tbuckley/cabot-search huggingface dataset:
Chemotherapy with FOLFOX IV in advanced gastric cancer
Authors: M. A. Garrido., G. Melgoza, H. Galindo, J. Madrid, C. Sanchez, M. G. Alvarez, E. Orellana
Journal: Journal of Clinical Oncology (2006)

14112 Background: Gastric cancer is the first cause of mortality for cancer in Chile. 65% is observed in advanced form and the median survival without surgery is 5,4 months. We hypothesised that chemotherapy and specially FOLFOX IV is an active regimen and has low toxicity in patient with advanced gastric cancer. The main evaluated objectives were: response, toxicity and survival of patient with advanced gastric cancer. Methods: Patients with gastric adenocarcinoma, stage IV that accepted chemotherapy with FOLFOX IV in any time of evolution were included. The evaluation of response was obtained with CT scan every two month. The characteristics of patients, chemotherapy responses, toxicity and global survival were analysed. Results: Between November 2003 and October 2005, 20 patients were included, the median age was 51,5 years (range 28–67), 80% male. Hepatic, peritoneal and lung metastases were the principal places of dissemination. The response rate in first line was: PR 66%, SD 17%, with overall response of 83% (12 patients). In second line the response was: PR 37%, SD 63% (8 patients). The average of treatment was 5,5 months. The median of response was 5 months (2–12). The median overall survival was 12 months. 50% of patients showed toxicity; digestive grade 2 in 2 patients, neurological grade 2 in 4 patients and only 1 patient showed grade 3 toxicity. Conclusions: FOLFOX IV is an active chemotherapy regiment with low toxicity profile in advanced gastric cancer. With these results we propose a Phase III trial would be feasible to perform. No significant financial relationships to disclose.
Changes in Pepsinogen lsozymes in Stomach Cancers Induced in Wistar Rats by N -Methyl- N ′-nitro- N -nitrosoguanidine and in Transplantable Gastric Carcinoma (SG2B) 2
Authors: Masae Tatematsu, Chie Furihata, Masao Hirose, Tomoyuki Shirai, Nobuyuki Ito, Yoko Nakajima, Takashi Sugimura
Journal: JNCI Journal of the National Cancer Institute (1977)

With the use of Wistar rats, changes in pepsinogen (Pg) isozymes, separated by polyacrylamide gel electrophoresis, were studied in 30 well-differentiated adenocarcinomas and 2 adenomas induced by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), 2 transplantable well-differentiated adenocarcinomas induced by MNNG and 4-nitroquinoline-1-oxide, and 21 nonneoplastic gastric mucosae Irritated by acetyl salicylic acid (ASA). The Pg content was significantly decreased in the gastric adenocarcinomas and adenomas; Pg 1, the fastest moving of the 3 Pg isozymes normally present in the pyloric mucosa, was greatly reduced or not detectable in 28 well-differentiated adenocarcinomas and 2 adenomas in the pylorus. Pg 1 was also not detectable in 2 transplanted well-differentiated adenocarcinomas originally induced in the pylorus and transplanted sc into the backs of newborn rats. Two (Pg 1, 2) of the 4 isozymes of Pg (Pg 1–4) in the fundic mucosa were also decreased or absent in 2 well-differentiated fundic adenocarcinomas; these adenocarcinomas gave the same electrophoretic patterns as did those of well-differentiated pyloric adenocarcinomas. No changes in Pg were found in fundic and pyloric mucosa irritated by ASA. Histochemically and ultrastructurally, adenocarcinomas and adenomas consisted of mixtures of the following three types of cells: cells resembling gastric pit mucous cells, pyloric gland cells, and cells without mucus. Tumors mainly consisting of pyloric glandlike cells showed the least decrease in Pg content, whereas those consisting of cells like gastric pit mucous cells and cells without mucus showed the greatest decrease in Pg content.
Intraoperative marking of a small pulmonary nodule with the multi-axis angiography system
Authors: Masahiro Mitsuoka, Yusuke Okamoto, Tohru Sakuragi, Yuji Takeda, Shigeki Morita
Journal: European Respiratory Journal (2012)

INTRODUCTION: Often cases are difficult to identify the localization of small pulmonary nodule during operation, preoperative CT guided marking have been described. However, there were some problems including air embolism, pneumothoracs or detection ratio. Now, we used Artis zeego (Siemens co ltd, Germany) which drew up a CT-like image during operation to determine the localization of the tumors for some cases. This is the first report of intraoperative marking using the Artis zeego. MATERIAL:Artis zeego is the first multi-axis angiography system based on robotic technology that can be positioned the way a physician wants. It can be controlled with far greater ease and precision than conventional C-arm system. METHODS: The patient was fixed lateral position under general anesthesia, and was sterilize and draped on the operation table. After marking to the pleura where was predicted the nearest portion from the nodule with a clip under the VATS view, Artis zeego was entered and provide a CT-like image. After Artis zeego was disconnected from the patient, the excision region was determined by the image. RESULTS: Four patients, five small pulmonary nodules were performed this procedure. All regions were successfully detected by the image and removed completely. Since this system did not provide to detect pulmonary regions, there were some problems including narrowing of the bed for lateral position, the little device, the elbow or equipments were easy to strike on the machine when rotation. CONCLUSIONS: This procedure could be an extremely useful and safety method for intraoperative marking a small pulmonary nodule. We also need to resolve some problems of this procedure such as the devices.
Phase IV study of first-line bevacizumab plus irinotecan and infusional 5-FU/LV in patients with metastatic colorectal cancer: AVIRI
Authors: A. F. Sobrero, S. Young, M. Balcewicz, S. Chiarra, R. Perez Carrion, P. Mainwaring, J. Gapski, S. Clarke, B. Langer, S. Ackland
Journal: Journal of Clinical Oncology (2007)

4068 Background: Bevacizumab (BEV) is a monoclonal antibody that inhibits tumour angiogenesis by targeting VEGF. In a phase III trial (AVF2107g), BEV significantly improved overall (OS) and progression-free survival (PFS) when combined with first-line irinotecan plus bolus 5-fluorouracil (5-FU)/leucovorin (LV) (IFL) in patients with metastatic colorectal cancer (mCRC). A multicentre, open-label trial is being conducted to evaluate the efficacy and safety of first-line BEV in combination with irinotecan and infusional 5-FU (FOLFIRI), a widely used first-line chemotherapy (CT) regimen. Methods: Patients had to have: mCRC; no surgery within 28 days; no prior CT for metastatic disease; ECOG PS 0/1, adequate organ function; no CNS metastases. CT consisted of a minimum of six cycles of irinotecan plus infusional 5-FU/LV according to the classical FOLFIRI regimen; variations like the simplified FOLFIRI and the weekly regimen were also allowed. BEV 5mg/kg was given on day 1 with CT and then every 2 weeks until disease progression. Tumour assessments were performed every 3 months during the first 12 months and every 4 months thereafter. Safety was assessed at the time of CT administration and every 4 weeks thereafter. The primary objective was PFS; secondary objectives included safety, overall response rate, time to response, duration of response and OS. Results: A total of 209 patients were enrolled at 31 centres worldwide, between April and November 2005. An interim analysis showed that the safety profile of BEV plus FOLFIRI appeared to be similar to that reported for Avastin plus IFL. The 44% overall response rate and 90% disease control rate are at least equivalent to that reported in comparable trials. Additionally, the 6 months PFS estimate of 82% was superior to that reported in AVF2107. Mature PFS data will be presented. Conclusions: AVIRI is the largest clinical trial, to date, to report data for BEV in combination with FOLFIRI in first-line patients with mCRC. The safety profile appears consistent with that observed in other BEV trials in mCRC, while the preliminary efficacy data suggest that this regimen is as active as the bolus regimen. No significant financial relationships to disclose.
Bacterial infection causes stress-induced memory dysfunction in mice
Authors: M. G. Gareau, E. Wine, D. M. Rodrigues, J. H. Cho, M. T. Whary, D. J. Philpott, G. MacQueen, P. M. Sherman
Journal: Gut (2010)

The brain-gut axis is a key regulator of normal intestinal physiology; for example, psychological stress is linked to altered gut barrier function, development of food allergies and changes in behaviour. Whether intestinal events, such as enteric bacterial infections and bacterial colonisation, exert a reciprocal effect on stress-associated behaviour is not well established.To determine the effects of either acute enteric infection or absence of gut microbiota on behaviour, including anxiety and non-spatial memory formation.Behaviour was assessed following infection with the non-invasive enteric pathogen, Citrobacter rodentium in both C57BL/6 mice and germ-free Swiss-Webster mice, in the presence or absence of acute water avoidance stress. Whether daily treatment with probiotics normalised behaviour was assessed, and potential mechanisms of action evaluated.No behavioural abnormalities were observed, either at the height of infection (10 days) or following bacterial clearance (30 days), in C rodentium-infected C57BL/6 mice. When infected mice were exposed to acute stress, however, memory dysfunction was apparent after infection (10 days and 30 days). Memory dysfunction was prevented by daily treatment of infected mice with probiotics. Memory was impaired in germ-free mice, with or without exposure to stress, in contrast to conventionally reared, control Swiss-Webster mice with an intact intestinal microbiota.The intestinal microbiota influences the ability to form memory. Memory dysfunction occurs in infected mice exposed to acute stress, while in the germ-free setting memory is altered at baseline.
Feline Oncornavirus-Associated Cell Membrane Antigen. II. Antibody Titers in Healthy Cats From Household and Laboratory Colony Environments&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: M Essex, S M Cotter, J L Carpenter, W D Hardy, P Hess, W Jarrett, J Schaller, D S Yohn
Journal: JNCI Journal of the National Cancer Institute (1975)

Antibody titers to the feline oncornavirusassociated cell membrane antigen (FOCMA) were determined for 447 healthy cats from laboratory colony and household environments. Only 2.7 percent of 221 cats from colony environments were antibody positive as compared to 50.4 percent of 256 cats from household environments. Incidence of FOCMA antibody and geometric mean antibody titer for pet cats from New York City representing single cat apartment habitats were substantially lower than values for unscreened cats from the Boston, Glasgow, and Detroit suburban environments. Geometric mean antibody titer for young adults in the Boston population was significantly higher than titers for kittens or aged cats. This may be due to greater mobility resulting in increased exposure to other cats. In contrast to the high frequency of FOCMA antibody positivity in pet-cat populations, less than 2 percent of the same groups were positive for virus group-specific antigen in peripheral blood leukocytes and platelets. This was interpreted as an indication that many more cats became infected with feline leukemia virus under natural conditions that the number developing persistent virus infection and/or clinical leukemia.
Incapacitated and Surrogateless Patients: Decision Making for the Surrogateless Patient: An Attempt to Improve Decision Making
Authors: David L. Williamson, Jason Lesandrini, Jinu Kamdar
Journal: The American Journal of Bioethics (2016)

Incapacitated and surrogateless patients are an ever-growing trend in the world of health care. Although the extent of the issue is unknown, 1 out 20 deaths in the intensive care unit (ICU) occurre...
Atrial remodelling in atrial fibrillation: CaMKII as a nodal proarrhythmic signal
Authors: Olurotimi O. Mesubi, Mark E. Anderson
Journal: Cardiovascular Research (2016)

CaMKII is a serine–threonine protein kinase that is abundant in myocardium. Emergent evidence suggests that CaMKII may play an important role in promoting atrial fibrillation (AF) by targeting a diverse array of proteins involved in membrane excitability, cell survival, calcium homeostasis, matrix remodelling, inflammation, and metabolism. Furthermore, CaMKII inhibition appears to protect against AF in animal models and correct proarrhythmic, defective intracellular Ca2+ homeostasis in fibrillating human atrial cells. This review considers current concepts and evidence from animal and human studies on the role of CaMKII in AF.
Accuracy of sentinel node biopsy after neoadjuvant chemotherapy in breast cancer patients.
Authors: M. Ito, S. Ohtani, K. Higaki
Journal: Journal of Clinical Oncology (2010)

e11021 Background: Sentinel node biopsy (SLN) in early breast cancer is widely used. However, about SLN after neoadjuvant chemotherapy (NAC), we don't have the consensus yet. NAC is increasingly used to downstage patients with progress breast cancer. This study was performed to evaluate the accuracy of SLN after NAC. Methods: A total of 1,436 patients with clinical lymph node negative breast cancer underwent SLN from 1999 to 2008. 242 patients with invasive breast cancer underwent SLN after NAC. The SLN was identified by the combined method that used the 99mTc-phytate and Indigocarmine. Results: After NAC, pathological complete response rate was 16.2%. Lymph node metastasis disappeared to 53.8% of the case that showed clear lymph node metastasis before NAC. In the NAC group the SLN identification rate, false-negative rate were 86.9%, 3.4%. In the non-NAC group its identification rate, false-negative rate were 94.9%, 3.2%. When we did not show clear lymph node metastasis before NAC, the SLN had never the false negative. When the SLN couldn't be identified, lymph node metastasis rate was 39.0% in NAC group. it was 25.8% in non-NAC group. Conclusions: For clinical lymph node negative before NAC, the SLN can be use safely and precisely. When the SLN cannot be identified, careful axillary dissection is necessary. No significant financial relationships to disclose.
Abstract 18002: S-adenosylhomocysteine Levels May Better Differentiate Between Normal Control, Subjects With Ckd Stages 3 and 4, and Subjects on Hemodialysis
Authors: Teodoro Bottiglieri, Matthew Williams, Erland Arning, Giovanni Filardo, Andrew Z Fenves, Cara East
Journal: Circulation (2013)

Patients on hemodialysis have higher levels of plasma total homocysteine (tHcy) and are at higher risk for atherosclerotic cardiovascular and vascular events, including death. However, secondary prevention trials to date have not shown any reduction in recurrent atherosclerotic events with B vitamin supplementation that lowers tHcy levels. Because high tHcy levels are still a good predictor of CV events, we investigated whether other metabolites related to tHcy metabolism and the methylation cycle may be altered in subjects at various stages of chronic kidney disease. Methods: We measured 6 intermediates of the methylation cycle in plasma using liquid chromatography mass spectroscopy: tHcy, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), cystathionine, asymmetric dimethylarginine (ADMA), and symmetric dimethylargine (SDMA). Subjects included 92 subjects enrolled in longitudinal studies of healthy aging and dementia (Controls), 21 subjects with chronic kidney disease stages 3 and 4 (CKD), and 25 subjects on hemodialysis (Dialysis). All samples were collected between 2004 and 2012. Results: T-test analysis (corrected for multiplicity using Bonferoni correction) results show that all 6 metabolites were statistically significantly higher (p-values &lt;0.05) in the CKD subjects than the Controls, and again statistically significantly higher (p-values &lt;0.05) in Dialysis subjects than in CKD subjects (see Figure). While ADMA may be an independent risk factor for CAD, both tHcy and SAH levels were the most discriminatory: tHcy levels were 2.8 fold higher in CKD and 4 fold higher in Dialysis; SAH levels were 2.9 fold higher in CKD and 8.7 fold higher in Dialysis. Conclusion: SAH is a potent inhibitor of methylation reactions and has been implicated in causing vascular pathology. Elevated levels of SAH in plasma may provide greater discrimination in assessing risk of vascular disease in patients with chronic kidney disease.
Substituting doxorubicin with nonpegylated liposomal doxorubicin (NPLD) in adjuvant/primary chemotherapy for early breast cancer, impact in cardiac function: A pilot study.
Authors: N. Davidson, A. Chalkidou, D. Houghton
Journal: Journal of Clinical Oncology (2010)

616 Background: NPLD (Myocet, Cephalon UK Ltd) is effective for the treatment of metastatic breast cancer and is less cardiotoxic than doxorubicin. However, there are currently limited data for NPLD in early breast cancer, where it may be particularly beneficial, as cardiotoxicity may be treatment-limiting and is a key survivorship issue. Methods: Consecutive patients with early breast cancer treated with NPLD substituting for doxorubicin were studied to evaluate change in cardiac function. Echocardiogram results and details of other treatments and disease progression were assessed. Results: 80 patients (median age 54 (33-77) years) were studied, with most receiving NPLD adjuvantly (76%; primary 24%) in sequence with a taxane (AC+T 73%; AC 8%; TAC 19%). 83% had radiotherapy and 16% received trastuzumab. The 48 evaluable patients had mean left ventricular ejection fraction (LVEF) values within the normal range (>50%) at baseline (64%), during chemotherapy (65%), < 4 months (63%) and >12 months (63%) after chemotherapy. There was no significant change in cardiac function whether NPLD was given as primary or adjuvant therapy, at baseline (65% vs. 64%), during (65% vs. 65%) or < 4 months after therapy (60% vs. 64%). No difference in cardiac function was observed when categorised by chemotherapy regimen at baseline (AC: 63%; AC+T: 63%; TAC: 67%), during (AC: 64%; AC+T: 65%; TAC: 67%) or < 4 after therapy (AC: no data; AC+T: 63%; TAC: 63%). There was also no difference in cardiac function between patients who did and did not receive trastuzumab at baseline (65% vs. 64%), during (64% vs. 66%), or < 4 months after therapy (65% vs. 62%). Results for age > 60 vs. < 60 years were also similar (baseline 67% vs. 63%; during 67% vs. 65%; or < 4 months after 64% vs. 63%). 8 (10%) of the 80 patients experienced disease recurrence/progression and 2 (3%) died. Conclusions: NPLD appears to have good cardiac tolerability and be efficacious in early breast cancer. Larger, longer-term studies are required to confirm these promising results to protect cardiac function, particularly when breast cancer patients are living longer with multiple lines of treatment for metastatic cancer. No significant financial relationships to disclose.
Circulating Antigen-Antibody Complex Associated With Epstein-Barr Virus in Recurrent Burkitt's Lymphoma2
Authors: Tatsu Mukojima, Peter Gunvén, George Klein
Journal: JNCI Journal of the National Cancer Institute (1973)

Four years after initial diagnosis and treatment, the sera from a patient with recurrent Burkitt's lymphoma showed a sudden decrease of antibodies to Epstein-Barr virus (EBV)-associated membrane antigens (MA). This decrease occurred several months before the recurrent tumor became cllnlcally apparent. Simultaneously, the sera developed a high anticomplementary activity (ACA). The ACA was associated with the globulin fraction as demonstrated by ammonium sulfate precipitation. Low pH treatment of the globulin of one serum and Amicon filtration restored anti-MA reactivity to the fraction retained above the filter (molecules >105 Daltons). These data seem to indicate that MA-antibody complexes were present in the patient's serum.
ADAMTS-4 promotes neurodegeneration in a mouse model of amyotrophic lateral sclerosis
Authors: Sighild Lemarchant, Yuriy Pomeshchik, Iurii Kidin, Virve Kärkkäinen, Piia Valonen, Sarka Lehtonen, Gundars Goldsteins, Tarja Malm, Katja Kanninen, Jari Koistinaho
Journal: Molecular Neurodegeneration (2016)

A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) proteoglycanases are specialized in the degradation of chondroitin sulfate proteoglycans and participate in mechanisms mediating neuroplasticity. Despite the beneficial effect of ADAMTS-4 on neurorepair after spinal cord injury, the functions of ADAMTS proteoglycanases in other CNS disease states have not been studied. Therefore, we investigated the expression, effects and associated mechanisms of ADAMTS-4 during amyotrophic lateral sclerosis (ALS) in the SOD1G93A mouse model. ADAMTS-4 expression and activity were reduced in the spinal cord of SOD1G93A mice at disease end-stage when compared to WT littermates. To counteract the loss of ADAMTS-4, SOD1G93A and WT mice were treated with saline or a recombinant ADAMTS-4 before symptom onset. Administration of ADAMTS-4 worsened the prognosis of SOD1G93A mice by accelerating clinical signs of neuromuscular dysfunctions. The worsened prognosis of ADAMTS-4-treated SOD1G93A mice was accompanied by increased degradation of perineuronal nets enwrapping motoneurons and increased motoneuron degeneration in the lumbar spinal cord. Motoneurons of ADAMTS-4-treated SOD1G93A mice were more vulnerable to degeneration most likely due to the loss of their extracellular matrix envelopes. The decrease of neurotrophic factor production induced by ADAMTS-4 in vitro and in vivo may also contribute to a hostile environment for motoneuron especially when devoid of a net. This study suggests that the reduction of ADAMTS-4 activity during the progression of ALS pathology may be an adaptive change to mitigate its neurodegenerative impact in CNS tissues. Therapies compensating the compromized ADAMTS-4 activity are likely not promising approaches for treating ALS.