tbuckley/cabot-search huggingface dataset:
FRI0319 Drug Retention Rates of Biologic Monotherapies for Patients with Rheumatoid Arthritis in Daily Clinical Practice; Using Multicenter Registry in Japan
Authors: H. Matsubara, T. Kojima, N. Ishiguro
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> In general, drug retention rate reflects the effectiveness and tolerability of the drug. In Japan, seven biological agents have been approved for the treatment of rheumatoid arthritis (RA). There is few data comparing the retention rates between biological monotherapies for RA patients in daily clinical practice. <h3>Objectives</h3> The purpose of this study is to compare the drug retention rates of three biological monotherapies with different target molecules, etanercept (ETN), tocilizumab (TCZ), abatacept (ABT). <h3>Methods</h3> We collected the data from the patients who started monotherapies with ETN, TCZ, ABT as first-biologics since 2008 and registered in the multicenter, large cohort of RA patients (Tsurumai Biologics Communication Registry; TBCR). We surveyed the following information: demographic data, disease activity (DAS28-CRP) at the baseline of each biological treatment. Drug retention rates were calculated by the Kaplan-Meier analysis and compared using the log-rank test among groups. We investigated drug retention rates for discontinuation due to insufficient effectiveness (IE) and adverse events (AE). To compare risks of drug discontinuation due to IE and AE for patients treated with these biological agents, the Cox proportional hazard model was applied. <h3>Results</h3> We analyzed 279 patients of 2072 patients registered in TBCR until March 2011 (141 patients in the ETN group, 63 patients in the TCZ group, 75 patients in the ABT group). The mean follow up time was 25.7 months. Table shows baseline characteristics of the groups (Table). The patients in the ABT group were older compared with other groups. Cumulative incidence rate for discontinuation due to insufficient effectiveness was significantly lower in the TCZ group (p=0.019, Fig.1A). Cumulative incidence rate for discontinuation due to adverse events was significantly lower in the ABT group (p=0.007, Fig.1B). Compared with TCZ group, the use of ABT was significantly associated with a lower risk of discontinuation due to AE (HR 0.081; 95% CI 0.009 to 0.737). <h3>Conclusions</h3> We demonstrated that TCZ monotherapy had a lower discontinuation rate due to IE and that ABT monotherapy had a lower discontinuation rate due to AE. <h3>Disclosure of Interest</h3> H. Matsubara: None declared, T. Kojima Speakers bureau: abbvie Japan, Chugai Pharmaceutical, Daiichi Sankyo Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Pfizer Japan, Takeda Pharmaceutical, N. Ishiguro Speakers bureau: abbvie Japan, Chugai Pharmaceutical, Daiichi Sankyo Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Pfizer Japan, Takeda Pharmaceutical <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5755
Positron Emission Tomography With Fluorine-18 Fluorodeoxyglucose To Evaluate Response of Early Breast Carcinoma Treated With Stereotaxic Interstitial Laser Therapy
Authors: N Nair, A Ali, K Dowlatshahi, M Fan, G Lamonica
Journal: Clinical Nuclear Medicine (2000)

Stereotaxic interstitial laser therapy is a promising new alternative to surgery to treat early-stage breast cancer. With this, laser energy coagulates the tumor with controlled heat, leading to fibrosis. Fluorodeoxyglucose positron emission tomography (FDG PET) scanning was performed in four patients treated by this technique to determine the degree of necrosis after interstitial laser therapy. The results showed that FDG PET scanning was in close agreement with histopathologic findings, confirming complete necrosis in one patient and variable response in the other three patients. Uptake of FDG appears to be a reliable means to monitor treatment response after interstitial laser therapy and may be useful in the management of breast cancer when used with this new procedure.
CYR61, Estrogen Receptor and FOXO3a: The Interplay in Aggressive Breast Carcinomas.
Authors: I. Espinoza, H. Liu, R. Busby, R. Lupu
Journal: Cancer Research (2009)

Abstract Estrogen receptors (ERs) play key roles in breast cancer development and influence treatment outcome in breast cancer patients. More than 60% of human breast cancer tumors express ER and many of those are Estrogen (E2) dependent. ER positive tumors are considered to have a good prognosis; however some tumors escape to E2 requirements. Thus, the identification of molecules that regulate ER function may facilitate development of breast cancer treatment strategies. The pro-angiogenic factor CYR61 induces breast cancer cells to bypass the normal estrogen requirements for growth and acquire an estrogen-independent and antiestrogen resistant phenotype. However, the mechanism by which CYR61 regulates the hormonal response in breast cancer is not well understood. We over-expressed CYR61 in the ER positive cells MCF-7 (MCF-7/CYR61). Our results demonstrated that CYR61 induces constitutive transcriptional activity of the ER, which is independent of E2. Moreover, we demonstrated that CYR61 co-localizes with the ER in the nucleus and casually CYR61 transcriptional activity is regulated, at least in part by FOXO3a binding site. In search of the mechanism by which CYR61 that modulates hormonal response we discovered that CYR61 and FOXO3a interact in the presence of E2. This functional interplay among CYR61/ER/FOXO3a most likely plays a critical role in blocking hormone-response of breast cancer growth in vitro and in vivo. Furthermore, these studies demonstrate that CYR61 and FOXO3a are novel therapeutic targets to halt hormone-independent breast carcinomas. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5145.
Adjuvant chemotherapy for early-stage breast cancer: Choice of regimen and associated hematologic toxicities in a metropolitan Australian hospital.
Authors: Katherine Mary Lovat, Hayden Christie, Ricky Che, Andrew Hill, Jasotha Sanmugarajah
Journal: Journal of Clinical Oncology (2012)

123 Background: The commonly used adjuvant chemotherapy regimens for early breast cancer include 5-fluorouracil, epirubicin, cyclophosphamide and docetaxel (FEC-D), docetaxel and cyclophosphamide (TC), doxorubicin and cyclophosphamide with or without paclitaxel and/or herceptin (AC combination) and docetaxel, carboplatin and trastuzumab (TCH). Hematologic toxicity from these regimens can be life threatening as well as cause significant morbidity for the patient and major costs to the health system. Granulocyte colony stimulating factor (GCSF) is frequently used to try and reduce these complications. In Australia, GCSF is funded for use as primary prophylaxis with docetaxel in combination with an anthracycline and cyclophosphamide. Secondary prophylaxis is available only after demonstration of prolonged severe neutropenia or an episode of febrile neutropenia (FN). Methods: Patients treated with adjuvant chemotherapy for early breast cancer at Gold Coast Hospital, Qld, Australia from February 2010 to February 2012 were identified. Patient charts were reviewed for incidence of neutropenia (neutrophil count &lt;1.0 x 10 9 /L), FN (temp ≥38°C), dose reductions or delays and use of GCSF. Results: 102 patients were treated over this time. Incidence of neutropenia, FN and use of GCSF are summarised below. 30 patients receiving FEC-D had a dose delay or reduction with the majority due to non-haematologic toxicities. 96% patients completed 6 cycles of treatment. Of the patients with FN in the TC group, half had received primary GCSF. No patients who were given primary GCSF experienced a dose delay. Similar trends were observed in the other treatment groups. Conclusions: Our results show that patients receiving FEC-D along with GCSF had lower rates of neutropenia and hospitalisations. Rates of neutropenia and dose delay are higher in the other groups. FEC-D is the most commonly used regimen in our institution likely due to the availability of GCSF. [Table: see text]
Stemming the Escalating Cost of Prescription Drugs: A Position Paper of the American College of Physicians
Authors: Hilary Daniel
Journal: Annals of Internal Medicine (2016)

This American College of Physicians position paper, initiated and written by its Health and Public Policy Committee and approved by the Board of Regents on 16 February 2016, reports policy recommendations from the American College of Physicians to address the escalating costs of prescription drugs in the United States. Prescription drugs play an important part in treating and preventing disease. However, the United States often pays more for some prescription drugs than other developed countries, and the high price and increasing costs associated with prescription medication is a major concern for patients, physicians, and payers. Pharmaceutical companies have considerable flexibility in how they price drugs, and the costs that payers and patients see are dependent on how payers are able to negotiate discounts or rebates. Beyond setting list prices are issues of regulatory approval, patents and intellectual property, assessment of value and cost-effectiveness, and health plan drug benefits. These issues are linked, and comprehensive efforts will be needed to affect how drugs are priced in the United States.
Abstract 4997: The expression PHLPP is regulated by the mTOR-P70S6K signaling pathway
Authors: Jianyu Liu, Tianyan Gao
Journal: Cancer Research (2010)

Abstract PHLPP is a novel family of protein phosphatases serving as negative regulators of Akt by directly dephosphorylating the kinase. Our previous studies have indicated a tumor suppressor role of PHLPP in human colon cancer. However, the regulation of PHLPP expression in cancer cells remains unknown. Here, we report that the expression of PHLPP protein is regulated by the mTOR-p70S6K pathway in colon and breast cancer cell lines. Treating cells with rapamycin, an inhibitor of mTOR, induces a marked decrease of PHLPP protein expression, and this rapamycin-mediated down-regulation of PHLPP expression is blocked by overexpression of a constitutively active mutant of p70S6K. Stable knockdown of TSC2, a negative regulator of mTOR, using lentiviral-based RNAi results in an increase of PHLPP expression, while knockdown of mTOR decreases the expression level of PHLPP protein. In addition, knockdown of 4E-BP1, a translation initiation inhibitor and a downstream effector of mTOR, results in an increase of PHLPP expression and resistance to rapamycin or Torin1 induced decrease of PHLPP expression in cells. Furthermore, amino acid starvation of cells, which inactivate the mTOR signaling, decreases PHLPP expression, and this is reversed by resupplying amino acids. Control experiments show that the rate of PHLPP degradation was not alerted significantly by rapamycin treatment or knockdown of TSC2. The real-time RT-PCR analysis reveals that the mRNA level of PHLPP remains constant in the TSC2 and mTOR knockdown or rapamycin treated cells. Taken together, these results suggest that the translation of PHLPP proteins is controlled by mTOR. Our studies identify a compensatory feedback regulation of Akt signaling in which the activation of Akt is negatively regulated by up-regulation of PHLPP protein in an mTOR-dependent manner. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4997.
Abstract 5524: Prostate cancer risk assessment model (PCRAM): a scoring model based on the Swedish Family-Cancer Database
Authors: Hassan Roudgari, Kari Hemminki, Andreas Brandt, Jan Sundquist, Mahdi Fallah
Journal: Cancer Research (2012)

Abstract Background: Many prostate cancer (PC) risk assessment models have been developed, however almost none include familial history. We aimed to produce a risk assessment model for PC based on familial background of related cancers. Method: 976,859 independent index men aged &amp;gt;=30 in year 1998 and their family members in the Swedish Family-Cancer Database (FCD 2010) were randomly divided into the development (60%) and the validation (40%) datasets (follow-up=10 years). The hazard ratio from Cox model for personal and family history was used to extrapolate risk scores. Results: Specified scores were for PC in situ at age&amp;lt;60 years in index man, 5; PC at age&amp;lt;60 in each first-degree relative (FDR), 15; PC at age&amp;gt;=60 in each FDR, 10; PC at age&amp;lt;60 in each second-degree relative, 5; breast cancer in each FDR, 2; oesophageal carcinoma in situ in index man, 2; and oesophagus cancer in each FDR, 2. The curve for score-group 26+ showed a sharp increasing slope from age 60-65 onward. The score-group 21-25 showed 15-40 times higher risk than the general population at age 38-45; ratio decreased to four-folds by age 60, and stayed about 3.5-times thereafter. The score-group 16-20 showed 10-fold increased risk at age&amp;lt;=41; risk ratio 4-6 at age 42-54; and 2.5-3.5-fold thereafter. The curves for score 0-5 and population risk almost overlapped. Based on our findings, if the milestone age for a prostate cancer screening program was 60 years or more, the recommended starting age for the men with the score-group 6-10 would be 54 years; score-group 11-15, 52 years; score-group 16-20, 50 years; score-group 21-25, 44 years; and for the score-group 26+ it should start before age 40. The concordance index in both the development and the validation sets was 0.885 (95% CI=0.883-0.888). No significant difference was found between curves from the development and the validation datasets (internally-validated using two-fold validation and bootstrapping). Conclusion: Familial history of relevant malignancies can be used as risk factors to estimate a man's prior risk of developing prostate cancer. PCRAM could satisfactorily assess risk of developing prostate cancer. 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 5524. doi:1538-7445.AM2012-5524
AB1366 Prevalence of rheumatoid arthritis and spondyloarthropathy in belgrade, serbia
Authors: M.I. Zlatkovic-Svenda, F. Guillemin, R.M. Stojanovic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> to estimate the prevalence of rheumatoid arthritis (RA) and spondyloarthropathy (SpA) in the capital town of Serbia, Belgrade <h3>Methods</h3> translation and cross-cultural adaptation of the original RA and SpA telephone detection Questionnaire to Serbian language was successful, preserving the validity of the original tool (1). Prevalence was estimated on a systemic sample - using every 100th number from the telephone list. The validated detection Questionnaire was administered in a first call, performed by 10 trained patient-interviewers. A second call was done by rheumatologist, who confirmed RA or SpA diagnosis on the basis of the patient records. In case of uncertain diagnosis, the patient was invited for clinical examination. <h3>Results</h3> A total of 5361 telephone numbers was called. After the exclusion of second residents, business places and children, 4340 persons were interviewed with a response rate of 61,8%. The second, rheumatologist call was received by 389 subjects, of whom 53 were clinically examined. A total of 14 RA cases and 9 SpA cases were detected, with crude prevalence rate of 0.53% (95% CI:0,25-0,80) for RA and 0.34% (95% CI:0,12-0,56) for SpA. The standardised prevalence rate according to Serbian census population data for Belgrade was 0,38% (95% CI:0,18-0,58) for RA and 0,28% (0,10-0,46) for SpA. <h3>Conclusions</h3> Crude prevalence rate for RA in the present study (0,53%) differs from that obtained earlier (2). Interestingly, using common classification criteria and a unique investigation method, the standardized RA and SpA prevalence rates for Belgrade (0,38% and 0,28%, respectively) were in the same range with those observed in France (3,4). <h3>References</h3> Zlatkovic-Svenda M, Stojanovic R, Guillemin F et al. Adaptation and validation of a telephone questionnaire – Serbian version for case detection of rheumatoid arthritis and spondyloarthropathy (multicentric Eular study).Clin and Exp Rheumatol. 2007; 25 (1): 75-84. Stojanovic R, Vlajinac H, Palic-Obradovic D, Janosevic S, Adanja B. Prevalence of rheumatoid arthritis in Belgrade, Yugoslavia. Br J Rheumatol. 1998 Jul;37(7):729-32. Guillemin F, Saraux A, Guggenbuhl P, Roux CH, Fardellone P, Le Bihan E, et al. Prevalence of rheumatoid arthritis in France: 2001. Ann Rheum Dis 2005;64:1427–30. Saraux A, Guillemin F, Guggenbuhl P, Roux CH, Fardellone P, Le Bihan E, et al. Prevalence of spondylarthropathies in France: 2001. Ann Rheum Dis 2005;64:1431–5. <h3>Disclosure of Interest</h3> None Declared
Expression of cell cycle-related proteins p27kip1, p21waf1 and p53 in node-negative invasive ductal carcinoma of the breast
Authors: H. Kourea, A. K. Koutras, V. Zolota, I. Grimani, E. Tzorakoeleptherakis, D. Koukouras, G. Fountzilas, H. Gogas, K. Kyriakou, H. P. Kalofonos
Journal: Journal of Clinical Oncology (2004)

669 Background: p27kip1 and p21waf1 proteins are universal inhibitors of cyclin-dependent kinases primarily inducing cell cycle arrest in the G1-S checkpoint, function shared with p53 tumor suppressor protein. We evaluated the expression of p27kip1, p21waf1 and p53 retrospectively in a series of node-negative breast carcinomas (NNBCs), since data regarding their prognostic significance in this tumor are contradictory. Methods: Formalin-fixed, paraffin-embedded tissue from 168 NNBCs was studied by immunohistochemistry, using monoclonal antibodies to p27kip1, p21waf1 and p53. The results were correlated with clinicopathological parameters and outcome. Results: Low p27kip1expression (in <50% of tumor nuclei) and p21waf1 expression (in 10% of tumor nuclei) was detected in 26% of NNBCs. p27kip1 loss was associated with high tumor grade (p<0.0001), age <50 years (p=0.01), and negative ER (p<0.0001) and PR (p=0.007) status. p53 overexpression was associated with negative ER (p<0.0001) and PR (p=0.002) status. No correlation was detected between p21waf1 and the examined parameters. Even though on univariate analysis p21waf1 was associated with disease-free survival (p=0.04), on multivariate analysis the examined proteins were not associated with disease-free or overall survival. Conclusions: Although, p27kip1 loss and p53 overexpression are correlated with high grade and negative steroid receptor status, the expression of these proteins does not affect prognosis of NNBC. p21waf1 expression is not correlated with the standard clinicopathological parameters or outcome in NNBC. No significant financial relationships to disclose.
SP0167 It’s not all in your head: The importance of a multidisciplinary team – a psychosocial perspective
Authors: R. Geenen
Journal: Annals of the Rheumatic Diseases (2013)

A simple model of the psychosocial dimension of rheumatic diseases would suggest a linear relation, in which the extent of disease severity and damage determine the degree of disability, which in turn influence the patient's psychological wellbeing. This model is not at all supported by research findings, which suggest a much more complex relation between the disease and its outcomes. Besides the disease process also behavioral (for example, avoidance of physical exercise), cognitive (for example, pessimistic thoughts) and emotional (for example, depression or anxiety) processes impact on symptoms such as pain and fatigue. Psychosocial processes may also indirectly impact on disease activity—for instance, as determinants of adherence to pharmacological treatment and of the likelihood of attending the physician in the event of a disease exacerbation. In the lecture, the importance of a multidisciplinary team and psychosocial perspective will be emphasized and demonstrated as well as the need to involve patients in care. <h3>Disclosure of Interest</h3> None Declared
Spectalung: Screening Patients with Thoracic Tumors for Efficient Clinical Trial Access
Authors: B. Besse, J. Menis, J. Adam, R. Dziadziuszko, B. Hasan, L. Lacroix, S. Peters, D.A. Lacombe, M. O'Brien, R.A. Stahel
Journal: Annals of Oncology (2015)
P29 Reduced expression of Tim-3 renders Th1 and Th17 effector cells less amenable to T-reg control in autoimmune hepatitis
Authors: R. Liberal, G. Mieli-Vergani, D. Vergani, M. S. Longhi
Journal: Gut (2011)

<h3>Introduction</h3> In autoimmune hepatitis (AIH), CD4 effector immune responses are permitted by defective CD4<sup>+</sup>CD25<sup>+</sup> regulatory T-cells (T-regs). In murine studies apoptosis of Th1 effector cells is mediated by binding of T-cell-immunoglobulin-and-mucin-domain3 (Tim-3) on their surface to Galectin-9 (Gal9) expressed by T-regs. In AIH, Tim-3 is down-modulated on CD4 effector cells. <h3>Aim</h3> To test the frequency of Tim-3<sup>+</sup> cells within the Th1, Th2 and Th17 subsets and to evaluate whether Tim-3 expression by CD4 effectors affects their responsiveness to T-reg control. <h3>Method</h3> 39 ANA/SMA<sup>+</sup> patients (23 females; median age: 13.9 years) and 16 healthy subjects (HS, 12 females; median age: 29.5 years) were studied. Cell phenotype was determined by cytofluorimetry using monoclonal antibodies to CD4, CD25 and TIM3. The frequency of cells positive for T-bet, GATA3 and RORC, transcription factors defining Th1, Th2 and Th17 cell subsets, was determined by intracellular staining. Proliferation of CD25<sup>−</sup>, CD25<sup>−</sup>Tim-3<sup>+</sup> and CD25<sup>−</sup>Tim-3<sup>−</sup> target cells was assessed by <sup>3</sup>H-thymidine incorporation after 5-day co-culture with T-regs. <h3>Results</h3> The frequency of Tim-3<sup>+</sup> cells within the Th1 and the Th17 subsets was lower in AIH than in HS (Th1: 5.1±0.7 vs 13.6±1.7, p&lt;0.001; Th17: 3.9±0.3 vs 8.2±1.1, p=0.02), while there was no difference for Th2 cells. In AIH, there was a negative correlation between the frequency of Tim-3<sup>+</sup> cells and AST levels (r= −0.47, p=0.002) and a positive correlation between the frequency of T-bet<sup>+</sup> cells and AST levels (r=0.69, p&lt;0.01). Addition of T-regs reduced cell proliferation by 26% (p=NS) in AIH and by 53% (p=0.007) in HS when undivided CD25<sup>-</sup> cells were used as targets; by 23% (p=NS) and by 25% (p=NS) when Tim-3<sup>−</sup> cells were the targets and by 47% (p=0.03) and by 62% (p=0.001) when the targets were Tim-3<sup>+</sup> cells. <h3>Conclusion</h3> In AIH, reduced frequency of Tim-3 within the Th1 and Th17 effector cell subsets renders them less prone to T-reg control, CD4 effector cell proliferation depending on the expression of Tim-3. T-bet expression characterises effector T-cells likely to mediate liver damage in AIH.
P796 NADPH OXIDASE (NOX 4) AND P22PHOX GENE POLYMORPHISMS ARE ASSOCIATED WITH HUMAN NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
Authors: F. Rabelo, J.T. Stefano, R.V. Lima, M. Seixas, T. Patente, D. Vanni, A.M. Cavaleiro, D.C. Mazo, F.J. Carrilho, M.L. Corrêa-Giannella, C. Oliveira
Journal: Journal of Hepatology (2014)