tbuckley/cabot-search huggingface dataset:
Significant improvement in recurrence-free survival (RFS) when capecitabine (X) is integrated into docetaxel (T) → 5-FU + epirubicin + cyclophosphamide (CEF) adjuvant therapy for high-risk early breast cancer (BC): interim analysis of the FinXX-trial.
Authors: H Joensuu, P Kellokumpu-Lehtinen, R Huovinen, A Jukkola-Vuorinen, R Asola, R Kokko, J Ahlgren, P Bono, M Tanner, H Lindman, for The Finnish Breast Cancer Group
Journal: Cancer Research (2009)

Abstract Abstract #82 Background: Adding X to T extends survival in patients (pts) with metastatic BC. The primary objective of the FinXX-trial is to compare RFS with XT→CEX vs. T→CEF as adjuvant therapy in pts with early BC. Secondary objectives are comparison of overall survival, distant RFS and safety. Methods: Between Jan 2004 and May 2007, 1500 pts were randomized to receive T x 3 → CEF x 3 (T 80mg/m² d1 → C 600mg/m² d1, E 75mg/m² d1, F 600mg/m² d1, q3 wks) or XT x 3 → CEX x 3 (T 60mg/m² d1 + X 900mg/m² bid d1–15 → C 600mg/m² d1, E 75mg/m² d1, X 900mg/m² bid d115, q3 wks). Results: 1496 pts were included in the ITT analysis (two pts withdrew consent, two had metastatic disease). The study population represented a high-risk group (90% node positive, 19% HER2 positive, 88% poorly or moderately differentiated tumors). The baseline characteristics were well balanced in the two treatment arms. After median follow-up of 3 years, there have been 134 events (deaths, distant or local relapses; Table). The significantly improved RFS rate was achieved despite a higher number of study treatment discontinuations in the X-containing arm (178 vs. 23 pts in the control arm; when XT was discontinued, the remaining XT cycles were replaced with an equal number of T cycles, and CEX cycles with CEF cycles). 75% of pts in the X-containing arm received all six planned cycles of therapy compared with 96% in the control arm. The adverse effect profiles of XT→CEX and T→CEF were in part different (Gr. 3/4 neutropenic fever/infection 10.0% vs. 20.2%, hand-foot syndrome 11.1% vs. 0.3%, diarrhea 6.2% vs. 3.4%, stomatitis 4.2% vs. 1.6%, myalgia 1.9% vs. 8.0%, respectively).&amp;#x2028; &amp;#x2028; Conclusions: The primary endpoint of this trial, to demonstrate a significant improvement in RFS, was achieved after median follow-up of 3 years. The hazard ratio of 0.66 (95% CI 0.47–0.94; p=0.020) for RFS translates into a 34% reduction in the rate of recurrences or deaths in pts receiving XT→CEX. This significant benefit was seen using an X dose of 900 mg/m² bid, and with a lower T dose in the XT arm than with T monotherapy. Overall survival data are not yet mature but a trend towards improvement (hazard ratio 0.66 [95% CI 0.401.07]; p=0.089) can be seen in the XT→CEX arm. The results suggest that the risk of breast cancer recurrence can be reduced substantially with integration of capecitabine into a taxane-/anthracycline-based regimen. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 82.
Another Scintigraphic Pattern of a Postsurgical Bile Leak
Authors: VISWESWARA R. TATINI, SUBHA RAMAN, DARLENE FINK-BENNETT
Journal: Clinical Nuclear Medicine (2002)

R. TATINI, VISWESWARA M.D.; RAMAN, SUBHA M.D.; FINK-BENNETT, DARLENE M.D. Author Information
Abstract 2862: Therapeutic intervention of preclinical symptoms in a NF1 mouse model
Authors: Huarui Zheng, Lou Chang, Yuan Zhu
Journal: Cancer Research (2010)

Abstract We previously generated a mouse model by using Schwann cell lineage-specific ablation of Nf1, which recapitulates human plexiform neurofibroma with high penetrance throughout the peripheral nerves including the sciatic nerves. Although it takes more than 12 months for these mutant mice to develop frank neurofibromas, we have identified pre-neoplastic phenotypes in mutant sciatic nerves at as early as 3 months of age. In sciatic nerves of mutant mice at post natal day 90 (P90), we identified a subset of non-myelinating Schwann cells (nmSCs) as early stage neurofibroma cells, which exhibit a spectrum of abnormalities. These abnormal nmSCs are either dissociated or dissociating from axons, often accompanied by axonal degeneration and mast cell infiltration. Proliferation of these abnormal nmSCs leads to significantly increased cellularity in mutant nerves. Altered mTOR (mammalian target of rapamycin) activity was also observed at this stage. Based upon these observations, we propose that deregulated mTOR activity may be underlying molecular mechanism of neurofibroma initiation. To test this hypothesis, we are using rapamycin, a mTOR inhibitor, to treat mice starting from P30 until P90, at which time point they are analyzed. The extent of pre-neoplastic phenotypes at P90 can serve as assays for the efficacy of this treatment. Our preliminary data show that rapamycin treatment may have effect in alleviating pre-neoplastic phenotypes in some mutant mice, evidenced by the absence of dissociated SCs and unassociated SCs, as well as decreased cellularity in the sciatic nerves of those mice. However, further experiments need to be done to confirm these results. 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 2862.
P57 * STEM CELL PLASTICITY AND TUMORIGENISIS: REGULATORY ROLES OF HEPARAN SULPHATE IN THE CANCER STEM CELL NICHE
Authors: R. Baty, A. Pisconti, J. Turnbull
Journal: Neuro-Oncology (2014)

INTRODUCTION: During the past few years, stem cells have received attention as a system for research and cell-based therapies due to their unique ability for self-renewal. However, concerns have arisen from our current knowledge regarding what permits a safe use of stem cells in tissue engineering strategies. Uncontrolled stem cell expansion is a major cause of cancer and tissue degeneration. Sub- populations of cancer cells have been identified in tumours, leading to the cancer stem cell hypothesis, and the potential to target these cells for effective new anti-cancer therapies. METHOD: Systems to be studied will include the role of extracellular HS on neuroblastoma cell lines influence on the phenotype of cancer cell lines. The methods to be used will include: neuroblastoma cell culture; proliferation and differentiaton assays, Immunophenotyping by fluorescent activated cell sorting (FACS) analysis, chemical biology (HS saccharide libraries & synthetic compounds), glycoanalysis (glycan purification; HPLC/FPLC, and glycan analysis) to study changes in HS molecular phenotype with neuroblastoma cells. RESULTS: When we analysed heparin- treated SKNAS cells by flow cytometry to identify the CD44+ sub-population, we observed that low concentrations of heparin (10 ng/ml) reduced the proportion of CD44+ cells in culture. Conversely, treatment with a modified (desulphated) heparin, the F3 compound, known to have anti-metastatic activity have shown no significant effect. on the proportion of CD44+ cells in the SKNAS cell cultures. CONCLUSION:These results suggest that: a) heparinoid compounds may be effective in reducing the proportion of CSCs in a tumour; b) this effect may have some selectivity for to certain HS structures, since highly sulphated heparin displayed differentially activity compared to a low sulphated heparin derivative.
The Hamman-Rich Syndrome
Authors: H. Richard Hoff
Journal: New England Journal of Medicine (1958)

SINCE the report of Hamman and Rich1 , 2 of a disease characterized by diffuse interstitial fibrosis of the lungs, the clinical syndrome and the characteristic pathology have been well defined. This condition, now popularly known as the Hamman-Rich syndrome, is generally considered to be of unknown etiology, although various theories have been propounded. Originally, it was thought to be related to a viral infection or a hypersensitivity reactions.1 , 2 Interstitial fibrosis of the lungs also occurs after attacks of influenzal pneumonia, scrub typhus or exposure to various chemical irritants. Recently, a similar clinicopathological condition was observed after therapy for hypertension with hydralazine. . . .
Divergent Routing of Positive and Negative Information from the Amygdala during Memory Retrieval
Authors: Anna Beyeler, Praneeth Namburi, Gordon F. Glober, Clémence Simonnet, Gwendolyn G. Calhoon, Garrett F. Conyers, Robert Luck, Craig P. Wildes, Kay M. Tye
Journal: Neuron (2016)
Abstract 5016: Epigenetics in renal cell carcinoma
Authors: Swathi Ramakrishnan, Paula Sotomayor, Kristin Lehet, Roberto Pili
Journal: Cancer Research (2012)

Abstract In 2011, an estimated 60,920 men and women will be diagnosed of which 13,120 will die of cancer of the kidney and renal pelvis. The current standard line of therapy includes surgery [partial or radical nephrectomy] or the use of molecular targeted agents such as antiangiogenic agents or immunotherapy. The common mutations found in renal cell carcinomas [RCC] are Von-Hippau Lindau [VHL] gene in clear cell RCC, c-met gene in papillary RCC type I, Fumarate hydratase [FH] gene in papillary type II or the Brit Hogg Dube’ [BHD] gene in chromophobe RCC. However there have been several studies indicating that some of the above genes like VHL can be silenced through promoter methylation as well. Hence, there has been an increasing focus on epigenetic modifications that can occur in RCCs, because of the possibility of reversing these epigenetic marks. There have been considerable reports on the use of agents such as histone deacetylase [HDAC] inhibitors or DNA methyl transferase inhibitors in different RCC cell lines or clinical trials. In this study, we looked at the HDAC expression and activity in matched tumor and non-tumor renal cell carcinoma tissue obtained from tissue procurement services at RPCI. Class I HDACs [HDAC 1, 2 and 3] and two members of class II HDACs [HDAC 4 and 5] are overexpressed in tumors compared to their non-tumor counterparts. In contrast, a class II member HDAC 6 level is lower in the tumor tissues relative to their non-tumor counterparts which corresponded to higher levels to acetylated α-tubulin in those tumors. However, these HDAC expression levels did not tend to have a correlation with grade or stage. We also established xenografts, that are implanted orthotopically and efforts are underway to obtain relatively faster growing tumors subcutaneously. Ongoing studies include defining the relation between expression and activity of HDACs in these tissues and the interaction and impact of other proteins with Class I and II HDACs [such as ER-α, Class III HDACs, VHL] in the context of common active pathways in tumors such as hypoxia [results of which will be available at the time of the meeting]. Further work also includes to look into other histone as well as DNA modifications, as well as enzymes that cause these modifications, in the matched tissues and to explore the potential use of histone or DNA modifying agents as part of RCC treatment. 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 5016. doi:1538-7445.AM2012-5016
Dissection sous-muqueuse endoscopique (DSME) du rectum et du côlon: résultats chez 37 patients
Authors: D Coumaros, F Vincent
Journal: Endoscopy (2011)

Patients et Méthodes: 37 patients (23H; 14 F) d'âge médian 68 ans (extrêmes: 38–82) ont été traités entre 2005 et 2010. Le générateur VIO 200 (ERBE) et divers bistouris étaient employés: Needle- (1), TT- (1), Flex- et IT- (1), Flex- (6), Flex- et Hook- (9) (Olympus), Hybrid- (ERBE) (1) Flush- (9), Ball-Tipped Flush-Knives (9) (Fujinon). Un embout distal (Olympus), du Sigmavisc (Life Europe), du sérum salé, une pince Coagrasper (Olympus) était utilisés et, 10 fois, une insufflation de CO2.
P75 Prognostic Implications Of The Modified Glasgow Prognostic Score In Early Stage Non-small Cell Lung Cancer
Authors: A. MacKenzie, E. Johnson, S. Tsim, K. Blyth
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> Up to 50% of patients treated radically for non-small cell lung cancer (NSCLC) subsequently present with metastatic disease. This is despite rigorous case-selection and the use of adjuvant therapies based on clinical and/or surgical staging. A simple, objective biomarker that identified patients at higher risk of recurrence might facilitate more effective multi-modality radical treatment. Since inflammation-based biomarkers offer robust prognostication in metastatic NSCLC, we hypothesised that the modified Glasgow Prognostic Score (mGPS), Neutrophil:Lymphocyte Ratio (NLR) and/or Platelet:Lymphocyte Ratio (PLR), measured prior to radical treatment would have utility in this regard. <h3>Methods</h3> Utilising a radiology database, we retrospectively identified all patients with Stage I-IIIa NSCLC who underwent radical treatment between August 2011 and August 2012. Electronic records were reviewed and baseline parameters, including blood results were recorded. mGPS (based on CRP and Albumin), NLR and PLR were calculated. All cases were subject to multidisciplinary assessment, detailed staging and 2-year follow-up. Kaplan-Meier plots were generated for mGPS, NLR, PLR and compared using log-rank for trend and log rank. Differences in mortality were quantified using Hazard Ratios (HR). Differences in stage proportion were compared using the Chi-Square z test. <h3>Results</h3> 97 patients were identified. 44/97 (45%) were male, mean age 70 (± 8) years. 54/97 (56%) underwent surgery, 43/97 (44%) underwent radical RT. NLR and PLR provided no useful prognostic information. In surgical patients only, increasing mGPS was associated with decreasing 2-year survival (see Figure 1(a)), with curve separation occurring 1 year post-resection. Pre-operative mGPS 1 and 2 were associated with HR for death of 3.9 (95% CI 0.8–39.5, p = 0.095) and 5.8 (95% CI 1.38–106, p = 0.02) relative to mGPS 0. There were less Stage I and more Stage II patients in the mGPS 1 group (see Figure 1(b)), mGPS 0 and 2 appeared well matched for stage. <h3>Conclusion</h3> These data suggest that pre-operative mGPS may be useful in risk-stratifying patients with early stage NSCLC. The late survival curve separation observed suggests recurrent malignancy rather than post-operative complications are likely to explain this. If confirmed prospectively, integration of mGPS into staging algorithms might allow more effective targeting of adjuvant therapies.
EARLY ACTIVATION OF GROWTH PATHWAYS IN MITRAL LEAFLETS EXPOSED TO AORTIC REGURGITATION: ACTIVE MECHANISM TO PREVENT FUNCTIONAL MITRAL REGURGITATION IN THE DILATED VENTRICLE
Authors: Ons Marsit, Olivier Royer, Marie-Claude Drolet, Marie Arsenault, Jacques Couet, Jonathan Beaudoin
Journal: Journal of the American College of Cardiology (2016)
CONVECTION-ENHANCED DELIVERY OF NIMUSTINE HYDROCHLORIDE FOR BRAINSTEM MALIGNANT GLIOMA: CURRENT STUDY AND DEVELOPMENT OF NEW DEVICE
Authors: R. Saito, Y. Sonoda, T. Tominaga
Journal: Neuro-Oncology (2014)

BACKGROUND: Convection-enhanced delivery (CED) is a technique that delivers therapeutic agents directly and effectively into the brain parenchyma. Glioma affecting brainstem is one of the important candidates that could be targeted with CED. In this report, we describe our recent effort to develop novel CED based therapeutic approach for gliomas affecting brainstem. METHODS: Direct local convection-enhanced delivery of nimustine hydrochloride (ACNU) monitored with real-time MRI is our strategy. We are now in clinical trial against recurrent malignant glioma cases affecting brainstem. Pilot feasibility study recruited three patients. Subsequently, until today, we have recruited 7 patients as Phase I trial. On the other hand, we have developed an ultrasound assisted infusion device for brainstem infusion. RESULTS: In the pilot study, CED of ACNU demonstrated an efficacy against a patient suffering recurrent glioblastoma at brainstem. Succeeding phase I study is still ongoing, but so far, CED of ACNU is safe and feasible even against brainstem disease. Although the new device we developed is still in pre-clinical development, improved distribution was achieved using this device. CONCLUSIONS: CED of ACNU can be safely performed with real-time MRI monitoring. This strategy can be a novel therapeutic approach for gliomas affecting brainstem. New ultrasound assisted device achieved improved distribution in animal brain. Clinical application is warranted. SECONDARY CATEGORY: Pediatrics.
Mutations within the Rhodopsin Gene in Patients with Autosomal Dominant Retinitis Pigmentosa
Authors: Thaddeus P. Dryja, Terri L. McGee, Lauri B. Hahn, Glenn S. Cowley, Jane E. Olsson, Elias Reichel, Michael A. Sandberg, Eliot L. Berson
Journal: New England Journal of Medicine (1990)

Night blindness is an early symptom of retinitis pigmentosa. The rod photoreceptors are responsible for night vision and use rhodopsin as the photosensitive pigment.
AB0028 Smoking induces expression of mic ligands of the activating immune receptor nkg2d
Authors: C. Ospelt, A. Engler, P. Künzler, R. E. Gay, B. A. Michel, S. Gay
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Even though it is well known that smokers have an increased risk to develop rheumatoid arthritis (RA) and other autoimmune diseases, nothing is known about the molecular mechanisms that lead to break of tolerance in smokers. The innate immune receptor NKG2D and its ligands MICA and MICB have previously been described to promote autoimmune reactions. Therefore, we analysed whether smoking leads to increased expression of NKG2D ligands and activates the NKG2D system. <h3>Methods</h3> RA and osteoarthritis (OA) synovial fibroblasts (SFs) were cultured from synovial tissues from patients undergoing joint replacement surgery. Real-time PCR was used to measure expression levels of NKG2D ligands in synovial tissues and SFs stimulated with 5% cigarette smoke extract (CSE). Peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers and co-cultured with RASFs and OASFs with and without CSE for 72h. Expression of surface NKG2D was measured by flow cytometry. <h3>Results</h3> To see whether smokers have increased levels of NKG2D ligands, we measured the expression of MICA, MICB, RAET1E, RAET1G, and ULBP1-3 in synovial tissues of RA patients (5 smokers, 6 non-smokers). Expression levels of MICA and MICB were significantly higher in synovial tissues of smokers than of non-smokers, while expression levels of the other NKG2D ligands were unchanged. Accordingly, RASFs stimulated with CSE in vitro produced 2.0-fold more MICA (p=0.03, n=6) and 1.5-fold more MICB (p=0.02, n=6) compared to unstimulated cells. To test whether the increased production of MICA and MICB by SFs after CSE stimulation was relevant for the activation of the NKG2D pathway on PBMCs, we performed co-culture experiments and measured internalization of the receptor on PBMCs after ligand binding. In co-cultures of PBMCs and OASFs stimulated with CSE, NKG2D was internalized and significantly less surface NKG2D was measureable on PBMCs after 72h compared to co-cultures without CSE. In co-cultures with PBMCs and RASFs however, no change in surface NKG2D was seen with addition of CSE even though RASFs produced similar amounts of MICA and MICB after CSE stimulation than OASFs. <h3>Conclusions</h3> Smoking induces the expression of the NKG2D ligands MICA and MICB in synovial tissues. Internalization and degradation of NKG2D after binding of MIC ligands is an important control mechanism to terminate the activation of NKG2D signaling pathways. Since MIC ligands secreted by RASFs fail to induce internalization of the receptor, continuous activation of NKG2D in joints of smokers might be a trigger for the development of RA in susceptible individuals. <h3>Acknowledgements</h3> This work was supported by Masterswich, IAR, IMI-BTCure <h3>Disclosure of Interest</h3> None Declared
AB0536 Tocilizumab offers clinical and ultrasonographic improvement in rheumatoid arthritis patients. Results of a 6 months follow-up study
Authors: I. Bouaddi, H. Rkain, S. Aktaou, H. Raissouni, L. Traki, L. Bouazzaoui, B. Benchakroun, L. Benbrahim, S. Rostom, F. Allali, R. Bahiri, B. Amine, K. Benbouazza, N. Hajjaj-Hassouni
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tocilizumab (TCZ) is a humanized anti-interleukin 6 (anti-IL 6) receptor antibody that has been demonstrated in previous clinical trials to improve rheumatoid arthritis (RA) and prevent radiographic progression. Musculoskeletal ultrasonography (MSUS) has increasingly been used as outcome measures in clinical trials of RA. Thus, we aimed to evaluate clinical and ultrasonographic (US) progression in RA patients treated with TCZ. <h3>Methods</h3> Twenty two consecutive patients, affected by RA [19 females, median age of 41 years (35,50), median disease duration of 72 months (36,171)] who were non-responders or partial responders to DMARDs therapy were commenced on Tocilizumab. The patients underwent clinical, laboratory, and assessment at baseline and after 6 months. The Disease Activity Score in 28 joints (DAS28) was recorded at inclusion and after a 6 months of therapy.The German ultrasound score included the following joints of the clinically dominant hand and foot: wrist, second and third metacarpophalangeal and proximal interphalangeal, and second and fifth metatarsophalangeal joints. Synovitis and synovial vascularity were scored semiquantitatively (grade 0–3) by gray-scale (GS) and power Doppler (PD) ultrasound. Clinical remission after 6 months of treatment was defined when DAS 28 was &lt;2.6. <h3>Results</h3> At baseline, the median DAS28 score was 5.2 (4.4, 6.2) and the synovitis scores were 9.5 (6.7, 15) in GS ultrasound and 2.5 (0,7.2) in PD ultrasound. After 6 months of therapy, the DAS28 significantly decreased to 1.6 (0.8,2.4); p&lt;0.001 and the GS and PD ultrasound scores significantly decreased to respectively 5 (4,6); p=0.001 and to 0.5 (0,1.7); p=0.04. Remission at 6 months was noted in 70% of patients. <h3>Conclusions</h3> This study indicates good evolution of RA patients under TCZ on basis on clinical and ultrasonographic findings. These results should be verified by further studies. <h3>Disclosure of Interest</h3> None Declared