tbuckley/cabot-search huggingface dataset:
Abstract LB-374: IGFBP-6, a novel prognostic biomarker in nasopharyngeal carcinoma (NPC) patients
Authors: Yi Lu, Qiuyan Chen, Weici Qi, Minghuang Hong, Atsushi Mizokami, Evan Keller, Jian Zhang
Journal: Cancer Research (2011)

Abstract A variety of cancer types, including NPC, that have metastasized to bone, have a dysregulated insulin-like growth factor (IGF) system. This suggests that IGF-IGF receptor axis may contribute to the interaction between host and cancer cells resulting in promotion of skeletal metastases. In this study, IGFBP6 expression levels were first determined by immunohistochemistry in clinical specimens from NPC patients (n=76). IGFBP6 was differentially expressed in malignant epithelia and in non-neoplastic tissues. The 5-year overall survival rate of IGFBP-6 negative and positive group was 27% and 73% (survival analysis P=0.007), respectively and the 5-year distant metastasis-free survival rate was 53% and 89% (P=0.002), respectively. Multivariate analysis in a Cox model showed that IGFBP-6 was an independent and positive prognostic biomarker in NPC patients. Furthermore, we found that in vitro cell proliferation and invasion were inhibited by recombinant IGFBP6 treatment in CNE2 cells but not in HK-1 cells. Finally, CNE2 cells were stably transfected with IGFBP6 short hairpin RNA (shRNA) or scrambled RNA. The cells were inoculated into the tibiae of SCID mice for 3 weeks. The IGFBP6 knockdown significantly enhanced CNE2 tumor growth in bone. These results indicate that IGFBP6 may play key roles in NPC tumor progression. We conclude that, for the first time, IGFBP-6 is a novel prognostic biomarker in NPC patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-374. doi:10.1158/1538-7445.AM2011-LB-374
Parenteral and Aerosol Administration of Antihistaminic Agents in the Treatment of Severe Bronchial Asthma
Authors: Hyman J. Rubitsky, Elliott Bresnick, Leon Levinson, George Risman, Maurice S. Segal
Journal: New England Journal of Medicine (1949)

IT IS a widely held opinion that bronchial asthma may be due to the liberation of free histamine from its usually bound state,1 2 3 4 although many conflicting observations make this view far from universal. The oral administration of "antihistaminic" drugs (blocking agents) has proved of limited value in the management of bronchial asthma.5 6 7 Recent observations by other investigators and the results of protection studies performed in our laboratory have suggested that the parenteral use of these drugs may be indicated in the treatment of severe bronchial asthma.Feldberg8 and Szczygielski9 have shown that histamine is capable of causing the release of . . .
226 A MODEL FOR DROPOUT ASSESSMENT OF CANDIDATES WITH OR WITHOUT HEPATOCELLULAR CARCINOMA ON A COMMON LIVER TRANSPLANT WAITING LIST
Authors: C. Toso, E. Dupuis-Lozeron, P. Majno, T. Berney, N. Kneteman, T. Perneger, P. Morel, G. Mentha, C. Combescure
Journal: Journal of Hepatology (2012)
Abstract 3671: First-line treatment of patients with disseminated poorly differentiated neuroendocrine carcinomas with carboplatin, etoposide, and vincristine
Authors: Marie T. Andresen, Ulrich Knigge, Carsten Palnæs Hansen, Jane Preuss Hasselby, Seppo W. Langer
Journal: Cancer Research (2010)

Abstract Background: The poorly differentiated neuroendocrine carcinomas (PDEC) represent a highly malignant tumor with an immense tendency to metastasize and a poor prognosis, with a median survival of approximately 6 months without treatment. Treatment based on platin and etoposide is widely recommended as palliative chemotherapy and corresponds to the treatment of extensive stage small cell lung cancer. The recommendation is based on relatively few, older studies, which did not use the 2000 WHO tumor classification, and no controlled, randomised studies have been published. Method: Successive chemonaïve patients with disseminated PDEC (small cell carcinomas excluded) allocated for treatment from May 2007 to June 2008 were identified. Patients received carboplatin AUC 5 IV day 1 + etoposide 100 mg/m2 PO day 1-3, and vincristine 1.3 mg/m2 (maximum 2.0 mg) IV day 1. Treatment was repeated every 3 weeks until progression or intolerable toxicity up to a maximum of 6 courses. Results: Twenty-two patients diagnosed with PDEC according to the 2000 WHO tumor classification were eligible for analysis, 11 females and 11 males. The median age was 61 years (range 35-80). Performance status: 0/1/2 = 9/11/2. All patients had disseminated disease. Immunohistochemical analyses of synaptophysin were positive in 21/22 (95.4%), and chromogranin A positive in 17/21 (80.9%). In one patient (4.5%) both analyses were negative; in 17/21 (80.9%) both were positive. The Ki-67 proliferation index ranged from 20% to 100%; the index reaching 50% or higher in 17 patients (77.2%). Octreotide scintigraphy was negative in 10 of 12 scanned patients (83,3%). Three patients (13.6%) achieved complete response (CR), 11 (50%) partial response (PR), 4 (18.2%) no change (NC), and 4 (18.2%) progressive disease (PD). The overall response rate (CR+PR) was 63.6%, and the disease control rate (CR+PR+NC) 81.8%. The median progression free survival time was 7.4 months. The median overall survival time was 10.5 months, and the 1-year survival 48%. Conclusion: In conclusion, treatment with carboplatin, etoposide, and vincristin in previously untreated patients with disseminated PDEC results in a noticeable survival benefit compared to untreated historical controls. The prognosis is however still poor. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 3671.
AB0068 Mitochondrial 8-oxoguanine dna glycosylase (ogg1) regulates the chondrocyte function and survival against catabolic stresses in osteoarthritis.
Authors: K. Yudoh
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> During the development of osteoarthritis (OA), mechanical and chemical stresses on articular cartilage change the stable cellular activities of chondrocytes and produce excess amounts of reactive oxygen species (ROS) as well as proinflammatory cytokines and chemokines. Previous studies have provided ample confirmation of the generation of ROS and the depletion of cellular antioxidants in degenerated articular cartilage. An oxidized form of guanine, 8-oxo-7,8-dihydroxyguanine (8-oxoguanine), is a major causative lesion for mutagenesis by ROS, because it can cause a stable base pair with adenine or cytosine during DNA replication. These mutations are thought to be involved in the pathogenesis of a variety of diseases, including degenerative diseases. <h3>Objectives</h3> This study identified mitochondrial Ogg1 as a pathogenic mechanism against catabolic factors in osteoarthritis (OA). <h3>Methods</h3> 8-oxoguanine and Ogg1 expressions were investigated in human OA cartilages (n=5) and rat OA cartilages (n=8) by immunohistologic analysis. We studied whether OA-related catabolic factors (H<sub>2</sub>O<sub>2</sub>, IL-1b) influence expressions of Ogg1 and 8-oxoguanine in OA chondrocytes and analyzed the relationship between the cellular activity (productions of proteoglycan and type II collagen) and Ogg1 expression in human chondrocytes. <h3>Results</h3> We observed the accumulation of an oxidized form of guanine, 8-oxoguanine, and down-regulation of its repair enzyme Ogg1 in OA rat and human chondrocytes. OA-related catabolic factors induced the over-expression of 8-oxoguanine and down-regulation of Ogg1 in chondrocytes. Furthermore, Ogg1 silencing using siRNA reduced chondrocyte activity and augments apoptosis in chondrocytes. <h3>Conclusions</h3> Our study suggests that Ogg1 prevents catabolic stress-mediated chondrocyte dysfunction and apoptosis that might be associated with the maintenance of articular cartilage. <h3>Disclosure of Interest</h3> None Declared
A memorable patient: Believe it or not
Authors: B S. Naik
Journal: BMJ (2002)

His diagnosis was refractory cardiac failure due to ischaemic heart disease. He had been seen and investigated by several cardiologists and was considered unfit for any cardiac intervention except for a heart transplant. He came to me a few weeks before his daughter's marriage and said he wanted to live until then. He was breathless and could barely move, with generalised oedema. I thoroughly went through his medical records. He had had a coronary angiogram and many echocardiograms and electrocardiograms at various cardiac centres. According to the NYHA heart failure classification, he had class IV symptoms in spite of taking a full dose of all possible drugs. I felt I had nothing to offer this patient.

Throughout my career I had noticed patients in this part of the world drink large quantities of water to gain “good health.” So, out of curiosity, I asked my patient how much water he drank every day. From his answer it was apparent that he was drinking over three litres of water a day. Now I knew the culprit behind his refractory cardiac failure.

I put the patient on strict fluid restriction and advised him to continue taking his drugs. A few weeks later, when I attended his daughter's marriage, he was able to climb two flights of stairs with ease to introduce me to the newly married couple.

It is important not only to carry out our state of the art investigations and treatment but also to advise patients about lifestyle modifications.
ALZHEIMER'S DISEASE
Authors: D. Rothschild
Journal: American Journal of Psychiatry (1934)

Five cases of Alzheimer's disease are reported and the literature is reviewed. All patients showed profound intellectual deterioration, motor unrest, affective changes and a disorder of speech. The age of onset ranged from 44 to 64. The duration of the illness varied from 2½ to 26 years. In one case the disease came to a standstill for more than two years. Certain observations suggested that exogenous factors could accelerate the progress of the disease. An increase of muscle tonus occurred in four cases. One patient presented a clinical picture resembling that observed in certain cases of Pick's lobar atrophy. Apraxia and visual agnosia were noted in one case and cerebellar signs in another. Symptoms suggestive of vegetative involvement were not uncommon. The disorder of speech did not conform to any of the classical types of aphasia. It was looked on as a manifestation of a general lowering of function to a more primitive level caused by diffuse changes in the brain. The chief histologic changes were nonspecific cell lesions, diffuse cell losses, senile plaques and neurofibril lesions of the Alzheimer type. These alterations showed a considerable degree of parallelism in the cerebral cortex but not elsewhere. The glial response was usually active. Hyaline-like vascular lesions were found in all cases. All parts of the cerebral cortex were affected. In most instances the parietal lobes, the cornu ammonis and the temporal lobes presented the severest damage. The observations indicated that the pathologic process could occasionally be accentuated enough in certain regions to produce focal symptoms. As a rule there was no close correspondence between the areas of greatest involvement and the individual cyto-architectural fields. The changes were usually most pronounced in the third layer of the cerebral cortex. The basal ganglia frequently showed considerable involvement. In one case marked alterations were observed in the cerebellum. The differences and resemblances between Alzheimer's disease and senile dementia and the various theories regarding the origin of the former are discussed. A consideration of all the facts lends support to the view that the clinicopathologic picture of Alzheimer's disease occurs in a rather heterogeneous group, the individual members of which may owe their origin to different etiologic agents. The possibility cannot be excluded that Alzheimer's disease may in most instances be caused by the same factors operative in senile dementia. The observations presented here tend to suggest that a close relationship between the two conditions is perhaps less frequent than has hitherto been supposed.
Abstract 1075: Cul1 Expression Is Increased in Early Stages of Human Melanoma
Authors: Guangdi Chen, Yabin Cheng, Magdalena Martinka, Gang Li
Journal: Cancer Research (2010)

Abstract As the largest family of ubiquitin-protein E3 ligases, the SCF (Skp1/Cullin/Rbx1/F-box protein) complexes ubiquitinate a broad range of proteins involved in cell cycle progression, signal transduction and transcription. Cullin1 (Cul1) serves as a rigid scaffold in SCF complex for Rbx1, Skp1 and F-box protein subunits assembly and aberrant expression of Cul1 is involved in dysfunction of SCF E3 ligases. To investigate the role of Cul1 in the development of melanoma, we examined the expression of Cul1 in melanocytic lesions at different stages and analyzed the correlation between Cul1 expression and clinicopathologic parameters by tissue microarray and immunohistochemistry. The result showed that Cul1 expression was significant increased in primary and metastatic melanoma compared with dysplastic nevi, while there was no significant difference of Cul1 expression between primary and metastatic melanoma, which suggested that Cul1 plays an important role in the initiation stage of melanoma development. We found knockdown of Cul1 inhibited melanoma cell growth and overexpression of Cul1 promoted melanoma cell growth through regulating CDK inhibitor p27Kip expression. Knockdown of Cul1 abrogated Skp2-induced p27 degradation in melanoma cells. These results suggested that Cul1 is involved in cell cycle regulation of melanoma cells via Cul1-dependent ubiquitination and degradation of the p27kip1 by SCFSkp2 complex. In conclusion, our data indicate that Cul1 may serve as a potential marker for human melanoma initiation and early diagnosis. 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 1075.
Effect of Nitric Oxide on Renal Function in Septic Shock
Authors: P.H.P. Groeneveld, J. Ringers, J.T. van Dissel
Journal: New England Journal of Medicine (1994)

To the Editor: Nitric oxide is a central mediator in septic shock because of its ability to relax smooth-muscle cells in arterial walls1. High levels of nitrate, one of the metabolites of nitric oxide, can be found in the serum of hypotensive patients with sepsis2,3. Several important features of nitric oxide in septic shock are illustrated by the case of a liver-transplant recipient who had two episodes of septic shock due to gram-negative bacteria, during which we measured blood concentrations of endotoxin, cytokines, and metabolites of nitric oxide (Table 1). A bout of septicemia due to Escherichia . . .
Evaluating the Differential Effect of Diet on Rat Carcinogenesis
Authors: CLIFFORD W. WELSCH
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Evaluating the Differential Effect of Diet on Rat Carcinogenesis Get access CLIFFORD W. WELSCH CLIFFORD W. WELSCH Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 17, 4 September 1991, Pages 1262–1263, https://doi.org/10.1093/jnci/83.17.1262-a Published: 04 September 1991
Abstract 1328: p53 represses microRNAs let-7a and let-7b in response to ionizing radiation
Authors: Anthony D. Saleh, Jason E. Savage, David Ly, Phuongmai Nguyen, Lui Cao, Benjamin P. Soule, Tu D. Dan, William DeGraff, Toren Finkel, Curtis C. Harris, James B. Mitchel, David Gius, Nicole L. Simone
Journal: Cancer Research (2010)

Abstract Radiation-induced free radicals damage cells resulting in a stress response that involves large scale changes in gene expression including microRNAs (miRNA). Specifically, decreased expression of the let-7 family of miRNA has been reported. let-7 regulates cell cycle and DNA repair proteins such as Ras, cyclin D1, Rad 18 and Rad 51, which can all effect the radiation response. However, the precise role of the let-7 family and the mechanisms regulating this repression has not been elucidated. In this study, we demonstrate a mechanism underlying the let-7a3 and let-7b response to radiation exposure. Using real time RT-PCR we demonstrate that let-7a and b expression decreases by 80-90% in response to 0.5-10 Gy doses of IR in cultured HCT116 colon cancer cells. This effect is also observed by RT-PCR in response to other sources of geneotoxic stress such as etoposide or UV irradiation suggesting that a reduction in let-7 is common among DNA damaging events. We also show that this decrease in expression of let-7a and b is dependent on p53 as the decrease is absent in HCT116 p53 knockout cells. Further analysis of the effect of p53 on let-7a3 and b expression by CHIP showed an association of p53 with a predicted binding site in the host gene promoter. After treatment of mice with radiation a decrease in let-7a and b expression is observed in radio sensitive tissues. However no decrease was observed in tissues collected from p53 KO mice. Transfection of additional let-7a or let-7b into HCT116 cells decreased survival after radiation treatment, but survival is unchanged by increased let-7 in HCT116 p53 knockout cells. These results suggest that p53 can directly repress let-7 expression. Also, let-7 may play an important role in the regulation and fine-tuning of the p53 cell stress response to radiation. Furthermore, therapeutics aimed at inducing over expression of let-7 may be useful as radiation sensitizers. 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 1328.
P426 INTRAPORTAL INFUSION OF BONE MARROW MONONUCLEAR OR CD133+ CELLS IN PATIENTS WITH DECOMPENSATED CIRRHOSIS: A DOUBLE-BLIND RANDOMIZED PLACEBO-CONTROLLED CLINICAL TRIAL
Authors: M. Vosough, N. Aghdami, H. Baharvand, R. Malekzadeh, M. Mohammadnejad
Journal: Journal of Hepatology (2014)
902 DEVELOPMENT AND VALIDATION OF PREDICTION MODELS FOR RISK OF HEPATOCELLULAR CARCINOMA AMONG HEPATITIS C VIRUS INFECTED PATIENTS
Authors: M.-H. Lee, S.-N. Lu, H.-I. Yang, C.-L. Jen, S.-L. You, L.-Y. Wang, Y. Yuan, G. Litalien, C.-J. Chen
Journal: Journal of Hepatology (2012)
ABLACIÓN DE LESIONES QUISTICAS PANCREATICAS GUIADA POR ECOENDOSCOPIA (EE): RESULTADOS PRELIMINARES
Authors: C González Asanza, B Merino Rodríguez, Ó Nogales Rincón, A Hernando, L Hernández, J García Lledó, P Menchén Fernández Pacheco
Journal: Endoscopy (2013)

Introducción: El manejo de las lesiones quísticas pancreáticas (LQP) es controvertido. La cirugía es el tratamiento de elección en las sintomáticas y en las mucinosas dado su potencial de malignización. Dada la morbimortalidad quirúrgica se han planteado técnicas de ablación local guiadas por EE con resultados preliminares prometedores, si bien en grupos de pacientes muy heterogéneos. Objetivo: Analizar la eficacia y seguridad del tratamiento ablativo con alcohol en LQP de origen mucinoso o sintomáticas que tengan una contraindicación quirúrgica. Material y Método: Estudio piloto prospectivo. Objetivo principal: eficacia de la inyección de etanol 80% guiada por EE en LQP de menos de 4 cm, oligoloculados. Objetivos: secundarios: estudio de seguridad, recidiva a largo plazo y efectos histológicos. La eficacia se mide por un observador independiente mediante resonancia magnética nuclear a los 3 y a los 12 meses. Definimos respuesta completa (RC) a la desparición del quiste y parcial (RP) a la disminución de más de un 25% del tamaño inicial. La comunicación con el Wirsung es un criterio de exclusión. El estudio ha sido aprobado por el comité ético de nuestro hospital y los cirujanos participan directamente como servicio colaborador. Resultados: Desde mayo del 2012 han cumplido criterios de inclusión 5 pacientes (2 mujeres) con quistes mucinosos de tamaños entre 18 y 30 mm, 3 de ellos biloculados. Todos en cabeza pancreática. Se han realizado 7 sesiones en los 5 pacientes existiendo RC a los 3 meses en 3 pacientes y RP en 1 paciente, considerando a un paciente como fracaso de tratamiento. En el tiempo de seguimiento realizado no se han detectado recidivas. Como efectos secundarios: 1 episodio de pancreatitis leve y 2 hiperamilasemias asintomáticas. Conclusiones: En nuestra limitada experiencia la ablación con etanol parece una técnica segura con resultados prometedores, aunque habrá que esperar a la conclusión del estudio.
Abstract PD07-04: Predicting Outcome with Ki67 in Primary Breast Cancer in the Neoadjuvant Setting
Authors: SP Li, R Burcombe, MJ Beresford, DE Kornbrot, M-L Seah, PJ Ostler, GD Wilson, A. Makris
Journal: Cancer Research (2010)

Abstract Background: The proliferation antigen Ki67 has been shown to be a reliable predictive marker of treatment efficacy in the neoadjuvant treatment of breast cancer but its prognostic significance remains uncertain. This study assesses Ki67 before and after neoadjuvant chemotherapy (NAC) in relation to long-term outcome. Methods: 117 patients with primary breast cancer due to undergo NAC were studied (median age 48 years, range 25-78; T2-4, N0-3, M0) and information gathered from a prospectively maintained database. Immunohistochemically derived Ki67 expression was obtained from pretreatment core biopsy and surgical specimens. Their relationship to DFS and OS was analyzed along with known prognostic variables (age, ER/PR/HER2 status, clinical and pathologic T and N stage, grade), NAC regimen, response and adjuvant treatment. Survival curves were estimated using the Kaplan-Meier method and a log-rank test used to determine significance using a two-tailed p-value of 0.05. A multivariate Cox proportional hazards regression model performed in a stepwise fashion was used to determine the prognostic value of each signifcant variable. Results: 84 patients with matched biopsy and surgical samples were assessable for pre and post NAC Ki67 levels. The majority (90%) received anthracycline based NAC (median number of cycles 6, range 2-6). On univariate analysis, the only significant pretreatment predictive factor for shorter DFS was higher clinical nodal stage (cN) (P&amp;lt;0.001). Posttreatment variables that predicted for worse DFS were: Ki67 at surgery (HR 1.52, p=0.048), pathologic nodal stage (pN) (p=0.001) and grade (p=0.013). On multivariate analysis, pN was the most powerful predictor for DFS (chi-squared test 19.8, 3 df, P&amp;lt;0.001). Univariate analysis of pretherapy factors for OS revealed that Ki67 at biopsy (HR 2.06, p=0.039), cN (HR 4.44, P&amp;lt;0.001) and PR positivity (HR 0.41, p=0.012) were significant. Significant posttreatment variables for OS were Ki67 at surgery (HR 2.01, p=0.006), pN (p=0.001), and grade (p=0.009). PR status and pN remained important predictors of OS on multivariate analyses. Conclusions: The expression of Ki67 is a widely accepted marker of cellular proliferation in breast cancer. Ki67 levels after NAC were a better predictor for long-term outcome than pretherapy Ki67, although nodal status appears to be the most powerful determinant overall. High Ki67 levels post NAC may identify patients with poorer outcomes who are candidates for further systemic therapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD07-04.