remission time. However, the increased remission had little effect on survival. Patients on CAV maintenance therapy survived marginally longer than those patients on no maintenance therapy, whereas patients who received CAV-HEM and no maintenance therapy survived longer than those on maintenance therapy. CAV-HEM was associated with significantly higher severity of complications (ie, mainly myelosuppression) than CAV (P = .01). Maintenance chemotherapy was associated with significantly more complications than no maintenance therapy. Patients on CAV-HEM lived significantly longer than those on CAV alone (45.9 weeks v 42.7 weeks; P = .002). Ten percent of patients treated on CAV-HEM survived at least 2 years, compared with 4% on CAV alone. In our study involving patients with extensive-disease SCLC, the alternating induction chemotherapy significantly increased the CR rates and had a small impact on long-term survival compared with the results achieved with standard induction chemotherapy. Moreover, when the alternating induction chemotherapy was used, long-term maintenance chemotherapy was not needed.
A New Complex Ph 1 Translocation Involving Three Chromosomes: Brief Communication 2
Authors: Shin-ichi Sonta, Avery A. Sandberg
Journal: JNCI Journal of the National Cancer Institute (1977)

A case of Ph1-positive chronic myelocytic leukemia associated with a complex translocation involving chromosomes No. 9, No. 17, and No. 22 was described. All cells in the marrow contained this complex karyotypic picture, and no cells with the usual type of Ph1 translocation were present. With banding analysis, the karyotypic picture consisted of 46,XX,t(9;22;17)(q34;q11;q21). The published cases of usual and complex Ph1 translocations were summarized in tabular form and some aspects of the translocations discussed.
Blood loss associated with musculoskeletal tumor surgery
Authors: A. Kawai, H. Kadota, U. Yamaguchi, Y. Morimoto, M. Endo, R. Nakayama, F. Nakatani, H. Chuman, Y. Beppu
Journal: Journal of Clinical Oncology (2005)

9052 Background: Information about the extent of operative blood loss and the subsequent need for transfusion is critical for optimal perioperative patient management. However, no organized data regarding the blood losses associated with musculoskeletal tumor surgery has been published to date. The present study therefore aimed to examine the extent of blood loss associated with various surgical procedures used for the treatment of musculoskeletal tumors in a large, well-defined sample. Methods: The records of 1,047 consecutive operations for musculoskeletal tumors, performed on 866 patients, were reviewed. The total blood loss, blood transfusion requirement, operative time and type of operation were recorded in each case. Results: The total blood loss ranged from 0 to 26,050 ml (median: 95 ml). The operative time ranged from 5 to 1,140 minutes (median: 105 minutes). There was a significant correlation between the total blood loss and the operative time (r=0.683, p<0.0001). The median blood loss was 10 ml in biopsies, 100 ml in curettages, 190 ml in amputations or disarticulations, 30 ml in marginal resections and 380 ml in wide resections (bone tumors: 2,155 ml, soft tissue tumors: 180 ml). As expected, wide resections for malignant tumors were associated with significantly more blood loss than marginal resections for benign ones (p<0.001). Also, resections of bone tumors were accompanied by significantly (p<0.001) more blood loss than those of soft tissue tumors. Blood transfusions were required after 210 (20.1%) operations. The incidence of transfusion was 0.4% in biopsies, 20.8% in curettages, 34.1% in amputations or disarticulations, 5.0% in marginal resections and 37.9% in wide resections (bone tumors: 73.3%, soft tissue tumors: 22.2%). Conclusions: Our results provide the first exhaustive data about blood loss and the subsequent need for transfusion after surgery for various kinds of musculoskeletal tumor. No significant financial relationships to disclose.
Antitumor effects of lenalidomide in combination with IDEC114 (anti CD80) in lymphoma bearing severe combined immunodeficiency (SCID) mouse model
Authors: N. M. Reddy, F. Hernandez-Ilizalituri, J. Knight, M. S. Czuczman
Journal: Journal of Clinical Oncology (2007)

3037 Background: Lenalidomide is a thalidomide analogue with immunomodulatory effects. We previously demonstrated that lenalidomide enhances the biological activity of rituximab. In our current work we further studied the effects of combining lenalidomide with IDEC114, a primatized anti-CD80 monoclonal antibody, which is undergoing clinical testing in B-cell lymphoma. Methods: Raji cells were exposed in vitro to lenalidomide (10μg/ml) or DMSO over five days. Changes in DNA synthesis were determined by [3H]-thymidine uptake. For ADCC and CMC assays, lenalidomide or control exposed Raji cells were labeled to 51 Cr and then exposed to IDEC114 or isotype control and PBMC’s or human serum. For in vivo studies, 6–8 week old SCID mice were inoculated with 1×10 6 Raji cells via tail vein injection and after a period of 72 hours animals were divided into four cohorts. Lenalidomide was administered intraperitoneally (i.p) at 0.5mg/kg/dose on days +3, +4, +8, +9, +13, +14, +18 and +19. IDEC114 was administered via tail vein injection at 10mg/kg/dose on days +5, +10, +15 and +20. Difference in survival between treatment groups was performed by Kaplan-Meier analysis. Results: In vitro exposure of Raji to lenalidomide for five consecutive days enhanced the anti-proliferative effects of IDEC114 when compared to control. In addition, an improvement in IDEC114-associated ADCC was observed in lenalidomide-exposed Raji cells. In vivo treatment of SCID mice with lenalidomide in combination with IDEC114 led to prolongation of survival (44 days) compared to either biological agent alone (p&lt;0.01). Conclusions: Our current research demonstrates that Lenalidomide when added to IDEC114 has augmented in vitro antitumor activity (i.e, antiproliferation and ADCC) and synergistic effects in vivo (i.e., prolongation of survival). We hypothesize and currently are evaluating whether the improvement in in vivo antitumor activity of IDEC114, when combined with Lenalidomide, is secondary to potential changes in the tumor microenvironment and/or IMiD-primed upregulation of NK cells and ADCC. This promising unique combination of biologics warrants evaluation as a clinical trial. (Supported by USPHS grant PO1-CA103985 from the National Cancer Institute.) No significant financial relationships to disclose.
Cost effective chemotherapy (irinotecan and cisplatin) for treatment of lung cancer in developing countries: Observations from India
Authors: D. Behera, R. Aggarwal, A. N. Aggarwal, D. Gupta, S. K. Jindal, S. C. Sharma, R. Kapoor, A. Jaiswal
Journal: Journal of Clinical Oncology (2008)

19121 Background: Cost factor is an important consideration and constraint in resource limited countries. A relatively cheaper drug combination of irinotecan and cisplatin was used by us in patients of advanced lung cancer (NSCLC and SCLC) and are an extension of our earlier experience. Methods: Chemotherapy was administered on an outpatient basis consisting of irinotecan 70mg/m2, and cisplatin (60 mg/m2) with proper hydration and anti-emetics every 28 days. Results: 257 histogically proven patients (104- small cell,153 non small type) were included. 44 are still receiving chemotherapy. Those who completed minimum three cycles were included for analysis. Data was analyzed for 74 small cell and 117 non-small types. There were 49 extensive and 25 limited stage small cell cancers. There were 152 males and 39 females. Performance status ranged from 70 to 100 (Kornofsky scale). 71 patients received local radiotherapy of 20 to 50Gy. 138 completed 5 cycles,39 completed four. The remaining received three cycles of chemotherapy at the time of data analysis. Complete response was observed in 27 (14.1%) and partial in 54 (28.2%). Lesions remained stable ranging from 8 weeks to 354 weeks (median of 30 weeks; for small cell lung cancer - 36 weeks and non-small cell lung cancer- 29weeks) before progression. The median survival has been 39+ weeks for those who completed five cycles. For others it has been 27+ weeks and they are still under follow up. 114 patients (59.7%) are surviving beyond 6 months, 37 patients (19.4%) beyond one year and 19 patients (9.9%) are still alive after 2 years. 65 patients gained weight (mean increase 4.3kg) 56 lost weight (2.4 kg). Performance status improved in 81and deteriorated in 39; in the remaining patients it was static. Side effects were minimal (alopecia, nausea, vomiting, diarrhea, skin changes and neuropathy). Conclusions: The regimen is effective and well tolerated in patients with new, relapsed or refractory SCLC and NSCLC. The cost of the present regimen is less than US$ 100 per cycle. Those who wish to take the advantage of chemotherapy, but could not afford high cost of therapy with taxanes/gemcitabine etc, irinotecan and cisplatin can be offered to them for improved survival. No significant financial relationships to disclose.
Parents Do Not Always Have to Get Their Way: Why Critical Congenital Heart Disease Screening for Newborns Should Be Mandatory
Authors: David Trafimow
Journal: The American Journal of Bioethics (2016)

In their target article, “Legal and Ethical Considerations in Allowing Religious Exemptions From Newborn Critical Congenital Heart Disease (CCHD) Screening,” Hom and colleagues (2016) argued that p...
Disease-free survival as a surrogate endpoint for overall survival in an adjuvant trial of curatively resected stomach cancer using individual patient data meta-analysis
Authors: T. Burzykowski, Y. Bang
Journal: Journal of Clinical Oncology (2009)

4517 Background: In investigations of the effectiveness of oncology drugs, overall survival (OS) is considered as the gold standard end point. However, the disadvantage of OS is that it requires an extended follow-up. A reasonable candidate for a surrogate for OS in the adjuvant setting is disease free survival (DFS). DFS is defined as recurrence of stomach cancer, all second cancers, or death from any cause. Recently, some evidence has been offered for the use of DFS as a surrogate for OS in, e.g., colorectal cancer. We evaluated 3 year DFS as a surrogate for 5 year OS in adjuvant trials of stomach cancer by using individual-patient data (IPD) meta- analysis validation criteria. Methods: The GASTRIC group initiated an IPD meta-analysis of all randomized clinical trials comparing chemotherapy versus surgery alone for patients with curatively resected stomach cancer. The validity of DFS at 3 years as a surrogate for OS at 5 years was investigated by using multiple analysis techniques, which included measures of correlation between the endpoints and between the treatment effects, and the percentage of agreement in the log-rank tests for the two endpoints at the trial level. Results: Among the 31 eligible trials, at most 25 collected the date of recurrence (5,014 pts). As of December 2008, IPD were available from 13 randomized controlled trials (3,161 patients). Seventy-seven percent of patients (1,280/1,652 pts) who recurred during the follow-up period, recurred within the first 3 years after study enrollment. At the trial level, 12 out of the 13 trials yielded the same conclusions for both endpoints at the 0.05 significance level. The R 2 value between both endpoints was equal to 0.97 and Spearman's rank correlation was equal to 0.92. The R 2 value between hazard ratios for OS and DFS was equal to 0.85 and Spearman's rank correlation was equal to 0.87. Conclusions: Our preliminary results, which are based on 63% of the targeted data, show that the 5-year OS and the 3-year DFS are highly correlated. Additionally, the hazard ratios for DFS and OS are also strongly associated. This suggests that 3-year DFS may be a good surrogate for a 5-year OS. The results based on the most recent update of the IPD will be presented during the conference. No significant financial relationships to disclose.