tbuckley/cabot-search huggingface dataset:
Quality of life (QOL) impact of adjuvant chemotherapy for early stage non-small cell lung cancer (NSCLC): Final analysis of JBR.10 randomized trial
Authors: A. Bezjak, C. W. Lee, K. Ding, T. Winton, M. Brundage, B. Graham, M. Whitehead, L. Seymour, F. A. Shepherd
Journal: Journal of Clinical Oncology (2007)

7585 Background: Adjuvant chemotherapy for early stage NSCLC is now standard of care, but its impact on QOL is not known. We report the final QOL analysis of JBR.10, a North American intergroup randomized trial of adjuvant cisplatin/vinorelbine compared to observation in patients (pts) with completely resected stage IB/II NSCLC (n=482). Methods: QOL, a secondary endpoint of JBR.10, was assessed using the EORTC QLQ-C30 and a trial-specific checklist at baseline, weeks 5 and 9 for those on chemotherapy, and at 3, 6, 9, 12, 18, 24, 30 and 36 months of follow up. A 10-point change in QOL scores from baseline was considered clinically significant. Results: QOL assessment was not mandatory for all pts; 186/242 (76.9%) pts randomized to chemotherapy completed the baseline QOL assessment, compared to 173/240 (72.1%) pts on the observation arm. The overall survival of pts contributing QOL data, and the effect of adjuvant chemotherapy, was not different from the entire study population. Baseline QOL in the two study arms was comparable, with low global QOL scores and a significant symptom burden, especially pain and fatigue, following thoracotomy. A significantly greater proportion of chemotherapy pts experienced worsening symptoms including fatigue (p=0.02), appetite, hair loss, nausea and vomiting. At 6 months, a higher proportion of pts on the observation arm reported improved QOL in the global (p = 0.002), physical (p=0.02) and functional domains, compared to pts on the chemotherapy arm. However, by the 9 month time-point, global QOL of patients on chemotherapy was comparable to QOL of patients on observation, as were the five functional domains. Numbness (change scores: 22 vs 6, p&lt;0.01) and pins &amp; needles in fingers/toes (change scores: 21 vs 5, p&lt;0.01) were the only symptoms that persisted, up to 24 months. Conclusion: Patients on adjuvant chemotherapy experience an initial slower recovery of QOL after thoracotomy, but following completion of treatment reach levels comparable to patients treated with surgery alone, in most aspects of QOL. [Table: see text]
PTU-068 Outcomes of disease modifying therapy delivered to crohn’s disease patients following intestinal resection: Abstract PTU-068 Table 1
Authors: A O’connor, J Taylor, N Rabb, D Gracie, K Leigh, N Scott, AC Ford, PJ Hamlin
Journal: Gut (2015)

<h3>Introduction</h3> Follow-up of patients resected for Crohn’s disease (CD) have shown that in the absence of treatment, the post-operative recurrence rate is 70–90% within one year of the operation and 83–100% within 3 years. Prophylactic medication and disease monitoring has been proven to decrease the rate of clinical and endoscopic recurrence. <h3>Method</h3> We aimed to examine current practices in our large tertiary referral centre on postoperative prescriptions of disease modifying therapy for CD. We performed a retrospective analysis by interrogating the pathology database over a five year period from 2009 to 2013 to identify cases and data was extracted by chart review. <h3>Results</h3> 152 resections were identified. 106 patients had been given disease-modifying therapy. 3 patients were involved in a drug trial and were excluded. 66.3% of patients had therapy commenced before the first followup colonoscopy or imaging had been performed. As first-line 79 patients had thiopurine monotherapy (64 azathioprine, 14 mercaptopurine, 1 tacrolimus). 11 patients had anti-tnf monotherapy (8 adalimumab, 2 infliximab, 1 certolizumab). 13 had combination therapy with an immunomodulator and an anti-tnf. The outcomes are outlined in Table 1. <h3>Conclusion</h3> While there is no clear benefit observed for drug therapy over no drug therapy, it is likely that those who receive no treatment have a selection bias of clinically silent disease or negative initial followup investigations. Among those in whom disease-modifying therapy is prescribed there is a trend for those on combination therapy to have a better clinical response as well as steroid free, repeat-resection free survival at end of followup. <h3>Disclosure of interest</h3> None Declared.
Milestone Survival: A Potential Intermediate Endpoint for Immune Checkpoint Inhibitors
Authors: Tai-Tsang Chen
Journal: JNCI Journal of the National Cancer Institute (2015)

Recent advancements in cancer immunotherapies offer diverse strategies for cancer treatment. Among the most promising approaches is the blockade of immune checkpoint molecules to activate antitumor immunity. With targeted immunotherapies of new mechanisms of action come greater challenges in study design and statistical analysis, as well as the need for refining clinical trial endpoints. The long-term survival and delayed clinical effects demonstrated by these therapies could result in substantial prolongation of study duration and loss of statistical power if these key attributes are not accounted for in the study design and statistical analyses. In the Brookings Conference on Clinical Cancer Research held in Washington, DC, in November 2013, several intermediate clinical endpoints, including milestone overall survival, were proposed for the evaluation of cancer immunotherapies to take into account the possibility of delayed treatment effect and to better characterize the clinical activity profile of such agents, particularly immune checkpoint inhibitors. In this manuscript, the use of milestone survival is described as a potential efficacy endpoint for immune checkpoint inhibitors in late-stage drug development that could potentially mitigate the challenge of accelerating the drug development process when the strength of this class of agents is derived from long-term follow-up.
Use of integrated genomic analysis to evaluate BRCA-associated protein 1 (BAP1) as a mutated gene in malignant pleural mesothelioma (MPM).
Authors: M. J. Bott, M. Brevet, B. S. Taylor, S. Shimizu, T. Ito, Q. Zhou, A. Olshen, M. F. Zakowski, V. W. Rusch, M. Ladanyi
Journal: Journal of Clinical Oncology (2010)

10506 Background: CDKN2A and NF2 are inactivated in most MPM, but no other recurrent mutations are known. To identify additional driver genes, we did an integrated analysis of copy number and expression data, followed by focused sequencing. Methods: Array comparative genomic hybridization (aCGH) data (Agilent 244K arrays) and gene expression data (Affymetrix U133A arrays) were generated from frozen samples of 53 MPM. To identify recurrent gains or losses of statistical significance, we used the RAE algorithm. Minimal common regions (MCR) of gain or loss were defined both by RAE and standard MCR analysis. Results: The 3 most frequent losses were 9p21 (CDKN2A), 22q (NF2), and 3p21. Recurrent gains of 5p and 7 were seen. We selected for sequencing 25 genes based on RAE and MCR analyses and integration with expression data, including some previously known genes (NF2 but not CDKN2A). The most commonly mutated gene (12/53; 23%) was the BRCA-associated Protein 1 (BAP1) gene at 3p21, encoding a de-ubiquitylating enzyme that interacts with the BRCA1 complex and other proteins. The discovery of BAP1 mutations in MPM was then confirmed in MPM cell lines (4/13 mutated; 31%) and in an additional set of 96 MPM tumors (12 mutated; 12.5%). Overall, the 28 mutations consisted of 6 nonsense mutations, 5 missense, 9 frameshifting indels, and 8 mutations at or near splice sites. Based on aCGH data, 30% of MPM show a loss of BAP1 and 42% show either loss or mutation. Tumors with BAP1 loss have lower BAP1 expression levels at RNA and protein levels. There was no correlation between BAP1 mutation, NF2 loss, and CDKN2A loss. Conclusions: We used integrated cancer genomics to identify BAP1 as a new and frequent target of inactivating somatic mutations in MPM. The possible involvement of BAP1 in DNA damage response or other processes regulated by ubiquitylation could provide new target pathways for MPM treatment but more work is needed to define the function of BAP1 in MPM cells. No significant financial relationships to disclose.
Detection of AML1/ETO Fusion Transcripts in Patients With t(8; 21) Acute Myeloid Leukemia After Allogeneic Bone Marrow Transplantation or Peripheral Blood Progenitor Cell Transplantation
Authors: Ahmet H. Elmaagacli, Dietrich W. Beelen, Jitka Stockova, Susanne Trzensky, Melanie Kroll, Ulrich W. Schaefer, Christina Stein, Bertram Opalka
Journal: Blood (1997)
Lymphocytes Forming Rosettes with Sheep Erythrocytes in Metastatic Pleural Effusions2
Authors: J. Y. Djeu, J. L. McCoy, G. B. Cannon, W. J. Reeves, W. H. West, R. B. Herberman
Journal: JNCI Journal of the National Cancer Institute (1976)

Percentages of lymphocytes forming rosettes with sheep erythrocytes at 29 degrees C were determined in 10 cancer patients with metastases to the pleural cavity. Compared with normal controls, the patients showed a decreased proportion of rosette-forming cells (RFC) in the peripheral blood. The same patients had elevated levels of RFC in their metastatic pleural effusions. However, 2 patients with benign diseases had normal levels of RFC in their peripheral blood and pleural transudates. These observations suggested that in cancer patients some T-cells might migrate from the peripheral blood and accumulate in sites of tumor infiltration such as the pleural cavity.
TCTAP A-016 Reduction in Ventricular Tachyarrhythmia with Prior Statin Therapy in Patients with Acute Myocardial Infarction
Authors: Jin Sup Park, Hye Won Lee, Jun-Hyok Oh, Han Cheol Lee, Kwang Soo Cha, Taek Jong Hong, Myung-Ho Jeong
Journal: Journal of the American College of Cardiology (2016)
Oxaliplatin and capecitabine after gemcitabine failure in patients with advanced pancreatic, biliary, and gallbladder adenocarcinoma (APBC)
Authors: A. Sancho, G. López-Vivanco, I. Diaz de Corcuera, J. Ferreiro, A. Moreno, X. Mielgo, R. Fernandez, N. Ancizar, E. Iruarrizaga, J. M. Mañe
Journal: Journal of Clinical Oncology (2008)

15625 Background: Patients (pts) with advanced pancreatic (P), biliary (B) and gallbladder (GB) adenocarcinoma have a poor prognosis. Gemcitabine (G) is the standard treatment for patients with APBC. There is no consensus about second line after progression disease. The aim of this study is to examine the efficacy and tolerability of Oxaliplatin (O) and Capecitabine (Cap) after G failure. Methods: From February 2005 to February 2007 18 pts with histologically proven unresectable or metastastic APBC, and refractory to G were included. Pts received CAPOX (O 130 mg/m2 D1 and Cap 1000 mg/m2 D2–14). Treatment cycles were repeated every 3 weeks and continued until progression or unacceptable toxicity. Results: Eighteen pts were evaluated: 12 male (66.7%); 6 female (33.3%), Median Age: 57 (range 4–72). PS 0/1/2: 6/9/3. Location: P: 9 (50%), B: 4 (22.2%), GB: 4 (22.2%), ampuloma: 1 (5.6%). Stages: III: 1 (5.6%), IV: 17 (94,6%). Median number of cycles: 3,5 (1–11). Grade 2/3 toxicity: Sensitive peripheral neurotoxicity 4/0; Hand-foot-syndrome 0/1, Diarrhea: 5/2, Nausea/vomiting: 4/0, Neutropenia: 1/1, Thrombocytopenia 2/0, Anemia 2/1: Fatigue: 6/4, Anorexia; 1/2. Overall response rate: Partial Response: 1/18 (5.6%), Stable Disease: 8/18 (44.4%), Progressive disease: 5/18 (27.8%). Four pts were not evaluated because early deaths. 27.7% of pts had a 50% or more decrease in Ca 19–9 levels. Median overall survival was 24.71 weeks (w) and median progression free survival was 16.71 w. The OS was higher in patients with PS0 and PS1 than pts with PS2 (p=0.001). Conclusions: Oxaliplatine and Capecitabine can be safely administered with tolerable safety profiles in pts with APBC previously treated with G. This study shows similar results in OS to infusional 5-Fluorouracil and oxaliplatin in ABPC (CONKO 0003). No significant financial relationships to disclose.
Impact of Enzalutamide on Skeletal Related Events (Sres), Pain and Quality of Life (Qol) in the Prevail Trial
Authors: Y. Loriot, K. Miller, C.N. Sternberg, K. Fizazi, J.S. de Bono, S. Chowdhury, C. Higano, S. Noonberg, S. Holmstrom, H. Mansbach, F.G. Perabo, D. Phung, C. Ivanescu, K. Skaltsa, T. Beer, B. Tombal
Journal: Annals of Oncology (2014)
Candidate driver genes involved in genome maintenance and DNA repair in Sézary syndrome
Authors: Wesley J. Woollard, Venu Pullabhatla, Anna Lorenc, Varsha M. Patel, Rosie M. Butler, Anthony Bayega, Nelema Begum, Farrah Bakr, Kiran Dedhia, Joshua Fisher, Silvia Aguilar-Duran, Charlotte Flanagan, Aria A. Ghasemi, Ricarda M. Hoffmann, Nubia Castillo-Mosquera, Elisabeth A. Nuttall, Arisa Paul, Ceri A. Roberts, Emmanouil G. Solomonidis, Rebecca Tarrant, Antoinette Yoxall, Carl Z. Beyers, Silvia Ferreira, Isabella Tosi, Michael A. Simpson, Emanuele de Rinaldis, Tracey J. Mitchell, Sean J. Whittaker
Journal: Blood (2016)
Decline in Mortality From Gastric Cancer in Native-Born and Foreign-Born Residents of New York City
Authors: M TERRIS, C E HALL
Journal: JNCI Journal of the National Cancer Institute (1963)

This study of mortality from gastric cancer in New York City disclosed that the decline between 1949–51 and 1959–61 occurred not only in the total population but also in males and females in each of 3 population groups: native-born whites, foreign-born whites, and Negroes. Furthermore, the decrease occurred in almost every age group within each category. It was concluded that the reduction in mortality could not be attributed to the decreasing proportion of a high risk group, the foreign-born, in the total population. The decline was greatest in those population groups with the lowest mortality rates in 1949–51. Examination of available data on accuracy of diagnosis did not support the hypothesis that the lower rate resulted from improvement in diagnostic accuracy. The findings of this and other studies indicate that the lower mortality from gastric cancer is probably not an artifact caused by demographic changes or improvements in diagnosis or treatment, but may well reflect a real decline in incidence due to environmental factors that remain unidentified.
Overcoming tumor antigen anergy in human malignancies using the novel indeolamine 2,3-dioxygenase (IDO) enzyme inhibitor, 1-methyl-D-tryptophan (1MT)
Authors: H. H. Soliman, S. Antonia, D. Sullivan, N. Vanahanian, C. Link
Journal: Journal of Clinical Oncology (2009)

3004 Background: The limited effect of cancer immunotherapy is due to the tumor's ability to induce host anergy towards its antigens. The enzyme indoleamine 2,3-dioxygenase (IDO) is thought to play a key role in anergy induction. IDO metabolizes tryptophan (trp) into immunosuppressive metabolites such as kynurenine (kyn). The oral IDO inhibitor, 1-methyl-D-tryptophan (1MT), was studied in preclinical models. The preclinical data support the activity of 1-MT in preventing T-cell anergy in TDLN, slowing growth of LLC mouse xenografts, and synergizing with chemotherapy in regression of autochthonous breast tumors in MMTV-Neu mice. This led to a phase I first-in-man trial using 1-MT in solid tumors. Methods: This is a phase I study treating adults with refractory solid malignancies. Patients are treated with up to 6 consecutive 28-day cycles starting at 200mg once daily. A 3+3 dose escalation to MTD is used. PK analysis, weekly labs, and CT scans every 2 cycles were done. Correlative studies include serum kyn/trp levels, T-reg cell quantification by flow, tumor IDO expression by IHC, and humoral immune response using a proprietary tumor antigen microarray. Results: Ten pts have recieved 1-MT at 200mg daily. Tumors treated included 1 esophageal, 1 peritoneal, 3 melanomas, 2 sarcomas, and 3 NSCLC. PK results show good bioavailability and a t1/2 of 2–4 hrs. Of the 7 evaluable pts, 4 had SD and 3 had PD. Attributable toxicities were 1 case of grade 1 fatigue and 2 cases of grade 2 hypophysitis. Both cases occurred in pts who received prior immunotherapies. Six new pts without prior immunotherapy were enrolled at the 200mg dose level. Five pts remain on treatment currently. Three pts had decreased T-reg cells after treatment with 1MT and 4 pts showed marked CRP increases. One pt had increased autoantibody titers against 3 tumor antigens compared to baseline. Conclusions: 1-MT appears to be an active, orally bioavailable, and reasonably well tolerated immunomodulator at 200mg daily. Development of hypophysitis in 2 patients indicates the drug can break tolerance resulting in autoimmunity. Enrollment to the trial continues. Future trials will combine 1-MT with other immunotherapies and chemotherapies for solid tumors. [Table: see text]
Brief Report: Monoclonal Gammopathy and Risk of Lymphoma and Multiple Myeloma in Patients With Primary Sjögren's Syndrome
Authors: Anne‐Laurence Tomi, Rakiba Belkhir, Gaétane Nocturne, Frédéric Desmoulins, Elisabeth Berge, Stephan Pavy, Corinne Miceli‐Richard, Xavier Mariette, Raphaèle Seror
Journal: Arthritis & Rheumatology (2015)

Objective To assess the link between monoclonal gammopathy (MG), disease activity, and incidence of malignant hematologic disorders (MHDs), including lymphoma and multiple myeloma (MM), in patients with primary Sjögren's syndrome (SS). Methods Screening for the presence of MG was performed in 352 primary SS patients. Each patient with MG was paired with 2 age‐ and sex‐matched primary SS controls without MG. Their characteristics were compared for the presence of risk factors for MG and for the relationship between MG and MHD. Results Twenty‐six of the 352 primary SS patients (7.4%) had MG; 88% were women, with a median age of 62.7 years (interquartile range [IQR] 50.3–69.1 years) and a median disease duration of 7.8 years (IQR 3.6–12.8 years). The parameters associated with MG on multivariate analysis were higher disease activity, as measured by either the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI; adjusted odds ratio [OR] 9.7, P = 0.0002) or the Clinical ESSDAI (adjusted OR 6.7, P = 0.001), and low C4 level (adjusted OR 3.4, P = 0.04). After a median follow‐up of 6.3 years (IQR 3.1–9.5 years), 10 patients with MG had developed an MHD (38.5%; 4 had lymphomas and 6 had MM), as compared with 4 patients in the control group (7.7%; all had lymphomas) (OR 7.5, P = 0.002). The only factor associated with the risk of MHDs was the presence of MG (adjusted OR 5.5, P = 0.02), which was principally associated with an increased risk of MM (23% versus 0%; P = 0.0009), but not lymphoma (15% versus 8%; P = 0.3). Conclusion The presence of MG was associated with higher disease activity and an increased risk of MHD in primary SS. In the presence of MG, the risk of MM was even higher than the risk of lymphoma. These results suggest that regular monitoring of primary SS patients with MG for the emergence of both lymphoma and MM is necessary.
HER2/neu incidence in early breast cancer and its correlation with others prognostic factors
Authors: G. R. Molina Barrios, M. Lavarda, M. L. Rizzi, C. Dubersarsky, G. D. Jarchum
Journal: Journal of Clinical Oncology (2008)

22195 Background: HER2/neu is an epidermal growth factor receptor with tirosin-kinase activity. Its amplification in 25–30% of breast cancer denotes more agressivity and differential responses to hormonal and chemotherapy treatment. Several therapeutic strategies that use anti HER2/neu antibodies (Trastuzumab) with or without chemotherapy has reported clinical benefit. We looked for the incidence of HER2/neu in our population and its relation with other prognostics factors. Methods: Retrospectively, we compiled data from clinical records belonging mainly to early breast cancer patients, who had consulted our Service from 1/2005 to 6/2006. We tested 109 patients for HER2/neu amplification by Inmunohistochemistry (IHC) and their results were correlated with others known pronostic factors using Chi2. We used Dako 0483 polyclonal antibodies. Results: Median age of our population was 56,6 years. Histological grade was classified as G I in 18,3%, G II in 70.6% and GIII in 11%. The most frequent histological type was invasive ductal adenocarcinoma (80,7%), invasive lobular and other variants (19.3%). Low mitotic index was positive in 18,3%, intermediate 61,5% and high 20,2%. Estrogen receptors (ER) were positive in 74,3%; while Proesterone Receptors (PR) were positive in 65,1%. Staging revealed that 51% of patients were SI, 42% SII and 4% SIII, 3% SIV. HER2/neu amplification was positive in 28,4% of our patients. Age, tumor size, stage, histologic type and grade, ER, PR and mitotic index were correlated with Her 2/neu status. In HER2/neu (+) patients 48,4% were ER negative, while in HER2/neu (-) 16,7% were ER (-) (p: 0.001). There was a tendency of correlation between histological grade I and HER2/neu (-) (p: 0.09). Regarding others prognostics variables, there were no significant associations. Conclusion: HER2/neu positivity in our population with early breast cancer determined by IHC was 28.4%, and it was correlaated with ER negativity. No significant financial relationships to disclose.
Characterization of the Cadherin–Catenin Complex of the Sea Anemone<i>Nematostella vectensis</i>and Implications for the Evolution of Metazoan Cell–Cell Adhesion
Authors: Donald Nathaniel Clarke, Phillip W Miller, Christopher J Lowe, William I Weis, William James Nelson
Journal: Molecular Biology and Evolution (2016)

The cadherin-catenin complex (CCC) mediates cell-cell adhesion in bilaterian animals by linking extracellular cadherin-based adhesions to the actin cytoskeleton. However, it is unknown whether the basic organization of the complex is conserved across all metazoans. We tested whether protein interactions and actin-binding properties of the CCC are conserved in a nonbilaterian animal, the sea anemone Nematostella vectensis We demonstrated that N. vectensis has a complete repertoire of cadherin-catenin proteins, including two classical cadherins, one α-catenin, and one β-catenin. Using size-exclusion chromatography and multi-angle light scattering, we showed that α-catenin and β-catenin formed a heterodimer that bound N. vectensis Cadherin-1 and -2. Nematostella vectensis α-catenin bound F-actin with equivalent affinity as either a monomer or an α/β-catenin heterodimer, and its affinity for F-actin was, in part, regulated by a novel insert between the N- and C-terminal domains. Nematostella vectensis α-catenin inhibited Arp2/3 complex-mediated nucleation of actin filaments, a regulatory property previously thought to be unique to mammalian αE-catenin. Thus, despite significant differences in sequence, the key interactions of the CCC are conserved between bilaterians and cnidarians, indicating that the core function of the CCC as a link between cell adhesions and the actin cytoskeleton is ancestral in the eumetazoans.