tbuckley/cabot-search huggingface dataset:
Growth factors in skin melanoma and nevi tissues.
Authors: Ekaterina Komarova, Elena Frantsiyants, Victoriya Pozdnyakova, Valeriya Bandovkina, Yulia Pogorelova, Nataliya Cheryarina
Journal: Journal of Clinical Oncology (2014)

e22235 Background: Several growth factors are involved in pathogenesis of melanoma that are produced by cells taking part in stimulation of growth and survival of cells (TGF-β, IFR-1) that further the transformation of melanocytes and their transition to the vertical growth stage, thus increasing the oncogenic potential of the tumor (FGF) related to angiogenesis (VEGF). Methods: The IFA method was used to determine the content of VEGF, VEGF-R, TGF-β, FGF, EGF, EGF-R, IFR-1, IFR-2 in 40 samples of skin melanoma tissue obtained in operative excision of the tumor (pT1-4N0-1M0) and 20 samples of skin nevi. As the control samples, the intact skin obtained of patients having no oncopathology was used. Results: It has been demonstrated that the level of TGF-β, FGF, EGF, EGF-R, IFR-1, IFR-2 in the pT1-2N0M0 melanoma tissue was 5.8, 1.4, 2.6, 1.4, 1.3, 3.5 times higher than the control indicators, respectively, and went up as the malignant process developed in case of pT3-4N0-1M0. In the nevi tissue, the level of TGF-β, IFR-1, IFR-2 had no valid change relative to the intact skin, and the content of FGF, EGF, EGF-R was not marked by any valid change relative to the values in the melanoma tissue. It was determined that the level of VEGF in the nevi tissue was similar to the intact skin values and it was 1.7 and 2 times higher in the melanoma tissue under pT1-2N0M0 and pT3-4N0-1M0, respectively. The content of VEGF-R both in the tissue of nevi and in that of the tumor was much higher than the control values – 1.7 and on average 6.5 times as high for pT1-4N0-1M0. The level VEGF/VEGF-R1 in tissue nevi was lower than the values in the intact skin in 1.8 times, but higher values in the tumor average 1.9 times. Conclusions: Metabolic condition of nevi tissue allows considering them a background disease of malignant neoplasms of skin and determines the possibilities of development of a therapy aimed at factors of growth and neoangiogenesis.
Abstract 17323: Polyinosinic-Polycytidylic Acid Primes Cardiac Progenitors From Human Induced Pluripotent Stem Cells for Enhanced Cell Therapy and Cardiomyocyte Maturation
Authors: Mitch Biermann, Wenxuan Cai, Di Lang, Jack Hermsen, Luke Profio, Annie Shao, Tianxiao Han, Marites Woon, Alexey Glukhov, Ying Ge, Timothy J Kamp
Journal: Circulation (2018)

Cardiomyocytes derived from human induced pluripotent stem cells (hiPS-CMs) hold promise for disease modeling, drug discovery, and therapy, but the challenge remains to create mature cardiomyocytes like those found in the adult heart. While groups have increased the maturity of hiPS-CMs in extended culture with electrical, metabolic, and mechanical stimulation, we hypothesized that epigenetic modulation during the formation of cardiac progenitors (hiPS-CPCs) could enhance their capacity to form mature CMs. We found that priming with the innate immune agonist polyinosinic-polycytidylic acid (pIC) decreased cardiac lineage-HDAC expression during the formation of hiPS-CPCs in defined small molecule monolayer differentiation. While both untreated and primed day 5 hiPS-CPCs contained equivalent &gt;80% purity of KDR+PDGRFα+ CPC populations, gene expression studies using RNAseq demonstrated that pIC priming enhanced the early cardiogenic and Notch signaling programs. When both groups were differentiated in basal media, primed hiPS-CPCs gave rise to more mature cardiomyocytes based on larger cell size, increased optical action potential upstroke velocity, greater oxidative metabolism, enhanced sarcomere maturation, and upregulated transcriptional markers of CM maturation including cTnI, cardiac actin, and αMHC. These maturation effects of pIC treatment were blocked by the Notch inhibitor DAPT. Most impressively, primed hiPS-CPCs improved survival as well as myocardial systolic/diastolic function in a mouse model of myocardial infarction (Figure). Conclusion: pIC-primed hiPS-CPCs with the capacity to give rise to hiPS-CMs of enhanced maturation hold promise for improved disease modeling, drug screening and cell therapy.
The feasibility to use minimal tumor samples for mutation analysis by multiplex PCR-based assay.
Authors: Yuichi Tambo, Ryohei Katayama, Noriko Yanagitani, Atsushi Horiike, Fumiyoshi Ohyanagi, Keita Kudo, Hironari Nishizawa, Takeshi Uenami, Hiroshi Gyotoku, Hiroshi Kobayashi, Naoya Fujita, Sakae Okumura, Yuichi Ishikawa, Takeshi Horai, Dora Dias-Santagata, Makoto Nishio
Journal: Journal of Clinical Oncology (2014)

e22060 Background: Several targeted agents and gene analysis are important for treatment of non-small cell lung cancer (NSCLC). The single gene examination is not sufficient to make the decision of treatment, and the development of multiplex gene examination is necessary. In this study we examined the feasibility of multiplex PCR-based method (SNaPshot) in the biopsy samples and cytology sample of lung cancer. Methods: Tumor samples including FFPE 63 surgical samples (60%), 24 transbronchial lung biopsy (TBLB) samples (22.9%), 8 needle biopsy samples (7.6%), and 7 pleural effusion (6.7%) and 3 cytology specimen (2.9%) were analyzed. After total nucleic acid purification, single mutation assay for EGFR mutations (Scorpion/ARMS) and SNaPshot for 14 cancer related gene mutations (BRAF, CTNNB1, EGFR, IDH1, KIT, KRAS, MAP2K1, NRAS, PIK3CA, PTEN, and others) were performed. ALK translocation was analyzed by immunohistochemistry (IHC) and FISH for the detection of ALK translocation. Results: Median total nucleic acid concentrations were 45.0, 4.45, 4.55, 3.4 and 41.2 ng/µl in surgical sample, TBLB sample, needle biopsy sample, cytology sample, and pleural effusion sample, respectively. Mutation frequency according to sample type is presented in table. We identified 1case of comcomitant EGFR (L858R)/PTEN (R130G) mutation and 1 case of comcomitant EGFR (Exon 19 del)/CTNBB (S45P) mutation. Concordance rate of Scopion/ARMS and SNaPshot for EGFR L858R mutation was 96.6% (28 of 29). Conclusions: SNaPshot analysis is feasible to detect somatic mutations even if limited amount of FFPE biopsy or cytology specimens obtained from NSCLC patients. N EGFR EGFR T790M EGFR PTEN EGFR CTNNB ALK KRAS PIK3CA PTEN IDH CTNNB Wild Surgical tissue 63 (%) 19 30.2% 1 1.6% 1 1.6% 1 1.6% 2 3.2% 6 9.5% 3 4.8% 1 1.6% 1 1.6% 0 0% 26 41.3% TBLB 24 (%) 8 33.3% 0 0% 0 0% 0 0% 1 4.2% 2 8.3% 0 0% 0 0% 0 0% 1 4.2% 12 50.0% Needle biopsy 8 (%) 2 25.0% 0 0% 0 0% 0 0% 0 0% 1 12.5% 0 0% 0 0% 0 0% 0 0% 4 50.0% Cytological sample 3 (%) 0 0% 0 0% 0 0% 0 0% 0 0% 1 33.3% 0 0% 1 33.3% 0 0% 0 0% 1 33.3% Pleural effusion 7 (%) 4 57.1% 1 14.3% 0 0% 0 0% 0 0% 0 0% 0 0% 0 0% 0 0% 0 0% 2 28.6% Total 105 (%) 33 31.4% 2 1.9% 1 1.0% 1 1.0% 3 2.9% 10 9.5% 3 2.9% 2 1.9% 1 1.0% 1 1.0% 45 42.9%
Seeding after biopsy of liver metastases in patients with primary colorectal and breast cancer.
Authors: Inna Markovna Chen, Torben Lorentzen, Dorte Linnemann, Christian Pallson Nolsøe, Bjørn Skjoldbye, Benny Vittrup Jensen, Dorte Nielsen
Journal: Journal of Clinical Oncology (2014)

e14545 Background: Seeding is a potential complication after liver metastases biopsy. Incidences reported in the sparse literature vary between 10-19% for colorectal cancer (CRC) and are unknown for breast cancer (BC). The aim of this retrospective study was to determine the frequency of tumor seeding after biopsy of CRC and BC liver metastases. Methods: Unselected liver biopsies performed in the period of 2005-2012 at our institution were extracted from the http://www.patobank.dk/. Review of records including imaging from patients with biopsy verified BC and CRC liver metastases was conducted. Results: Of a total 2,981 biopsies we identified 278 CRC and 155 BC patients with biopsy verified liver metastases. During the median follow-up of 25 months after biopsy (range 3-253), no seeding was recorded in BC patients. Within the median follow-up of 34 months (range 3-111), 17/278 patients with CRC (6%) were found suspicious for seeding; three patients (1.1%) had undoubtedly biopsy related seeding, which became apparent 6, 9, and 26 months after biopsy, respectively; in nine patients (3.2%) seeding occurred due to either biopsy or other interventions; and five patients had seeding, which were assessed as a consequence of other invasive procedures than biopsy. Mean interval for seeding occurrence was not defined, since six patients had been exposed to several potential hazardous biopsies. Neither biopsy technique nor number of attempts influenced seeding. In post-biopsy course 6/17 patients (35%) were diagnosed with either carcinosis or ascites, or both and no patient had intestinal obstruction. Resection of abdominal wall recurrences was performed in 13/17 patients and 2/17 received radiation. Four patients are still alive and 13/17 patients died from cancer related progression, in particular due to liver metastases. The median overall survival of the 17 patients with seeding was 70 months compared to 39 months of patients without seeding. Conclusions: The results showed no seeding in BC patients. Seeding rate after biopsy in CRC patients is not negligible, however, without affecting outcome. Based upon the presented data, indication for liver biopsy should be carefully considered in potential resectable CRC candidates.
Media reporting of practice-changing clinical trials in oncology: A North American perspective.
Authors: Peter Andrew, Michael M. Vickers, Stephen O'Connor, Patricia A. Tang
Journal: Journal of Clinical Oncology (2014)

6538 Background: The median time interval from phase III trial completion to public availability of results is 29 months. Our primary objective was to characterize the accuracy of information regarding ASCO 2012 Clinical Cancer Advances (CCA, n=17) as reported by the media and Internet; important public sources during that time. Methods: The first articles referencing CCA conference material were collected from newspapers, cable news, cancer websites, and industry websites. Two investigators independently rated the completeness of information using a 15-point scoring system [media reporting score (MRS)]. Statistical analyses were by Kruskal-Wallis one-way ANOVA-by-ranks test with post hoc analysis (Statistica, Statsoft Inc., Tulsa, Oklahoma, USA). Results: From 163 media articles, 107 (66%) had sufficient data for analysis. Per MRS, information was most complete from industry > cancer websites > newspapers > cable news (Table; Kruskal-Wallis H test = 8.52; df = 3; p<0.05). The most commonly omitted items were: study limitations > exclusion criteria > conflict of interest > other. Conclusions: The media should be encouraged to use a standardized reporting template and provide access to original source information. Newspapers Cable news Cancer websites Industry websites (New York Times, Wall Street Journal, and Globe & Mail) (CNN, Fox News, and CTV News) (ascopost.com, cancer.org, and cancer.gov) MRS; mean (range) 53 (49-57) 41 (39-46) 62 (58-67) 67 (58-73) Outcomes; % (n) Benefits not quantified 16 (5) 9 (2) 7 (3) 0 (0) Quantified benefits 84 (27) 91 (22) 93 (38) 100 (0) - Relative 56 (18) 75 (18) 12 (5) 0 (0) - Absolute 6 (2) 13 (3) 53 (22) 100 (10) - Relative and absolute 22 (7) 4 (1) 27 (11) 0 (0) Adverse events; % (n) Not reported 53 (17) 42 (10) 29 (12) 0 (0) Reported 47 (15) 58 (14) 71 (29) 100 (10) - With incidence 13 (4) 21 (5) 63 (26) 90 (9) Conflict of interest; % (n) Not reported 41 (13) 75 (18) 22 (9) 100 (0) Reported 59 (19) 25 (6) 78 (32) 0 (0) Link to original CCA article; % (n) 20 (6) 18 (4) 64 (26) 43 (4)
Rethinking How Antibiotics Are Prescribed
Authors: Pranita D. Tamma, Melissa A. Miller, Sara E. Cosgrove
Journal: JAMA (2018)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
The L-type calcium channel current modulation mechanism: the plot thickens and fogs
Authors: Brooke M. Ahern, Jonathan Satin
Journal: Journal of Clinical Investigation (2019)

Stressful situations provoke the fight-or-flight response, incurring rapid elevation of cardiac output via activation of protein kinase A (PKA). In this issue of the JCI, Yang et al. focus on the L-type calcium channel complex (LTCC), and their findings require reexamination of dogmatic principles. LTCC phosphorylation sites identified and studied to date are dispensable for PKA modulation of LTCC; however, a CaVβ2-CaV1.2 calcium channel interaction is now shown to be required. Yang et al. suggest a new hypothesis that LTCC modulation involves rearrangement of auxiliary proteins within the LTCC. However, we still do not know the targets of PKA that mediate LTCC modulation.
Abstract 14795: The Protective Role of Macrophage Migration Inhibitory Factor (MIF) in Acute Kidney Injury After Cardiac Surgery
Authors: Luisa S Averdunk, Andreas Goetzenich, Juergen Bernhagen, Richard Bucala, Christian Stoppe
Journal: Circulation (2017)

Background: Acute kidney injury (AKI) is a highly prevalent complication after cardiac surgery. Macrophage migration inhibitory factor (MIF) represents a stress-regulating cytokine that was shown t...
Assessment of tumoral heterogeneity in NSCLC treated with bevacizumab: A prospective study.
Authors: Connie Yip, Nunzia Tacelli, Martine Remy-Jardin, Paul Bassett, Gary J. R. Cook, David B. Landau, Vicky Goh
Journal: Journal of Clinical Oncology (2014)

e19124 Background: Imaging heterogeneity may reflect biological heterogeneity. Changes in tumoral heterogeneity in NSCLC treated with chemotherapy ± bevacizumab in a prospective study, and their associations with treatment response were assessed. Methods: Forty patients (34 males; mean 60y) with advanced/metastatic NSCLC were treated with platinum-based chemotherapy (Group 1, n=23) or chemotherapy + bevacizumab (Group 2, n=17), and underwent contrast-enhanced CT at baseline, after 1, 3 and 6 cycles of chemotherapy. Radiological response was assessed using both RECIST 1.1 and Crabb criteria. 63 target lesions were selected for heterogeneity analysis generating global and locoregional parameters using first, second, higher-order and model-based methods. Heterogeneity parameters between the two groups were compared using Mann-Whitney U test. Associations between heterogeneity parameters and best radiological response were assessed using univariate and multivariate logistic regressions. A p-value <0.01 was considered significant. Results: More responders were identified using Crabb compared to RECIST criteria: 10 (43%) by Crabb and 8 (35%) by RECIST in Group 1, and 8 (47%) and 7 (41%) in Group 2 respectively. There was no significant difference in the absolute and relative changes in all categories of heterogeneity values between the two groups. Several locoregional heterogeneity parameters were associated with response (Table). Combination of two or more heterogeneity parameters did not improve the predictive value compared to a single parameter. Conclusions: Changes in locoregional heterogeneity parameters were associated with antiangiogenic treatment response in NSCLC. Univariate regression showing the odds of a response for a 1% increase in the heterogeneity values from baseline. Heterogeneity parameters RECIST 1.1 Crabb OR (95% CI) P value OR (95% CI) P value Locoregional Short run emphasis 1.51 (1.14-1.99) 0.004 1.05 (1.02-1.08) 0.002 Contrast 1.13 (0.99-1.30) 0.06 1.04 (1.01-1.06) 0.003 Run percentage 0.91 (0.85-0.97) 0.003 0.93 (0.89-0.97) 0.001 Intensity variability 0.91 (0.84-0.98) 0.01 0.94 (0.91-0.98) 0.001 Run length variability 0.88 (0.81-0.96) 0.006 0.86 (0.77-0.96) 0.009
21st-Century Genetics in Psychiatric Residency Training
Authors: Aaron D. Besterman, Daniel Moreno-De-Luca, John I. Nurnberger
Journal: JAMA Psychiatry (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 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
Validation of a nomogram predicting nonsentinel lymphnode metastases among patients with breast cancer after neoadjuvant chemotherapy (NACT): A transSENTINA substudy.
Authors: Cornelia Liedtke, Dennis Goerlich, Ingo Bauerfeind, Tanja Fehm, Barbara Fleige, Gisela Helms, Annette Lebeau, Annette Staebler, Gunter Von Minckwitz, Michael Untch, Thorsten Kuehn
Journal: Journal of Clinical Oncology (2014)

e12022 Background: The optimal timing for sentinel lymph node biopsy (SLNB) in the setting of NACT is still unclear. Recent studies such as SENTINA suggest that performing SLNB in patients with a cN1 status before but converting to a cN0 status through NACT may result in an unacceptable false-negative rate. There is a need to predict non-SLN status and tailor axillary surgery after NACT. We validated the Jeruss-Nomogramm to predict non-SLN lymph node metastases after primary surgery in patients after NACT. Methods: The SENTINA trial was described in length last year. The Jeruss-nomogram includes lymphovascular invasion after NACT , detection method, multicentricity after NACT, clinical initial nodal involvement, and pathologic tumor size after NACT. It was applied to patients converting froom cN1 to cN0 status through NACT (arm C) but with histologically positive SLN (ypN+). The performance of the nomograms was evaluated by the area under the receiver operator curve (AUC). Results: This subgroup comprised 592 patients with 153 patients having a positive SLN after NACT and had all available data to run the nomogram. Our calculations result in an AUC-value of 0.659 (CI: 0.571 – 0.746, p=0.001) showing a significantly better performance than by random choice (AUC=0.5). For this analysis, we selected a cutpoint of 90% showing reasonable sensitivity (0.81) but low specificity (0.438). A subgroup of 75 patients from SENTINA having complete data for all nomograms shows a better performance of the Jeruss nomogram (0.709, CI: 0.587-0.832) which was still lower compared to e.g. the MSKCC nomogram with the best predictive value among the established nomograms (AUC=0.821, CI: 0.724-0.917). Conclusions: Validation of the Jeruss nomogram in the post-neoadjuvant setting yielded AUC values lower than in the original validation cohort lower than those of nomograms from patients with primary surgery (MSKCC) suggesting predictive inferiority of the prior nomogram compared to others. Our results show that nomograms predicting non-SLN status need to be optimized to avoid full axillary dissection in patients after NACT.
REBECA: A phase I study of bevacizumab (BEV) and whole-brain radiation therapy (WBRT) for treatment of solid tumors brain metastases (BM), EudraCT: 2009-015977-11.
Authors: Christelle Levy, Djelila Allouache, Joelle Lacroix, Audrey Emmanuelle Dugue, Stephane Supiot, Marc-Andre Mahe, Marianne Leheurteur, Chantal Hanzen, Youlia M. Kirova, Francois Campana, Emilie Le Rhun, Louis Gras, Marie-Pierre Sunyach, Iona Hrab, Julien Geffrelot, Katharina Gunzer, Jean-Marc Constans, Jean-Michel Grellard, Benedicte Clarisse, Xavier Paoletti
Journal: Journal of Clinical Oncology (2014)

2054 Background: BM, the most frequent malignancy in the central nervous system, remains of poor prognosis. Standard treatment is WBRT. Neo-angiogenesis plays an important role in BM growth. Angiogenesis inhibitors, particularly agents targeting the VEGF/VEGFR pathway like BEV, could be optimal partners of radiotherapy (RT) for treating BM. Adding BEV to standard RT-based treatment of newly diagnosed glioblastoma improves progression free survival. REBECA aims at assessing the recommended phase II dose (RP2D) of BEV plus WBRT for BM and delivering preliminary efficacy data. Methods: A multicentric phase I trial assessed BEV combined to conventional WBRT for unresectable BM of solid tumors with a 3+3 dose-escalation design. BEV was administered every 2 weeks (wks) for a total of 3 injections at day 1, 15 and 29 (5, 10 or 15 mg/kg for dose levels (DL) 0, 1 and 2) with WBRT starting at day 15, for a total dose of 30 Gy in 15 fractions/3 wks. DL3 consisted in BEV 15 mg/kg with WBRT delivered from day 15 in 30 Gy/10 fractions/2 wks. Safety was evaluated using NCI-CTCAE v3. BM response was assessed 6 wks and 3 months after the end of treatment by MRI using RECIST 1.1 criteria. Results: Among 21 patients (pts) enrolled (including 14 breast cancers), 19 were treated: 3 in DL0, 4 in DL1, 3 in DL2 and 9 in DL3, including 3, 3, 3 and 7 pts assessable for dose limiting toxicity (DLT), respectively. No DLT occurred: DL3 could be defined as RP2D. Among the 19 pts, treatment-related toxicity (excluding alopecia) included a grade(gr) 2 asthenia at DL1 and 7 gr2 (2 HTA, 1 asthenia, 1 digestive disorders, 1 mouth dryness, 1 lymphopenia and 1 liver injuries) occurring in 4 out of 9 pts at DL3. Gr1 events were noted for 7 pts in all DLs: HTA, headache, asthenia, nausea/vomiting, pain and appetite loss. No BM progression was observed during treatment but 2 pts at DL1 and 1 pt at DL3 died of disease progression during the 3 months post-treatment period. Per Protocol efficacy analysis concerned 16 pts: 8 had a BM partial response (1/3 at DL0, 1/3 at DL1, 2/3 at DL2, 4/7 at DL3). Conclusions: In absence of DLT, BEV+WBRT appears safe for the treatment of BM. DL3 seems optimal for further efficacy evaluation in phase II trials. Clinical trial information: NCT01332929.