tbuckley/cabot-search huggingface dataset:
Effect of testosterone treatment in hypogonadal men on prostate cancer risk: Results of a prospective comparative study—8 years follow-up analysis to age-matched controls.
Authors: Dany-Jan Yassin, Lukas Manka, Aksam Yassin, Peter Hammerer
Journal: Journal of Clinical Oncology (2014)

e16051^ Background: Evaluation of prostate cancer (CaP) prevalence in elderly hypogonadal subjects under long-term testosterone treatment (TRT) compared with age-matched control group. Methods: 261 hypogonadal patients (59.5 ± 8.4years) received injectable long-acting testosterone undecanoate (TU) 1000 mg, compared to 260 eugonadal men (58 ± 6.8 years) visiting the clinic for check up. The monitoring included co-morbidities, medication, International Prostate Symptom Score (IPSS), PSA, digital rectal examination (DRE), prostate volume measured by transrectal ultrasound (TRUS). Biopsies were performed at PSA velocity > 0.75 mg/L in a year. Data entry and analyses were done with the usage of SPSS 14.0 software package. Continuous variables are presented as mean values ± standard deviation. The chi square test was applied to compare frequencies between groups. P < 0.05 considered statistically significant. Results: Hypogonadal patients have at baseline lower PSA and smaller prostates (0.68 ± 0.4 mg/L and 25.6 ± 1.4 ml) p ≤ 0.001 and p ≤ 0.001. Control subjects had initially PSA of 2.42 ± 1.2 mg /L, and prostate volume 38.4 ± 2.42 ml. Patients with PSA velocity in the observation period that was > 0,75 mg /L, underwent TRUS-guided biopsies. In TRT group 6/26 who underwent biopsies showed CaP, three of them unilateral with up to 10% tumor cells in a core. Gleason scores were 3+2 or 3+3. In the 260 control subjects, 19/53 who underwent biopsies showed CaP, 14 of them bilateral, with a significantly higher Gleason score of 3+3 till 4+5 and up to 80% tumor cells in a core (p ≤ 0.000). No subject of both groups showed any abnormality in rectal palpation. Conclusions: Hypogonadal subjects have smaller prostates and lower PSA than eugonadal ones. TRT doesn´t increase CaP incidence. TRT group had smaller tumors and less malignancy. Hypogonadism offers no protection against the development of biopsy-detectable prostate cancer. Lower levels of testosterone were associated with an increased risk of cancer.
Live cell in vitro prognostic utilizing biophysical and molecular biomarkers for measuring local growth and metastatic potential in prostate cancer.
Authors: Ashok C. Chander, Michael S. Manak, Senthil K. Ramu, Wendell R. Su, Thiagu Meyyappan, Brad J. Hogan, Matt J. Whitfield, Jonathan S. Varsanik
Journal: Journal of Clinical Oncology (2014)

e22133 Background: Prostate cancer is a genetically heterogeneous disease that currently lacks sufficient biomarkers to assess and predict its aggressiveness and metastatic potential. Utilizing emerging biomarkers and prognostic platforms may improve patient outcomes by adding functional molecular and cellular information towards better understanding the local growth and metastatic potential of cells derived from biopsy, specifically in low grade and intermediate grade cancers (Gleason 3+3, 3+4, 4+3). Methods: Towards developing a lab-on-a-chip diagnostic platform, we report a microfluidic device that can be utilized to culture biopsy samples ex vivo enabling automated imaging of label-free and label-based, molecular and biophysical biomarkers. Results: The device is functionalized with an extracellular matrix formulation that is sufficient to sustain adhesion and survival of primary prostate cells dissociated from overnight shipped fresh tissue samples on both plastic and glass substrates for greater than seven days as determined by cell morphology and total cell count. We demonstrate that a set of phenotypic, molecular, and biophysical biomarkers consisting of cell size, cell motility velocity, protein localization, protein dynamics, and metabolic activity, can be measured on live cells. Secondary biomarker metrics can be derived from these primary biomarkers termed Metastatic Potential (MP) and Oncogenic Potential (OP) that are calculated using unbiased machine vision algorithms. Concordance analysis supports that OP & MP, derived from primary biomarkers, are statistically significant in distinguishing between normal and malignant cells derived from primary tissue samples. Conclusions: These results constitute the first step in a clinical validation model that will demonstrate the capability of a live-cell in vitro diagnostic lab-on-a-chip platform to generate scoring metrics of Metastatic Potential (MP) and Oncogeneic Potential (OP). These metrics are designed to discriminate between aggressive - , non-aggressive - malignant and normal samples, ultimately to risk stratify prostate cancer to avoid unnecessary surgery or radiation.
Development of a simple discriminator for the health status groups proposed by the International Society of Geriatric Oncology and its validation study in elderly Japanese patients with castration-resistant prostate cancer.
Authors: Kazumi Kamoi, Jean Pierre Droz, Koji Okihara, Fumiya Hongo, Yoshio Naya, Terukazu Nakamura, Tsuneharu Miki
Journal: Journal of Clinical Oncology (2014)

e20525 Background: SIOG recommendation is particular to allow various treatment regimens which covers wide range of comorbidities. However, the classifying system of patient comorbidity status is complicated. To utilize SIOG recommendation easier in clinical practice, we developed a new grouping tool which consists of only four queries and performed a validation study in elderly Japanese patients with castration-resistant prostate cancer (CRPC). Methods: In October 2013, we conducted an international seminar focusing on the simplification of the SIOG guidelines with Dr. Droz and the Japanese Prostate Cancer Chemotherapy Group for Elderly Men (JPCEM). In this seminar, our original check sheet for the classification of patient’s status was newly developed. The primary change of the classification tool was to select 6 significant comorbidities from 12 items. Japanese urologists were asked to use the new tool for the classification of elderly CRPC patients. In this study, we asked the urologists to cooperate in our survey, based on the evaluation by this item to determine the dose and interval of docetaxel chemotherapy (standard regimen: 70-75 mg/m2, tri-weekly; adapted regimen: other doses and intervals). Patients aged >70 years were evaluated. The dose and interval of docetaxel before the seminar (regimen adherence) were retrospectively investigated based on the JPCEM database (Takaha et al., Urol Int, 2012). Results: The rate of adherence to the standard/adapted regimen according to the groups was 40% (8/20) before the seminar based on the retrospective data but 89% (25/28) after the seminar, showing significant improvement (p <0.01) after education by new grouping tool. Based on the retrospective data, a patient was classified as group 3, but palliative care was selected. After the education, 2 (included in the 25 patients showing regimen adherence) were classified as group 3, and an adapted regimen was adopted. Conclusions: Our study revealed that the education using the new check sheet contributed to improvement in the quality of chemotherapy in elderly patients with prostate cancer.
Abstract 14635: Exosomes Containing Archaeal DNA Are Increased in the Serum of Heart Failure Chagas’ Disease Patients
Authors: Maria L Higuchi, Joyce T Kawakami, Renata N Ikegami, Marcia M Reis, Barbara Ianni, Paula Buck, Sandrigo Mangini, Edimar Bocchi, Ludhmila A Hajjar
Journal: Circulation (2015)

Introduction: Exosome are microparticles smaller than 100nm, and have been described to prevent myocardial dysfunction. In accordance, we have found large amount of electron dense lipidic exosomes (EDexo) containing collagenase, in the serum of asymptomatic indeterminate form (IF) patients (pts) with Chagas’ disease (CD), in negative correlation with free collagenase. On the other hand, heart failure (HF) has been associated with increased levels of microparticles and we previously have detected pathogenic archaea in the myocardium of HFCD pts. Hypothesis: Demonstrate that exosomes present in the serum of HF CD pts are derived from archaea , being different from EDexo present in IF CD pts. Methods: Sera from 9 HF (07 males) and 13 from IF chagasic pts (04 males) were submitted to a gradient separation, with a mannitol/ sucrose rich solution. After centrifugation, the supernatant samples were rich in ED exosomes, which were studied by in situ hibridization at electron microscopy, using archaea DNA probe ARCH915. The numbers of EDexo and archaea DNA dots were counted in 4 photos representing the richest places of each case in x50K magnification. Comparison between HF and IF was performed by T test or Mann Whitney and correlation by Spearman test. A difference P&lt;0.05 was considered significant.Results: HF group presented lower numbers of ED exo than IF (5.6 ± 8.3 vs 42.5 ± 56.6), P &lt;0.001, however their EDexo contained higher amount of archaeal DNA dots (1.5 ± 3.0 vs 0.2 ± 0.5, P =0.02). A higher amount of extracellular archaeal DNA in HF than IF (63.0 ± 150 vs 11.1 ± 13.1, P &lt;0.001) had positive correlation with numbers of EDexo (r=0.66, P =0.01), but not in IF(r=0.29, P =0.10). Conclusions: EDexo present in the serum of HF CD pts are carrying and seem to release archaeal DNA, differently from those present in asymptomatic IF CD pts, which do not contain archaeal DNA and could have a protective role removing abnormal proteins linked to development of HF.
Optimized Beta-Globin Expression and Enucleation from Induced Red Blood Cells for In Vitro Modeling of Sickle Cell Disease
Authors: Tolulope O Rosanwo, Melissa Kinney, Martha A Clark, Linda T Vo, R. Grant Rowe, Natasha M. Archer, Matthew M Heeney, Thorsten Schlaeger, Daniel E. Bauer, Mark D. Fleming, Manoj T Duraisingh, Stuart H. Orkin, Carlo Brugnara, Trista North, George Q. Daley
Journal: Blood (2018)
Targeting Wnt/β-Catenin and BCL-2, Two Critical Survival Factors, Synergistically Induces Apoptosis in AML Via Rac1-Mediated MCL-1 Inhibition
Authors: Xiangmeng Wang, Po Yee Mak, Wencai Ma, Xiaoping Su, Hong Mu, Wenjing Tao, Michael Andreeff, Bing Z Carter
Journal: Blood (2018)
Profile analysis of microRNA-messengerRNA expression modules in squamous cell carcinomas of the meso- and hypopharynx.
Authors: Gabor Pajkos, Lajos Olasz, Istvan Szanyi, Eva Orosz, Katalin Gombos
Journal: Journal of Clinical Oncology (2014)

e22229 Background: Head and neck squamous cell carcinoma (HNSCC) is characterized by elevated constitutive activity or aberrant regulation of NFκB signal transduction. NFκB acts as a survival factor for malignant cells by its anti-apoptotic function and plays as an important link between inflammation and cancer. Our aim was to characterize miRNA-mRNA interactive modules acting on the NFkB signalling pathway and set up a panel of RNA markers that can be responsible for the malignant behaviour. Methods: Meso- and hypopharynx SCC and autologous normal mucosal samples were collected from 24 patients for microRNAs (miR-21, -27a, -34a,-93, -146a,-148a, -155, 196a, -203, -205, -221) with their predicted target mRNAs (Rel-A and p50), the NFκB signal suppressor (Ikbkg) and activator Ikk1 , receptor Tlr1 and Vegf as an NFκBdownstream target. Expressions were measured in LightCycler 480 PCR system and results were calculated by using relative quantification with the 2-dCp method. Statistical evaluation was carried out by paired sample t-test and ROC curve analysis. Results: 92% of the HNSCC samples were found to express significant alteration on the miRNA panel. t-test analysis revealed four of the analysed miRNAs miR-21, miR-27a, miR-34a, miR146a, miR-155, miR-205 and miR-221 as having statistically significant expression changes in the tumours. Meso-and hypopharynx tumours showed significant differences only considering miR-27a and miR-146a expressions. ROC curve analysis testing accuracy of the miR expressions found to be over 90% for miR- 221 and higher than 90% in case of miR-21, miR-155. 73% of the miRNA overexpressing tumors were found to have significant overexpressions of Nfκb1 Rel-A, Tlr1 and Vegf. Conclusions: Our data confirm the role of miR-21, miR-155 and miR-221 in HNSCC and suggest their co-regulatory with the NFκB signalling pathway. These molecular markers also seem to be potentially useful for molecular cancer detection. Apart from the heterogeneous genetic alterations leading to the formation of HNSCC, this group of tumour can be characterized by consistent and specific molecular changes and behave as a homogenous group in terms of miRNA-mRNA gene expression.
Abstract 18567: Inhibition of Prolyl Hydroxylase to Enhance Sdf-1 Expression for Augmented Cxcr4+ Cell Recruitment and Cardiac Repair
Authors: Santhosh Kumar Ghadge, Moritz Messner, Thi Van Pham, Maximilian Doppelhammer, Andreas Petry, Agnes Goerlach, Britta Husse, Wolfgang-Michael Franz, Marc-Michael Zaruba
Journal: Circulation (2016)

Aims: SDF-1/CXCR4 activation facilitates myocardial repair. Since SDF-1 is only upregulated for a short time after myocardial infarction (MI) targeting of regenerative CXCR4+ cells is limited. We aimed to reactivate the HIF-1α target genes SDF-1 and CXCR4 by prolyl hydroxylase inhibition (PHI) to augment CXCR4+ cell recruitment and myocardial repair. Methods and Results: SDF-1 and CXCR4 expression was analysed under normoxia and ischemia ± PHI utilizing SDF-1-EGFP and CXCR4-EGFP reporter mice. In bone marrow (BM) CXCR4-EGFP was predominantly expressed in CD45+/CXCR4-EGFP+/CD11b+ leukocytes. After MI CD45+/CXCR4-EGFP+/CD11b+ leukocytes significantly increased. In the heart CD45+/CXCR4-EGFP+ cells also predominantly co-expressed CD11b+, but also angiogenic CD31+, CD34+, c-kit+, Flk1+ markers, and stem cell populations like ACC133+, and Lin-/c-kit+/Sca-1+ significantly increased after ischemia. In vitro, PHI with 500μM dimethyloxalylglycine (DMOG) upregulated SDF-1 mRNA expression after 24 h in human microva...
Impact of perioperative blood transfusion on survival in patients with the upper gastrointestinal cancers.
Authors: Keisuke Kosumi, Yoshifumi Baba, Kazuto Harada, Ryuichi Karashima, Satoshi Ida, Yu Imamura, Shiro Iwagami, Yuji Miyamoto, Yasuo Sakamoto, Naoya Yoshida, Hideo Baba
Journal: Journal of Clinical Oncology (2014)

e15010 Background: Perioperative blood transfusion (PBT) generally increases postoperative morbidity and mortality. Although some reports demonstrated the relationship between PBT and poor prognosis in some cancers, the effect of PBT in the upper gastrointestinal cancers remains controversial. Thus, we analyzed the relationships between PBT and clinical, pathological and prognostic features in patients who were treated by resection for the upper gastrointestinal cancers (esophageal cancer and gastric cancer). Methods: We analyzed 507 patients with the upper gastrointestinal cancers received radical operation between April 2005 and December 2010. The Cox proportional hazards model was used to compute mortality hazard ratio, adjusting for clinical, pathological and prognostic features. Throughout this study, the term “prognostic marker” is used in the context of the REMARK Guidelines. Results: PBT was significantly correlated with esophageal cancer (P<0.0001), mean age (P=0.011), male sex (P=0.033), body mass index (P=0.027), double cancer (P=0.040), present of neoadjuvant therapy (P<0.0001), operating time (<0.0001), blood loss (P<0.0001), high tumor depth (P<0.0001), lymph node involvement (P<0.0001) and high tumor stage (P<0.0001). Patients with PBT experienced significantly shorter overall survival than patients without PBT [log-rank p<0.0001; univariate HR= 3.28, 95% confidence interval (CI) 2.27–4.73; p<0.0001; multivariate HR 2.05; 95% CI, 1.38–3.04; p=0.0004]. We examined whether the influence of PBT on overall survival was modified by any of the clinical and pathologic variables. We did not observe a significant interaction between PBT and any of the covariates (all P for interaction >0.10). Conclusions: We demonstrated a correlation between PBT and poor prognosis in the upper gastrointestinal cancer patients. This finding suggested that PBT may impact on clinical outcome. Further studies are needed to examine biological mechanisms by which PBT affects tumor aggressive behavior.
Genotype-Phenotype Correlation in Congenital TTP: New Insights from a Multicentre Study with 121 Patients
Authors: Anette Anette Van Dorland, Magnus Mansouri Taleghani, Kenneth Dale Friedman, James George, Ingrid Hrachovinova, Paul Knöbl, Bernhard Lammle, Masanori Matsumoto, Anne Sophie von Krogh, Reinhard Schneppenheim, Isabella Aebi-Huber, Bütikofer Lukas, Zuzana Cermakova, Petter Quist-Paulsen, Deirdra Terrell, Sara K. Vesely, Yoshihiro Fujimura, Johanna A. Kremer Hovinga Strebel
Journal: Blood (2018)
Goblet cell appendiceal tumors: Management, clinical, outcomes and survival in 48 cases.
Authors: Roberta Elisa Rossi, Tu Vinh Luong, Martyn E. Caplin, Christina Thirlwell, Tim Meyer, Jorge Garcia-Hernandez, Alex Baneke, Dario Conte, Christos Toumpanakis
Journal: Journal of Clinical Oncology (2014)

e14555 Background: Goblet cell appendiceal tumors (GCATs) are clinically more aggressive, and have a worse outcome than midgut neuroendocrine tumors (NETs). Guidelines for management of GCATs are limited due to the rarity of the disease and the lack of prospectively collected data. Methods: A retrospective case-study analysis was performed in patients with a histological diagnosis of GCATs. Patients were evaluated clinically, biochemically, and radiologically Results: There were 48 patients identified (TNM stage I-II: 27, stage III : 15, stage IV: 6). Median follow-up was 44 months and was complete in all patients. There were 33/48 patients presented with acute appendicitis. There were 44/48 patients had initial appendectomy, followed by prophylactic right hemicolectomy in 41 patients. There were 10/48 patients who had recurrent disease [median time to recurrence: 28 months (range 4-159)]. Of those, nine received systemic chemotherapy (FOLFOX or FOLFIRI), which was also given in 5/48 patients with disseminated disease at diagnosis. Partial response, stable disease and disease progression was noted in 22%, 22% and 56%, respectively. Chemotherapy was also administered in 9/48 patients who had residual disease, after right hemicolectomy, and no evidence of recurrence was noted in 6/9. Median progression-free-survival was 44 months (range 3-159) and overall five-year survival rate was 41.6%. Conclusions: GCATs have a worse prognosis than midgut NETs. A prophylactic right hemicolectomy is advised to reduce the risk of recurrence. Systemic chemotherapy, using FOLFOX, has encouraging results and should be considered as adjuvant therapy or treatment of advanced disease. Prospective studies are needed to define the role of role of systemic therapy.
Placebo Controlled Functional Analysis of Eltrombopag in a Preclinical Xenograft Model of Myelodysplastic Syndromes (MDS)
Authors: Nanni Schmitt, Eva Altrock, Johann-Christoph Jann, Johanna Flach, Carla Sens-Albert, Justine Danner, Stefanie Uhlig, Jovita Pressler, Iris Palme, Verena Nowak, Julia Obländer, Lena Drangmeister, Franziska La Meir, Georgia Metzgeroth, Florian Nolte, Wolf-Karsten Hofmann, Daniel Nowak
Journal: Blood (2018)
Chlorhexidine and octenidine use, carriage of qac genes, and reduced antiseptic susceptibility in methicillin-resistant Staphylococcus aureus isolates from a healthcare network
Authors: H.L. Htun, P.Y. Hon, M.T.G. Holden, B. Ang, A. Chow
Journal: Clinical Microbiology and Infection (2019)
Characterization of the mTOR autophosphorylation site, S2481, as a novel biomarker in renal cell carcinoma (RCC).
Authors: Lauren Christine Harshman, Karra Muller, Chii-Dean Lin, James D. Brooks, John Higgins, Jon Berglin, Tony Hunter, Jeremy Copp
Journal: Journal of Clinical Oncology (2014)

4571 Background: mTOR inhibitors have clinical utility in VEGF-refractory RCC and may be useful in non-clear cell disease. In general, mTOR inhibition is inferior to targeting VEGF in the treatment-naïve setting. However, some patients clearly demonstrate mTOR-dependent disease. It is critical that new biomarkers are identified to optimize patient selection for mTOR-targeting therapeutics. One such potential marker, the mTOR autophosphorylation site, S2481, is a direct readout of mTOR activation. The objective of this pilot study was to analyze the levels of phospho-S2481 in different RCC subtypes. Methods: Utilizing standard immunohistochemistry methods, archived, formalin-fixed paraffin-embedded primary tumor samples from an existing tissue microarray of patients with clear cell (cc, n=203), chromophobe (n=21) and papillary RCC (n=38) were stained for the presence of phospho-S2481. Samples from transitional cell carcinoma cases (n=38) were included as a control. Mean scores from the four cancer subtypes were calculated, and the Kruskal-Wallis test was applied to demonstrate the statistical relevance of the mean scores. Covariates such as stage, grade, age, and tumor size were analyzed by logistic regression. Results: ccRCC patients were most likely to have high levels of phospho-S2481 staining (mean=2.08), while the TCC controls had the lowest amount (mean=1.11), with papillary and chromophobe falling in between (mean=1.41 and 1.38 respectively). The mean score difference among the four cancer subtypes was highly significant (Chi-square statistic: 54.51, p <.0001). Tumor size and cancer subtype were highly correlated with the score (p<.01). Comparison of the odds ratios for the three RCC subtypes demonstrated that ccRCC cases were three times more likely to have high levels of phospho-S2481 and four times more likely than papillary RCC (p<.05). Conclusions: Phospho-S2481 may have the ability to classify RCC patients of different subtypes. Exploration of phospho-S2481’s ability to predict patient response to mTOR inhibitors is under way.