tbuckley/cabot-search huggingface dataset:
The Complexities of Colorectal Cancer Screening
Authors: Chyke A. Doubeni
Journal: JAMA Internal Medicine (2016)

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Biopsy for custom-made treatment: mRNA expression level of cancer-critical genes from gastric/colorectal cancer tissues obtained by endoscopic biopsy.
Authors: Kazuhiko Tamura, Takafumi Watanabe, Masanobu Enomoto, Hideo Sudou, Jiro Ogata, Shigeki Satou, Yoshiaki Kataba, Yoshiaki Osaka, Yuu Takagi, Akihiko Tsuchida, Tatsuya Aoki
Journal: Journal of Clinical Oncology (2012)

33 Background: In this study, we measured the mRNA expression level of cancer-critical genes from the gastric/colorectal cancer tissues obtained through endoscopic biopsy before treatments and compared its consistency with the sample tissues surgically resected from identical cases. Methods: The study was made on 13 gastric and 19 colorectal cancer cases with patients’ consent. We picked identical cases and measured mRNA expression levels from the tissues endoscopically taken before treatment and the surgically resected ones. For the measurement, DNP (DanenbergTumorProfile) method was used. Examination items are as follows: TS, DPD, TP, FPGS, GGH, DHFR, ERCC1, Topo-I, EGFR, and VEGF. Results: Upon comparing the consistency between endoscopically sampled biopsy tissues and surgically taken tissues from identical cases, it was found that eight out of ten items showed strong correlations in colorectal cancer cases. The results are as follows: FPGS(r=0.91, p&lt;0.001); GGH(r=0.87, p&lt;0.001); EGFR(r=0.86, p&lt;0.001); Topo I (r=0.81, p&lt;0.001); TS(r=0.79, p&lt;0.001); DHFR(r=0.70, p&lt;0.01); VEGF(r=0.67, p&lt;0.01); and TP(r=0.62, p&lt;0.05). In case of gastric cancers, strong correlations were found in three out of ten items with the following results: EGFR (r=0.98, p&lt;0.001); TS (r=0.91, p&lt;0.001; and DPD (r=0.74, p&lt;0.05). Conclusions: Today’s progresses of preoperative chemotherapy and radiotherapy and developments of endoscopic and surgical treatments allow diverse options for treatments. In such circumstances, the significance of knowing the expression of cancer-critical genes between individuals before treatment in conducting custom-made treatment is profound. There are two issues in applying the expression of cancer-critical genes found through endoscopic biopsy: one is whether enough cancer cells can be obtained through biopsy, and the other is whether the sampled cancer cells reflect the characteristics of primary focus. While there remain issues to be addressed, certain results were achieved in this study. Currently, we are working on accumulating cases to compare them and find out whether the results can be applied to custom-made treatments.
A novel repeat biopsy nomogram based on three-dimensional extended biopsy.
Authors: M. Sakura, S. Kawakami, J. Ishioka, Y. Fujii, N. Numao, K. Saito, F. Koga, H. Masuda, I. Fukui, K. Kihara
Journal: Journal of Clinical Oncology (2011)

111 Background: There is no perfect cohort in which nomograms are developed because no biopsy method can detect all cancers. To minimize this inherent verification bias, having a cohort with fewer false negative cases is advantageous. Based on a cohort examined with three-dimensional (3D) extended biopsy protocol, we developed a novel nomogram for diagnosis of prostate cancer on repeat biopsy. Methods: Of 4,074 consecutive male patients undergoing prostate biopsy at our institutions between 2000 and 2009, 775 men with at least one previous negative biopsy underwent repeat biopsy with 3D protocol. Men with previous atypical glands or atypical small acinar proliferation and/or without available prostate-specific antigen (PSA) kinetics information were excluded. The remaining 515 men constituted the study cohort. We developed a logistic regression-based nomogram with 70% of the cohort selected randomly; we validated it with the remaining 30%. Predictive accuracy and performance characteristics were assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots, respectively. The threshold probability was evaluated with decision curve analysis. Results: We developed a novel repeat biopsy nomogram incorporating age, free to total PSA ratio, prostate volume, history of previous extended biopsy, and PSA doubling time. Validation confirmed predictive accuracy with an AUC value of 0.791. Calibration plots showed good agreement. The decision curve of the nomogram was superior to the decision curve of biopsying all men in a range of threshold probability over 0.15. At the threshold of 0.2, the number of unnecessary biopsies could be reduced by 10 per 100, without missing PCa. Conclusions: We developed a novel repeat biopsy nomogram based on a cohort examined with 3D extended biopsy. This repeat biopsy nomogram is clinically beneficial, saving a substantial number of unnecessary biopsies. No significant financial relationships to disclose.
VT-464: A novel, selective inhibitor of P450c17(CYP17)-17,20 lyase for castration-refractory prostate cancer (CRPC).
Authors: Joel Robert Eisner, David H Abbott, Ian M Bird, Stephen W Rafferty, William R Moore, Robert J Schotzinger
Journal: Journal of Clinical Oncology (2012)

198 Background: CYP17 is a single protein with two distinct enzyme activities, 17 α-hydroxylase (hydroxylase) and 17,20-lyase (lyase). Reduction of extragonadal androgen production through CYP17 inhibition is a validated CRPC treatment paradigm. While treatment with the recently-approved CYP17 inhibitor, abiraterone acetate (AA), increases overall survival in post-docetaxel CRPC patients (de Bono et al, N Engl J Med 2011; 364:1995–2005), it is also associated with cortisol (F) suppression and increased steroid concentrations up-stream of CYP17 hydroxylase. The clinical candidate VT-464 is an oral, non-steroidal, lyase-selective CYP17 inhibitor. The study objectives were to compare VT-464 to abiraterone in regards to in vitro selectivity and to compare VT-464 to AA in regards to in vivo primate endocrine response. Methods: Human CYP17 hydroxylase and lyase IC 50 values were determined for VT-464 and abiraterone in vitro. Plasma progesterone (P), F, and testosterone (T) responses were measured 0-24 hours after single subcutaneous doses of AA (12.5 mg/kg), VT-464 (6.25 and 12.5 mg/kg), or vehicle in adult, castrate, male rhesus monkeys. Results: Human lyase and hydroxylase IC 50 values were 69nM and 670nM for VT-464 and 15nM and 2.5nM for abiraterone, respectively. AA and both dose levels of VT-464 produced a similar overall reduction in plasma T, compared to vehicle (p ≤ 0.009). AA treatment resulted in an elevated plasma P (peak increase &gt;9,000%; p ≤ 0.05), compared to both VT-464 treatments and vehicle. F was not affected by either VT-464 dose, whereas AA resulted in F suppression (p ≤ 0.005) compared to vehicle. Conclusions: VT-464 was 10-fold more selective for human CYP17 lyase vs. hydroxylase inhibition. This selectivity was associated with androgen suppression, but not increases of up-stream steroids or F suppression in male monkeys. In contrast, abiraterone was 6-fold more selective for hydroxylase vs. lyase inhibition resulting in associations with increased up-stream steroids and F suppression in AA-treated male monkeys, consistent with clinical observations in CRPC. VT-464 may thus provide a more lyase-selective alternative to AA for extra-gonadal androgen suppression in CRPC.
Efficacy and Safety of Nilotinib in Elderly Patients with Imatinib-Resistant or -;Intolerant Chronic Myeloid Leukemia (CML) in Chronic Phase (CP): A Sub-Analysis of the ENACT (Expanding Nilotinib Access in Clinical Trials) Study.
Authors: Philipp D. le Coutre, Anna Turkina, Dong-Wook Kim, Bernadeta Ceglarek, Giuliana Alimena, Haifa Kathrin Al-Ali, Zhixiang Shen, Saengsuree Jootar, Graeme Smith, Carmino Antonio De Souza, Pedro Enrique Dorlhiac-Llacer, David A Rizzieri, Tomasz Szczudlo, Myriam Berton, Jim Wang, Si-Tien Wang, Franck Emmanuel Nicolini
Journal: Blood (2009)
A Phase I Study of Oral 6-Thioguanine, Followed by Continuous Infusion Cytarabine, Followed by Intramuscular PEG-Asparaginase (“TGAP”) in Children with Relapsed or Refractory Acute Leukemia or Non-Hodgkin’s Lymphoma.
Authors: Cecilia H. Fu, Janet L. Franklin, Paul Gaynon, Colleen McCarthy, Edward Panosyan, Stuart E. Siegel, Vassilios I. Avramis
Journal: Blood (2006)
The role of PET-CT in the follow-up of patients with urothelial cancer diagnosis.
Authors: G. Jankilevich, F. Ogresta, L. Gennari, A. Ominetti, M. Bermudez, F. Peña, M. Eleta
Journal: Journal of Clinical Oncology (2011)

291 Background: Positron emission tomography (PET) is an imaging technique whose principle is the detection of metabolic activity of tumor cells but in urology its use had been restricted due to urinary excretion of the radiotracer and overlap with urological structures, the use of hybrid PET (PET-CT) would allow its use for monitoring patients with urothelial tumors. Methods: Between 2007 and 2010 we performed PET-TC images in consecutive patients with suspected recurrences in CT scan or MRI. All patients had renal, bladder and uretral cancer and were treated with urothelial cancer diagnosis. We evaluate the usefulness of FDG PET-CT and its impact on behavior therapy in suspected recurrence in patients with urothelial carcinoma, compared with conventional studies. Results: 17 patients were studied for suspected recurrence. All patients had positive images previously on CT scan and MRI; positive PET-TC was observed in 14 and 3 studies were negative. The positive PET-CT showed more number of lesions and change the medical and surgical strategy. Of the three studies negative on PET- CT none had recurrence and remain disease free. PET/CT is in a great benefit to the detection recurrence in the follow up of patients with urothelial cancer diagnosis. These results showed an increased sensitivity and specificity over previous work with conventional PET technology. In the series studied, the implementation of PET-CT (FDG) in the follow up of patients with urothelial tumors were an useful tool. Conclusions: PET/CT is in a great benefit to the detection recurrence in the follow up of patients with urothelial cancer diagnosis. These results showed an increased sensitivity and specificity over previous work with conventional PET technology. In the series studied, the implementation of PET-CT (FDG) in the follow up of patients with urothelial tumors were an useful tool. However, multicenter studies and more patients are required to define its role. No significant financial relationships to disclose.
Identification of context-dependent expression quantitative trait loci in whole blood
Authors: Daria V Zhernakova, Patrick Deelen, Martijn Vermaat, Maarten van Iterson, Michiel van Galen, Wibowo Arindrarto, Peter van 't Hof, Hailiang Mei, Freerk van Dijk, Harm-Jan Westra, Marc Jan Bonder, Jeroen van Rooij, Marijn Verkerk, P Mila Jhamai, Matthijs Moed, Szymon M Kielbasa, Jan Bot, Irene Nooren, René Pool, Jenny van Dongen, Jouke J Hottenga, Coen D A Stehouwer, Carla J H van der Kallen, Casper G Schalkwijk, Alexandra Zhernakova, Yang Li, Ettje F Tigchelaar, Niek de Klein, Marian Beekman, Joris Deelen, Diana van Heemst, Leonard H van den Berg, Albert Hofman, André G Uitterlinden, Marleen M J van Greevenbroek, Jan H Veldink, Dorret I Boomsma, Cornelia M van Duijn, Cisca Wijmenga, P Eline Slagboom, Morris A Swertz, Aaron Isaacs, Joyce B J van Meurs, Rick Jansen, Bastiaan T Heijmans, Peter A C 't Hoen, Lude Franke
Journal: Nature Genetics (2016)
The association between smoking and LINE-1 hypomethylation (global DNA hypomethylation) in normal esophageal epithelium of patients with esophageal squamous cell carcinoma.
Authors: Shiro Iwagami, Yoshifumi Baba, Masayuki Watanabe, Hironobu Shigaki, Keisuke Miyake, Satoshi Ida, Yohei Nagai, Takatsugu Ishimoto, Masaaki Iwatsuki, Yasuo Sakamoto, Yuji Miyamoto, Hideo Baba
Journal: Journal of Clinical Oncology (2012)

41 Background: DNA methylation is a major epigenetic mechanism in X-chromosome inactivation, imprinting and repression of transposable elements and endogenous retroviral sequences. Global DNA hypomethylation appears to play an important role in genomic instability, leading to cancer development. DNA methylation in the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of global DNA methylation level. Smoking and alcohol is extremely important as the etiology of esophageal squamous cell carcinoma. Nonetheless, whether or not smoking and alcohol affect LINE-1 methylation level in normal esophageal epithelium of esophageal cancer patients remains uncertain. Methods: We quantified LINE-1 methylation of normal esophageal mucosa using pyrosequencing technology in 118 resected esophageal squamous cell carcinomas. The data on smoking (Brinkman index, absence or presence) and alcohol amount are available in all cases. We excluded preoperatively treated cases. Results: LINE-1 methylation in normal esophageal epithelium of esophageal cancer patients ranged from 57.1 to 92.8 of 0-100 scale (N=118; mean 81.2; median 80.0; standard deviation 7.2). LINE-1 methylation level (continuous variable) was significantly associated with Brickman index (continuous variable) (r=0.12, p=0.0002); heavy smoker had lower LINE-1 methylation level of normal esophageal mucosa. LINE-1 methylation level was lower in patients with smoking history (mean 79.7) than in patients without smoking history (mean 83.2) (p=0.034). Alcohol assumption was not associated with LINE-1 methylation level (r=0.003, p=0.58). Conclusions: Smoking was associated with LINE-1 hypomethylation in esophageal normal epithelium, suggesting the possibility of epigenetic field effects caused by cigarette in esophageal tumorigenesis. Considering that DNA methylation alterations are reversible and can thus be targets for chemoprevention, our findings may have clinical implication.
Autoinflammation in pyoderma gangrenosum and its syndromic form (pyoderma gangrenosum, acne and suppurative hidradenitis)
Authors: A.V. Marzano, G. Damiani, I. Ceccherini, E. Berti, M. Gattorno, M. Cugno
Journal: British Journal of Dermatology (2016)

Pyoderma gangrenosum (PG) is a rare skin disease characterized clinically by ulcers with undermined borders, and histologically by neutrophil-rich infiltrates. PG may occur alone, in syndromic forms or associated with systemic diseases, such as inflammatory bowel disease and haematological or rheumatological disorders.To determine a specific genetic background related to autoinflammation for PG.We assessed autoinflammation by evaluating the cytokine profile and genes involved in classic autoinflammatory diseases in 13 patients with PG and in seven patients with the syndromic form, known as PASH (pyoderma gangrenosum, acne and suppurative hidradenitis).In skin samples, the expression of interleukin (IL)-1β and its receptors, IL-17 and its receptor, and tumour necrosis factor-α and its receptors were significantly higher in both PG (P = 0·001) and in PASH (P < 0·001) than in controls. The chemokines IL-8; chemokine (C-X-C motif) ligand 1/2/3; chemokine (C-X-C motif) ligand 16; and RANTES (regulated on activation, normal T-cell-expressed and secreted) were also overexpressed. Cases of PG and PASH showed mutations in the autoinflammatory genes MEFV, NLRP3, NLRP12, NOD2, LPIN2 and PSTPIP1.Overexpression of cytokines/chemokines, along with genetic changes, supports the hypothesis that PG and its syndromic form, PASH, are a spectrum of polygenic autoinflammatory conditions.
Clinical outcomes after transperineal template-guided prostate biopsy.
Authors: Richard A. Hsi, Randall James Moeller, Marc Mitchell, Scott Bildsten, Paul Kozlowski, Christopher R. Porter
Journal: Journal of Clinical Oncology (2012)

156 Background: To assess clinical outcomes after transperineal template-guided prostate biopsy (TTPB) including detection rates, pathologic features, clinical relevance and morbidity. Methods: Forty eight men underwent TTPB. All patients had at least one (range 1–4) prior negative transrectal ultrasound-guided (TRUS) prostate biopsy and no prostate cancer diagnosis. The mean pre-biopsy PSA of the entire group was 13.1 ng/ml (range 4.5–46.4). The mean number of cores sampled was 24.7 (range 22–28). Results: The rate of prostate cancer detection was 52% (25/48). Clinically significant prostate cancer, defined as intermediate (n=9) and high (n=11) risk disease using D’Amico criteria, was found in 80% (20/25) of positive biopsy cases. Seventy-two percent of all positive biopsy cores were anatomically located in the anterior or anterolateral positions within the prostate. Urinary retention requiring catheterization after the procedure developed in 6% (3/48) of patients. No patients developed rectal or infectious complications after TTPB. Conclusions: TTPB is a well tolerated procedure resulting in a significant rate of cancer detection. Biopsies were frequently found to be positive in the anterior half of the prostate. Clinically significant disease was found in a high percentage of patients.
Predictors of Early Death in Childhood Acute Promyelocytic Leukemia: Results of an International Retrospective Study
Authors: Oussama Abla, Raul C. Ribeiro, Anna Maria Testi, Pau Montesinos Fernández, Ursula Creutzig, Lillian Sung, Giancarlo Di Giuseppe, Derek Stephens, Henrik Hasle, Gertjan J.L. Kaspers, Luciano Dalla-Pozza, Alvaro Lassaletta, Martin S. Tallman, Franco Locatelli, Dirk Reinhardt, Johann Hitzler, Miguel A. Sanz
Journal: Blood (2015)
High-dose-rate (HDR) brachytherapy with external beam radiotherapy for localized high-risk prostate cancer: Five-year results in 122 patients.
Authors: Toshihiro Yamamoto, Masahito Kido, Hiroshi Sasaki, Jun Miki, Takahiro Kimura, Kenta Miki, Hiroki Yamada, Manabu Aoki, Shin Egawa
Journal: Journal of Clinical Oncology (2012)

91 Background: To present outcome and morbidity of high-dose-rate (HDR) brachytherapy with external beam radiotherapy (EBRT) for localized high risk prostate cancer. Methods: Between May 2005 and April 2009, 122 patients underwent Ir-192 HDR brachytherapy with EBRT and passed after HDR bachytherapy more than one year. The median follow-up was 46 months (range 2-76 months). All patients were high risk and localized prostate cancer. Median PSA was 40.2ng/ml (range 4.1-366ng/ml). Median Gleason Score was 8 (range 6-10). All patients were treated over six months neo-adjuvant hormonal therapy and over twenty-four months adjuvant hormonal therapy. Results: Only one patient had died of lung small cell carcinoma. 14 patients had revealed biochemical failure(BCF) by Phoenix definition. 5-year biochemical free rate was 78%. Clinical T3 group is significant worse than clinical T1-T2 group(5-y BCF 73% vs 81%, p&lt;0.05). Of the 122 patients, only one patient displayed Grade 3 late GI toxicity. There were no other acute nor late severe toxicity. Conclusions: HDR brachytherapy for localized high risk prostate cancer resulted in good outcomes and had comparatively minor toxicity. Clinical T3 patients was poor outcome than clinical T1-2.
Metabolomic signature of esophageal cancer.
Authors: Vanessa Wylie Davis, Dan E. Schiller, Michael B. Sawyer
Journal: Journal of Clinical Oncology (2012)

21 Background: Esophageal cancer is a pervasive malignancy, and early detection combined with newer therapeutic targets could alter the landscape of this condition. Metabolomic profiling offers one such innovative opportunity. We applied metabolomic techniques to identify urinary metabolites uniquely associated with this condition. Methods: Urine samples from patients with histologically confirmed esophageal cancer (n=66) and healthy volunteers (n=25) were collected and examined using 1H-NMR spectroscopy. Targeted profiling of spectra using Chenomx NMR Suite 7.0 software permitted detection and quantification of 66 distinct metabolites. Unsupervised (principal component analysis, PCA) and supervised (partial least-squares discriminant analysis, PLS-DA) multivariate pattern recognition techniques were applied to discriminate between sample spectra of esophageal cancer patients and healthy volunteers using SIMCA-P (version 11, Umetrics, Umeå, Sweden). Results: Significant differences were found when comparing concentrations of 59 metabolites in urines of healthy volunteers and esophageal cancer patients. Those metabolites contributing most class discriminating information included choline, urea, 2-aminobutyrate, and 3-hydoxybutyrate. Clear distinctions between patients with esophageal cancer and healthy controls were noted when PLS-DA was applied to the data set. Model parameters for both goodness of fit R2, and predictive capability Q2, were high (R2 = 0.867; Q2 = 0.732). Model validity was tested using response permutation and results were suggestive of excellent predictive power (see Figure). Conclusions: Urinary metabolomics identified a discrete signature associated with esophageal cancer compared to healthy controls. This profile has the potential to aid in diagnosis and development of new therapeutic targets.