tbuckley/cabot-search huggingface dataset:
Review of injection techniques for spermatogonial stem cell transplantation
Authors: Murat Gul, Simone Hildorf, Lihua Dong, Jorgen Thorup, Eva R Hoffmann, Christian Fuglesang S Jensen, Jens Sønksen, Dina Cortes, Jens Fedder, Claus Yding Andersen, Ellen Goossens
Journal: Human Reproduction Update (2020)

Abstract BACKGROUND Although the prognosis of childhood cancer survivors has increased dramatically during recent years, chemotherapy and radiation treatments for cancer and other conditions may lead to permanent infertility in prepubertal boys. Recent developments have shown that spermatogonial stem cell (SSC) transplantation may be a hope for restoring fertility in adult survivors of childhood cancers. For this reason, several centres around the world are collecting and cryopreserving testicular tissue or cells anticipating that, in the near future, some patients will return for SSC transplantation. This review summarizes the current knowledge and utility of SSC transplantation techniques. OBJECTIVE AND RATIONALE The aim of this narrative review is to provide an overview of the currently used experimental injection techniques for SSC transplantation in animal and human testes. This is crucial in understanding and determining the role of the different techniques necessary for successful transplantation. SEARCH METHODS A comprehensive review of peer-reviewed publications on this topic was performed using the PubMed and Google Scholar databases. The search was limited to English language work and studies between 1994 (from the first study on SSC transplantation) and April 2019. Key search terms included mouse, rat, boar, ram, dog, sheep, goat, cattle, monkey, human, cadaver, testes, SSC transplantation, injection and technique. OUTCOMES This review provides an extensive clinical overview of the current research in the field of human SSC transplantation. Rete testis injection with ultrasonography guidance currently seems the most promising injection technique thus far; however, the ability to draw clear conclusions is limited due to long ischemia time of cadaver testis, the relatively decreased volume of the testis, the diminishing size of seminiferous tubules, a lack of intratesticular pressure and leakage into the interstitium during the injection on human cadaver testis. Current evidence does not support improved outcomes from multiple infusions through the rete testes. Overall, further optimization is required to increase the efficiency and safety of the infusion method. WIDER IMPLICATIONS Identifying a favourable injection method for SSC transplantation will provide insight into the mechanisms of successful assisted human reproduction. Future research could focus on reducing leakage and establishing the optimal infusion cell concentrations and pressure.
Prognostic and predictive effects of a gene expression signature for NRF2 pathway activation in lung squamous cell carcinoma (SqCC).
Authors: David W. Cescon, Desmond She, ChangQi Zhu, Shingo Sakashita, Melania Pintilie, Frances A. Shepherd, Ming Sound Tsao
Journal: Journal of Clinical Oncology (2013)

7517 Background: Genomic profiling of SqCC in TCGA identified somatic alterations that activate the NRF2 transcriptional program – a master regulator of the oxidative stress response – in ~35% of tumors (NFE2L2 mutations/amplifications, KEAP1 or CUL3 mutations/deletions). This pathway has been implicated in resistance to chemotherapy. To evaluate the clinical significance of this molecular subset, we developed a gene expression classifier and tested this signature as a predictor of adjuvant chemotherapy benefit with cisplatin/vinorelbine (cis/vin) in a subset of SqCC patients with microarray data from the NCIC JBR.10 Phase III clinical trial. Methods: Logistic regression (LR) and SAM analysis were independently applied to 104 TCGA SqCC cases that had both microarray gene expression and mutation data to identify genes associated with NRF2 pathway mutational status. Overlapping genes were used to define the signature, which was then tested in 3 independent SqCC datasets (62 JBR.10; 54 UHN; 129 UM) to evaluate the prognostic and predictive values of putative NRF2 pathway activation. Results: 29 genes comprising the signature were identified by overlap between LR (291 genes) and SAM (45 genes). The signature consistently separated SqCC into 2 groups in all datasets, corresponding to putatively activated and wild type (WT) NRF2 pathway tumors. No prognostic effect of the activated signature was observed in independent datasets (UHN HR 0.86, 95%CI 0.28 – 2.67; UM HR 1.43, 95%CI 0.82 – 2.48). Similarly, in JBR10, no prognostic effect was observed in the observation arm (n=24, HR 0.66, 95%CI 0.13 – 3.29). A trend toward improved survival with adjuvant chemotherapy was observed in patients with the WT signature (HR 0.34, 95%CI 0.08 – 1.78, p=0.13), but not in patients with the activated signature (HR 1.16, 95%CI 0.19 – 6.97, p=0.87; interaction p=0.18). Conclusions: A gene expression signature based on mutational activation of the NRF2 pathway may be predictive of benefit from adjuvant cis/vin in SqCC. Patients with NRF2 pathway activating somatic alterations may have reduced benefit from this therapy. Validation of this potentially "actionable" finding in additional datasets is necessary.
INCESSANT FOCAL ATRIAL TACHYCARDIA DURING PREGNANCY AND POSTPARTUM PERIOD
Authors: Jose Ramon Benitez, Gabriela Andrea Bustillos Garcia, Juan Alan Fuentes Mendoza, Elizabeth Gomez Ureña, Pedro Arredondo Ruiz, G. Laura De Jesus, Enrique Alessio Garibo Luna
Journal: Journal of the American College of Cardiology (2020)
THE IMPACT OF NONSTEROIDAL ANTI-INFLAMMATORY DRUG USE ON PROGNOSIS IN PATIENTS HOSPITALIZED FOR ACUTE HEART FAILURE
Authors: Thiratest Leesutipornchai, Thanaporn Ratchataswan, Palapun Waitayangkoon, Aunchalee Jaroenlapnopparat, Supanee Sinphurmsukskul, Aekarach Ariyachaipanich
Journal: Journal of the American College of Cardiology (2020)
Genomewide single nucleotide polymorphism microarray mapping for prediction of outcome of neuroblastoma patients
Authors: E. Hiyama, H. Yamaoka, A. Kamimatsuse, M. Onitake, T. Sueda, M. Nishiyama, K. Hiyama
Journal: Journal of Clinical Oncology (2006)

9010 Background: Neuroblastoma is a biologically and genetically heterogeneous tumor and demonstrates favorable or unfavorable outcomes. However, the number of subgroups in neuroblastoma and natural history of each subgroup remain unclear. In Japan, nation-wide neuroblasotma mass-screening (MS) project had been performed on 6-month-old babies for 20 years that might have detected almost all neuroblastomas including regressing/ maturing tumors developed in this period. We surveyed more than 3,600 neuroblasotma cases including approximately 2,000 MS detecting cases. In this study, we examined genetic alterations in the representative cases using genome-wide SNP array and compared with the clinical courses. Methods: Genomic DNA was extracted from 198 neuroblastoma samples. SNP array (Affimetrix GeneChip Human mapping Array100K) was used to determine genome-wide aberrations. Chromosome aberrations were confirmed by BAC array and FISH examination. Expression profiles of these tumors were also examined using whole genome microarray (Codelink and Affimetrix Array U133 plus2). Results: SNP arrays could frequently identify chromosomal aberrations and allelic imbalances including 1p and 11q loss and MYCN amplification in unfavorable tumors. Then, we broadly classified the chromosome aberrations in neuroblastoma into four types: whole gain/loss type, partial gain/loss type, MYCN amplified type, and silent type with no large alterations. Almost all tumors with whole gain/loss type showed favorable prognosis, while MYCN amplified type and partial gain/loss type showed unfavorable outcome. In 32 tumors with silent type, 18 unfavorable tumors had small deletions and/or gains in 1p, 2p, 3p, 11q, and/or 17q but the remaining 16 favorable cases did not. The expression analysis of the unfavorable tumors showed high expression of several genes (DDX1, NAG, NME1, MAC30) in these loci. Conclusions: Genome-wide genetic analysis classified neuroblastoma into four types, which are useful to predict the outcome of patients. In the silent type, unfavorable tumors revealed several genes to predict the outcome of the patients. These data provided important candidates of indicators for risk assessment and of therapeutic targets for unfavorable neuroblastoma. No significant financial relationships to disclose.
AN UNDERRECOGNIZED AND UNDERREPORTED POST-PROCEDURAL COMPLICATION OF A COMMON CARDIAC PROCEDURE: AN OVERLAP PRESENTATION OF THE PERICARDIAL DECOMPRESSION SYNDROME AND STRESS CARDIOMYOPATHY FOLLOWING A THERAPEUTIC PERICARDIOCENTESIS
Authors: Roberto Cerrud-Rodriguez, Mohammed Algodi, Ahmad Alkhalil, Jay Chudow, Syed Muhammad Ibrahim Rashid, Mario Garcia, James Tauras, Hussein Shaqra, Giora Weisz
Journal: Journal of the American College of Cardiology (2020)
Efficacy study of metronomic chemotherapy in metastatic NSCLC.
Authors: B. J. Srinivas, Nayak Radheshyam, C. Gunasagar, Eriat Govind, Veldore H. Vidya, Rao M. Raghavendra, Mangesh Kamat, Roy Siddartha
Journal: Journal of Clinical Oncology (2013)

e19092 Background: Metastatic lung cancer patients are at best treated palliatively. We evaluated the effects of metronomic chemotherapy on survival outcomes in this population. Methods: Thirty four subjects with treatment refractory (n=26) and treatment naive (n=7) metastatic lung cancer were included in a open label single arm efficacy study of metronomic chemotherapy. Patients were given a chemotherapy regimen of Tab. Cyclophsophamide 50 mg once daily and cap. etoposide 50 mg once daily, 3 weeks on and one week off in 28 day cycle over a minimum period of 3 months or until the progression of their disease whichever was earlier. Patients were assessed for treatment response using RECIST criteria (version 1.1) and duration of progression free survival and overall survival. Data were analysed using Kaplan Meier survival analysis. Results: The mean age of the study population was 63.4 ±11.2 years. The mean duration of metronomic chemotherapy was 94.9 ±60.4 days. Overall 64.7% had progressive disease and 26.5% had stable disease. There was a significant improvement in overall survival in those with ECOG performance status of 1 compared to ECOG status of 2 (median survival =240 vs.52 days, Log Rank Mantel Cox =11.32, p=0.001) and pathology grade 2 compared to grade 3 (median survival =200 vs. 37 days, Breslows Wilcoxon =5.76, p=0.02) and stable disease on RECIST compared to progressive disease following metronomic chemotherapy (Median survival =360 vs. 50 days, Log Rank Mantel Cox =8.68, p=0.003). There was also a significant improvement in progression free survival in those with ECOG performance status of 1 compared to ECOG status of 2 (median survival =98 vs. 52 days, Log Rank Mantel Cox =6.62, p=0.001) and in grade 2 compared to grade 3 disease (mean survival =97 vs.32 days, Log Rank Mantel Cox =4.73, p=0.03). Tumor load and multiple organ sites of disease did not seem to influence survival. Conclusions: The results suggest stable response in about one third of study population, favorable progression free and overall survival rates following metronomic chemotherapy. Performance status is important predictors in this category of population.
Novel blood biomarker panel detects human colorectal cancer
Authors: M. Han, C. T. Liew, H. W. Zhang, K. T. Yip, Z. Y. Song, H. M. Li, X. P. Geng, L. X. Zhu, K. W. Marshall, C. C. Liew
Journal: Journal of Clinical Oncology (2006)

3611 Background: Human colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States, and early detection is critical to improve prognosis. To date, we have applied our unique methodology (the Sentinel Principle) to identify blood-based gene expressed biomarkers for several diseases including osteoarthritis, bladder cancer and psychiatric disorders. In the present CRC study, we identified gene signatures from blood cells and characterized a set of biomarkers able to differentiate patients with CRC from controls. Methods: Microarray: 31 blood RNA sample (15 controls; 16 CRC) were profiled using Affymetrix U133Plus2.0 GeneChips. Differentially expressed genes were identified using the non-parametric, Wilcoxon-Mann-Whitney test. SYBR Green real-time RT-PCR: a subset of identified genes was assayed using 115 samples (57 controls; 58 CRC). Logistic regression was used to assess the ability of linear combinations of specific transcripts to distinguish CRC from controls. The diagnostic power for each combination was evaluated by AUC of the Receiver Operating Characteristic (ROC) curve. Blind Test: 83 samples were assayed (45 controls and 38 CRC). Results: Microarray data: 2,779 probes were significantly different in blood gene expression profiles from controls and those from CRC (p&lt;0.05). Real-time RT-PCR: Two up-regulated genes (cytidine deaminase, 1.3 fold with p&lt;0.001; MGC20553 /FERM domain containing 3, 1.2 fold with p=0.031) and three down-regulated genes were validated (B-cell scaffold protein with ankyrin repeats 1, 0.43 fold with p&lt;0.001; B-cell novel protein 1, 0.44 fold with p&lt;0.001; membrane-spanning 4-domains, subfamily A, member 1, 0.44 with p&lt;0.001). Combination analysis: The AUC was 0.883 (95%, C.I. 0.810–0.935) for the best linear combination of these 5 genes. At a cut-off of -1.1, the sensitivity and specificity were 98% and 51%, respectively. Blind Test: The 5-gene set gave sensitivity of 95% (36/38) and specificity of 42% (19/45) with an overall accuracy of 66%. Conclusions: Gene expression signatures from peripheral blood differentiate between CRC patients and controls. The five-gene panel showed high classification performance and could be used as a novel screening tool for CRC. [Table: see text]
Molecular Imaging of Cardiac Allograft Rejection
Authors: Farhan Chaudhry, Matthew K.M.Y. Adapoe, Kipp W. Johnson, Navneet Narula, Aditya Shekhar, Hideki Kawai, Julian K. Horwitz, Jinhua Liu, Yansui Li, Koon Y. Pak, Jeffrey Mattis, Andre L. Moreira, Phillip D. Levy, H. William Strauss, Artiom Petrov, Peter S. Heeger, Jagat Narula
Journal: JACC. Cardiovascular imaging (2020)
A Multilevel Mediational Model of the Association of Neighborhood Deprivation With Risk for Nonaffective Psychosis
Authors: Kenneth S. Kendler, Henrik Ohlsson
Journal: JAMA Psychiatry (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
A multipeptide vaccine plus toll-like receptor agonists in melanoma patients, with evaluation of the vaccine site microenvironment and sentinel immunized node (Mel58; NCT01585350).
Authors: Craig L. Slingluff, Gina R. Petroni, Kimberly A. Chianese-Bullock, William W. Grosh, Geoffrey R. Weiss
Journal: Journal of Clinical Oncology (2013)

TPS3125 Background: Recent data show clinical activity of cancer vaccines containing a defined cancer antigen, and a peptide vaccine for melanoma. However, immune responses to peptide vaccines are often transient and of low magnitude. The most common adjuvant for peptide vaccines for melanoma has been an incomplete Freund’s adjuvant (IFA), which may have suboptimal adjuvant properties. Toll-like receptor (TLR) agonists offer the potential to improve the magnitude and persistence of antitumor T cell responses, either in combination with IFA or alone. CD40 ligation at the vaccine site microenvironment (VSME) may also improve adjuvant activity of TLR agonists and may be provided by CD4 T cell activation. We report a clinical trial of a multipeptide vaccine using TLR agonists and IFA, with correlative studies in 3 immunologic compartments. Methods: This trial is enrolling patients with resected stage IIB-IV melanoma (n=48) and is designed to evaluate the safety and immunogenicity of vaccination with peptides and either of 2 toll-like receptor agonists (TLR3 agonist polyICLC; TLR4 agonist endotoxin), with or without IFA. Patients are vaccinated 6 times over 12 weeks with 12 Class I MHC-restricted nonamer peptides. An immunogenic tetanus helper peptide is included to activate CD4 T cells in the VSME and secondarily to ligate CD40. Goals include safety assessment, measures of CD8 T cell responses, and characterization of cellular and molecular events induced in the blood, VSME and vaccine-draining node (sentinel immunized node, SIN), as well as a preliminary assessment of whether vaccination with TLR agonists improves the persistence of CD8 and CD4 T cell responses to melanoma antigens compared to prior studies with IFA. This includes a first-in-humans evaluation of the safety and immunogenicity of LPS, a classic TLR4 agonist, as a vaccine adjuvant. Thus, there is a novel dose-escalation phase with this adjuvant, which has been safely administered in other settings by intravenous and inhalation routes. An aim of this study is to identify an improved adjuvant for use in future trials combining peptides with other immune therapies. Clinical trial information: NCT01585350.
Prognostic significance of ATP-binding cassette (ABC) and solute carrier (SLC) transporters in pancreatic ductal adenocarcinoma (PDAC).
Authors: Beatrice Mohelnikova-Duchonova, Veronika Brynychova, Martin Oliverius, Jan Hlavsa, Eva Honsova, Jan Mazanec, Bohuslav Melichar, Zdenek Kala, Pavel Soucek
Journal: Journal of Clinical Oncology (2013)

11051 Background: Resistance against anticancer drugs significantly limits the clinical use and efficacy. One of the most important mechanisms of the multidrug resistance is low accumulation of the drug in cancer cells caused by an increased efflux (mediated mainly by ABCs) or by a decreased uptake (mediated by some members of SLCs). The aim of the present study was to investigate prognostic importance of 13 anticancer drug-relevant SLCs and all 49 human ABCs in PDAC patients in association with clinical and pathological characteristics and the tumor KRAS mutation status. Methods: Tumors and adjacent non-neoplastic pancreatic tissues were obtained from 50 patients with histologically verified PDAC. The transcript profile of ABCs and SLCs was assessed using quantitative real-time PCR. KRAS mutations in exon 2 were assessed by high-resolution melting analysis and sequencing. Associations of transcript levels with clinical parameters were assessed by non-parametric Mann-Whitney tests. The Kaplan-Meier method with the log-rank test and Cox regression were used for analysis of overall survival (OS). Results: Most transporters investigated were deregulated in PDAC and 14 ABCs or SLCs were associated with clinical characteristics. Up-regulation of 7 drug resistance-associated ABC efflux transporters and down-regulation of 5 drug uptake-relevant SLC transporters was observed in tumors vs. non-neoplastic tissues. Moreover, expression levels of SLC28A1 and SLC22A1 were associated with OS of all patients (P=0.001). High transcript levels of SLC29A3 and SLC22A3 significantly predicted longer OS in chemotherapy-treated patients (P=0.004 and P=0.038, respectively). No association of ABC and SLC expression with KRAS mutation status was observed. Conclusions: Up-regulation of numerous drug resistance-associated ABCs and down-regulation of SLCs implicated in drug uptake may explain the generally very poor response of PDAC to cytotoxic agents. This study also identified some ABCs and SLCs as potential prognostic and predictive factors in PDAC. Supported by the Czech Science Foundation grant P301/12/1734 and CZ.1.05/2.1.00/03.0076 European Regional Development Fund.
INCIDENCE AND PREDICTORS OF SIX-MONTH READMISSIONS IN CRITICAL LIMB ISCHEMIA: A NATIONWIDE STUDY
Authors: Prakash Acharya, Sagar Ranka, Zubair Shah, Prince Sethi, Brianna Stack, Adam Alli, Zafar Ali, Kamal Gupta
Journal: Journal of the American College of Cardiology (2020)
BEMPEDOIC ACID 180 MG + EZETIMIBE 10 MG FIXED-DOSE COMBINATION VS EZETIMIBE ALONE OR PLACEBO IN PATIENTS WITH TYPE 2 DIABETES AND HYPERCHOLESTEROLEMIA
Authors: Harold Bays, Seth Baum, Eliot Brinton, Jorge Plutzky, JoAnn Flaim, Zhan Ye, Christie M. Ballantyne
Journal: Journal of the American College of Cardiology (2020)
Trabectedin to induce mitochondrial membrane potential dissipation and reactive oxygen species generation in breast cancer cells.
Authors: Harika Atmaca, Emir Bozkurt, Burcu Cakar, Zeki Gokhan Surmeli, Selim Uzunoglu, Ruchan Uslu, Burcak Karaca
Journal: Journal of Clinical Oncology (2013)

e13580 Background: Trabectedin (Yondelis; ET-743) is a tetrahydroisoquinoline alkaloid that was originally derived from the marine tunicate Ecteinascidia turbinata and is currently prepared synthetically. It ıs currently used for the treatment of soft tissue sarcomas. It has been shown that Trabectedin provides the production of superoxides near the DNA strand, resulting in DNA backbone cleavage and cell apoptosis, however the apoptotic mechanisms of Trabectedin is still very limited. The objective of this study is to investigate the underlying mechanisms of apoptosis Trabectedin in two human breast cancer cell lines (MDA-MB-231 and MDA-MB-453) and one human immortalized non-transformed breast epithelial cell line (MCF-10A), to see if similar oxidation processes take place in breast cancer. Methods: Cytotoxicity was assessed by XTT cell viability assay. Apoptosis was shown by measuring DNA fragmentation, caspase 3/7 activation. Mitochondrial membrane potential (MMP) was evaluated by TMRE dye. Measurement of reactive oxygen species (ROS) was done by using Glutathione S-Transferase (GST) Assay Kit and CM-H2DCFDA dye. Results: Trabectedin induced the cytotoxicity in breast cancer cells in a time and dose dependent manner. Moreover, it increased DNA fragmentation and the MMP dissipation in tested breast cancer cells. The levels of ROS production in parallel with GST enzyme activity were sharply increased by Trabectedin treatment. Conclusions: This is the first study to investigate the role of Trabectedin activity and mechanisms of apoptosis in human breast cancer cells. These preliminary results might show us a way to use Trabectedin alone, or in combination for breast cancer treatment in near future.