tbuckley/cabot-search huggingface dataset:
CN-04 * TREATMENT OF PEDIATRIC CEREBRAL RADIATION NECROSIS: A META-ANALYSIS
Authors: N. Drezner, E. Wells, G. Vezina, C.-y. Ho, R. Packer, E. Hwang
Journal: Neuro-Oncology (2014)

BACKGROUND: Cerebral radiation necrosis (CRN) is a well-characterized toxicity of radiation therapy that can result in significant neurologic deficits and be life threatening. Treatment for CRN has included surgical resection, corticosteroids, hyperbaric oxygen therapy (HBOT), and bevacizumab among other modalities, but no consensus approach has been identified. Given the paucity of pediatric CRN data, we sought to codify the approaches to treatment of radiation necrosis in pediatric patients. METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL) and Ovid MEDLINE were searched to identify all relevant pediatric reports. RESULTS: Thirty-one pediatric patients, twenty-six with primary central nervous system tumors and four with arteriovenous malformations developed CRN, diagnosed by characteristic MRI findings, most (n = 28) with accompanying neurologic deficits. Patients received treatment with steroids alone (n = 5) or steroids followed by bevacizumab (n = 11) or HBOT (n = 12). Three asymptomatic patients did not receive intervention. 10/11 patients treated with steroids and bevacizumab, and 11/12 treated with steroids and HBOT improved. In all cases of steroid-resistent CRN, addition of bevacizumab induced improvement except in one case of disease progression. One patient treated with steroids alone died with progressive neurologic deterioration. With the exception of steroid-related adverse events, there were no reported significant side effects. CONCLUSIONS: Due to the small numbers of pediatric patients with CRN, analysis of treatment modalities is confined to limited reports. Furthermore, cases of CRN are likely underreported as we have seen much higher rates of CRN than the 3-5% reported in the literature at our institution in the past five years. The most common treatment following steroid initiation is addition of either bevacizumab or HBOT with good success. However, larger randomized controlled trials are needed to establish a definitive treatment algorithm that can be applied to children affected by CRN.
PRÓTESIS EN EL TRATAMIENTO DE LA ESTENOSIS ESOFÁGICA BENIGNA: ¿SON REALMENTE EFECTIVAS?
Authors: O Nogales Rincón, B Merino Rodríguez, C González Asanza, P Menchén Fernández-Pacheco
Journal: Endoscopy (2011)

Introducción: La estenosis esofágica benigna es una patología frecuente. El tratamiento habitual es la dilatación endoscópica. Sin embargo, existe un porcentaje que son refractarias (no respuesta o recurrencia precoz), constituyendo un reto terapéutico.
Abstract 5514: Comorbidities are associated with breast cancer in African-American and Hispanic women
Authors: Marianna Sarkissyan, Yanyuan Wu, Marianne Carlota, Jaydutt V. Vadgama
Journal: Cancer Research (2012)

Abstract Objectives and Background: The presence of comorbidities, such as diabetes mellitus type II and hypertension may influence health outcomes from breast cancer. Women from underserved populations, particularly African-American and Hispanic women suffer from a disproportionate burden of comorbidities which may contribute to the health disparities observed in these women. The aims of the present study were to evaluate the distribution and association of comorbidities, specifically diabetes and hypertension, in African-American and Hispanic women and breast cancer. Furthermore, the present study investigated the consequence of comorbidity on survival in underserved women with breast cancer. Methods: A cross-sectional cohort of 428 African-American and Hispanic women from Los Angeles was assessed to determine the association between comorbidity and breast cancer. Clinical data were obtained by medical record abstraction. The results were assessed using logistic regression with multivariate analysis. Kaplan-Meier survival analysis was used to evaluate disease-free survival. Results: Our study identified a high frequency of comorbidity, especially hypertension and hypertension with diabetes in African-American women (38% and 14%, respectively) and Hispanic women (12% and 9%, respectively). Multivariate logistic regression analysis revealed a significant association between multiple comorbidity and breast cancer (odds ratio [OR] = 2.3; P=0.032). Furthermore, multiple comorbidity was significantly associated with obesity, especially in breast cancer patients (P &amp;lt; 0.05). There was also a trend towards significance for the association between multiple comorbidity and decreased five-year disease-free survival. Notably, the presence of comorbidity significantly modulated five-year disease-free survival based on breast cancer tumor subtype (P &amp;lt; 0.05). Implications and Next Steps: In sum, our study highlights a cohort of women who may be at a high risk for health inequalities due to the presence of comorbidity and should be considered for intervention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5514. doi:1538-7445.AM2012-5514
Mimicking the cardiac cycle in intact cardiomyocytes using diastolic and systolic force clamps; measuring power output
Authors: Michiel Helmes, Aref Najafi, Bradley M. Palmer, Ernst Breel, Niek Rijnveld, Davide Iannuzzi, Jolanda van der Velden
Journal: Cardiovascular Research (2016)

A single isolated cardiomyocyte is the smallest functional unit of the heart. Yet, all single isolated cardiomyocyte experiments have been limited by the lack of proper methods that could reproduce a physiological cardiac cycle. We aimed to investigate the contractile properties of a single cardiomyocyte that correctly mimic the cardiac cycle. By adjusting the parameters of the feedback loop, using a suitably engineered feedback system and recording the developed force and the length of a single rat cardiomyocyte during contraction and relaxation, we were able to construct force–length (FL) relations analogous to the pressure–volume (PV) relations at the whole heart level. From the cardiac loop graphs, we obtained, for the first time, the power generated by one single cardiomyocyte. Here, we introduce a new approach that by combining mechanics, electronics, and a new type optical force transducer can measure the FL relationship of a single isolated cardiomyocyte undergoing a mechanical loop that mimics the PV cycle of a beating heart.
PROSPECTIVE, RANDOMIZED, OPEN-LABEL, MULTICENTER TRIAL TO COMPARE BETWEEN PROVISIONAL VERSUS ROUTINE KISSING BALLOON TECHNIQUE AFTER MAIN VESSEL CROSSOVER STENTING FOR BIFURCATED LESIONS (PROTECT-SB): THE EXTENT AND SEVERITY OF MYOCARDIAL ISCHEMIA AND LONG TERM FOLLOW-UP
Authors: Masahiro Yamawaki, Masaki Fujita, Shinya Sasaki, Masanori Tsurugida, Motoharu Araki, Hiroshi Ishimori, Masatsugu Nakano, Keisuke Hirano, Yoshiaki Ito, Reiko Tsukahara, Toshiya Muramatsu
Journal: Journal of the American College of Cardiology (2016)
INVOLUTIONAL ILLNESSES
Authors: C. DOWNING TAIT, G. C. BURNS
Journal: American Journal of Psychiatry (1951)

Judging from a study of 379 sanitarium patients with follow-up information on 114, the previously reported effectiveness of convulsive therapy in involutional psychoses, especially in depressions, is reaffirmed, as is the low incidence of complications with such therapy. At present, convulsive therapy, supplemented by less intensive psychotherapy (as contrasted with psychoanalysis) appears to be the therapeutic program of choice in these patients. With a therapeutic orientation, the diagnostic term involutional psychoses appears to retain its usefulness. Further study of motor discharge in induced convulsions may help elucidate the mechanisms of psychotic depressions. Other long-range follow-up studies would be of value in determining the future course and ultimate results of electroconvulsive therapy in patients who have suffered from involutional illnesses.
Charles Christopher Nicholson Roberts
Authors: T. N. R. J. Wheeler
Journal: BMJ (2014)

Charles Christopher Nicholson Roberts (“ Chris”) was the quintessential family doctor. He was brought up in a medical environment; his father was a GP in Ludlow and his grandfather a paediatric surgeon.

After attending Shrewsbury School, he went on to gain a place at Clare College, Cambridge, and completed his clinical studies at the Middlesex Hospital Medical School. After qualifying his junior hospital appointments ranged far and wide, including a year …
Gastric compression due to a cystic liver metastasis of vulvar carcinoma diagnosed by endoscopic ultrasound-guided fine-needle aspiration
Authors: César Lopes, Régis de Garcia, Gabriel Santos, Antônio Hartmann, Antônio Kalil
Journal: Endoscopy (2014)

A 63-year-old woman who was complaining of epigastric pain and abdominal fullness underwent an upper gastrointestinal endoscopy, which revealed a bulge in the lesser curvature and anterior wall of the gastric body ([Fig. 1]). A computed tomography (CT) scan and a sectorial endoscopic ultrasound (EUS) using an Olympus GF-UCT140-AL5 (Olympus America Inc., New York, USA) coupled to an ultrasound unit (Aloka Prosound alfa-5 SX) detected a 5-cm cyst in the caudate lobe of the liver ([Fig. 2]). A definitive diagnosis was obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Only a single needle pass was performed with a 19-gauge needle (EchoTip Ultra Echo-19; Cook Medical, Winston-Salem, North Carolina, USA), and the content of the cyst (90 mL) was completely aspirated. A cystic liver metastasis of vulvar carcinoma was confirmed by immunohistochemistry that was consistent with this diagnosis ([Fig. 3]). The patient subsequently underwent surgery, with complete resection of the lesion.
Abstract 4712: Target epigenetic regulation at a specific genomic region by using DNA binding molecules and HDACi
Authors: Hiroki Nagase, Takayoshi Watanabe, Nobuko Koshikawa
Journal: Cancer Research (2012)

Abstract Pyrrole-Imidazole (PI) polyamide molecule was originally designed from structures of natural DNA binding molecule, such as Distamicine and Diocarbamicine and has been recognized as a synthetic molecule which binds the minor groove of Watson-Click base pair of double-stranded DNA in a sequence-dependent manner. We hypothesized conjugates between this synthetic DNA binding molecule and Histone Deacetylase inhibitor (HDACi) of Suberoylanilide hydroxamic acid (SAHA) should regulate histone acetylation in a specific region of the genome. We have taken two strategies to confirm this hypothesis. One is the candidate gene approach and another is chemical library approach. We synthesized a PI polyamide targeted the p16INK4a tumor suppressor gene and also synthesized a library of sequence-specific PI polyamides conjugated with the potent HDAC inhibitor, termed PIP-SAHA and screened their effect on the expression of tumor suppressor genes and Yamanaka factors, respectively. Chromatin immunoprecipitation analysis revealed SAHA-PIP induce acetylation of Histone H4 and H3 in the promoter region of p16, Oct-4 and Nanog. SAHA-PIP showed significant induction against c-Myc, Oct-3/4, Sox-2, and Klf-4, respectively in MEF but did not show significant induction of tumor suppressor p16 transcription. We also confirmed only SAHA did not show such histon acetylation and transcription induction, which implicated the role of PI polyamide conjugates in the induction of histone acetylation in specific genomic regions. Furthermore, a significant change in MEF morphology was demonstrated with our hit SAHA-PIPs. Those data suggests that a capability of PIP-SAHA regulate histone modification in a genomic sequence specific manner and promote agents for reprogramming efficiency in order to generate iPSCs, although the endogenous tumor suppressor gene expression was not observed, probably by means of “double lock” epigenetic silencing of tumor suppressor gene. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4712. doi:1538-7445.AM2012-4712
Drainage trans-bulbaire de la voie biliaire principale par voie écho-endoscopique chez des malades ictériques préalablement traités par pose d'une prothèse duodénale
Authors: E Ben Soussan, C Pauphilet, JF Lefebvre
Journal: Endoscopy (2011)

Introduction: Jusque récemment, le drainage biliaire des patients ayant une sténose duodénale infranchissable du duodénum pour un cancer du pancréas se faisait par voie trans-hépatique. Les possibilités actuelles de drainage des voies biliaires par voie écho-endoscopique ont ouvert de nouvelles perspectives thérapeutiques endoscopiques. Le but de cette étude prospective a été d'évaluer la faisabilité et la morbidité à court terme de pose d'une prothèse biliaire métallique par voie écho-endoscopique et trans-bulbaire chez des patients ictériques initialement traités par pose d'une prothèse duodénale.
Abstract B77: Chk1-Lats2-14-3-3 is a novel signaling pathway that regulates the P-body formation in response to DNA damage
Authors: Nobuhiro Okada, Norikazu Yabuta, Hiroshi Nojima
Journal: Cancer Research (2009)

Abstract Purpose: Lats2 (Large tumor suppressor 2), a member of the conserved Lats kinase family, is a human tumor suppressor gene. We previously reported that Lats2 knockout in mice displays embryonic lethality and the MEFs from Lats2−/− mice causes mitotic defects including centrosome fragmentation and cytokinesis defects associated with nuclear enlargement and multinucleation. DNA damage response (DDR) plays an essential role in maintaining the integrity of the genome and is crucial for cancer avoidance. The purpose of this study is to investigate the role of Lats2 in DDR, which prevents chromosome instability and malignant progression of human cancer by keeping the chromosome stability. MicroRNAs (miRNAs), endogenous RNAs of approximately 22 nucleotides, play an important role in the regulation of gene expression: miRNAs are incorporated into miRNA-induced silencing complexes (miRISCs), which leads to either cleavage or translational repression of targeted mRNAs. mRNA processing bodies (P-bodies) are sites where untranslated mRNAs accumulate, and mRNA degradation, translational repression, and mRNA surveillance take place. Methods: We raised two phospho-specific antibodies against the phosphorylation sites of Lats2 by Chk1 and 14-3-3 by Lats2 to analyze the phosphorylation status and localization by Western blot and immunocytochemical analyses. Moreover, we established myc-tagged U2OS/siLats2 strains that stably expressed Lats2 mutated the phosphorylation site to alanine or aspartic acid, and examined the effects of those on DNA damage signaling pathway. Results: We found that Lats2 is phophorylated by Chk1 and/or Chk2 in response to DNA damage, which induced the phosphorylation of 14-3-3 by Lats2. Immunocytochemical analysis using a phospho-specific antibody against 14-3-3 revealed that the phosphorylated 14-3-3 localized to the P-body, and these signals are enhanced in response to DNA damage. We propose here that 14-3-3 is a novel regulatory protein for P-body formation that promotes the miRNA-mediated gene silencing. Indeed, depletion of 14-3-3 or Lats2 reduced the localization to the P-body of both 14-3-3 and a putative P-body scaffold protein, GW182. Eventually, this pathway regulates the translesion synthesis (TLS), a process that synthesizes DNA across DNA lesion, through p21 translational repression by miRNA. Conclusion: We conclude that Chk1-Lats2-14-3-3 axis is a novel DNA damage signaling pathway that regulates the P-body assembly, thereby causing the translational repression of target genes via miRNA. These results provide the first evidence for a mechanism in which the DNA damage response pathway regulates miRNA-mediated translational repression through P-body assembly. Citation Information: Cancer Res 2009;69(23 Suppl):B77.
EIGHT-YEAR CLINICAL OUTCOME OF SIROLIMUS-ELUTING STENT IMPLANTATION FOR CHRONIC TOTAL OCCLUSION LESIONS COMPARED WITH NON-CHRONIC TOTAL OCCLUSION LESIONS
Authors: Mizuki Miura, Shoichi Kuramitsu, Hiroyuki Jinnouchi, Takashi Hiromasa, Hisaki Masuda, Yuhei Yamaji, Yukiko Matsumura, Yoshimitsu Soga, Shinichi Shirai, Kenji Ando
Journal: Journal of the American College of Cardiology (2016)
Case 36-2001
Authors: Raphael Dolin, Eugene J. Mark
Journal: New England Journal of Medicine (2001)

Presentation of CaseA 57-year-old man was admitted to the hospital, for the sixth time, in January because of fever and cough.The patient had a 25-year history of seronegative rheumatoid arthritis and a 20-year history of diabetes mellitus type 2, complicated by retinopathy and peripheral neuropathy. One year before the first admission (34 months before the current admission) bronchiolitis obliterans with organizing pneumonia was diagnosed on the basis of a biopsy (Figure 1). Treatment with prednisone in small doses improved the patient's dyspnea.While the prednisone dose was being tapered, symptoms consistent with recurrent bronchiolitis obliterans with organizing pneumonia, . . .
Abstract 2408: CD44s is required for a tumor-initiating stem-like mesenchymal phenotype in hepatocellular carcinoma via ligand-independent c-Met activation
Authors: Hien T. Dang, Wei Ding, Carl Bart Rountree
Journal: Cancer Research (2012)

Abstract c-Met, a high affinity receptor for hepatocyte growth factor (HGF), plays a critical role in cancer growth, invasion and metastasis. Hepatocellular carcinoma (HCC) patients with active HGF/c-Met signaling have a significantly worse prognosis. CD44, the receptor for hyaluronic acid, is utilized as a surface marker to identify mesenchymal tumor-initiating stem-like cells (TISC) in several cancers. CD44v6 (spice variant 6) has been shown to promote HGF activation of c-Met. In this work, we examine the role of CD44s as a deregulator and activator of c-Met signaling in HCC. In a transcriptome profile analysis of 149 human HCC cases, we identified a significant positive correlation (R2=0.8993) between up-regulated CD44 and c-Met expression. The human HCC cell lines MHCC97-H and Huh7 were further utilized to investigate the direct relationship between c-Met and CD44s. Metastatic MHCC97-H cells are 95% CD44+ and demonstrate ligand-independent c-Met activation. CD44+/c-Met+ MHCC97-H cells demonstrate a mesenchymal phenotype with low expression of E-cadherin, high level of tumorsphere formation, increased expression of fibronectin and Zeb2 compared to Huh7 cells, which have are CD44neg/c-Metneg. In MHCC97-H cells, a direct interaction between CD44s and c-Met was demonstrated by immunoprecipitation/immuno-blot analysis. Transient and stable inhibition of c-Met in MHCC97-H cells results in increased E-cadherin, decreased CD44s, and reduced tumor-initiating characteristics and loss of tumorsphere formation. Likewise, inhibition of CD44s demonstrates similar phenotype with increased E-cadherin, decreased tumorsphere formation, and decreased c-Met activation and loss of downstream Akt and Erk phosphorylation. CD44s knockdown recovered c-Met to a regulated HGF-dependent state. Selective inhibition of either PI3K (Ly294002) or MAPK (PD98059) pathways in MHCC97-H cells demonstrate that PI3K/Akt activation signals drive CD44s expression in a feed forward fashion. Conversely, the over-expression of CD44s in Huh7 cells demonstrates a mesenchymal phenotype with fibroblastic-like cell morphology, decreased E-cadherin, increased Zeb1, increased PI3K/Akt signaling, and increased tumorsphere formation compared to control Huh7 cells. Selective inhibition of PI3K/Akt signaling in CD44+ Huh7 cells resulted in reduced CD44s expression and decreased tumorsphere formation. In conclusion, CD44s induces a mesenchymal phenotype and tumor initiating characteristics in HCC through the deregulation of c-Met and activation of a positive feedback loop through PI3K/Akt signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2408. doi:1538-7445.AM2012-2408
Abstract 5410: Modulating metabolic homeostasis as a therapeutic tool for leukemia.
Authors: Ramy R. Attia, Jaeki Min, Rodney K. Guy
Journal: Cancer Research (2013)

Abstract Genetic studies in humans and rodents support the notion that alterations in metabolic homeostasis can directly contribute to carcinogenesis and metabolic processes may be targets for therapy. The nuclear hormone receptors (NR) control a wide variety of metabolic processes by regulating the expression of genes encoding key enzymes, transporters, and other mediators. Therefore we explored potential links between cellular metabolic control by NRs and viability of cancer cells. In this study we tested the effect of 127 NR modulators, targeting receptors known to be important in regulating metabolism or known to be viable cancer targets on the growth of different leukemic cells lines. Of the compounds tested 8, mainly targeting ER and RAR, induced significant apoptosis in these leukemias. The effects of the 8 active compounds on mitochondrial metabolism were tested in Jurkat cells and 5 compounds significantly reduced lactate levels. However, only the synthetic retinoid (CD437) significantly affected pyruvate dehydrogenase complex activity. CD437 also effected the expression of genes involved in leukemia development and therapeutic responses with the PKC pathway being the primary target. CD437 induced PKC Kinase activity and activated its downstream signals AKT and JNK. CD437 downregulated CPT-1a,and decreased the overall O2 consumption rate. Additional CD437 induced genes included those involved in the mitochondrial respiratory complex I and III and increased the production of ROS. Our results indicate that the apoptotic effect of CD437 can be linked to its regulation of mitochondrial oxidative metabolism. Citation Format: Ramy R. Attia, Jaeki Min, Rodney K. Guy. Modulating metabolic homeostasis as a therapeutic tool for leukemia. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5410. doi:10.1158/1538-7445.AM2013-5410