tbuckley/cabot-search huggingface dataset:
<i>p53</i> and its influence in adenocarcinoma stomach
Authors: C. M. Servarayan, A. Chandramohan, D. Datta, K. Manickavasagam
Journal: Journal of Clinical Oncology (2009)

e15685 Background: Gastric cancer is the second most common cause of the malignancy in the world after lung cancer. Various pathogenesis have been given for the adenocarcinoma, like mutation in the E-catherin gene, amplification of COX-2, HGF/ SF, VEGF; deletion of FHIT, APC, p53 but none have provided a definite target for treatment. Methods: This is a immunohistochemical prospective experiment study done on 76 cases of Gastric Adenocarcinoma.The location of the tumors were recorded as in the proximal stomach (fundus and body) and distal stomach (antrum, prepylorus, and pylorus). PAb1801 clonewas obtained from the ZYMED LABORATRIES, San Franscisco. A standardised immunohistochemical method was followed in this study. Results: p53 mutations were seen 41 out of 76 cases(53.95%). And 23 out of 41(56.09%) cases of p53 expression of the total mutated cases expressed p53 100%. 20 out of 36 cases (55.55%) of age below 60 yrs and 21 out of 40 cases (52.55%) of age above 60 yrs were p53 positive. 33 out of 60 (55%)of the males and 8 out of 16 (50%) females were reported of having gastric adenocarcinoma with p53expression. The histology of the tissue samples from the gastric adenocarcinoma patients had following relationship with the p53 immunoreactivity, 20 out of 37 cases(54.05%) of the well differentiated,7 out of 17 cases (41.18% )of the moderately differentiated, and and 13 out of 21 cases(61.90%) of the poorly differentiated gastric adenocarcinoma showed positive immunoreactivity. 15 out of 33 cases (45.45%)were localized to the proximal stomach and 30 out of 52 cases (57.69%)were localized to the distal stomach. 52.63 % of the non-mucinous type of gastric adenocarcinoma showed positive p53 immunoreactivity. Conclusions: The TP53 mutation is slightly more common in males than females, with greater occurrence in the late years of life. The mutation is more marked in the poorly differentiated gastric adenocarcinoma. The antral, pylorus,and the prepyloric parts of the stomach( the distal stomach) are more prone for mutated p53 induced adenocarcinoma. No significant financial relationships to disclose.
Prevention of Spontaneous Tumors of Aged Mice by Immunopharmacologic Manipulation: Study of Immune Antitumor Mechanisms2
Authors: Martine Bruley-Rosset, Thierry Hercend, Jean Martinez, Henry Rappaport, Georges Mathé
Journal: JNCI Journal of the National Cancer Institute (1981)

Effects produced by long-term application of three immune modifiers (azimexon, retinoic acid, and tuftsin) on the depressed immune systems of 18-month-old inbred C57BU6 female mice were investigated. The effect of each agent was examined on four cell types (cytotoxic T-cells, K-cells, NK cells, and macrophages) possibly involved in antitumor defenses and on the spontaneous tumor development that accompanied advancing age. Three substances chosen for this study appeared able to alter immune parameters, and each one displayed its own pattern of activity. Common to all three agents were an increase of age-depressed tumoricidal activity of peritoneal macrophages and no effect on the depressed NK activity of spleen cells. Retinoic acid increased splenic K-cell activity, already elevated in aged mice and unaffected by the other two agents. Cytotoxic Tcell activity, diminished by age, was stimulated considerably by retinoic acid and by tuftsin but only slightly by azimexon. Histopathologic studies revealed a decrease in the incidence of spontaneous tumors in the 3 treated groups. This decrease was statistically significant in the retinoic acid- and tuftsin-treated groups when compared with the incidence in untreated mice of the same age. Correlation of drug-induced modifications of the immune system with tumor incidence in aged mice was attempted.
Induction Chemotherapy with Docetaxel, Cisplatin and Fluorouracil (Tpf) in Locally Advanced Head and Neck Cancer–Single Center Retrospective Analysis
Authors: M. Cassiano Neves, A. Rosinha, J. Magalhaes, A.F.M.F. Castro, C.M.P. Vieira, I. Azevedo, J.D. Silva
Journal: Annals of Oncology (2014)
Problem behaviors and peer interactions of young children with a manic- depressive parent
Authors: C Zahn-Waxler, D H McKnew, E M Cummings, Y B Davenport, M Radke-Yarrow
Journal: American Journal of Psychiatry (1984)

By the age of 2 years, children with a manic-depressive parent were already found to be experiencing substantial psychiatric problems. The authors examined the ways in which these early problems then become embedded in social relationships. Naturalistic observations and experimental manipulations of the emotional environment were used to measure 2-year-old children's regulation of emotion, aggression, and altruism during peer interactions. Children with a manic-depressive parent had difficulty in sharing with their friends and in handling hostility, showing maladaptive patterns of aggression. The social and emotional problems of these children were similar to the interpersonal problems of their manic-depressive parents.
P0521 : Characterization and validation of angiogenic genetic variants related to chronic hepatitis C progression to hepatocellular carcinoma
Authors: R. López-Rodríguez, M.J. Borque-Iñurrita, Á. Hernández-Bartolomé, Y. Rodríguez-Muñoz, J.R. Vidal-Castiñeira, L. Rodrigo, J. García-Samaniego, A. Madejón, F. Abad-Santos, J.M. Ladero, P. Muñoz de Rueda, J. Salmerón, A. Martín-Algíbez, A. Aransay, L. García-Buey, J. Mendoza, Y. Real, L. González-Moreno, R. Moreno-Otero, P. Sanz-Cameno
Journal: Journal of Hepatology (2015)
OC-031 Rectogismoid biopsies are sufficient to confirm intestinal involvement in symptomatic patients with acute or chronic graft versus host disease: a retrospective observational study
Authors: P Pavlidis, L Floro, K Raj, D McLornan, H DeLavallade, T Pagliuca, V Potter, G Mufti, B Hayee
Journal: Gut (2015)

<h3>Introduction</h3> Intestinal Graft versus host disease (iGvHD) is a common complication of haematopoetic stem cell transplantation (HSCT) associated with significant morbidity and mortality. Gastroenterologists are frequently consulted to assist with the diagnosis which is based on histological findings. Endoscopic evaluation practice varies between units with some favouring symptom guided investigations and others advocating lower gi endoscopy with rectosigmoid biopsies as the approach with the highest sensitivity. In this study we describe the diagnostic efficacy of upper versus lower gi endoscopy (and biopsy sampling) in supporting the diagnosis of iGvHD. <h3>Method</h3> Post HSCT patients with symptoms suggestive of iGvHD who underwent simultaneous upper and lower gi endoscopy in one centre over the last 3 years were identified through prospectively kept electronic patient records. All of them had biopsies taken during procedure from relevant areas (duodenum, terminal ileum, right colon, L colon/rectosimgoid). Continuous variables are presented as medians followed by interquartile range. Categorical comparisons were performed using chi-square test. Predictive values are followed by 95% confidence intervals. <h3>Results</h3> We identified 32 eligible patients [median age: 50 (33, 60), female: male ratio 1:1). Presenting gi symptoms included diarrhoea: 29/32 (88%), anorexia/ weight loss: 14/32 (44%), nausea/vomiting: 11/32 (34%), abdominal pain/ bloating: 4/32 (13%), rectal bleeding: 3/32 (10%). The median time post HSCT was 107 (55, 178) with 15 patients presenting in &lt;100 and 17 in &gt;100 days post liver transplantation. There were 8/15 (53%) patients diagnosed with acute GvHD and 10/17 (59%) with chronic GvHD affecting the gut. There was no difference in the gi segments involved in acute and chronic forms of iGvHD, with 18/18 patients having left colon/rectosigmoid, 14/18 (77%) right colon, 8/18 (44%) terminal ileal and 3/18 (16%) duodenal involvement. Duodenal biopsies were positive in only 3/8 (38%) patients with small bowel involvement based on a positive terminal ileal biopsy. The negative predictive value of duodenal biopsies for the diagnosis of iGvHD was 68% (53, 81). <h3>Conclusion</h3> iGvHD in either acute or chronic form appears to always affect the rectosigmoid/ left colon. A flexible sigmoidoscopy with biopsies should suffice to rule in or out the diagnosis. Duodenal biopsies do not appear to provide any additional diagnostic benefit in the context of iGvHD investigation. <h3>Disclosure of interest</h3> None Declared.
Liposomal cisplatin and paclitaxel versus cisplatin and paclitaxel in advanced NSCLC
Authors: G. P. Stathopoulos, P. Michalopoulou, D. Antoniou, J. Dimitroulis, P. Giamboudakis, K. Marosis, J. Stathopoulos, G. Tsoukalas, T. Grigoratou
Journal: Journal of Clinical Oncology (2007)

7684 Background: A new liposomal formulation of Cisplatin has been tested in a phase I and phase II trial in advanced solid tumors as a single agent or in combination with Gemcitabine or paclitaxel. It is a non-myelotoxic and non-nephrotoxic agent. Effectiveness has been shown, in particular when it is combined with a second agent. Objectives, comparison of toxicity, efficacy of liposomal cisplatin (lipoplatin) versus cisplatin both combined with paclitaxel for non-small cell lung cancer patients. It is a preliminary report of the study which is on-going. Methods: From April 2006 till December 2006, 61 patients were recruited. 54 are evaluable for response and toxicity. Were all untreated. Median age 65 (42–80). They were randomized in two arms A and B. Arm A patients -27- were treated with lipoplatin-paclitaxel and Arm B patients -27- with cisplatin-paclitaxel. Arm A: 24 male, 3 female, histology: 10 squamous, 10 adenocarcinomas, 7 undifferentiated. Stage: IIIa 4 patients, IIIb 11 pat., IV 12 pat. Arm B: 25 males, 2 female, histology: 11 squamous, 11 adenocarcinomas, 5 undifferentiated, stage IIIa 2 pat., IIIb 14 pat., IV 11 pat. Arm A Chemotherapy: Lipoplatin 200 mg/m 2 Paclitaxel 135 mg/m 2 administered on day 1 repeated every 2 weeks. Lipoplatin infused for 8 hours in 5% dextrose 1 lt. Arm B: cisplatin 75 mg/m 2 (hydration of 2 lt) and paclitaxel 135 mg/m 2 , every two weeks. Each day treatment was 1 cycle and the plan was to give 9 cycles per patient unless disease progression was detected before 9th cycle. Results: Response: Arm A: PR: 48.15% SD: 37.03% PD: 3.7% and clinical benefit 11.11%. Arm B: PR 44.44% SD 44.44% PD: 3.7% and clinical benefit 7.41%. Toxicity: Arm A: Renal toxicity in 1 pat. (3.70%) neurotoxicity grade I-II in 7 pat. (25.92%) Nausea-vomit in 5 patients (18.52%) Myelotoxicity Grade I-II in 10 pat. (37.04%). Arm B: Renal toxicity in 7 pat. (25.92%), Neurotoxicity Grade I-III in 12 pat. (44.44%) Nausea-vomit in 7 pat. (25.92%) Myelotoxicity Grade I-III in 17 pat. (62.96%). Conclusions: Preliminary results showed liposomal cisplatin compared with cisplatin each one combined with paclitaxel, the response rate was similar but toxicity and in particular nephrotoxicity, neurotoxicity, and myelotoxicity was significantly lower in liposomal cisplatin arm. No significant financial relationships to disclose.
Gaythorne Derrick Teague
Authors: Paul Main, Joy Main
Journal: BMJ (2016)

Gaythorne Derrick Teague was born in Bedminster, Bristol, and grew up in a working class family. He was proud of his roots and always referred to himself as a Bedminster boy. He attended Luckwell School and the former South Central School before securing a place at Cotham Grammar School. He turned down the opportunity to go to Oxford University because his parents could not afford to send him away from home. Instead he read medicine at Bristol University. He once said that the death of his younger brother from blood poisoning in Bristol General Hospital in 1936, before antibiotics were available, had a lot to do with his interest in medicine. He recalled, as a medical student during the second world war, being on duty on the roofs of various civic buildings in Bristol, with the remit of dealing with incendiary bombs during the blitz. As a young man he served as a leader in the 171 Bedminster scout troop and helped to run an Anglican youth group.

He initially joined Dr Pollard, who practised on Coronation Road, the “Harley …
Activation of CD8+ tumor infiltrating lymphocytes by bavituximab in a 3D ex vivo system of lung cancer patients.
Authors: Soner Altiok, Melanie Mediavilla Valera, Jenny Kreahling, David Noyes, Tiffany N Razabdouski, Nikoletta L. Kallinteris, Joseph Shan, Scott Joseph Antonia
Journal: Journal of Clinical Oncology (2015)

3060 Background: Bavituximab is a chimeric monoclonal antibody that targets the membrane phospholipid phosphatidylserine (PS) exposed on endothelial cells and cancer cells in solid tumors. Bavituximab blocks PS-mediated immune suppression in the tumor microenvironment. Methods: Fresh tumor tissues from consented patients with adenocarcinoma of the lung extracted at the time of surgical resection were utilized in a proprietary 3D ex vivo tumor miscrosphere assay to assess the immunomodulatory effects of bavituximab and potential immunosuppressive mechanisms such as expression of PD-1, CTLA-4, LAG3, TIM3, BTLA, and adenosine A2A receptor on the CD4+ and CD8+ tumor infiltrating T-cells. 3D tumor microspheres were prepared and cells were treated ex vivo with f(ab)’2version of bavituximab, bavituximab, docetaxel, and a combination of bavituximab and docetaxel for 36 hours within an intact tumor microenvironment. Flow cytometry analysis evaluated treatment-mediated activation of TILs and changes in CD4, CD8 and Treg (CD25+/CD127-) subpopulations. A multiplex human cytokine assay was used to simultaneously analyze the differential secretion of cytokines. Additionally, a NanoString platform containing probes to quantitate 770 immune function genes was used to determine potential positive or negative associations between expression of immune function genes and TIL activation by bavituximab. Results: Bavituximab induces activation of TILs in 3D ex vivo tumor microsphere model of lung cancer, as evaluated by a significant increase in IFNgamma, TNF-a, and GM-CSF secretion. Flow cytometry analysis revealed that this effect was associated with low PD-1 expression on CD8 cells, but did not correlate with expression of other immune inhibitory molecules. Conclusions: Our preliminary data support the use of bavituximab as an immunomodulatory treatment in adenocarcinoma of the lung by enhancing the activation of CD8+ TIL that correlates with increased cytokine production by lymphoid and myeloid cells. We identified PD-1 expression as a potential biomarker of response to bavituximab treatment, suggesting that the interruption of the PD-1/PD-L1 axis may enhance the bavituximab effect in lung cancer.
Evaluation of Ki-67 measured in benign breast tissue acquired from premenopausal women treated with a flaxseed derivative
Authors: C. J. Fabian, Q. J. Khan, P. Sharma, S. Baxa, T. Metheny, C. M. Zalles, B. F. Kimler
Journal: Journal of Clinical Oncology (2009)

1507 Background: The lignans enterolactone and enterodiol are derived from the action of gut bacteria on ingested secoisolariciresinol diglycoside (SDG) which is commonly found in flaxseed. Enterolactone and enterodiol are thought to impair mammary carcinogenesis via reduction in aromatase activity and the mid-cycle surge of luteinizing hormone. We assessed the modulatory activity of 1 year of SDG on a number of risk biomarkers for breast cancer in a prospective phase II pilot study. We report the effect of SDG on the primary endpoint, proliferation in benign breast tissue as measured by Ki-67 immunocytochemistry, in the first 35 women completing study. Methods: Premenopausal women age 21 to 55 at increased risk for breast cancer underwent a baseline random periareolar fine needle aspiration (RPFNA) between the first and tenth days of their menstrual cycle. Those with RPFNA evidence of hyperplasia and Ki-67 greater than or equal to 2% were invited to participate. Women taking flaxseed or oral contraceptives were ineligible. All women took one Brevail (lignan research) capsule containing 50 mg of SDG daily. Ki-67 staining was performed with DAKO M7240 antibody on hematoxylin counterstained slides and the number of cells staining positive in 500 cells within hyperplastic clusters was counted. Results: Forty-nine women were enrolled on study between February 2006 and June 2008. Of these, four stopped prematurely, 10 women have not completed, and 35 have completed study and undergone follow-up RPFNA. Baseline characteristics of the 35 women completing study are as follows: median age 44 (range 29–50), median baseline 5-year Gail model risk 1.6% (range 0.1%-5.7%), median Ki-67 4.2% (range 2.0%-16.8%). Thirty seven percent had hyperplasia without atypia, and 63% had atypia. At repeat RPFNA, Ki-67 expression was reduced (median value of 2.0%, range 0%-15.2%); with 29 of the 35 women demonstrating a decrease (median relative reduction of 0.70). Conclusions: Based upon reduction in Ki-67 expression in hyperplastic benign breast tissue after 12 months, 50 mg of SDG administered daily as Brevail appears promising as a preventive. Supported in part by grant R21 CA117847 from the National Cancer Institute. No significant financial relationships to disclose.
Germline Mutations in Predisposition Genes in Pediatric Cancer
Authors: Jinghui Zhang, Michael F. Walsh, Gang Wu, Michael N. Edmonson, Tanja A. Gruber, John Easton, Dale Hedges, Xiaotu Ma, Xin Zhou, Donald A. Yergeau, Mark R. Wilkinson, Bhavin Vadodaria, Xiang Chen, Rose B. McGee, Stacy Hines-Dowell, Regina Nuccio, Emily Quinn, Sheila A. Shurtleff, Michael Rusch, Aman Patel, Jared B. Becksfort, Shuoguo Wang, Meaghann S. Weaver, Li Ding, Elaine R. Mardis, Richard K. Wilson, Amar Gajjar, David W. Ellison, Alberto S. Pappo, Ching-Hon Pui, Kim E. Nichols, James R. Downing
Journal: New England Journal of Medicine (2015)

The prevalence and spectrum of predisposing mutations among children and adolescents with cancer are largely unknown. Knowledge of such mutations may improve the understanding of tumorigenesis, direct patient care, and enable genetic counseling of patients and families.In 1120 patients younger than 20 years of age, we sequenced the whole genomes (in 595 patients), whole exomes (in 456), or both (in 69). We analyzed the DNA sequences of 565 genes, including 60 that have been associated with autosomal dominant cancer-predisposition syndromes, for the presence of germline mutations. The pathogenicity of the mutations was determined by a panel of medical experts with the use of cancer-specific and locus-specific genetic databases, the medical literature, computational predictions, and second hits identified in the tumor genome. The same approach was used to analyze data from 966 persons who did not have known cancer in the 1000 Genomes Project, and a similar approach was used to analyze data from an autism study (from 515 persons with autism and 208 persons without autism).Mutations that were deemed to be pathogenic or probably pathogenic were identified in 95 patients with cancer (8.5%), as compared with 1.1% of the persons in the 1000 Genomes Project and 0.6% of the participants in the autism study. The most commonly mutated genes in the affected patients were TP53 (in 50 patients), APC (in 6), BRCA2 (in 6), NF1 (in 4), PMS2 (in 4), RB1 (in 3), and RUNX1 (in 3). A total of 18 additional patients had protein-truncating mutations in tumor-suppressor genes. Of the 58 patients with a predisposing mutation and available information on family history, 23 (40%) had a family history of cancer.Germline mutations in cancer-predisposing genes were identified in 8.5% of the children and adolescents with cancer. Family history did not predict the presence of an underlying predisposition syndrome in most patients. (Funded by the American Lebanese Syrian Associated Charities and the National Cancer Institute.).
Treatment outcome after induction chemotherapy before allogeneic hematopoietic SCT in patients with advanced MDS
Authors: C. A. Ramos, A. A. Jakubowski, F. Boulad, E. B. Papadopoulos, J. W. Young, N. A. Kernan, M. A. Perales, T. N. Small, E. Berman, R. J. O’Reilly, H. R. Castro-Malaspina
Journal: Journal of Clinical Oncology (2006)

6502 Background: The need for induction chemotherapy (IC) before allogeneic hematopoietic stem cell transplant (alloSCT) in advanced myelodysplatic syndrome (MDS) remains controversial. Methods: This is a retrospective analysis of the remission rate in 99 patients with advanced MDS (≥5% marrow blasts) and acute myeloid leukemia (AML, ≥ 20% blasts) evolving from MDS, who were treated with IC before receiving cytoreduction for SCT. These patients were referred to MSKCC for alloSCT from 6/1980 to 10/2004, and subsequently underwent an unmodified or T cell-depleted (TCD) SCT from a matched or mismatched related or unrelated donor after myeloablative cytoreduction in the majority. Results: All patients had MDS at diagnosis: 33% had high risk (HR), 22% intermediate risk (IR) and 42% good risk (GR) cytogenetics; 38% had HR, 32% IR-2 and 25% IR-1 IPSS. The median age was 43 (range 2–66). 76% had primary and 24% had secondary MDS (chemotherapy or radiation). At the time of IC, 64% had frank AML, 33% RAEB-1 and 2, and 3% CMML-2. A combination of an anthracycline (Ac) and standard dose (SD) cytarabine (AraC) was administered to 53% of the patients. Other regimens included Ac with high dose (HD) AraC (15%), Ac with SD AraC and etoposide (15%), HD AraC alone (8%), and HD AraC with etoposide (4%). 26% of patients required a second line regimen and 4% went on to a third. None of the patients died of complications due to IC. CR was achieved in 60% of patients overall (64% in those receiving Ac + SD AraC ± etoposide and 52% for HD AraC ± Ac ± etoposide). The CR rate was 65% in primary and 42% in secondary MDS, and was similar in adults (60%) and children (56%). CR rates were 44% in HR, 68% in IR, and 65% in GR cytogenetics; 58% in HR, 59% in IR-2, and 60% in IR-1 IPSS. According to disease status at IC, the CR rate was 60% for RAEB-1 and 2 and 59% for AML. 12% of complete responders relapsed prior to cytoreduction for SCT. 49% of all patients underwent a TCD SCT from an HLA identical sibling. There are no long term survivors after SCT in patients who did not achieve CR after IC, in contrast to 47% overall survival at 10 years for responders. Conclusions: IC in advanced MDS is associated with a high rate of CR. IC before cytoreduction for SCT is an effective approach to reduce the burden of disease particularly prior to TCD SCT. No significant financial relationships to disclose.
In Vivo Targeting Of Acute Myeloid Leukemia Using CpG-Stat3 siRNA Results In T Cell-Dependent Tumor Eradication
Authors: Dewan Md Sakib Hossain, Cedric Dos Santos, Qifang Zhang, Anna Kozlowska, Hongjun Liu, Chan Gao, Dayson Moreira, Piotr Swiderski, Agnieszka Jozwiak, Justin Kline, Stephen J. Forman, Ravi Bhatia, Ya-Huei Kuo, Marcin Kortylewski
Journal: Blood (2013)
A Randomised Phase Ii Trial of Dexamethasone Versus Prednisolone in Castration Resistant Prostate Cancer
Authors: C. Parker, R. Venkitaraman, D. Lorente, V. Murthy, K. Thomas, R. Ahiabor, D. Dearnaley, R. Huddart, J.S. de Bono
Journal: Annals of Oncology (2014)
Phase 2 Study of Otlertuzumab (TRU-016), an Anti-CD37 ADAPTIRTM Protein, in Combination with Bendamustine Vs Bendamustine Alone in Patients with Relapsed Chronic Lymphocytic Leukemia (CLL) - Updated Results
Authors: Tadeusz Robak, Andrzej Hellman, Javier Loscertales, Ewa Lech-Maranda, John M. Pagel, Anthony R. Mato, John C. Byrd, Farrukh Awan, Holger Hebart, Jose A Garcia-Marco, Brian T. Hill, Michael Hallek, Scott Stromatt, Janusz Kloczko
Journal: Blood (2014)