tbuckley/cabot-search huggingface dataset:
Clinical Evaluation of Nuclear Matrix Protein 22 (NMP22) in Urine as a Novel Marker for Urothelial Cancer
Authors: N Miyanaga, H Akaza, S Ishikawa, M Ohtani, R Noguchi, K Kawai, K Koiso, M Kobayashi, A Koyama, T Takahashi
Journal: European Urology (1997)
Cross platform comparison of multigene predictors of response to neoadjuvant paclitaxel/FAC chemotherapy in breast cancer generated by cDNA arrays and Affymetrix GeneChips
Authors: L. Pusztai, J. Wang, K. Coombes, S. Hoersch, M. Ayers, J. Ross, K. Hess, G. Hortobagyi, W. Symmans, J. Stec
Journal: Journal of Clinical Oncology (2004)

503 Background: Transcriptional profiling is under study as a clinical research tool to classify cancer into clinically relevant sub-groups. Comparison of results across multiple laboratories and platforms is critical for the future development of a useful diagnostic test. Methods: In this study, we compared muligene predictors developed on 2 distinct profiling platforms Affymetrix GeneChip and Millennium cDNA arrays using pre-treatment fine needle aspirates of 33 breast cancer patients. RNA was hybridized from the same samples to both arrays. We independently identified gene expression signatures associated with pathologic complete response (pCR) to neoadjuvant paclitaxel followed by 5-FU, doxorubicin, cyclophosphamide chemotherapy on each platfrom and examined their predictive value on the other platform. Results: Only 30 % of all measurements of corresponding genes on both platforms showed Person correlation coefficient of ≥ 0.7, 54 % of cDNA clones matched with ≥ 1 probe sets on the Affy chip and there was large variation in probe set to probe set correlation with the matching cDNA result. The top response discriminating gene lists consisted of 182 genes for Affy p≤0.006 and 45 for cDNA, p≤ 0.002, with only 17 gene overlap. The top genes performed well in intra-platform supervised hierarchical clustering each correctly separating 91% of cases. However cross-platform application resulted in substantially lower clustering accuracy of 45% (Affy to cDNA) and 79% (cDNA to Affy). When only the 17 overlapping genes were used for clustering 67% (Affy) and 64% (cDNA) of cases were correctly clustered. Similar results were obtained when linear discriminant analysis and Generic Algorithm were used for outcome prediction. Conclusion: Distinct predictive marker sets can be identified from the same samples using different gene expression profiling platforms. Predictors perform well on one platform but cross-platform comparisons are less informative. Misclassification rates may be slightly improved with careful gene selection of probes with high correlation coefficients. No significant financial relationships to disclose.
Microarray cluster analysis reveals individual genes and biological processes associated with COPD
Authors: Dimitris Kampas, Nikolaos Soulitzis, Eirini Neofytou, Nikolaos M. Siafakas
Journal: European Respiratory Journal (2014)

Background: COPD is a multifactorial degenerative disease, mainly caused by smoking. However, several other mechanisms contribute to the development and progression of COPD, including inflammatory response by infiltrating macrophages and lymphocytes, abnormal cellular growth, increased apoptosis, extracellular matrix destruction, oxidative DNA damage repair and transcription activation.  Objective: To identify, with the help of genome-wide analysis tools, the intracellular pathways, and the individual genes within them, that are associated with COPD.  Methods: Gene expression microarrays, conducted on lung tissue samples from 5 selected COPD patients (GOLD stage II) and 5 non-COPD smokers using the U133 Plus 2.0 Array chip by Affymetrix, were clustered according to gene biological functions.  Results: Cluster analysis within biological pathways that are associated with COPD revealed numerous genes of interest: A) Apoptosis: IL-1B, Perforin 1, K-RAS, AKT1, FGF2, TP63; B) Aging: TIMP3, Decorin, JUN, PTEN, TGFB3; C) Oxidative stress: TLR4, peroxiredoxins, OGG1, APOE, DUOX1; D) Inflammation: CCL18, Thrombospondin 1, ANXA1, HDAC9, IL-1A; E) Extracellular matrix: fibronectin 1, CCDC80, VHL, NF1; F) Transcription regulation: MAPK1, HIF1A, STAT1, HDAC1, SMAD5, SP7. Additionally, several less known pathways were also flagged: I) respiratory gaseous exchange; II) chromatin organization; III) protein methylation; IV) oxidative demethylation; V) surfactant homeostasis.  Conclusions: Our findings suggest that apart from well described genes that possibly play a significant role in COPD, there are biological pathways and gene clusters that are also worth investigating.
Modulation of renal kallikrein production by dietary protein in streptozotocin-induced diabetic rats.
Authors: A A Jaffa, R H Silva, B Kim, R K Mayfield
Journal: Journal of the American Society of Nephrology (1996)

Renal kallikrein levels and excretion rates are increased in insulin-treated diabetic rats with hyperfiltration, and inhibition of kallikrein or blockade of kinin receptors reduces GFR and RPF. In contrast, insulin-deprived severely (SD) diabetic rats that display renal vasoconstriction show reduced levels and excretion rates of renal kallikrein. In these two models, dietary protein manipulation was utilized to study further the relationships between renal kallikrein and renal hemodynamic regulation. Insulin-deprived SD and insulin-treated moderately diabetic (MD) rats were fed a low (9%), normal (25%), and a high (50%) protein diet. In SD rats fed the 50% protein diet, GFR, RPF, and kallikrein excretion rate were increased compared with SD rats fed the 25% protein diet (GFR, 2.66 +/- 0.16 versus 1.74 +/- 0.30 mL/min; RPF, 7.78 +/- 0.58 versus 5.14 +/- 1.03 mL/min; total kallikrein, 248 +/- 24 versus 120 +/- 30 micrograms/24 h, SD 50% versus SD 25%, respectively; P < 0.005). In MD rats fed the 9% protein diet, GFR, RPF, and kallikrein excretion rate were significantly reduced compared with MD 25% protein-fed rats (GFR, 1.54 +/- 0.07 versus 1.95 +/- 0.09 mL/min; RPF, 5.58 +/- 0.35 versus 7.81 +/- 0.35 mL/min; total kallikrein, 119 +/- 8.3 versus 219 +/- 15 micrograms/24 h, MD 9% versus MD 25%, respectively; P < 0.005). Protein restriction in normal nondiabetic rats resulted in a twofold decrease in kallikrein mRNA levels. These findings suggest that the renal hemodynamic response to dietary protein manipulation in diabetic rats could be mediated via changes in renal kallikrein-kinin system activity.
Targeting Warburg Effect in Cancers with PEGylated Glucose
Authors: Karthikeyan Narayanan, Nandanan Erathodiyil, Began Gopalan, Shiya Chong, Andrew C. A. Wan, Jackie Y. Ying
Journal: Advanced Healthcare Materials (2016)

In highly proliferative cancer cells, energy is predominantly produced by a high rate of glycolysis, followed by lactic acid fermentation, despite the availability of oxygen – an observation known as the Warburg effect. As a consequence, cells employing this glycolytic pathway require high uptake of glucose and increased metabolic rates to maintain their proliferation. It has been hypothesized that by blocking glucose uptake using modified glucose molecules, apoptosis in the cancer cells can be induced. In this study, it has been showed that several poly(ethylene glycol) (PEG)‐modified glucose compounds could reduce cell proliferation in various cancer cell lines by a phenomenon that blocked the availability of the glucose transporters and reduced AKT1 (serine/threonine‐specific protein kinase) activation. Xenograft cancer models that are intravenously administered with glucose‐conjugated branched PEG (GBrP) daily for 14 d show little tumor development, as compared to the control group without GBrP treatment. The toxicological effects and the pharmacokinetics of the PEGylated glucose are studied in rodents. The PEGylated glucose exerts no systemic toxicity at 40 mg kg −1 dosage. However, doses above 80 mg kg −1 show dose‐dependent toxicity in all the organs analyzed. The present results suggest PEGylated glucose as a promising “metabolic therapy” approach for the treatment of cancer.
Durable responses and long-term progression-free survival observed in a phase II study of MDX-010 alone or in combination with dacarbazine (DTIC) in metastatic melanoma
Authors: S. A. Fischkoff, E. Hersh, J. Weber, J. Powderly, K. Khan, A. Pavlick, W. Samlowski, S. O’Day, G. Nichol, M. Yellin
Journal: Journal of Clinical Oncology (2005)

7525 Background: CTLA-4 is a negative regulator of cytotoxic T cell responses and may contribute to tumor escape from immune surveillance. MDX-010 is an IgG1κ fully human monoclonal antibody that blocks CTLA-4 function and is being studied in patients with metastatic melanoma and other malignancies. The current Phase II study was conducted to determine the safety and efficacy of MDX-010 when given alone or in combination with dacarbazine in chemotherapy and vaccine naïve patients with unresectable metastatic melanoma. Dacarbazine is an FDA approved agent for metastatic melanoma with an approximate 10% objective response rate (ORR) but no demonstrable survival benefit. Long-term follow-up data on response duration and median progression-free survival for this Phase II study is now reported. Methods: Patients were randomized to receive MDX-010 at 3 mg/kg monthly x 4 (arm A; n=37) or MDX-010 in combination with dacarbazine 250 mg/m2 for 5 days monthly x 4 (arm B; n=35). Clinical response was measured by RECIST at week 12 and patients were followed every 3 months until disease progression. Results: In Arm A there were 2 PRs (ORR 5%) and 4 SD. In Arm B there were 2 CRs and 4 PRs (ORR 17%) as well as 4 SDs. Long-term durable objective responses and disease stabilization have been observed in both monotherapy and combination arms of the study. In Arm A the 2 PRs are continuing at 11.9+ and 14+ months and 1 patient with SD is ongoing at 18.2+ months. In Arm B the 2 CRs are continuing at 12.6+ and 16.3+ months, and 1 PR is ongoing at 16.7+ months. The median progression-free survival in Arm A is 82 days and 99 days in Arm B. Conclusions: MDX-010 alone or in combination with dacarbazine can induce durable (i.e., greater than 1 year) objective clinical responses in previously untreated patients with metastatic melanoma. Furthermore, the ORR observed in patients treated with the combination of dacarbazine and MDX-010 appears higher than that reported with dacarbazine alone. The combination of dacarbazine plus MDX-010 merits further study in patients with metastatic melanoma. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Medarex Medarex Medarex Medarex Medarex
Efficacy and Safety of Pazopanib for Unresectable Soft Tissue Sarcoma: a Retrospective Study
Authors: Shukuei Ito, Masanobu Takahashi, Shunsuke Sugiyama, Ken Saijyou, Hiroshi Soeda, Natuko Chiba, Takahiro Mori, Hideki Shimodaira, Shunsuke Katou, Chikashi Ishioka
Journal: Annals of Oncology (2014)
Development of Preneoplastic and Neoplastic Lesions of the Liver in Male Rats Given 0.025 Percent &lt;italic&gt;N&lt;/italic&gt;-2-Fluorenyldiacetamide&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Melvin D. Reuber
Journal: JNCI Journal of the National Cancer Institute (1965)

Three hundred sixty-eight male rats were fed 0.025 percent N-2-fluorenyldiacetamide in a semisynthetic diet for varying periods until there were hyperplastic lesions of the liver. The carcinogenic diet was then discontinued so that the evolution of such lesions could be studied. Cirrhosis developed simultaneously with hyperplasia of the parenchymal cells as long as the carcinogen was fed. After feeding of the carcinogen was discontinued, the cirrhosis decreased in severity and regressed whereas the hyperplastic hepatic cells continued to grow. The change of the parenchymal cells from hyperplastic to neoplastic took place gradually over a long period. Before becoming well-developed carcinomas, areas of hyperplasia passed through the stages of nodules of hyperplasia, nodules with atypical cells, and small hepatocellular carcinomas. Most carcinomas were well differentiated histologically, with the remaining highly or poorly differentiated. Only a few of the earliest hyperplastic lesions progressed to carcinomas. Some of them disappeared. Most underwent degenerative cytoplasmic changes. On the other hand, the nodules of hyperplasia, present when the carcinogen was discontinued, usually developed into hepatocellular carcinomas or remained as nodules. The rate at which the hyperplastic lesions grew depended on the duration of carcinogen administration; the lesions developed most typically after 16 weeks on carcinogenic diet. With shorter or longer periods of feeding, it was more difficult to distinguish histologically between hyperplastic nodules and well-differentiated hepatocellular carcinomas because the cords were so well formed in the carcinomas. The biological behavior of the carcinomas depended on the morphologic pattern, size, and duration of carcinogen feeding.
The aspirin-induced long non-coding RNA OLA1P2 blocks phosphorylated STAT3 homodimer formation
Authors: Haiyan Guo, Jun Liu, Qiwen Ben, Yuehong Qu, Man Li, Ying Wang, Wantao Chen, Jianjun Zhang
Journal: Genome biology (2016)

Although the chemopreventive effects of aspirin have been extensively investigated, the roles of many cell components, such as long non-coding RNAs, in these effects are still not completely understood. We identify an aspirin-induced upregulated lncRNA, OLA1P2, in human colorectal cancer. Aspirin induces demethylation of the FOXD3 promoter and promotes expression of the FOXD3 gene. Subsequently, upregulated FOXD3 protein transcriptionally activates lncRNA OLA1P2 expression. OLA1P2 upregulation markedly affects STAT3 signaling pathway activity by inhibiting the nuclear import of phosphorylated STAT3. The phosphorylation of tyrosine-705 of STAT3 is the first step in OLA1P2 binding, and the formation of phosphorylated STAT3 homodimers is subsequently blocked. OLA1P2 interacts directly with STAT3 due to OLA1P2 sharing the same conservative STAT3 transcription response element as STAT3 targets. Regular use of aspirin dramatically decreases the number of metastatic nodules of cancer cells in immunodeficient mouse lungs, and OLA1P2 silencing markedly weakens the anti-metastatic activity of aspirin in the lungs. Additionally, low OLA1P2 levels are associated with malignant transformation and lower overall survival in cancers. The present study finds that the aspirin-FOXD3-OLA1P2-STAT3 axis exhibits exciting anticancer effects and provides new insights into the chemopreventive mechanisms underlying aspirin use.
More computer use during consultations is linked to lower patient satisfaction
Authors: Jacqui Wise
Journal: BMJ (2015)

Doctors who use the computer heavily during a consultation can leave patients feeling dissatisfied, a small observational study published in JAMA Internal Medicine has found.1

The research was carried out at a “safety net” clinic in a public hospital serving a population with poor proficiency in English and limited health literacy. The researchers recorded 71 …
A randomized phase II trial of <sup>177</sup>lu radiolabeled monoclonal antibody J591 (<sup>177</sup>Lu-J591) and ketoconazole in patients (pts) with high-risk castrate biochemically relapsed prostate cancer (PC) after local therapy.
Authors: S. T. Tagawa, J. Osborne, P. J. Christos, S. Vallabhajosula, K. Petrillo, K. Nadeau, L. Tyrell, H. Beltran, S. J. Goldsmith, D. M. Nanus
Journal: Journal of Clinical Oncology (2010)

TPS248 Background: Biochemical recurrence without evidence of PC on standard CT/MRI and bone scans after local therapy is common. Salvage radiotherapy affords a cure to a proportion of pts with biochemical relapse, but most suffer disease progression because of micrometastatic PC outside of the radiation field. J591 is a monoclonal antibody that targets the extracellular domain of prostate specific membrane antigen (PSMA). A phase II trial of single-dose 177Lu-J591 radioimmunotherapy (RIT) in pts with progressive, metastatic castration-resistant prostate cancer (CRPC) demonstrated excellent targeting of metastatic sites, efficacy, and acceptable toxicity (Tagawa et al, ASCO 2008). In general, RIT appears to have its greatest impact in the setting of minimal disease (Kaminski NEJM 2005; Leonard JCO2005; Press JCO 2006) and the beta emission of 177Lu is best suited for lesions 1-3 mm in diameter (O'Donoghue J Nuc Med 1995) (i.e. micrometastatic disease). Methods: Men with high-risk CRPC (PSA doubling time < 8 months and/or PSA > 20 [Smith JCO 2005]) and no evidence of disease on CT/MRI and bone scans are randomized in a 2:1 fashion to receive double-blinded 177Lu-J951 vs 111In-J591 (control) and will undergo planar gamma camera imaging with SPECT following infusion. All pts receive ketoconazole plus hydrocortisone. The primary endpoint of the study is 18-month metastasis-free survival. 140 pts will be treated to allow 80% power with a 2-sided alpha of 5% to detect a 25% absolute difference (50% vs. 75% metastasis free) in radiographically apparent metastasis at 18 months (with interim analysis after 50% of pts have at least 12 months follow- up). Secondary/exploratory endpoints include evaluation of radiolabeled J591 imaging to detect sites of metastases not apparent on standard CT/MRI and bone scan, validation of adrenal androgen levels as biomarkers for ketoconazole (Ryan Clin Cancer Res 2007), analysis of circulating tumor cells for PSMA expression and to predict the appearance of radiographic metastases, and exploration of plasma markers of hemostasis, fibrinolysis, and angiogenesis as biomarkers. No significant financial relationships to disclose.
Family background and sexual abuse associated with eating disorders
Authors: J F Kinzl, C Traweger, V Guenther, W Biebl
Journal: American Journal of Psychiatry (1994)

The authors examined the possible relationship of negative early familial experiences and childhood sexual abuse to the later development of eating disorders.Three anonymous questionnaires--a sexual abuse screening checklist, the Biographic Inventory for Diagnosis of Behavioral Disturbances, and the Eating Disorder Inventory--were distributed to 350 female university students.Of the 202 women who completed the questionnaires, 44 (21.8%) were victims of childhood sexual abuse. There were no significant differences in the total or the subscale scores on the Eating Disorder Inventory among women with no, one, or repeated incidents of sexual abuse. However, women who reported an adverse family background displayed significantly higher Eating Disorder Inventory total and subscale scores than did women who assessed family background as a secure base.The data in this nonclinical female cohort suggest that childhood sexual abuse is neither necessary nor sufficient for the later development of an eating disorder, while an adverse family background may be an important etiological factor.
Abstract 13680: Impact of Estimated Glomerular Filtration Rate and Proteinuria on Contrast-induced Nephropathy in Patients With Cardiac Catheterization
Authors: Yoshihiko Saito, Makoto Watanabe, Kazutaka Aonuma, Atsushi Hirayama, Nagara Tamaki, Hiroyuki Tsutsui, Toyoaki Murohara, Hisao Ogawa, Takashi Akasaka, Michihiro Yoshimura, Akira Satoh, Tadateru Takayama, Mamoru Sakakibara, Susumu Suzuki, Kenichi Ishigami
Journal: Circulation (2014)

Background: Contrast induced nephropathy (CIN) has been a subject of concern to cardiologists in recent year because CIN is associated with increased morbidity, mortality, and healthcare expense. Incidence and risks of contrast induced nephropathy (CIN) after cardiac catheterization are not clear in Japan. Objective: The aim of this study is to investigate the pre-procedural predictors of CIN. Methods: This study, named the study for CIN after cardiac catheterization in Japan (the CINC-J study), is a multicenter cohort study, which examined 1021 patients undergoing cardiac catheterization from 29 hospitals in all over Japan. We divided into 4 groups on the basis of estimated glomerular filtration rate (eGFR: &gt;60 ml•min-1•1.73m-2 = Normal, 45 to 60 = Mild, 30 to 45 = Moderate, &lt;30 = Severe). CIN was defined as an increase in serum creatinine level of 0.5mg/dl or 25% from 48 to 72 hours after contrast-medium injection. Results: The incidence of CIN was significantly higher in patients with proteinuria than those without proteinuria (13.6% vs. 2.8%, p&lt;0.001). In patients without proteinuria, the incidence of CIN was not increased with reducing eGFR, however, in patients with proteinuria, the incidence of CIN was significantly increased with reducing eGFR as shown in the figure. Multivariate-logistic-regression analysis revealed that proteinuria (hazard ratio=3.77; 95% CI: 1.54 to 9.10), contrast volume/eGFR (hazard ratio=1.29; 95% CI: 1.01 to 1.62), Ca antagonist (hazard ratio=3.46; 95% CI: 1.36 to 9.94) were independent predictors of CIN. Conclusions: Proteinuria is the strongest predictor for CIN after cardiac catheterization.
Prognostic Impact of <i>IL6</i> Genetic Variants in Patients with Metastatic Colorectal Cancer Treated with Bevacizumab-Based Chemotherapy
Authors: Satoshi Matsusaka, Diana L. Hanna, Shu Cao, Wu Zhang, Dongyun Yang, Yan Ning, Yu Sunakawa, Satoshi Okazaki, Martin D. Berger, Yuji Miyamato, Anish Parekh, Sebastian Stintzing, Fotios Loupakis, Heinz-Josef Lenz
Journal: Clinical Cancer Research (2016)

The IL6/STAT3 axis promotes inflammation, angiogenesis, and cancer. The effect of genetic variants within this pathway on benefit from antiangiogenic cancer therapy is unknown. We tested whether SNPs in genes involved in IL6/STAT3 signaling can predict efficacy of bevacizumab-based chemotherapy in metastatic colorectal cancer (mCRC) patients.Associations between potentially functional IL6 (rs2069837 and rs1800795) and STAT3 (rs744166 and rs4796793) SNPs and clinical outcomes [progression-free survival (PFS), overall survival, and tumor response rate] were evaluated in mCRC patients receiving first-line FOLFIRI plus bevacizumab in two randomized phase III trials: TRIBE (n = 223, training cohort) and FIRE-3 (n = 288, validation cohort). Patients receiving FOLFIRI plus cetuximab in FIRE-3 (n = 264) served as a control cohort. The interaction between genotype and primary tumor location with clinical outcomes was examined. Genomic DNA isolated from whole blood or tumor tissue was analyzed by PCR-based direct sequencing.Patients with an IL6 rs2069837 G allele treated with FOLFIRI plus bevacizumab had an inferior PFS than those with the A/A genotype in TRIBE [9.4 vs. 11.1 months; HR = 1.53; 95% confidence interval (CI), 1.12-2.10; P = 0.004] and FIRE-3 (8.8 vs. 10.9 months; HR = 1.40; 95% CI, 1.06-1.85; P = 0.015). These associations were confirmed in multivariable analyses and were not seen in the control cohort. In subgroup analysis, the effect of IL6 rs2069837 on PFS was present only in patients with left-sided cancers, but the test for interaction was not significant.IL6 rs2069837 genotype is a clinically relevant prognostic factor in mCRC patients treated with first-line bevacizumab-based chemotherapy. Clin Cancer Res; 22(13); 3218-26. ©2016 AACR.