tbuckley/cabot-search huggingface dataset:
Sequential FEC 100-Docetaxel (T) Neoadjuvant Chemotherapy (NCT) in Stage II-III Operable Breast Cancer.
Authors: P. Dubray, P. Dubray, C. Abrial, C. Abrial, M. Mouret-Reynier, M. Mouret-Reynier, B. Nayl, B. Nayl, E. Thivat, E. Thivat, P. Gimbergues, J. Achard, F. Penault-Llorca, F. Penault-Llorca, P. Chollet, P. Chollet, P. Chollet, P. Chollet, X. Durando, X. Durando, X. Durando
Journal: Cancer Research (2009)

Abstract Background: NCT is increasingly used for operable breast cancer to allow breast conservation. Our objective was to evaluate clinical and pathological response after sequential NCT of 3 cycles of FEC 100- 3 cycles of T. This chemotherapy is currently the reference in the adjuvant setting in France.In PACS 01 trial (Roche et al. J Clin Oncol, 2006) FEC followed by T significantly improved 5 years overall survival rates (90.7%) compared to 6 FEC 100 in node-positive breast cancer. However this active combination has not yet been evaluated in NCT.Methods: 101 patients (pts) from February 2005 to September 2008 with pathologically confirmed stage II-III untreated operable breast cancer received 3 cycles (c) of FEC 100 (epirubicin 100 mg/m² + 5-fluorouracil and cyclophosphamide 500mg/m²) followed by 3 c of T (100mg/m²) every 3 weeks. pCR was defined according to Chevallier's (Am J Clin Oncol, 1993) as level 1 and 2 and to Sataloff's classification (J Am Coll Surg, 1995) as grade A. A clinical, mammography and ultrasound breast evaluation was performed at baseline, after 3 c and before surgery.Results: Median age was 52.3 years [28-72]. Median diameter of the tumor was 42 mm [14-100]. 83 pts had a ductal, 14 a lobular, 3 ductal and lobular, 1 another carcinoma. 8.9% were grade I SBR, 58.4% grade II SBR, 28.7% grade III SBR and 4% unspecified. 74 (73.3%) tumors were HR+, 9(8.9%) Her-2 + and 18(17.8%) triple negative. 55 pts (54.4%) were premenopausal.After 3 cycles of FEC 100, ultrasound objective response rate (ORR) was 15%: 13 pts had a partial response and 2 pts had a complete response.After 6 cycles of NCT, ultrasound ORR was 62.5%: 53 pts had a partial response and 7 pts had a complete response.Most frequent grade (G) 3-4 adverse events were neutropenia which occured in 16 pts (15.8%) with G 3 febrile neutropenia in 11 pts (10.9%) (G-CSF optional). Most frequent G 1-2 averse events were nausea which occured in 43 pts(42.6%), myalgia in 27 pts(26.7%) and stomatitis in 23 pts(22.8%).After the completion of NCT, 76 pts (75.2%) underwent breast-conserving surgery. 12(11.9%) achieved pCR using Chevallier's classification and 15(14.8%) using Sataloff's classification.Conclusion: Sequential NCT with FEC followed by T was active and relatively well tolerated. Breast-conserving rate appeared satisfactory. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1105.
Observational GHEA Study: Adjuvant-Trastuzumab-Treatment of HER2-Positive Breast Carcinoma.
Authors: M. Campiglio, E. Tagliabue, A. Balsari, R. Bufalino, E. Ferri, S. Menard
Journal: Cancer Research (2009)

Abstract Background: GHEA (Group HErceptin in Adiuvant treatment), an Italian multicentric observational study, was designed with the aim to investigate on adjuvant trastuzumab-therapy of HER2-positive breast carcinomas in conventional clinical setting.Material and Methods: Eligible patients should have been treated with trastuzumab in adjuvant setting and were collected among 35 oncologic Italian centers.Results: The patient registered so far in the GHEA database (500 pts) had a median age of 52 years and 64% were in post-menopause at the time of trastuzumab therapy. Primary breast tumor were mainly of ductal type (93%) of high grade (59% were GIII) and small in size (58% T1, 35% T2, 4% T3 and 3% T4). 12% of the samples included in GHEA were classified as T1micro, T1a and T1b, three categories generally not included in clinical trials. ER and PgR positive tumors were 58% and 51%, respectively and more than 53% presented in situ component. Positive lymph-nodes were present in 53% of cases. 15% of the patients received neo-adjuvant therapy prior surgery and adjuvant treatment. In the neo-adjuvant therapy, 95% of patients received anthracycline–based regimens and 72% were treated with taxanes. In adjuvant setting 89% of patients received anthracycline–based regimens and only 43% were treated with taxanes. 88% of the patients completed 1-year-trastuzumab treatment. Median exposure time of the series was 26 months. To date, 6% of the patients presented distant metastasis (i.e. bones, liver, lung, SNC) and half of them progressed during trastuzumab treatment.Discussion: The purpose of the present study is to gather information from a large number of patients related to the effect of adjuvant trastuzumab treatment in conventional clinical setting, the treatment of tumor categories not included in clinical trails and the therapies used at the relapse of these patients. All together, these data are warranted to design further clinical trials to better define guide-line for trastuzumab adjuvant therapy and for the treatment of these patients at relapse.Supported by AIRC and Roche. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5112.
T6 The role of IL-17A in a mouse model of pulmonary infection caused by streptococcus pneumoniae is strain dependent
Authors: ND Ritchie, TJ Mitchell, TJ Evans
Journal: Thorax (2013)

<h3>Background</h3> The cytokines interleukin 17A and interleukin 22 are known to be important in host defence against Gram-negative infection. However, their role in the innate immune response to pneumococci remains poorly understood. We aimed to investigate the role of these cytokines in an animal model of pneumococcal infection. <h3>Methods </h3> Wild type (WT), IL-17 receptor A-/- (IL17RAKO) and IL-22-/- C57Bl/6 mice were infected intranasally with serotype 4 (TIGR4) and serotype 3 (SRL1) pneumococci. Neutrophils for <i>in vitro</i> experiments were obtained by peritoneal lavage following injection of casein. <h3>Results </h3> TIGR4 was cleared from the lungs of mice within 48 hours but invaded early in the course of the infection causing bacteraemia and disseminated infection. In contrast, SRL1 invaded into blood late in the course of infection but caused a dense consolidative pneumonia with purulent empyema. IL-17A and IL-22 were detected in alveolar lavage within 6 hours of infection but fell in later infection suggesting an innate source. Contrasting results were obtained when knockout animals were infected. In TIGR4 infection, IL17RAKO were more susceptible to infection (P = 0.04) and this was due to an increased incidence of early bacteraemia in these animals. In contrast, following SRL1 infection in IL17RAKO animals, there was improved survival (P = 0.004). In both types of infection, IL22KO animals demonstrated an intermediate phenotype that did not reach statistical significance. IL17RAKO mice had decreased neutrophils in blood and lung within 24 hours of infection in keeping with the known biological actions of IL-17A. Studies using isolated cells showed that TIGR4 was phagocytosed and killed by neutrophils but uptake and killing of SRL1 was ineffective. Experiments with fluorescent bacteria confirmed poor neutrophil uptake of SRL1 relative to TIGR4. Depletion of WT mouse neutrophils with a monoclonal antibody demonstrated a trend towards delayed mortality and improved outcome in SRL1 infection.
ERCP in complete situs inversus viscerum using a “mirror image” technique
Authors: F. García-Fernández, J. Infantes, Y. Torres, F. Mendoza, F. Alcazar
Journal: Endoscopy (2010)

Complete situs inversus viscerum (SIV) is a rare autosomal recessive congenital anomaly that consists of complete left–right inversion of the viscera. Certain associated malformations have been reported.
SAT0511 Achieving Consensus in Ultrasonography Synovitis Scoring in Rheumatoid Arthritis
Authors: P. Cheung, K. O. Kong, L. C. Chew, F. Chia, W. G. Law, T. Y. Lian, Y. K. Tan, Y. K. Cheng
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ultrasonography (US) is a sensitive method for synovitis detection in clinical practice but interobserver variation in both acquisition and image intepretation is still a key concern [1]. Various semiquantitative synovitis scoring methods have been proposed in the past for B-mode and PDUS. Recently, the OMERACT US Task Force also proposed the EULAR-OMERACT PDUS composite scoring which had moderate to excellent reliability [2]. However, this has not been tested formally outside of the steering group. <h3>Objectives</h3> The objective was to evaluate if a collegiate small group consensus would improve US synovitis assessment and scoring in patients with rheumatoid arthritis, in both still images and in image acquisition. <h3>Methods</h3> Eight rheumatologists from Singapore participated in a 1 day consensus meeting in November 2012, divided into (i) still-image interpretation and consensus followed by (ii) image acquisition and interpretation, according to definitions and synovitis scoring rules endorsed by OMERACT and TUI (Targeted Ultrasound Initiative). Interobserver reliability of semiquantitative scoring in B-mode, Power Doppler (PDUS) and EULAR-OMERACT PDUS composite score was assessed by intraclass correlation co-efficient (ICC). Agreement at the joint region level was calculated using prevalence-adjusted-biased-adjusted-kappa (PABAK). <h3>Results</h3> For B-mode still images, ICC was good at 0.75 (95%CI 0.66-0.82) while for PDUS images this was excellent; ICC=0.88 (95%CI 0.83-0.92). During image acquisition and interpretation, B-mode scoring showed ICC=0.75 (95%CI 0.66-0.84) while for PDUS the ICC was lower at 0.59 (95%CI 0.48-0.72). The ICC for EULAR-OMERACT PDUS composite synovitis scoring was good at 0.77 (95%CI 0.68-0.85). At the joint level, agreement varied with PABAK being excellent in the small joints of the hands but poor to fair in the wrists, elbows, ankles and MTP, and no agreement at the knees (PABAK range -0.34 to 0.85). <h3>Conclusions</h3> A consensus meeting between colleagues was useful in improving interobserver variation in synovitis scoring by ultrasonography, but agreement in non-hand joints is still a problem, requiring further standardisation. <h3>References</h3> Cheung PP, Dougados M, Gossec L. Reliability of ultrasonography to detect synovitis in rheumatoid arthritis: a systematic literature review of 35 studies (1415 patients). Arthritis Care Res (Hoboken) 2010; 62:323-34. Naredo E, Wakefield R, Iagnocco A, et al. The OMERACT Ultrasound Task Force - Perspectives. J Rheumatol 2011;38:2063-7. <h3>Disclosure of Interest</h3> None Declared
Variable Phenotypic Expression of an X-Linked Recessive Lymphoproliferative Syndrome
Authors: David T. Purtilo, Daniel DeFlorio, Lindsey M. Hutt, Jag Bhawan, James P. S. Yang, Ralph Otto, William Edwards
Journal: New England Journal of Medicine (1977)

Investigation of a family with cancer in boys revealed that at least 20 males had the X-linked recessive lymphoproliferative syndrome. A variety of phenotypes occurred: aproliferative phenotypes consisted of aplastic anemia, agranulocytosis or acquired hypogammaglobulinemia; and proliferative phenotypes of B cells included disorders associated with the Epstein-Barr virus, American Burkitt's lymphoma, immunoblastic sarcoma of B cells, fatal infectious mononucleosis or plasmacytoma. The lymphoproliferative disorders observed in males could have resulted from an immunodeficiency to Epstein-Barr virus. The variable phenotypic expression could have resulted from individual differences in the viral dose, duration of exposure and age at which the boys were exposed to the virus. Aproliferative phenotypes such as acquired hypogammaglobulinemia could have ensued from excessive suppressor-cell activity on B cells, whereas proliferative phenotypes such as Burkitt's lymphoma or fatal infectious mononucleosis could have resulted from infection by Epstein-Barr virus and failure to stop proliferation of B cells.
AB0618 Comparison of mycophenolate mofetil and intravenous cyclophosphamide as induction therapy in korean patients with lupus nephritis
Authors: D.-J. Park, T.-J. Kim, Y.-W. Park, S.-S. Lee
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Although intravenous cyclophosphamide (IVC) pulses are generally accepted as standard therapy for induction treatment of active proliferative lupus nephritis (LN), several clinical trials have suggested that mycophenolate mofetil (MMF) is at least as effective as IVC. The efficacy of IVC varies among racial and ethnic groups and IVC is less effective in patients of African or Hispanic descent. In contrast, MMF seems to be consistently effective in all racial/ethnic groups. Nevertheless, it is necessary to compare these two treatment modalities among different racial or ethnic groups, particularly in Asia. This study compared the efficacy of MMF and IVC as induction treatment for LN in ethnically homogeneous Korean patients. <h3>Methods</h3> This study enrolled 49 LN patients with available kidney biopsy specimens. Sociodemographic, clinical, laboratory, and treatment-related data at the time of kidney biopsy and during follow-up were obtained by reviewing the patients' charts. The renal biopsy specimens were reclassified according to the ISN-RPS classification, by a renal pathologist blinded to the previous classification. The renal outcome, i.e., complete response (CR), partial response (PR), and non-response (NR), after 6 and 12 months was defined according to the ACR 2006 response criteria for proliferative and membranous renal disease in clinical trials. <h3>Results</h3> Of the 49 patients, 28 (57.1%) were treated with IVC and 21 (42.9%) with MMF, both in combination with prednisolone. The baseline characteristics of the two groups were comparable, except that the IVC-treated patients had lower platelet counts (<i>p</i>=0.026), lower C3 levels (<i>p</i>=0.007), and higher activity scores (<i>p</i>=0.021) in the renal biopsy compared to the MMF-treated patients. CR was seen in 9 of 21 patients (42.9%) receiving MMF and 14 of 28 patients (50.0%) receiving IVC after 6 months treatment (<i>p</i>=0.450) and in 11 of 21 patients (52.4%) in the MMF group and 13 of 28 patients (46.4%) in the IVC group at 1 year (<i>p</i>=0.745). The number of patients achieving PR and NR did not differ significantly at 6 and 12 months between the treatment groups. <h3>Conclusions</h3> These findings suggest that the efficacy of oral MMF at 1 year does not differ from that of IVC in induction treatment of LN in ethnically homogeneous Korean patients. MMF may be considered first-line induction therapy for treating LN in these patients. <h3>Disclosure of Interest</h3> None Declared
FRI0427 Tumor necrosis factor blocking agents inhibit the progression of preclinical atherosclerosis in patients with ankylosing spondylitis
Authors: A. M. Van Sijl, I. C. van Eijk, M. J. Peters, E. H. Serne, I. H. van der Horst-Bruinsma, Y. M. Smulders, M. T. Nurmohamed
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ankylosing spondylitis (AS) is associated with an increased cardiovascular (CV) risk that might be due to the chronic underlying inflammatory process, but is still unknown whether treatment with TNF inhibitors reduce the increased CV risk. <h3>Objectives</h3> We investigated whether preclinical atherosclerosis of the carotid arteries in patients with AS were reduced after use of TNF inhibitors in an observational cohort study. <h3>Methods</h3> 67 out of 82 AS patients who underwent ultrasonography at baseline returned for follow-up. Of the 67 remaining AS patients, 11 discontinued use of TNF inhibitors. Assessments of AS related factors and CV risk factors were measured at baseline and repeated at follow-up. B-mode carotid ultrasonography was used to investigate arterial wall parameters, including intima-media thickness (IMT) and Young's elastic modulus (YEM). <h3>Results</h3> After 5 years of follow-up, IMT did not change significantly (+0.012, p-value= 0.561) in those who continued the use of TNF inhibitors, whereas IMT increased significantly (+0.060, p-value=0.025) in AS patients who discontinued use of TNF inhibitors. Compared to prior studies in rheumatoid arthritis (a disease with comparable CV risk as in AS) AS patients who discontinued TNF inhibitors had a comparable yearly increase in IMT, while patients who continued use of TNF inhibitors had a 5-fold lower increase in IMT. Duration of use of TNF inhibitors (in years) was associated with stabilization or regression of IMT, odds ratio (95%&gt;confidence interval): 1.67 (1.04-2.63). Also, YEM improved significantly in patients who continued TNF inhibitors (+0.037, p-value=0.002) but not in patients who discontinued TNF inhibitors. <h3>Image/graph</h3> <h3>Conclusions</h3> (Continuous) use of TNF inhibitors might stabilize or slow down IMT progression in AS patients, reflecting a decreased CV risk in these patients. Unfavourable changes in IMT were associated with equally unfavourable changes in AS related factors, while unfavourable changes in YEM were associated with unfavourable changes in lipid levels. More research is needed to investigate the relationship between improvement in AS-related disease acitivity indices and improvement in IMT or vascular stiffness. <h3>Disclosure of Interest</h3> None Declared
Phase II Study of a HER-2/Neu (HER2) Intracellular Domain (ICD) Vaccine Given Concurrently with Trastuzumab in Patients with Newly Diagnosed Advanced Stage Breast Cancer.
Authors: M. Disis, Y. Dang, N. Bates, D. Higgins, J. Childs, M. Slota, A. Coveler, E. Jackson, J. Waisman, L. Salazar
Journal: Cancer Research (2009)

Abstract HER2 is a tumor antigen in breast cancer and several trials have demonstrated that breast cancer patients can be immunized against this protein. We have developed HER2 peptide based vaccines that are aimed at eliciting CD4+ Th1 tumor antigen specific T cell responses. Th1 effectors provide immunologic memory, enhance cross priming which will allow the elaboration of tumor specific CD8+ T cells, and stimulate epitope spreading which we have shown to be a potential biomarker of clinical response. 52 patients will be enrolled with the primary objective to determine relapse free survival after active immunization. Eligible patients are newly diagnosed with Stage III (B or C) or Stage IV breast cancer and begin vaccination within 6 months of starting maintenance trastuzumab. This interim report will present data on the first 25 patients enrolled; 21 stage IV and 4 locally advanced patients. The vaccine is well tolerated with all adverse events (AE) being Grade I or 2. The most common AE is injection site reaction. Moreover, the combination of HER2 vaccination with trastuzumab did not result in additive cardiac toxicity in these patients. Immune responses were evaluated by IFN-gamma ELISPOT. To date, 88% of patients immunized developed significant immunity to the components of the ICD vaccine. The majority, 75%, developed robust immunity to the HER2 protein. Our group has recently demonstrated that a broadening of immunity throughout the HER2 protein, to components of the protein that weren't in the vaccine, i.e. epitope spreading, may be associated with improved survival in vaccinated patients. 63% of immunized patients demonstrated evidence of intramolecular epitope spreading. We questioned whether such high frequencies of homing Type 1 T cells might modulate the immunosuppressive tumor microenvironment, so we evaluated whether circulating serum immunosuppressive cytokines were impacted by immunization. TGF-beta is an immunosuppressive cytokine secreted by tumor stroma and regulatory T cells. We found that the levels of serum TGF-beta decreased significantly in the majority of patients after vaccination. We further analyzed the correlation between the change of serum levels of TGF-beta post vaccination and HER2 ICD vaccine-induced T cell responses. We found that the greater the magnitude of the HER2 specific T cell response, as demonstrated by IFN-gamma secretion, the greater the decrease in serum TGF-beta (p=0.0045, r=0.742). The correlation between the increased epitope spreading T cell response and decreased levels of TGF-beta was even more significant (p=0.0003). The median overall survival has not been reached with 100% of patients alive at this time. Relapse free survival data will be presented. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5102.
Abstract LB-187: Modulation of redox status: An alternative approach for prevention and treatment of prostate cancer
Authors: Trinath P. Das, Suman Suman, Thippeswamy Gulappa, Vittal Kurisetty, Aditi Shirish Vadodkar, Rajkumar Lakshmanaswamy, Chendil Damodaran
Journal: Cancer Research (2012)

Abstract Radical prostectomy, radiation treatment, and/or hormone ablation therapy are the first lines of treatment for prostate cancer (CaP). Despite initial sensitivity to these treatments, CaP eventually progresses to castration-resistant CaP (CRPC), which is both aggressive and refractory to current therapeutic options. Accordingly, there is a tremendous need for a novel agent that can either retard or prevent the emergence of CRPC. Changes in reactive oxygen species (ROS) play a pivotal role in these processes. For example, a moderate increase in ROS promotes cell proliferation, but excessive amounts of ROS can induce apoptosis in cancer cells. Hence, it is possible to manipulate the redox (oxidative stress) system to selectively kill cancer cells. Psoralidin (Pso), a natural bioactive compound derived from Psoralea Corylifolia which is extensively used in Asian and African medicines, is an orally bioavailable dietary agent. We are the first group to demonstrate that Pso is non-toxic to normal prostate epithelial cells but specifically targets CaP cell lines (PC-3, DU-145, LnCaP and C4-2B) by inhibiting Akt and its downstream pro-survival signaling pathways. While dissecting the upstream events of Akt, we found that Pso generates ROS production and inhibits Akt mediated pro-survival signaling in both cell cultures and animal models of CRPC. Importantly, over expression of antioxidants, genetically (SOD/Catalase) or pharmacologically N-acetylcysteine (NAC) or treatment with ROS inhibitors Rotenone (mitochondrial) or Diphenylenel iodonium DPI (extra mitochondrial) inhibited Pso induced oxidative stress (both Intracellular and NADPH oxidase mediated) in CaP cells. Further, Pso in combination with anti-oxidants/ROS inhibitors significantly decreased the migratory and invasive property of CaP cell lines. Currently, we are delineating the role of Pso induced non-mitochondrial ROS generation, by analyzing expression patterns of NADPH oxidase and their subunits. We will apply genetic and/or pharmacological approaches to determine the key Pso target in CaP cell lines. Further, our chemopreventive and chemotherapeutic studies of Pso in both xenograft models and pilot experiments in transgenic adenocarcinoma of mouse prostate (TRAMP) model showed that Pso inhibits prostate tumor growth. These studies may suggest modulation of redox status could be a novel and powerful approach to chemoprevention and/or treatment of CaP. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-187. doi:1538-7445.AM2012-LB-187
The Oregon ACO Experiment — Bold Design, Challenging Execution
Authors: Eric C. Stecker
Journal: New England Journal of Medicine (2013)

Interview with Dr. Eric Stecker on Oregon's experiment with accountable care organizations for Medicaid and CHIP beneficiaries. (10:25)Download Oregon has embarked on an ambitious program centered on accountable care organizations (ACOs) that aims to change Medicaid financing and health care delivery. The experiment highlights both the bold vision of ACO-based health care reform and the challenges it faces.