tbuckley/cabot-search huggingface dataset:
Clinical Features of Hypertrophic Cardiomyopathy Caused by a Lys183 Deletion Mutation in the Cardiac Troponin I Gene
Authors: HiromasaKokado, MasamiShimizu, HiroyukiYoshio, HidekazuIno, KazuyasuOkeie, YoritoEmoto, ToruMatsuyama, MasatoYamaguchi, ToshihikoYasuda, NoboruFujino, HidekiIto, HiroshiMabuchi
Journal: Circulation (2000)

Background—Mutations that cause hypertrophic cardiomyopathy (HCM) have been identified in 9 genes that code proteins in the sarcomere. Previous reports have demonstrated that cardiac troponin I (cTnI) gene mutations may account for familial HCM; however, the clinical characteristics and prognosis of patients with HCM caused by cTnI gene mutations are not known. Methods and Results—We analyzed cTnI gene mutations in 130 unrelated probands with HCM and their families to clarify the genotype-phenotype correlations. We identified 25 individuals in 7 families with a Lys183 deletion (Lys183 del) mutation in exon 7 of the cTnI gene. The disease penetrance in subjects aged >20 years was 88% by echocardiography and 96% by ECG. Sudden death occurred in 7 individuals of 4 families at any age. Overall, 7 (43.8%) of 16 individuals aged >40 years had left ventricular systolic dysfunction, and 3 (18.8%) displayed dilated cardiomyopathy-like features. Of affected individuals, 4 of 5 individuals aged >40 years followed by...
Vasomotor Reactions to Heat among Patients with Arterial Disease
Authors: Traviswinsor
Journal: Circulation (1950)

Plethysmographic studies of the vasomotor reactions of the digits accompanying body heating were of value in the early detection of peripheral arterial disease. In normal individuals, labile vasomotor activity was shown by great changes in digital volume (a large pulse, alpha and beta waves). These changes were diminished or absent in patients with peripheral arterial disease.
Abstract 1462: The oncogene MYC induces chromosomal instability through dysregulating mitotic progression evoking a dependency on TPX2
Authors: Julia Rohrberg, Alexandra Corella, Moufida Taileb, Marie-Lena Jokisch, Roman Camarda, Sanjeev Balakrishnan, Alicia Zhou, Andrei Goga
Journal: Cancer Research (2018)

Abstract More than 70% of common solid tumors are aneuploid. Aneuploidy has been implicated in tumorigenesis for decades. A direct cause of aneuploidy is chromosomal instability (CIN) that fuels tumor evolution by providing a heterogeneous subpopulation of cells that contributes to the lethal outcome of cancer, metastasis, therapeutic failure, and drug resistance. The oncogene c-MYC is overexpressed in many cancers and has been shown to induce structural and numerical chromosomal aberrations and aneuploidy. While the role of MYC in overcoming the G1/S checkpoint is well established, the role of MYC in altering mitotic dynamics and eliciting CIN remains poorly understood. Here, we identify a direct influence of increased MYC expression on mitotic progression and spindle assembly. We observe MYC-dependent microtubule nucleation and polymerization defects in mitosis. MYC overexpression induces altered spindle morphology promoting chromosome segregation defects resulting in micronuclei formation, CIN and aneuploidy. Importantly, attenuation of MYC expression reverses the mitotic defects observed, even in established tumor cell lines, implicating an ongoing role for MYC in the persistence of a CIN phenotype in tumors. Gene expression data reveal that MYC regulates numerous genes involved in mitosis, kinetochore function and microtubule behavior. We performed a screen to identify microtubule regulators required for the survival of MYC overexpressing cells. MYC overexpressing cells are reliant on high TPX2 expression, a master microtubule regulator. High TPX2 expression is permissive for mitotic spindle assembly and chromosome segregation in MYC high cells, while TPX2 depletion attenuates cell viability and tumor growth in vivo. Our data suggest that TPX2 is a transcriptional target of MYC. We postulate that high levels of TPX2 are required to tolerate mitotic stress induced by MYC. TPX2 compensates for impaired mitotic progression and prevents the development of physiologically intolerable levels of CIN. High levels of TPX2 might be required for tumors with oncogene-induced mitotic stress to faithfully proceed through mitosis providing an explanation for the abundant upregulation of TPX2 in cancer. Thus, we describe a conditional role for MYC in altering spindle assembly and dynamics, resulting in a dependency on TPX2 for tumor survival. Citation Format: Julia Rohrberg, Alexandra Corella, Moufida Taileb, Marie-Lena Jokisch, Roman Camarda, Sanjeev Balakrishnan, Alicia Zhou, Andrei Goga. The oncogene MYC induces chromosomal instability through dysregulating mitotic progression evoking a dependency on TPX2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1462.
LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3
Authors: Tianyou Liu, Zhiyang Han, Huanyu Li, Yuekun Zhu, Ziquan Sun, Anlong Zhu
Journal: Molecular Cancer (2018)

Accumulating evidences show that long noncoding RNAs (lncRNA) play essential roles in the development and progression of various malignancies. However, their functions remains poorly understood and many lncRNAs have not been defined in colorectal cancer (CRC). In this study, we investigated the role of DLEU1 in CRC.Quantitative real-time PCR was used to detect the expression of DLEU1 and survival analysis was adopted to explore the association between DLEU1 expression and the prognosis of CRC patients. CRC cells were stably transfected with lentivirus approach and cell proliferation, migration, invasion and cell apoptosis, as well as tumorigenesis in nude mice were performed to assess the effects of DLEU1 in BCa. Biotin-coupled probe pull down assay, RNA immunoprecipitation and Fluorescence in situ hybridization assays were conducted to confirm the relationship between DLEU1 and SMARCA1.Here we revealed that DLEU1 was crucial for activation of KPNA3 by recruiting SMARCA1, an essential subunit of the NURF chromatin remodeling complex, in CRC. DLEU1 was indispensible for the deposition of SMARCA1 at the promoter of KPNA3 gene. Increased expression of DLEU1 and KPNA3 was observed in human CRC tissues. And higher expression of DLEU1 or KPNA3 in patients indicates lower survival rate and poorer prognosis. DLEU1 knockdown remarkably inhibited CRC cell proliferation, migration and invasion in vitro and in vivo while overexpressing KPNA3 in the meantime reversed it.Our results identify DLEU1 as a key regulator by a novel DLEU1/SMARCA1/KPNA3 axis in CRC development and progression, which may provide a potential biomarker and therapeutic target for the management of CRC.
Synergistic Effect of Persistent Chlamydia pneumoniae Infection, Autoimmunity, and Inflammation on Coronary Risk
Authors: TiinaHuittinen, MaijaLeinonen, LeenaTenkanen, HannaVirkkunen, MattiMänttäri, TimoPalosuo, VesaManninen, PekkaSaikku
Journal: Circulation (2003)

Background— Given the role of chronic infections, autoimmunity, and inflammation in atherosclerosis, we studied the joint effect of chronic Chlamydia pneumoniae infection, persistently elevated human heat-shock protein 60 (hHsp60) antibodies, and C-reactive protein (CRP) on coronary risk. Methods and Results— The participants for this prospective nested case-control study were obtained from the Helsinki Heart Study, during which 241 nonfatal myocardial infarctions or coronary deaths occurred among 4081 dyslipidemic middle-aged men. Serum samples taken at baseline and 3 to 6 months before the coronary events that occurred during the 8.5-year period were analyzed for antibodies to C pneumoniae and hHsp60 and the CRP concentration. Compared with persistently low levels, the risk of coronary events was 2-fold for persistently elevated immunocomplex (IC)-bound and/or serum IgA antibodies to C pneumoniae (OR, 1.96; 95% CI, 1.14 to 3.36) and also for serum IgA antibodies to hHsp60 (OR, 2.11; 95% CI, 1.08 to 4.13...
Mechanisms of Action of Troglitazone in the Prevention of High Glucose–Induced Migration and Proliferation of Cultured Coronary Smooth Muscle Cells
Authors: KenichiYasunari, MasakazuKohno, HiroakiKano, KojiYokokawa, MiekoMinami, JunichiYoshikawa
Journal: Circulation Research (1997)

Abstract Recent findings suggest that high glucose levels may promote atherosclerosis in coronary vascular smooth muscle cells (VSMCs). To explore the intracellular mechanisms of action by which troglitazone affects this process, we examined the effect of troglitazone on the migration and growth characteristics of cultured rabbit coronary VSMCs. Treatment with chronic high glucose medium (22.2 mmol/L) for 5 days increased VSMC migration by 92%, [3H]thymidine incorporation by 135%, and cell number by 32% compared with VSMCs treated with normal glucose (5.5 mmol/L glucose+16.6 mmol/L mannose) medium. Troglitazone at 100 nmol/L and 1 μmol/L significantly suppressed high glucose–induced VSMC migration by 34% and 42%, respectively, the proliferative effect (as measured by cell number) by 17% and 27%, and [3H]thymidine incorporation by 45% and 60% (n=6, P<.05). The high glucose–induced impairment of insulin-mediated [3H]deoxyglucose uptake was blocked by a protein kinase C (PKC) inhibitor (calphostin C, 1 μmol/...
Abstract 3251: TaqMan Advanced miRNA cDNA Synthesis Kit to simultaneously study expression of miRNA and mRNA and to detect somatic mutations by qPCR
Authors: Kathleen Hayashibara, Harita Veereshlingam, Malte Buchholz
Journal: Cancer Research (2018)

Abstract MicroRNAs (miRNA) are a class of small non-coding RNAs (approximately 21 nt long) that bind complementary sequences in target mRNAs to specifically regulate gene expression. Aberrant regulation of miRNAs and their targets has been associated with several diseases including cancer. The relationship between miRNA and mRNA has been found to be important in cancer development and progression. Simultaneous expression studies of miRNA and mRNA and detection of mutations in mRNA transcripts can be valuable in understanding molecular mechanisms that have an underlying role in various diseases. We demonstrate the technical verification of a novel method to reverse-transcribe and pre-amplify miRNA and mRNA from sample-limiting serum research samples using the TaqMan® Advanced miRNA cDNA Synthesis Kit. Based on results from previous studies, a signature of 49 mRNA and 37 miRNA targets has been identified that may help distinguish between benign and malignant pancreatic tissues. In this study, these targets and an additional set of transcript mutations were analyzed in serum from normal and test samples. TaqMan assays for miRNA and mRNA targets and custom TaqMan Mutation Detection Assays were placed on TaqMan Array Cards to facilitate investigation of several samples in a single experiment. Results demonstrate that transcript mutations can be detected and miRNA and mRNA targets can be reliably quantified from a single reverse transcription reaction. (For research use only. Not for use in diagnostic purposes.) Citation Format: Kathleen Hayashibara, Harita Veereshlingam, Malte Buchholz. TaqMan Advanced miRNA cDNA Synthesis Kit to simultaneously study expression of miRNA and mRNA and to detect somatic mutations by qPCR [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3251.
Abstract 2475: Long noncoding RNA NNT-AS1 sponges miR-424 to promote the progression and metastasis of gastric cancer
Authors: Beibei Chen, Qingfang Zhao, Lulu Guan, Huifang Lv, Liangyu Bie, Jinxi Huang, Jitian Li, Jianying Zhang, Xiaobing Chen
Journal: Cancer Research (2018)

Abstract Background: Long noncoding RNAs (lncRNAs) have been illustrated to function as important regulator in carcinogenesis and cancer progression. However, the roles of lncRNA NNT-AS1 in gastric cancer remain unclear. In present study, we investigate the expression level of NNT-AS1 in gastric cancer tissue and the role on gastric cancer cells tumorigenesis. Methods: NNT-AS1 expression level was measured using RT-PCR. The prognosis and survival rate of gastric cancer patients with high/low expression of NNT-AS1 was tracked and analyzed. Cellular experiments were performed to test the role of NNT-AS1 on gastric cancer phenotype, including proliferation analysis, transwell assay, EMT-related marker blots and xenograft mice assay. Bioinformatics online program and luciferase assay were performed to predict and verify the potential miRNAs targeting NNT-AS1. Results: NNT-AS1 expression level was significantly upregulated in 55 cases of gastric cancer tissue samples compared with adjacent normal tissue. Besides, the aberrantly enhanced NNT-AS1 expression predicted poor prognosis and lower survival rate. In vitro, NNT-AS1 knockdown suppressed the gastric cancer cells proliferation, invasion and EMT-related marker (N-cadherin and vimentin) expression. In vivo, lentivirus mediated NNT-AS1 silencing decreased the tumor growth. MiR-503 was verified to be the target miRNA of NNT-AS1 using bioinformatics online program and luciferase assay. Furthermore, miR-424 could reverse the role of NNT-AS1 on gastric cancer cells. Conclusion: In conclusion, our study indicates that NNT-AS1 sponges miR-424 to facilitate gastric cancer cells invasion and metastasis, revealing the oncogenic role of NNT-AS1 on gastric cancer cells. Citation Format: Beibei Chen, Qingfang Zhao, Lulu Guan, Huifang Lv, Liangyu Bie, Jinxi Huang, Jitian Li, Jianying Zhang, Xiaobing Chen. Long noncoding RNA NNT-AS1 sponges miR-424 to promote the progression and metastasis of gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2475.
Abstract 15873: Adverse Cardiac and Pulmonary Vascular Change in Patients With Subclinical and Clinical Copd
Authors: JieCao, KathyHalloran, JoshuaCheng, MichaelPassick, NoraNgai
Journal: Circulation (2014)

Background: COPD is associated with altered right ventricular (RV) and pulmonary vascular function. However, little is known about such change in patients with subclinical COPD. Methods: Thirty nine volunteers were recruited prospectively to undergo echocardiography, MRI and pulmonary function test (PFT). COPD was defined as FEV1/FVC 75% with no smoking history (N=9). Cardiac function was assessed by cine MRI. All subjects underwent first pass lung perfusion using a partial Fourier saturation recovery SSFP technique. The absolute lung perfusion was calculated using dynamic contrast signal in the pulmonary artery as input and that in the lungs. Total lung blood volume was the function of mean blood transit time and cardiac output in main pulmonary artery (PA). Results: Average FEV1/FVC was 84±6%, 73±3% and 50±15% for normal, subclinical and c...
Abstract 3984: Combination S6K and TAM tyrosine kinase targeting in PTEN-deficient glioma
Authors: Kelli N. Ennis, Pranjal Sarma, Catherine A. Behrmann, Jie Wang, David R. Plas
Journal: Cancer Research (2018)

Abstract Loss of PTEN is one of the most frequent driver events in primary glioblastoma, conferring the ability to reconfigure metabolism and enhance apoptosis resistance to transformed glial cells. The ribosomal S6 protein kinases (S6Ks) are hyperactivated in PTEN-deficient settings, and genetic inactivation studies have shown that S6K1 deficiency can reduce the oncogenic growth of PTEN-deficient neoplasia. Investigating pharmacologic agents, we found that the S6K inhibitor LY-2584702 selectively elicits cytotoxic responses in PTEN-deficient cells when combined with the TAM kinase inactivating agent BMS-777607. Combined knockdown of TAM kinases sensitized cells to single agent treatment with LY-2584702. Conversely, expression of activated S6K1 or elevated AXL protected from combination treatment. These results indicate that both the TAMS and S6K1 are key regulators of survival in PTEN deficient cells. Citation Format: Kelli N. Ennis, Pranjal Sarma, Catherine A. Behrmann, Jie Wang, David R. Plas. Combination S6K and TAM tyrosine kinase targeting in PTEN-deficient glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3984.
Abstract 3843: The potential of heat shock proteins 70/90 as molecular therapeutic targets in breast cancer
Authors: Ho Young Kim, Sanghwa Kim, Lee Su Kim
Journal: Cancer Research (2018)

Abstract Purpose: Heat shock proteins (hsps) are molecular chaperones that are synthesized by cells in response to various stress conditions. The expression of hsps have been shown to be associated with carcinogenesis and the expression of hsps have been implicated in the biological behavior of tumors. Recently, hsps have emerged as novel molecular targets in anticancer protocols. The objectives of this study were to investigate the significance of hsp 70/90 in breast carcinogenesis and effect of geldanamycin (a blocker of hsp 90) and quercetin (a blocker of hsp 70) on growth inhibition in different breast cancer cell lines. Methods: Breast tissues from 82 patients were obtained between January 2010 and December 2010 at the Division of Breast &amp; Endocrine Surgery, Hallym University Sacred Heart Hospital. Expression of hsp 70/90 was studied by immunohistochemistry (IHC) on tissue sections from 63 breast carcinomas and 19 benign breast tissues. Both cytoplasmic and nuclear expression was measured. Expression of hsp 70/90 was also analyzed by use of a Western blot with the breast cancer cell lines. We next investigated the effects of blockers of hsp 70/90 on cell growth of the human breast cancer cell lines. Results: More prominent hsp 90 expression was observed in malignant tissue than in benign tissue by both cytoplasmic and nuclear IHC staining (p&amp;lt;0.001, p&amp;lt;0.001). Nuclear hsp 90 expression was associated with a positive lymph node status (p=0.003) and the presence of poorly differentiated tumors (p=0.028). Expression of hsp 70 was not different in malignant and benign tissues as determined by both cytoplasmic and nuclear IHC staining. The breast cancer cell lines all expressed hsp 70/90. Geldanamycin markedly inhibited the cell growth of these breast cancer cell lines in a dose dependent manner and induced apoptosis in the cell lines. Quercetin inhibited cell growth of the cell lines less efficiently. Conclusion: The expression of hsp 90 was associated with breast carcinogenesis and the presence of more aggressive tumors. Geldanamycin inhibited cell growth of hsp 90 expressing breast cancer cell lines. We suggest that Hsp 90 may be a possible molecular target against breast cancer. Citation Format: Ho Young Kim, Sanghwa Kim, Lee Su Kim. The potential of heat shock proteins 70/90 as molecular therapeutic targets in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3843.
Potential Ionic Mechanism for Repolarization Differences Between Canine Right and Left Atrium
Authors: DanshiLi, LimingZhang, JamesKneller, StanleyNattel
Journal: Circulation Research (2001)

Abstract—Experimental and clinical evidence suggests a critical role for the left atrium (LA) in atrial fibrillation (AF). In animal models, repolarization is faster in the LA than in the right atrium (RA), leading to more stable reentry circuits with a shorter intrinsic period in the LA. The ionic mechanisms underlying LA-RA repolarization differences are unknown. Therefore, we evaluated ionic currents and action potentials (APs) with the whole-cell patch clamp in isolated canine atrial myocytes. The density of the rapid delayed rectifier current (IKr) was greater in the LA (eg, 1.83±0.10 pA/pF at +20 mV) than in the RA (1.15±0.07 pA/pF, P<0.01; n=16 cells per group). The slow and ultrarapid delayed rectifier, the inward rectifier, L-type Ca2+, and transient outward K+ currents were all comparable in the LA and RA. There were no differences in kinetic or voltage-dependent properties of currents in LA versus RA. Western blots of ether-a-go-go–related gene (ERG) protein in three RA and corresponding LA reg...
Abstract 4103: Utility of multispectral optoacoustic tomography in imaging pancreatic tumors using a uPA-probe
Authors: Akiko Chiba, Abhilash Samykutty, Mary Smith, Lacey McNally
Journal: Cancer Research (2018)

Abstract Background: Pancreatic cancer has the lowest 5-year survival rate of all cancer types. Current methods of pancreatic cancer screening, diagnosis and treatment have failed to improve outcome in the last few decades. Potential explanation for this failure may be explained by the hypovascularized nature of pancreatic cancer, making conventional chemotherapy and imaging modality suboptimal. There is a potential for improved imaging using a new imaging modality, multispectral optoacoustic tomography (MSOT). We hypothesize that a using urokinase plasminogen activator (uPA) contrast agent while using MSOT imaging would improve identification of orthotopic pancreatic cancer in xenografts. Methods: Expression of uPA receptor (uPAR) were evaluated in pancreatic tumor cell lines, Panc1, S2CP9, MiaPaca-2 and S2VP10 using western blot. A uPA targeted contrast agent was created using standard bioconjugation methods with the Hilite 750 near infrared (NIR) dye. Five SCID mice were orthotopically implanted with S2CP9 (1.5 x 105) and 5 additional SCID mice were implanted with MiaPaCa2 (2.0 x 106) pancreatic tumor cells. When tumor size reached 3mm, 200µL of 100 nM uPA-750 probe or 750 dye alone was injected into mice. Biodistribution and accumulation of the uPA-750 probe was visualized using MSOT imaged at 2-hour intervals for 8 hours and at 24 hours. Accumulation of uPA-750 probe was evaluated in the tumor, liver, and kidney using NIR fluorescent imaging. Results: All pancreatic cancer cell line expressed uPAR with the highest in S2CP9 cells (3.0x), S2VP10 (2.5x), Panc1 (1.77x) and MiaPaca-2 (1.3x). In vivo, peak intensity of uPA-750 probe was successfully detected using MSOT at 4 hours, within the pancreas tumor in slices from 37mm-41mm. uPA-750 probe was undetectable within the tumor after 8 hours. Using ex vivo NIR fluorescence imaging, uPA-probe signal was detected only within the pancreatic tumor, however, no signal was detected in the liver or kidney. Conclusion: This study demonstrated MSOT imaging using uPA-probe as a contract agent may lead to improved pancreatic cancer detection which may lead to improvement in overall outcome. Citation Format: Akiko Chiba, Abhilash Samykutty, Mary Smith, Lacey McNally. Utility of multispectral optoacoustic tomography in imaging pancreatic tumors using a uPA-probe [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4103.