tbuckley/cabot-search huggingface dataset:
Cardiac Fibrotic Remodeling on a Chip with Dynamic Mechanical Stimulation
Authors: Ming Kong, Junmin Lee, Iman K. Yazdi, Amir K. Miri, Yi‐Dong Lin, Jungmok Seo, Yu Shrike Zhang, Ali Khademhosseini, Su Ryon Shin
Journal: Advanced Healthcare Materials (2019)

Cardiac tissue is characterized by being dynamic and contractile, imparting the important role of biomechanical cues in the regulation of normal physiological activity or pathological remodeling. However, the dynamic mechanical tension ability also varies due to extracellular matrix remodeling in fibrosis, accompanied with the phenotypic transition from cardiac fibroblasts (CFs) to myofibroblasts. It is hypothesized that the dynamic mechanical tension ability regulates cardiac phenotypic transition within fibrosis in a strain-mediated manner. In this study, a microdevice that is able to simultaneously and accurately mimic the biomechanical properties of the cardiac physiological and pathological microenvironment is developed. The microdevice can apply cyclic compressions with gradient magnitudes (5-20%) and tunable frequency onto gelatin methacryloyl (GelMA) hydrogels laden with CFs, and also enables the integration of cytokines. The strain-response correlations between mechanical compression and CFs spreading, and proliferation and fibrotic phenotype remolding, are investigated. Results reveal that mechanical compression plays a crucial role in the CFs phenotypic transition, depending on the strain of mechanical load and myofibroblast maturity of CFs encapsulated in GelMA hydrogels. The results provide evidence regarding the strain-response correlation of mechanical stimulation in CFs phenotypic remodeling, which can be used to develop new preventive or therapeutic strategies for cardiac fibrosis.
Comparison of the therapeutic effects of microwave ablation and surgical resection for small hepatocellular carcinoma.
Authors: Ji-Run Peng, Wei-Hua Zhu, Qi-Qi Xu, Li-Yun Gan, Sheng-Min Zheng, Da-Fang Zhang, Zhong-Tian Jin, Shu Li, Ji-Ye Zhu, Xi-Sheng Leng
Journal: Journal of Clinical Oncology (2014)

e15124 Background: To compare the clinical effects of microwave ablation (MWA) and surgical resection in the treatment of small hepatocellular carcinoma (SHCC). Methods: 65 SHCC patients with intact clinical data were enrolled in this study. Among them, 30 patients were treated by MWA, and the other 35 were treated by hepatectomy, with an average age of 59 years. According to the follow-up results, the Kaplan-Meier cumulative survival rates of 1-, 3- and 5-year of the two groups were respectively calculated and statistically compared. Results: Up to December 31, 2102, except one patient who was lost to follow-up, the other patients of MWA group were followed up with an average time of 36 months, the mean survival time of MWA group was 73 months, and the 1-, 3- and 5-year cumulative survival rate was 92.9%, 83.2% and 59.5%, respectively. The average follow-up time of the surgical resection group was 41 months, the mean survival time was 73 months, and the 1- , 3- and 5-year cumulative survival rate was 97.1%, 83.2% and 78.8%, respectively. There was no significant difference between the two group (Log Rank test, P=0.410). The 1-, 3- and 5-year cumulative survival rate of the 21 primary SHCC patients in MWA group was 89.5%, 82.0% and 57.4%, respectively. The 1-, 3- and 5-year cumulative survival rate of 9 recurrent SHCC patients in MWA group was 100%, 87.5% and 66.6%, respectively. There was no significant difference between the two group (Log Rank test, P=0.793). Besides, the 1-, 3- and 5-year cumulative survival rate of 9 recurrent SHCC patients in MWA group was not significantly different from that the 35 patients treated by hepatectomy (Log Rank test, P=0.082). Conclusions: The SHCC patients treated by MWA can achieve good short-term and long-term therapeutic effects, which is similar to that of SHCC patients treated by hepatectomy. The therapeutic effect of the recurrent SHCC patients received MWA therapy is equal to that of the primary SHCC patients received MWA therapy, and it is not significantly different from that of SHCC patients treated by surgical resection.
What Is the Optimal Time to Initiate Hypomethylating Agents (HMA) in Higher Risk Myelodysplastic Syndromes (MDS)?
Authors: Rami S. Komrokji, Najla Al Ali, David A Sallman, Eric Padron, Aziz Nazha, David P. Steensma, Amy E. DeZern, Gail J. Roboz, Guillermo Garcia-Manero, Mikkael A. Sekeres, Jeffrey E. Lancet, Alan F. List
Journal: Blood (2018)
Carelessness About Surfactant Dose—A Cultural Problem, a Legal Issue, or an Open Research Question?
Authors: Silvia Foligno, Daniele De Luca
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Abstract 11773: N-3 Polyunsaturated Fatty Acids Inhibit Inflammatory Responses in Macrophages by the Reduction of Toll-like Receptor 4 Expression in Lipid Rafts, Leading to the Suppression of Atherogenesis in Apolipoprotein E Deficient Mice
Authors: Akira Takashima, Daiju Fukuda, Kimie Tanaka, Yasutomi Higashikuni, Yoichiro Hirata, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Michio Shimabukuro, Masataka Sata
Journal: Circulation (2015)

Introduction: Macrophages promote inflammatory responses, contributing to the development of atherosclerosis. Lipid rafts in macrophages facilitate inflammatory responses by gathering inflammatory molecules such as toll-like receptor 4 (TLR4). Whereas, n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), incorporated into the plasma membrane cause functional alteration of lipid rafts. Here, we tested the hypothesis that n-3 PUFAs decrease macrophage activation by the reduction of TLR4 expression in lipid rafts and attenuate atherogenesis in apolipoprotein E knockout (ApoE KO) mice. Methods and Results: ApoE KO mice were fed western-type diets supplemented with 2.5% EPA, 5% omega-3-acid ethyl esters which include 2.3% EPA and 1.9% DHA (EPA+DHA), or none of n-3 PUFAs (control group) from 8-week-old for 20 weeks. Blood pressure and plasma total cholesterol level did not differ in these groups. En face Sudan IV staining of the aorta revealed that n-3 PUFAs treatment significantly attenuated atherogenesis compared with control group, and the effect was enhanced in EPA+DHA group (P&lt; 0.05). Histological or quantitative RT-PCR analyses demonstrated that EPA+DHA treatment decreased lipid deposition, MMP-9 expression, and macrophage accumulation in atherosclerotic lesions in the aorta compared with control group (P&lt;0.05, P&lt;0.01 and P&lt;0.01, respectively). In vitro experiment using RAW264.7, a murine macrophage cell line, demonstrated that n-3 PUFAs attenuated the up-regulation of MMP-9 and MCP-1 induced by LPS. Isolation of lipid rafts from RAW264.7 by sucrose gradient ultracentrifugation demonstrated that n-3 PUFAs suppressed LPS-induced TLR4 expression in lipid rafts. Lipid raft disruption by methyl-β-cyclodextrin, the membrane cholesterol depleting agent, suppressed LPS-induced up-regulation of MMP-9 and MCP-1 in this cell type. Conclusions: N-3 PUFAs inhibited inflammatory responses in macrophages by the reduction of TLR4 expression in lipid rafts, leading to the suppression of atherogenesis in ApoE KO mice. Our results suggested that lipid rafts in macrophages may serve as a potential therapeutic target for atherosclerosis.
The role of irradiated heart and left ventricular volumes in heart failure occurrence after childhood cancer
Authors: Imène Mansouri, Rodrigue S. Allodji, Catherine Hill, Chiraz El‐Fayech, François Pein, Stéphanie Diallo, Boris Schwartz, Giao Vu‐Bezin, Cristina Veres, Vincent Souchard, Agnès Dumas, Stéphanie Bolle, Cécile Thomas‐Teinturier, Hélène Pacquement, Martine Munzer, Pierre‐Yves Bondiau, Delphine Berchery, Brice Fresneau, Odile Oberlin, Ibrahima Diallo, Florent De Vathaire, Nadia Haddy
Journal: European Journal of Heart Failure (2018)
Abstract 17877: Global Longitudinal Strain as a Predictor of Right Ventricular Pacing-Induced Cardiomyopathy
Authors: Jung Yeon Chin, Ki-Woon Kang, Sang Hyun Park, Won-ho Kim, Kyung Tae Jung, Yu Jeong Choi
Journal: Circulation (2017)

Introduction: Frequent right ventricular (RV) pacing can lead to a decline in left ventricular (LV) function. Hypothesis: This study aimed to identify echocardiographic predictor of RV pacing-induc...
Treatment of Metastatic Prostate Cancer in 2018
Authors: Chung-Han Lee, Philip Kantoff
Journal: JAMA Oncology (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 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
Increased risk of second malignant neoplasms (SMN) in young children with embryonal rhabdomyosarcoma (ERMS): Evidence for a cancer predisposition syndrome?
Authors: Renata Parada Amorim, Rafaela Naves, Natasha M. Archer, Simone Hettmer, A. Lindsay Frazier, Lisa Diller, Karina Braga Ribeiro, Carlos Rodriguez-Galindo
Journal: Journal of Clinical Oncology (2014)

10042 Background: Germline TP53 mutations have been recently described in children with anaplastic EMRS, suggesting a possible association with Li-Fraumeni syndrome (LFS). In this population-based study we aimed to assess the risk of SMN according to distinct rhabdomyosarcoma (RMS) subtypes and age groups that could identify high-risk individuals who warrant close surveillance. Methods: Data from SEER-9 (1973-2010) from children ages 0-19 with RMS were analyzed. Standardized incidence ratios (SIR) and corresponding 95% confidence intervals (95% CI) were calculated using SEERStat 8.1.2. Results: 1,151 children (median age=7 years) with RMS were included. Histologies were embryonal (58.2%), alveolar (24.8%), not otherwise specified (NOS) (14.3%), mixed (1.4%), and pleomorphic (1.3%).Twenty-nine SMN were identified, resulting in five-fold increased risk (SIR= 5.69, 95% CI 3.81-8.17). The increase in risk was attributable to second solid tumors, which were consistent with the LFS spectrum, and it was higher for pleomorphic type (SIR=15.77, 95% CI 1.91-56.96). Risk of SMN was higher among those treated at a younger age [children < 2 yrs at diagnosis (SIR=13.38, 95% CI 4.34-31.22) vs. children > 10 yrs (SIR=3.35, 95% CI 1.53-6.35)]. Among children < 2 yrs, those with ERMS histology were at greatest risk (SIR=14.72, 95% CI 4.01–37.70), and it increased when embryonal and NOS histologies were combined (SIR=19.08, 95% CI 6.20-44.54). Among children ages 5-9, the risk was the highest for children 5-9 yrs with pleomorphic type (SIR=314.95, 95% CI 7.91-1,754.80). The risk of SMN was independent of the use of radiation (RT) to the primary (RT: SIR=6.50, 95% CI 3.97–10.03 vs. no RT SIR=4.57, 95% CI 2.09-8.68,). Patients < 5 years receiving RT had higher risk than older patients (SIR=10.52, 95% CI 4.23-21.68 vs. SIR=3.07, 95% CI 1.46-8.65 for > 10 years, respectively). Conclusions: Children with RMS are at high risk of developing SMN. This risk is particularly higher for a subgroup of young children with embryonal or pleomorphic histology, and is independent of the use of RT, suggesting a constitutional predisposition.
Domain-specific PD-L1 protein measurement in non-small cell lung cancer (NSCLC).
Authors: Joseph Francis McLaughlin, Kurt Schalper, Daniel E. Carvajal-Hausdorf, Vamsidhar Velcheti, Herbert Haack, Matthew Silver, Sarah B. Goldberg, Roy S. Herbst, David L. Rimm
Journal: Journal of Clinical Oncology (2014)

8064 Background: PD-L1 protein expression is being explored as a companion predictive test for anti-PD-1 therapies. Studies from our group, however, reveal limitations of available antibodies and indicate that different immunohistochemical (IHC) methods yield discordant results. Differential results have been seen when comparing antibodies targeting the extracellular (EC) versus intracellular (IC) domains. Here, we studied the specificity of anti-PD-L1 antibodies using quantitative fluorescence (QIF) and the performance of two of them in NSCLC. Methods: We measured PD-L1 protein expression using antibody clones E1L3N (IC) and E1J2J (EC) in 509 NSCLC tumor samples represented in two tissue microarrays (YTMA79, n=204 and YTMA250, n=305). Antibody specificity was tested using QIF in formalin-fixed paraffin-embedded (FFPE) samples from human placenta and Mel624 transfectants. PD-L1 signal was determined in the tumor compartment using the AQUAmethod. In YTMA79, scores were compared with previous data using 5H1 antibody (EC). Reproducibility was assessed by staining serial cuts, and the correlation coefficient (R2) was calculated. For survival analysis, PD-L1 signal was used as a continuous score, or binarized with cutoffs defined by X-tile. Results: Of eight antibodies tested, only three (5H1, E1L3N, and E1J2J) validated. The serial section reproducibility was high for 5H1 (R2>0.9), and lower for E1L3N and E1J2J (R2 range 0.54-0.93). The regression coefficient of scores and dynamic range of the antibodies were dissimilar. The EC domain antibodies E1J2J and 5H1 showed no correlation with the IC antibody E1L3N. There were trends toward association with better outcome with each antibody, but the level of significance was a function of the experimental cutpoints and is only considered exploratory. Conclusions: Evaluation of PD-L1expression in NSCLC samples using validated antibodies targeting different protein domains produced discordant results. This could be due to different antibody affinities, cross reactivity, or distinct target epitopes. Evaluation of the predictive value of these antibodies for anti-cancer immunotherapies is currently underway.
A phase II clinical trial of preoperative chemoradiotherapy (CRT) with oral S-1 plus bevacizumab in patients with middle or lower rectal adenocarcinoma.
Authors: Sotaro Sadahiro, Toshiyuki Suzuki, Akira Tanaka, Kazutake Okada, Gota Saito, Akemi Kamijo
Journal: Journal of Clinical Oncology (2014)

575 Background: Preoperative CRT decreases local failure and increases sphincter preservation in patients with clinical stage II or III rectal cancer. Patients with ypCR after CRT reveal better oncologic outcomes. S-1 is an oral fluoropyrimidine with radiosensitizing activity. We previously reported preoperative CRT with S-1 was effective (ypCR 22.2%) and safe (Oncology 2011). Combining bevacizumab with 5-FU- or capecitabine-based CRT had been reported to provide promising results. We evaluated the effectiveness and safety of bevacizumab plus S-1-based CRT. Methods: The subjects were 46 patients with clinical stage II or III adenocarcinoma of the mid or low rectum enrolled from Feb. 2011 through May 2013. Pelvic radiotherapy was given in a total dose of 45 Gy, delivered in 25 factions. S-1 (80 mg/m 2 /day) was given orally twice daily for a total of 28 days during weeks 1, 2, 4, and 5. Bevacizumab (5 mg/kg) was administered a total of 3 times at day 1, 15, and 29. Mesorectal excision was performed 6 to 8 weeks after the completion of CRT. The primary endpoint was the ypCR rate. Secondary endpoints were the degree of tumor shrinkage, sphincter-preservation rate, and safety. Results: Clinical stage was II in 13 patients and III in 33. The median interval from the completion of CRT to surgery was 8 weeks (range, 4 to 9). The ypCR rate was 21.7% (10/46), with a T downstaging rate of 54.3% and an N downstaging rate of 50.0%. The degree of tumor shrinkage was 51.8 ± 16.6% (mean ± SD) on barium enema and 77.7 ± 11.1% on a volumetric analysis based on MRI. The sphincter-preservation rate was 76.1% (35/46). Grade 3 or higher adverse event occurring during CRT was leukopenia in 1 patient (2.2%). Surgery was not postponed because of adverse events in any patient. However, 63.0% of the patients had anal pain (grade 1, 6 patients; grade 2, 23). Postoperative complications occurred in 32.6%: anastomotic leakage in 25.7% (9/35) in LAR and perineal wound dehiscence in 18.2% (2/11) in APR. Conclusions: CRT with S-1 plus bevacizumab had similar antitumor effectiveness and adverse events as CRT only with S-1, but was associated with higher incidences of perioperative complications related to wound healing. Clinical trial information: 10R-113.
Decreased skin perfusion due to chemotherapy-induced peripheral neuropathy in breast cancer patients, and improvement by wearing stockings.
Authors: Tsuyoshi Ohno, Hiroki Yoshioka, Mikiko Kosaka, Sadayuki Matsuda, Takashi Mine, Maiko de Kerckhove, Charles de Kerckhove, Junji Irie, Keiji Inoue, Masashi Haraguchi, Masachika Kitajima, Shinichiro Ito, Hirotaka Tokai, Takayuki Tanaka
Journal: Journal of Clinical Oncology (2014)

e20677 Background: Nanoparticle albumin-bound paclitaxel (nab-PTX) has become a key drug used in chemotherapy for breast cancer, but it often causes adverse effects such as peripheral neuropathy. No effective management has so far been established. We have applied a 3S approach to peripheral neuropathy based on two concepts: compression therapy using stockings and sleeves, and pharmacological therapy using selectedprophylactic medications, including goshajinkigan, a herbal medicine. We previously reported better CTCAE grades and notably superior nab-PTX dosage maintenance in a 3S group compared to a control group with no prophylactic treatment. Regarding the mechanism responsible for the effects of 3S, no relationship had yet been clarified between the grades of chemotherapy-induced peripheral neuropathy (CIPN) and skin perfusion. Therefore, the aim of the present study was to elucidate whether compression therapy using stockings is related to the skin blood perfusion of the lower limbs. Methods: We used a laser Doppler blood flow meter (NL-101 Nahri Nexis Japan) to measure the perfusion of the skin. The blood perfusion of the lower limbs was measured before and after stocking use in a 3S prophylactic treatment group (n=50) and in a control group of healthy volunteers using the same procedure (n=50). Results: In the control group, the median skin perfusion level of the lower limbs before wearing stockings was 10.9 ± 3.8 mL/min/100g, which tended to increase after stocking use to 11.8 ± 4.3 mL/min/100g (p=0.063). In the 3S group of nab-PTX chemotherapy patients, the median skin perfusion level before stocking use was 8.7 ± 3.3 mL/min/100g, which was notably lower than the control group level before stockings were worn (p < 0.01). Of note, the median skin perfusion level significantly increased to 11.3 ± 3.8 mL/min/100g (p< 0.001) in the 3S after stocking use. Conclusions: This study demonstrated that the skin perfusion of the lower limbs is decreased following nab-PTX chemotherapy, and also that the skin perfusion is improved by compression therapy. Compression therapy may therefore lead to alleviation of CIPN, thus supporting our use of the 3S treatment.
Invariant Patterns of Clonal Succession Determines Specific Phenotypic and Clinical Features of Myelodysplastic Syndromes (MDS)
Authors: Yasunobu Nagata, Hideki Makishima, Tetsuichi Yoshizato, Hiromichi Suzuki, Cassandra M. Hirsch, Abhinav Goyal, Hassan Awada, Mohammad Fahad B. Asad, Teodora Kuzmanovic, Bartlomiej P. Przychodzen, Kenichi Yoshida, Kenichi Chiba, Hiroko Tanaka, Yuichi Shiraishi, Satoru Miyano, Sudipto Mukherjee, Tomas Radivoyevitch, Thomas Laframboise, Aziz Nazha, Mikkael A. Sekeres, Torsten Haferlach, Seishi Ogawa, Jaroslaw P. Maciejewski
Journal: Blood (2018)
First line treatment of metastatic colorectal cancer: Are clinical trial results reproducible in real-life practice?
Authors: Ron Lewin, Omer Gal, Aaron Sulkes, Noa Gordon, Irit Ben-Aharon, Ofer Purim, Gali Perel, Yulia Kundel, Assaf Moore, Olga Ulitsky, Baruch Brenner
Journal: Journal of Clinical Oncology (2018)

836 Background: Treatment of metastatic colorectal cancer (mCRC) has greatly advanced over the past decade, based on data from randomized controlled trials (RCTs). This raises the question whether results of RCTs, performed on selected patients (pts), do reflect outcomes in real-life practice. The aim of this study was to summarize our experience in the treatment of mCRC and compare it to data reported in RCTs. Methods: A retrospective single-institution study on consecutive mCRC pts treated with first-line bevacizumab-containing regimens in our institute between 2006 and 2014. Results: The study included 300 pts, of whom 54% were males. Median age was 67 years (range 28-90), 26% aged ≥ 75 years. ECOG performance status was ≤1 in 93%. The primary tumor site was right colon in 37%, left colon in 40%, rectal in 23% and 1% of pts had synchronous tumors. RAS status was available in 60%, of whom 55% had wild-type alleles. 46% of pts had a single metastatic site, including 27% with liver-limited disease, and 54% had multiple metastatic sites. Irinotecan-based chemotherapy was used in 66%, oxaliplatin-based chemotherapy in 29% and flouropyrimidine monotherapy in 5%. Curative metastasectomy during 1 st line treatment was performed in 29%. Grade ≥3 hematological and non-hematological toxicities were reported in 24% and 38% of pts, respectively. Second and third line treatments were administered to 75% and 66% of pts, respectively; 73% of pts received both irinotecan and oxaliplatin through their treatment course and 76% of those with wild-type RAS were treated with anti-EGFR therapy. Overall response rate and disease control rate were 69% and 89%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 17 and 28 months, respectively. In a sub-group analysis on "RCT-like population", excluding pts ≥ 75 years, ECOG PS ≥ 3 and/or mutated/unknown RAS status, median PFS and OS were 15 and 29 months, respectively. Conclusions: The results of this study suggest that, if adhered to international clinical guidelines, outcomes reported in RCTs are indeed reproducible in routine clinical practice in unselected real-life pts. Additional data, with more pts and longer follow-up, will be presented.