tbuckley/cabot-search huggingface dataset:
Soluble human plasminogen kringle 5 domain acts as a 2-pronged anti-cancer agent inhibiting both endothelial cells and tumor-associated macrophages
Authors: Sabrina R. Perri, Borhane Annabi, Laurence Lejeune, Moöra François, Richard Béliveau, Jacques Galipeau
Journal: Cancer Research (2005)

3013  Objective: The urgent need for the development of novel and potent anti-glioma therapeutics as well as the importance of angiogenesis in glioma growth has fueled the identification and characterization of numerous antiangiogenic agents. The fifth kringle domain of human plasminogen (hK5) has been expressed as a recombinant protein in bacteria and been found to be more potent than angiostatin (K1-K4) or any of the plasminogen kringles expressed individually in inhibiting growth factor stimulated proliferation of endothelial cells in vitro. Hypothesis: We propose that tumor-targeted K5 cDNA expression may act as an effective therapeutic intervention as part of a cancer gene therapy strategy. To test this hypothesis, we have developed a K5-expressing retroviral vector, characterized the angiostatic activity of the de novo produced K5 peptide in vitro and tested its ability to affect the recruitment of host-derived tumor infiltrating endothelial as well as inflammatory cells implicated in tumor angiogenesis in vivo. Methods and Results: Human glioma cells were retrovirally-engineered to express functional soluble histidine-tagged hK5 protein (hK5His) and shown to significantly suppress in vitro human umbilical vein endothelial cell migration (P
BERMUDA: a novel deep transfer learning method for single-cell RNA sequencing batch correction reveals hidden high-resolution cellular subtypes
Authors: Tongxin Wang, Travis S. Johnson, Wei Shao, Zixiao Lu, Bryan R. Helm, Jie Zhang, Kun Huang
Journal: Genome biology (2019)

To fully utilize the power of single-cell RNA sequencing (scRNA-seq) technologies for identifying cell lineages and bona fide transcriptional signals, it is necessary to combine data from multiple experiments. We present BERMUDA (Batch Effect ReMoval Using Deep Autoencoders), a novel transfer-learning-based method for batch effect correction in scRNA-seq data. BERMUDA effectively combines different batches of scRNA-seq data with vastly different cell population compositions and amplifies biological signals by transferring information among batches. We demonstrate that BERMUDA outperforms existing methods for removing batch effects and distinguishing cell types in multiple simulated and real scRNA-seq datasets.
The Amount of Evidence Needed to Support ERBB2 as a Biomarker for Resistance to EGFR Inhibitors in Metastatic Colorectal Cancer—In Reply
Authors: Giacomo Bregni, Stefania Sciallero, Alberto Sobrero
Journal: JAMA Oncology (2019)

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 Oncology 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 Oncology journal
Abstract #3540: A study of the unfolding thermodynamics of DNA with 8-oxo-7,8-dihydro-2\#8217;-deoxyguanosine: Experimental evidence for reduced stability
Authors: Barry Gold, Sreelkha Singh, Luis Marky
Journal: Cancer Research (2009)

The oxidation of DNA is a major pathway for DNA damage, which if not repaired can lead to mutations and an increase in the incidence of cancer. The predominant lesion formed in DNA exposed to oxidizing agents is 8-oxoguanine (oxoG). The oxoG lesion is removed from the nucleotide pool by the hydrolysis of oxoGTP by MutT and from ds-DNA by 8-oxoguanine-DNA glycosylase (OGG). Locating oxoG in the midst of unmodified DNA by OGG requires a combination of rapid scanning for the lesion followed by specific excision. As is the case with other glycosylases, OGG excises its substrate by trapping it an extrahelical conformation. High-resolution structural analyses of DNA with oxoG by NMR and X-ray crystallography show that the base pairing is very similar to a Watson-Crick G\#8226;C pair [Lipscomb et al. (1995) Proc. Natl. Acad. Sci. USA92, 719; Oda et al. (1991) Nucleic Acids Res. 19, 1407]. However, the NMR provided evidence for a 3-5 °C decrease in thermal stability. The origin of this destabilization was not experimentally addressed. To understand how oxoG affects DNA stability, we initiated a thorough thermodynamic study to understand how the oxoGC base pair affects DNA stability, hydration and cation binding. Our UV melting and differential scanning calorimetry studies demonstrate that G to oxoG substitution affords duplexes with lower stabilities (\#916;\#916;G° of ~3 kcal/mol DNA), lower folding heats (\#916;\#916;Hcal of ~ 13-40 kcal/mol DNA), lower uptake of counterions (\#916;\#916;nion of 0.6-0.8 mol Na+/mol DNA), and lower immobilization of water molecules (\#916;\#916;nw of 17-27 mol H2O/mol DNA). Assuming a local effect of the oxoG lesion, the reduced stability of the duplex vs. the random coil states for oligomers with oxoG\#8226;C indicates that the extrahelical state of oxoG is relatively more stable vs. the fully stacked duplex than in the case of an extrahelical G in a G\#8226;C base pair. This is explained in terms of its higher flexibility, which is due to a lower binding of both ions and water molecules. Supported by grants: RO1CA29088 from NIH and MCB-0315746 from the National Science Foundation.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3540.
Abstract 202: Early Reprogramming Derived Cocktail FIJs Supports Cardiomyocyte Proliferation for Heart Regeneration
Authors: Yuan-Yuan Cheng
Journal: Circulation Research (2016)

Although remnant cardiomyocytes (CMs) possess a certain degree of proliferative ability, their regenerative efficiency is too low for cardiac regeneration after injury. As terminally differentiated cells, CMs are considered difficult to successfully reprogram into iPSCs. In this study, a modified reprogramming method was employed to avoid damage to the CMs, and the resulting CM-derived iPSCs were characterized their pluripotency and differentiative abilities. During the early stages of reprogramming, we observed sequential morphological changes in both CMs and non-CMs, but alkaline phosphatase assay revealed that CMs demonstrate a time-delayed sequence of events compared to non-CMs. In order to identify the specific events preceding colony formation, total RNA was purified for microarray analysis on day 0, 2, 4, and 6 of the reprogramming process. There were several interesting changes revealing such as up-regulation of sterol synthesis in non-CMs and down-regulation of chemokines in CMs on day 2. Most importantly, we detected significant enhanced mitosis for CMs on day 2. Nevertheless, typical iPSC-like colonies were clearly observed after 6 days of reprogramming in both cell types. In the purpose of bringing CM back to regain proliferative ability for heart regeneration, the candidates were selected from the microarray results on day 2 of the reprogramming. Triple combined gene cocktail FIJs was determined supporting CM proliferation with 7 times higher Ki-67 + or H3P + population % in neonatal murine CMs in vitro . The same supportive role of FIJs was also confirmed in adult mice showing higher H3P + adult CMs in vivo . Furthermore, heart function detected by echocardiography was significantly improved and less fibrosis shown by trichrome staining after the triple gene cocktail treatment in adult mice suffering from myocardial infarction, and this improvement was owing to the enhanced CM proliferation. In conclusion, triple gene cocktail selected from CM reprogramming day 2 provides valuable information for inducing remnant CM proliferation for heart regeneration.
Prognostic factors for metastatic renal cell carcinoma patients with removed metastases: A multicenter study of 559 patients.
Authors: Sei Naito, Hidefumi Kinoshita, Tsunenori Kondo, Nobuo Shinohara, Takashi Kasahara, Kazutaka Saito, Tatsuya Takayama, Naoya Masumori, Toshiro Terachi, Seiichiro Ozono, Seiji Naito, Yoshihiko Tomita
Journal: Journal of Clinical Oncology (2012)

e15071 Background: Metastasectomy considered to prolong survival in patients with metastatic renal cell carcinoma (mRCC). However, data on the indications for metastasectomy are limited. We aimed to examine the prognosis and the prognostic factors of mRCC patients who underwent metastasectomy. Methods: We sent questionnaires to Japanese hospitals and collected the data of patients who were diagnosed with mRCC between January 1988 and December 2009 and who had their metastatic lesions removed. We calculated the overall survival between metastasectomy and death or until the last follow-up. We also analyzed the relationship between survival and clinical features and identified adverse prognostic factors by multivariate analysis. Furthermore, we identified the group with a poor prognosis on the basis of the number of prognostic factors for which the patients were positive. These findings were internally validated using bootstrap procedures and the c-index. Results: We collected the data of 559 patients from 48 institutions. The median overall survival period was 80 months (95% CI, 69.7-90.6 months). We detected 5 adverse prognostic factors: incomplete resection by metastasectomy (hazard ratio, 1.75; p = 0.0169); brain metastasis (hazard ratio, 3.26; p = 0.0002); C-reactive protein levels of &gt;1.0 mg/dl (hazard ratio, 2.84; p &lt; 0.0001); Eastern Cooperative Oncology Group performance status of &gt;1 (hazard ratio, 1.65; p = 0.0274); and the worst nuclear grade, i.e., the nuclei of tumor cells are larger than those of normal tubular cells (hazard ratio, 1.59; p = 0.0348). Patients positive for 3 or more of theseadverse prognostic factors had a worse prognosis (median overall survival, 24 months) than those positive for less than 3 factors (median overall survival, 105 months). The c-index for this model was 0.65 at 2 years. Conclusions: We identified 5 adverse prognostic factors for predicting the survival of patients who underwent metastasectomy.
Abstract #2511: Lysophosphatidic acid enhances the motility of oral carcinoma cells and decreases their sensitivity to mitochondrial-mediated apoptosis
Authors: Steven Johnson, Jason Mansell, Ian Paterson
Journal: Cancer Research (2009)

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide, accounting for more than 250,000 new cases each year. The 5-year survival rate is approximately 50% and new, targeted approaches for therapy are urgently needed. Lysophosphatidic acid (LPA) is a bioactive lipid that regulates many biological processes associated with cancer development and progression, such as proliferation, migration and apoptosis and deregulated LPA signaling has been demonstrated in a limited number of tumour types. The role of LPA in the pathogenesis of OSCC warrants investigation, not least because LPA is present in significant amounts in saliva. Lysophospholipid levels are elevated in vivo in a number of pathophysiological states and we demonstrate that 6/7 OSCC cell lines secreted LPA into the culture medium, as determined by ELISA. Using quantitative real-time PCR we show that OSCC cell lines express LPA receptors 1-3 and that the LPA3 receptor is over-expressed in 6/7 OSCC cell lines relative to non-tumour derived control cells. Treatment of OSCC cell lines with LPA (1-5µM) had little effect on cell proliferation, but greatly stimulated cell motility in colony dispersal assays, causing colonies to disperse into single, highly migratory cells with an elongated morphology and lamellipodia. Similarly, LPA stimulated OSCC cell migration in Boyden chamber-style chemotactic assays. LPA-induced cell migration was dependent on the MEK, ROCK and Rac-1 signaling pathways. Ultraviolet B (UVB) radiation was used to examine the effect of LPA on mitochondrial-mediated apoptosis. With 50 mJ/cm2 irradiation there was a significant reduction in cell death in OSCC cells treated with 5µM LPA compared to untreated controls (t-test, p = 0.002). By contrast, LPA had no significant effect on non-tumour derived keratinocytes (t-test, p = 1.00). The results of the present study indicate that de-regulated LPA production and/or signaling may contribute to a more aggressive phenotype in OSCC. Work is ongoing to examine the precise role of the LPA3 receptor in this context and to determine whether LPA and its receptors may be used as targets for therapeutic intervention.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2511.
Influence of chronic inflammation on prostate carcinogenesis: A five year follow-up study
Authors: Gregory T. Maclennan, Rosana Eisenberg, Ranleigh L. Fleshman, Michael Taylor, Pingfu Fu, Martin I. Resnick, Sanjay Gupta
Journal: Cancer Research (2006)

1474  The relationship between inflammation and cancer has been established in some forms of human malignancies. Whether chronic prostatic inflammation contributes to prostate carcinogenesis is unclear. The purpose of this study was to investigate an association between chronic inflammation and prostate carcinogenesis. Prostate needle biopsies from 177 patients with clinical parameters suspicious for malignancy were examined, paying particular heed to the presence and extent of inflammation in these initial biopsies. Findings in any subsequent follow-up biopsies over the next 5 years were reviewed and correlated with the initial results. Of 177 needle biopsy cases, chronic inflammation was observed in 81% (144/177); 19% (33/177) had no inflammation. Of 144 cases with inflammation, 15% (22/144) showed only inflammation, 15% (22/144) showed simple atrophy, 39% (54/144) showed PAH/PIA lesions, 8% (12/144) showed HGPIN, 20% (29/144) showed adenocarcinoma, and 3% (5/144) showed atypical small acinar proliferation (ASAP). In biopsy specimens without inflammation, 9% (3/33) showed simple atrophy, 9% (3/33) showed HGPIN, 30% (10/33) showed adenocarcinoma, and 6% (2/33) showed ASAP whereas 46% (15/33) had no diagnostic findings. A significant association between serum PSA and inflammation grade was observed in needle biopsies. Repeat biopsies within 5 years in patients with chronic inflammation showed adenocarcinoma in 4% (6/144) of cases initially showing only chronic inflammation, 10% (15/144) with initial PAH/PIA lesions, 5% (7/144) of those with initial HGPIN lesions and 0.7% (1/144) with initial ASAP. HGPIN was subsequently found in 5% (7/144) of PAH/PIA and 1% (2/144) with initial simple atrophy. In sharp contrast, in 33 cases initially showing no inflammation, adenocarcinoma was subsequently found in 6% (2 of 33 patients). One of these patients had HGPIN and the other had ASAP on initial biopsy. Taken together, these results suggest that chronic inflammation may be a significant risk factor for the development of prostatic adenocarcinoma.
Risk of gout flares after vaccination
Authors: Shih-Wei Lai, Yu-Hung Kuo, Kuan-Fu Liao
Journal: Annals of the Rheumatic Diseases (2019)

Gout is a common inflammatory joint disease worldwide, in part because the global prevalence of gout was rising.1 The direct relationship between the elevated levels of uric acid and gout attack is well-recognised. Several risk factors for gout attack are found, including dietary factors, medications and comorbidities.2 Recently, a case-crossover study conducted by Yokose et al published in Annals of the Rheumatic Diseases revealed that vaccination in the prior 2 days was associated with a twofold increased odds of gout attack when compared with no vaccine periods (adjusted OR 1.99; 95% CI 1.01 to 3.89).3 Some points not shown in the original article are …
When a Vital Sign Leads a Country Astray—The Opioid Epidemic
Authors: Brooke A. Chidgey, Katharine L. McGinigle, Peggy P. McNaull
Journal: JAMA Surgery (2019)

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 Surgery 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 Surgery journal
Development of a Novel Risk Prediction Model for Sudden Cardiac Death in Childhood Hypertrophic Cardiomyopathy (HCM Risk-Kids)
Authors: Gabrielle Norrish, Tao Ding, Ella Field, Lidia Ziólkowska, Iacopo Olivotto, Giuseppe Limongelli, Aristides Anastasakis, Robert Weintraub, Elena Biagini, Luca Ragni, Terence Prendiville, Sophie Duignan, Karen McLeod, Maria Ilina, Adrián Fernández, Regina Bökenkamp, Anwar Baban, Peter Kubuš, Piers E. F. Daubeney, Georgia Sarquella-Brugada, Sergi Cesar, Chiara Marrone, Vinay Bhole, Constancio Medrano, Orhan Uzun, Elspeth Brown, Ferran Gran, Francisco J. Castro, Graham Stuart, Gabriele Vignati, Roberto Barriales-Villa, Luis G. Guereta, Satish Adwani, Katie Linter, Tara Bharucha, Pablo Garcia-Pavia, Torsten B. Rasmussen, Margherita M. Calcagnino, Caroline B. Jones, Hans De Wilde, J. Toru-Kubo, Tiziana Felice, Jens Mogensen, Sujeev Mathur, Zdenka Reinhardt, Constantinos O’Mahony, Perry M. Elliott, Rumana Z. Omar, Juan P. Kaski
Journal: JAMA Cardiology (2019)

Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM), but there is no validated algorithm to identify those at highest risk.
Hydroxyl radical formation and DNA damage mediated by human NADPH-cytochrome P450 reductase
Authors: Vladimir Mishin, Joshua P. Gray, Diane E. Heck, Jeffrey D. Laskin
Journal: Cancer Research (2006)

3556  It is well recognized that reactive oxygen intermediates (ROI), in particular, hydroxyl radicals, can damage DNA and contribute to the carcinogenic process. Cytochrome P450 reductase (NADPH:ferrihemoprotein oxidoreductase, EC 1.6.2.4) is a microsomal flavoprotein present in almost all epithelial cells. Its major function is to transfer electrons to cytochrome P450. In the presence of oxygen and utilizing NADPH as a source of reducing equivalents, an unusual property of the enzyme is its ability to generate ROI in the absence of cytochrome P450 substrates. In the present studies we characterized this process using human recombinant cytochrome P450 reductase. We found that the enzyme readily synthesizes superoxide anion and hydrogen peroxide, as measured by superoxide-mediated oxidation of hydroethidine, and hydrogen peroxide and peroxidase-mediated oxidation of 10-acetyl-3,7-dihydroxyphenoxazine, respectively. These reactions were NADPH-dependent and not altered specifically by various recombinant P450’s and their substrates/inhibitors including zoxazolamine (10-200 μM) and α-naphthoflavone (1 μM), specific for CYP1A2, buprenorphine (3-100 μM) and ketoconazole (1 μM), specific CYP3A4, and chlorzoxazone (10-200 μM), a specific CYP2E1 substrate. Despite formation of superoxide anion and hydrogen peroxide by the enzyme, no hydroxyl radical formation was detected, as measured by oxidation of terephthalate, either in the absence or presence of cytochrome P450 substrates, unless redox active iron (Fe/EDTA complexes) was added to the reaction mix. In the presence of redox active iron, a dose-dependent formation of hydroxyl radical was detected with respect to NADPH and enzyme concentrations. Using plasmid DNA unwinding assays, NADPH-dependent cytochrome P450 reductase mediated formation of hydroxyl radicals, but not superoxide anion or hydrogen peroxide, was found to damage DNA as determined by alterations in migration of DNA in agarose gels. Taken together, our data indicate that cytochrome P450 reductase is able to continually generate ROI in the presence of NADPH. We speculate that regulation of production of DNA damaging hydroxyl radicals will depend on the composition of microsomal constituents including cytochrome P450 reductase, the cellular content of antioxidants, and the accessibility of redox active iron in the microsomal electron transport chain. Supported by NIH grants CA093798, CA100994 and ES05022.