tbuckley/cabot-search huggingface dataset:
Abstract 2149: Analysis of the cancer-specific correlation between genomic copy number aberration and gene expression in colorectal cancer
Authors: Masaaki Iwatsuki, Koshi Mimori, Hideo Baba, Masaki Mori
Journal: Cancer Research (2010)

Abstract Background: Recently, the technical innovation in molecular biological fields such as laser micro-dissection (LMD), cDNA microarray and array-based comparative genomic hybridization (array-CGH) have made it possible to analysis both genomic alteration and aberrant gene expression simultaneously at the level of cancer cell obtained from human cancer tissues. The aim of current study is to identify the novel genes to predict disease recurrence or prognosis with the concordant relationship between genomic alterations and aberrant gene expression during the progression of colorectal cancer (CRC). Materials and Methods: Candidate gene was found using cDNA microarray and array-CGH after LMD in 133 Japanese CRC. We picked up the several genes among the overexpressing genes with genomic amplification on the responsible loci in CRC. The expression of representative gene and its clinicopathlogical significance, including prognosis were evaluated another subset of 98 CRC cases. Results: We demonstrated that a correlation between chromosomal aberrations and gene expression in CRC was found in 8q, 13q and 20q. We identified 185 genes overexpressig in specific CRC cells among the genes on these chromosomes. We focused on SUGT1 (13q), which is associated with the assembling of kinetochore proteins at the metaphase of the cell cycle. SUGT1 mRNA expression was evaluated in 98 CRC cases to determine the clinicopathological significance of SUGT1 expression. The mean level of SUGT1 mRNA expression in tumor tissue specimens was significantly higher than in non-tumor tissue. The high SUGT1 expression group was characterized by a significantly elevated frequency of recurrence and a significantly poorer prognosis than the low expression group. Furthermore, SUGT1 expression was found to be a significant factor affecting five year overall survival following surgery in multivariate analysis (p = 0.04). Conclusion: We performed cDNA microarray and array-CGH analysis after LMD in a large scale study of Japanese CRC patients to identify new genomically amplified genes and determine the impact of their presence. Our results indicate that identified genes are not influenced by epigenetic alteration or microRNA. Furthermore, from a technical point of view, it is easier to handle genomic DNA than mRNA, as the latter is fragile, and unstable. Therefore, our findings suggest that this method of analysis might uncover additional genes indicative of patient prognosis and sensitivity to anticancer drugs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2149.
A Comparison of Lipiodol Chemoembolization and Conservative Treatment for Unresectable Hepatocellular Carcinoma
Journal: New England Journal of Medicine (1995)

Chemoembolization with lipiodol (iodized oil) is widely used to treat patients with unresectable hepatocellular carcinoma. Severe side effects have been reported, and improved survival has not been clearly demonstrated.Patients with unresectable hepatocellular carcinoma who did not have severe liver disease and who met additional entry criteria were randomly assigned to receive either lipiodol chemoembolization (70 mg of cisplatin, 10 ml of lipiodol, and gelatin-sponge [Gelfoam] particles delivered through the hepatic artery) or conservative management involving treatment of complications and pain. Courses of treatment were to be given every two months for a maximum of four courses. The main end point was survival.The study was stopped in December, 1992, after a sequential analysis showed the lack of the expected benefit from chemoembolization. As of October 1, 1994, 39 of the 50 patients assigned to chemoembolization and 40 of the 46 patients assigned to conservative management had died. Twenty-six patients assigned to chemoembolization received all four courses of treatment. There was no significant difference in survival between the two groups, although there was a trend favoring the chemoembolization group (estimated relative risk of death in the control group, 1.4; 95 percent confidence interval, 0.9 to 2.2; P = 0.13). The comparison of survival between the two groups was not substantially changed by adjustments for differences in base-line and prognostic characteristics (adjusted relative risk, 1.3; 95 percent confidence interval, 0.8 to 2.1; P = 0.31). At one year, the estimated survival rates were 62 percent in the chemoembolization group (95 percent confidence interval, 48.6 to 75.4 percent) and 43.5 percent in the conservative-management group (95 percent confidence interval, 29.2 to 57.8 percent). In the chemoembolization group, tumor growth, as assessed by tumor size and serum alpha-fetoprotein concentration, was reduced and the incidence of portal obstruction was lower than in the conservative-management group. Liver failure occurred after 47 courses of treatment in 30 patients assigned to chemoembolization.In a group of patients with unresectable hepatocellular carcinoma but without severe liver disease, lipiodol chemoembolization reduced tumor growth, often caused acute liver failure, and did not significantly improve survival.
Gallium-67 SPECT/CT for Abdominal Abscess
Authors: Mei-Fang Cheng, Jei-Yie Huang, Deng-Yu Han, Pei-Ying Hsu, Ruoh-Fang Yen
Journal: Clinical Nuclear Medicine (2011)

An 80-year-old woman, who had suffered from end-stage renal disease under peritoneal dialysis, was presented with intermittent fever, leukocytosis, and elevated C-reactive protein for 4 months. She did not have symptom of abdominal pain. Culture of ascites showed Klebsiella pneumoniae. Abdominal utrasonography was negative. Whole-body gallium-67 imaging showed a segmental uptake mimicking bowels in right abdomen. SPECT/CT revealed the uptake in a soft tissue density beneath the abdominal wall instead of bowels. Contrast-enhanced CT demonstrated a low-density mass with peripheral enhancement at the aforementioned area. Her clinical condition stabilized gradually after CT-guided percutaneous drainage of pus from the abscess.
A new large-diameter overtube for endoscopic submucosal dissection in the colon
Authors: K. Okamoto, N. Muguruma, S. Kitamura, Y. Fujino, T. Goji, H. Yano, T. Kimura, H. Miyamoto, T. Okahisa, T. Takayama
Journal: Endoscopy (2012)

The single-balloon overtube was initially developed for deeper insertion of the scope into the small bowel [1]. Ohya et al. [2] reported that use of the balloon overtube improved access to the lesion and facilitated scope manipulation in colorectal endoscopic submucosal dissection (ESD). Here we report our experience with a newly developed balloon overtube for colorectal ESD, especially in the right colon.
Multidrug Resistance: Molecular Biology Clinical Relevance
Authors: M. Rothenberg, V. Ling
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Multidrug Resistance: Molecular Biology Clinical Relevance Get access Mace Rothenberg, Mace Rothenberg Division of Cancer Treatment, National Cancer InstituteBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Victor Ling Victor Ling * Division of Biological Research, The Ontario Cancer InstituteToronto, ON, Canada *Correspondence to: Dr. Victor Ling, Division of Biological Research, The Ontario Cancer Institute, 500 Sherbourne St., Toronto, ON, Canada M4X 1K9. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 12, 21 June 1989, Pages 907–910, https://doi.org/10.1093/jnci/81.12.907 Published: 21 June 1989 Article history Received: 08 May 1989 Accepted: 08 May 1989 Published: 21 June 1989
Lessons from a Public Health Emergency — Importation of Wild Poliovirus to Israel
Authors: Eran Kopel, Ehud Kaliner, Itamar Grotto
Journal: New England Journal of Medicine (2014)

In 2013, samples from routine environmental surveillance at a sewage-treatment plant in Israel tested positive for wild-type poliovirus. In response, Israeli health policymakers ramped up environmental surveillance and launched supplementary immunization activities.
Bacterial Meningitis: Pathogenesis, Pathophysiology, and Progress
Authors: Franklin H. Epstein, Vincent Quagliarello, W. Michael Scheld
Journal: New England Journal of Medicine (1992)

FIFTY years after the advent of antibiotics for clinical use, bacterial meningitis remains an important cause of morbidity and mortality. As such, it represents a unique human infectious disease, because the pathophysiologic effects of disease progression and suboptimal outcomes occur despite bacteriologic cure of the infection.1 Specifically, the mortality rate for adults who have Streptococcus pneumoniae meningitis remains 20 to 30 percent,2 , 3 with neurologic morbidity affecting half of survivors.4 The incidence of persistent sensorineural hearing loss in children who survive bacterial meningitis is 10 percent (31 percent of those with S. pneumoniae are affected) — a finding with critical implications . . .
AB0487 Decreased SLE Disease Activity and Corticosteroid Usage and NO Renal Flares during Belimumab Treatment
Authors: I. Parodis, E. Svenungsson, M. Axelsson, I. Gunnarsson
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Belimumab is a recombinant monoclonal antibody that specifically binds to soluble B-lymphocyte stimulator, thereby reducing autoantibody levels. It is the only biologic agent approved for treatment of Systemic Lupus Erythematosus (SLE). <h3>Objectives</h3> The aim of this study was to investigate the effects of belimumab given as an add-on to patients with active SLE despite standard-of-care therapy, with focus on low-active lupus nephritis (LN) patients. <h3>Methods</h3> Fourteen patients were included. Clinical data were acquired at baseline and week 12, 26 and 52. Disease activity was assessed using SLE Disease Activity Index 2000 (SLEDAI-2K) and Systemic Lupus Activity Measure (SLAM). The primary organ manifestations comprised arthritis (n=9), skin involvement (n=11), serositis (n=3), involvement of the central nervous system (n=4) and cytopenias (n=3). Nine patients with former LN were included (median proteinuria at baseline 0.2 g/day, range 0.01-0.4 g/day). <h3>Results</h3> At baseline, all patients received oral prednisolone (mean dose 11, range 5-20 mg/day), 9 received antimalarials, 3 mycophenolate mofetil, 2 azathioprine, and 1 cyclosporine. The median SLEDAI and SLAM scores were 10 (range 2-24) and 12 (range 5-23), respectively. One patient withdrew due to allergic reaction. Significant decreases of SLAM and SLEDAI were seen at week 26 (p=0.001 and p=0.007, respectively) and 52 (p=0.028 and p=0.012, respectively). Prednisolone dosages were significantly decreased compared to baseline at week 26 (p=0.003) and 52 (p=0.008). Ten patients had low complement at baseline. We observed no significant increase in C3/C4 levels. In the patients with former LN, no renal flare was observed during the observation period. The grade of proteinuria remained unchanged at week 26 (median 0.14 g/day, range 0.01-0.5 g/day) and 52 (median 0.13 g/day, range 0.02-0.24 g/day). No severe adverse events were noted. <h3>Conclusions</h3> Belimumab treatment decreased SLE disease activity and reduced corticosteroid usage. Despite the limited number of patients, our observations indicate that belimumab may prevent renal flares and may be used in patients with former LN and persistent low-grade proteinuria. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3876
AB0636 Late-onset systemic lupus erythematosus: Clinical features, course and prognosis
Authors: A. Tomic Lucic, R. Petrovic, M. Radak Perovic, D. Milovanovic, M. Veselinovic, S. Zivanovic, M. Petrovic
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> There are contradictory opinions if late-onset systemic lupus erythematosus (SLE) is associated with a different, more benign disease course and better prognosis than early-onset SLE. <h3>Objectives</h3> The objective of study was to evaluate the clinical manifestations, course, treatment and prognosis of late-onset SLE. <h3>Methods</h3> Patients who developed SLE after/or at the age of 50 years were considered late-onset SLE and compared to a group of randomly selected patients aged younger than 50 years at the diagnosis, matched for disease duration. <h3>Results</h3> Lower frequency of cutaneous manifestations (p=0.01) and higher frequency of cytopenia (p=0.02) was registrated at the SLE onset in late-onset group. Atypical clinical presentation of SLE contributed to a longer delay of diagnosis in late-onset patients (p=0.005), who fullfiled less American College of Rheumatology crteria at the diagnosis (p=0.022). Cumulative incidence of clinical manifestations showed lower frequency of cutaneous (p=0.017), neuropsychiatric manifestations(p=0.021), lupus nephritis (p=0.006) and higher frequency of Sjogren$′ $s syndrome (p=0.025) in late-onset group. Late-onset patients received lower corticosteroid (p=0.006) and cyclophosphamide doses (p=0.001), and had more cyclophosphamide induced complications (p=0.005). Higher prevalence of comorbid conditions was noticed in late-onset group. (p&lt;0.0005). <h3>Conclusions</h3> Despite the less maior organ involvement, and more benign course of disease, late-onset SLE has worse prognosis, because of the higher frequency of comorbid conditions, due to the aging and longer exposition to a classical vascular risk factors. <h3>References</h3> Boddaert J., Huong DL, Amoura Z, Wechsler B, Godeau P, Piette JC. Late-onset systemic lupus erythematosus: a personal series of 47 patients and pooled analysis of 714 cases in literature. Medicine (Baltimore) 2004; 83: 348-59. Appenzeller S., Pereira DA, Costallat LT. Greater accrual damage in late-onset systemic lupus erythematosus: long-term follow –up study. Lupus 2008; 17(11): 1023-8. Lalani S, Pope J, de Leon F, Peschen C. Clinical features and prognosis of late onset systemic lupus erythematosus: results from the 1000 faces of lupus study. J Rheumathol 2010; 37(1):38-44. Rovensky J, Tuchynova A. Systemic lupus erythematosus in the elderly. Autoimmunity Rev 2008; 7: 235-9. Bertoli AM, Alacron GS, Calvo-Alen J, Fernandez M, Vila LM, Reveille JD. LUMINA Study Group. systemic lupus etrythematosus in multietnic US cohort. XXXIII. Clinical features, course and outcome in patients with late-onset disease. Arthritis Rheum 2006; 54 (5): 1580-7. <h3>Disclosure of Interest</h3> None Declared
Abstract LB-65: Protein kinase Cε, which is linked to development of squamous cell carcinomas, potentiates ultraviolet radiation-induced expression of novel transcription factors GATA and PAX, which regulates expression of cell survival genes
Authors: Mohammad S. Jamal, Bilal B. Hafeez, Ajit K. Verma
Journal: Cancer Research (2012)

Abstract Protein kinase C epsilon (PKCε) is among the six PKC isoforms (α, δ, ε, η, μ, ξ) expressed in both mouse and human skin. We have reported that epidermal PKCε levels dictate the susceptibility of PKCε transgenic mice (TG) to the development of squamous cell carcinomas (SCC) elicited by repeated exposures to ultraviolet radiation (UVR). Histologically, SCC in TG mice, like human SCC, is poorly differentiated and metastatic. To find clues about the mechanism by which PKCε may impart susceptibility to UVR-induced development of SCC, we compared the effects of UVR treatment of TG mice with their wildtype (WT) littermates on global transcription factors (TFs) activation profile. In this experiment, mice were exposed to UVR (2kj/m2) four times (Monday, Wednesday, Friday and Monday). At 1hr and 3hrs post last UVR exposure, these mice were sacrificed. Nuclear lysates were prepared from the scraped epidermis of these mice. To screen for unknown TFs, we employed the Panomics Combo Protein array, which contains consensus complimentary sequences of 345 TFs binding sites. Array results from samples of UVR exposed mice were directly compared to the unexposed mice. TFs that had increased over 2-fold in the UVR exposure experiments were scored as positive for activation. We observed (&amp;gt;2-fold) activation of 70 TFs as early as 1hr post UVR exposure. Among all seventy TFs, highly activated TFs were GATA-1, GATA-2, PAX-4, PAX-6, PAX-8, Thy-1BP, HFH-2, HFH-3, HIF-1, CEA, HOXD8/9/10, AhR/Amt, and MUSF. We performed the validation of various activated TFs and among them we found that GATA and PAX families of transcription factors were found activated. UVR-induced expression level of GATA-1, GATA-2, PAX-4 was enhanced in PKCε over-expressing transgenic mice as compared to wild-type littermates. We employed the Genego program and found that VEGFR-2, CyclinD1, Bcl-2, c-Myc, BMP-4, WT1 and survivin are the downstream target genes of GATA1 and GATA-2. All of these genes are known to play role in the cell survival pathway. We have previously shown that PKCε overexpressing transgenic mice also exhibit constitutive activation of Stat3. Taken together, we conclude that PKCε-mediated activation of Stat-3, GATA-1, GATA-2 and PAX-4 may contribute to the susceptibility of PKCε transgenic mice to UVR-induced development of SCC. (Support: NIH Grant CA 35368) 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 LB-65. doi:1538-7445.AM2012-LB-65
Bordetella Pertussis Whole-Cell Vaccine Inhibits Specific IgE, Inflammation and Airway Remodeling in a Murine Model of Asthma
Authors: Marcelo Vivolo Aun, Fernanda Arantes-Costa, Beatriz Mangueira Saraiva-Romanholo, Francine Maria Almeida, Thayse Regina Brüggermann, Milton Arruda Martins, Jorge Kalil, Pedro Giavina-Bianchi
Journal: Journal of Allergy and Clinical Immunology (2015)
Abstract 1900: Hypoxia induces accumulation of lysosomal proteins within mitochondria.
Authors: Yasuyuki Nakamura, Masaki Yoshida, Noriaki Kitamura, Hiroki Kamino, Ryuya Murai, Yuri Saito, Hitoya Sano, Hirofumi Arakawa
Journal: Cancer Research (2013)

Abstract Mitochondrial quality control (MQC) plays a critical role in maintaining a healthy status of mitochondria, preventing aging, cancer, and a variety of degenerative diseases. However, the mechanism largely remains unclear. Recently, we discovered a novel MQC mechanism regulated by Mieap, a p53-inducible protein, in which Mieap induces intramitochondrial lysosome-like organella that plays a critical role in the elimination of oxidized mitochondrial proteins (designated MALM for Mieap-induced accumulation of lysosome-like organelles within mitochondria) in response to mitochondrial damage (1-4). Here, we report a physiological role of the MALM function. Hypoxia dramatically induced accumulation of lysosomal proteins within mitochondria without the destruction of mitochondrial structure in both human normal mammary epithelial cells (HMEC4s) and mouse embryonic fibroblasts cells (MEFs). In response to the hypoxic stress, the MALM was inducible in ATG5-KO, ATG7-KO, and PINK1-KO MEFs, but not in p53-KO and Mieap-KO MEFs, suggesting that the phenomenon is completely different from canonical autophagy. In the MALM-deficient cells, hypoxia caused an increase of mitochondrial reactive oxygen species (ROS) generation and accumulation of oxidized proteins within the mitochondria. Surprisingly, the MALM-deficient cells in the hypoxic condition revealed enhanced activities of cell migration and invasion. This phenotype was totally cancelled by a ROS scavenger reagent, Ebselen. These results suggest that the MALM is a universal and fundamental function in the cell (at least from mouse to human), which plays a critical role in MQC under hypoxia. Alteration of the MALM function in cancer cells could facilitate cancer invasion and metastasis via mitochondrial ROS generated by unhealthy mitochondria. 1. Miyamoto Y et al. PLoS ONE 6: e16054, 2011 2. Kitamura N et al. PLoS ONE 6: e16060, 2011 3. Nakamura Y et al. PLoS ONE 7: e30767, 2012 4. Miyamoto T et al. Sci Rep 2: 379, 2012 Citation Format: Yasuyuki Nakamura, Masaki Yoshida, Noriaki Kitamura, Hiroki Kamino, Ryuya Murai, Yuri Saito, Hitoya Sano, Hirofumi Arakawa. Hypoxia induces accumulation of lysosomal proteins within mitochondria. [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 1900. doi:10.1158/1538-7445.AM2013-1900
Abstract 2168: Dual targeting of the AKT/mTOR signaling pathwayinhibits mesothelioma: Targeted therapies against multiple activated receptor tyrosine kinases.
Authors: Shengmei Zhou, Li Liu, Weijiang Hu, Hailong Li, Fanguo Meng, Haimeng Zhou, Jonathan A. Fletcher, Wenbin Ou
Journal: Cancer Research (2013)

Abstract Mesothelioma is a notoriously chemotherapy-resistant neoplasm, as is evident in the dismal overall survival for patients with this asbestos-associated disease. The receptor tyrosine kinases EGFR and MET are activated in subsets of mesothelioma, suggesting these kinases might represent novel therapeutic targets. However, clinical trials have not shown activity for EGFR inhibitors in mesothelioma. We had previously demonstrated activation of multiple receptor tyrosine kinases, including EGFR, MET, and AXL, in individual mesothelioma cell lines, targeting HSP90 suppressed the multiple activated RTKs in mesothelioma cell lines, resulting in apo-apoptotic and anti-proliferative effects. Thus, we hypothesized that a coordinated network of multi-RTK activation contributes collectively to activate PI3-K/AKT/mTOR and/or RAF/MAPK signalings for the tumorigenesis of mesothelioma. Herein, we demonstrate abnormal activation of the PI3-K/AKT/p70S6K and RAF/MEK/MAPK pathways in mesothelioma, as compared with normal mesothelial cells. Multiple receptor tyrosine kinases, including EGFR, MET, and AXL, in individual mesothelioma cell lines, collectively activated survival signaling intermediate AKT, but not MAPK. The anti-proliferative responses of the coordinate inhibition of these multi-kinase signaling were comparable with suppression of PI3-K/AKT/mTOR pathway. Dual targeting AKT/mTOR signaling has substantially greater effect on mesothelioma proliferation and survival, compared to inhibition of individual activated kinases and downstream signaling alone, suggesting that no one activated RTK is the predominant oncogenic control mechanism in mesothelioma and PI3-K/AKT/mTOR is a crucial survival pathway. The AKT/mTOR signaling inhibition by BEZ235 resulting in pro-apoptotic and anti-proliferative effects in mesothelioma, was associated with the blockage of MDM2-p53 interaction. Citation Format: Shengmei Zhou, Li Liu, Weijiang Hu, Hailong Li, Fanguo Meng, Haimeng Zhou, Jonathan A. Fletcher, Wenbin Ou. Dual targeting of the AKT/mTOR signaling pathwayinhibits mesothelioma: Targeted therapies against multiple activated receptor tyrosine kinases. [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 2168. doi:10.1158/1538-7445.AM2013-2168