tbuckley/cabot-search huggingface dataset:
Gene markers of progression of Barrett’s metaplasia to carcinoma.
Authors: Wolfgang Kemmner
Journal: Journal of Clinical Oncology (2012)

46 Background: The incidence of esophageal adenocarcinoma (EAC) has increased strongly during the past 30 years and 5-year survival remained poor at approximately 20%. Barrett’s esophagus (BE) metaplasia is considered to be the key precursor lesion of EAC. The aim of this study was to generate and validate biomarkers to stratify patients with BE in terms of their risk for developing cancer. Methods: We studied gene expression profiling of normal esophageal squamous epithelium (NE), BE, intraepithelial neoplasia (IEN) and esophageal adenocarcinoma (EAC). Laser capture microdissection (LMD) technique was applied to procure cells from defined regions. Microarray results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in a second and independent cohort. Furthermore, immunohistochemistry was performed on a third independent cohort. Results: The expression profile of BE was compared to EAC and NE resulting in a short list of 16 genes which were differentially expressed among all 3 groups. Hierarchical clustering of all samples based on the expression of these 16 candidate marker genes allowed a clear discrimination of NE, BE and EAC. Validation of the microarray results in an independent patient cohort by qRT-PCR confirmed that the genes CTHRC1, INHBA, PROCR and ADH7 expression correlate with the histological progression to EAC. Accordingly, immunohistochemistry showed that the presence of CTHRC1 and INHBA was high only in EAC. Conclusions: Here, we focus on neoplastic progression and describe a set of genes representing potential biomarkers to predict oesophageal Barrett’s adenocarcinoma at its early stage. These biomarkers can be determined by quantitative expression analysis, which will complement conventional semi-quantitative immunohistochemical analysis in the future. This work was feasible only through intensive cross-discipline collaboration between clinical researchers, pathologists, and basic molecular researchers and is thought to be the starting point for a long-term multicenter study on the clinical validation of the putative markers described here.
Identification of ADAMTS13 Peptide Sequences Recognized by Autoantibodies in Patients with Acquired Thrombotic Thrombocytopenic Purpura.
Authors: Yusuke Yamaguchi, Takanori Moriki, Hideo Wada, Masanori Matsumoto, Yoshihiro Fujimura, Terumichi Nakagawa, Atsuko Igari, Yasuo Ikeda, Mitsuru Murata
Journal: Blood (2008)
Infliximab Drives Gamma-Delta T Cell Expansion In Crohn's Disease – a Predictor of Lymphoma Risk?
Authors: Jens Kelsen, Heinrich Schwindt, Anders Dige, Francesco d'Amore, Finn Skou Pedersen, J∅rgen Agnholt, Lisbet Ambrosius Christensen, Jens Frederik Dahlerup, Christian Lodberg Hvas
Journal: Blood (2010)
Effect of Phlebotomy Therapy On Hemoglobin Concentration and Tricuspid Regurgitation Velocity in Chuvash Polycythemia.
Authors: Galina Y Miasnikova, Xiaomei Niu, Mehdi Nouraie, Adelina I Sergueeva, Daniel J Okhotin, Tatiana Ammosova, Sergei Nekhai, Zakari Aliyu, Craig Sable, Niti Dham, Victor R. Gordeuk
Journal: Blood (2009)
Fludarabine-Based Reduced Intensity Regimen for Matched Related Donor Stem Cell Transplantation in Acquired Severe Aplastic Anemia
Authors: Khaled M Ghanem, Mohamed A. Kharfan-Dabaja, Hassan El-Solh, Nariman Harris, Nabila Kreidieh, Rita Nehme, Samar A. Muwakkit, Raya Saab, Ali Bazarbachi, Miguel R Abboud
Journal: Blood (2016)
The Prodrug AQ4N Displays Potent Anti-Tumor Activity in a Xenotransplantation Model of Primary Human Acute Lymphoblastic Leukemia.
Authors: Bart A. Nijmeijer, Marianke L.J. Van Schie, Susan E. Alters, Alvin Wong, Jeffrey L. Cleland, Roelof Willemze, J.H. Frederik Falkenburg
Journal: Blood (2005)
Percutaneous radiofrequency ablation therapy as a first choice for renal tumor in patients with von Hippel-Lindau disease.
Authors: K. Uematsu, T. Saika, D. Kanbara, Y. Kobayashi, H. Gobara, T. Hiraki, H. Mimura, S. Kanazawa, Y. Nasu, H. Kumon
Journal: Journal of Clinical Oncology (2011)

375 Background: Forty percent of patients with von Hippel-Lindau (VHL) disease have multifocal, bilateral renal cell carcinoma (RCC). The advent of ablative therapy has allowed many of these tumors to be approached percutaneously. Probe-based radiofrequency ablation (RFA) have recently been shown to be feasible nephron-sparing therapies for RCC, and have been proposed as first-line treatments for patients with VHL. We evaluated the feasibility, safety and therapeutic effects of RFA for VHL patients. Methods: We reviewed the outcomes of VHL patients with RCC treated by RFA from 2003 to 2010. Follow-up consisted of serum creatinine measurement, physical examination and serial contrast enhanced computerized tomography or magnetic resonance imaging. Results: The 42 tumors of 15 patients (23-70 years old, median 40) received a total of 43 RFA treatments to a 7 to 28 mm renal tumor (median 16). Seven of the patients had bilateral renal tumors. Tumor enhancement was eliminated and the renal function was preserved after the treatment in all tumors. There were no major complications related to the procedures though eight of small subcapsular hematomas, one of hematuria, one of small urine overflow, and one of nausea were seen after RFA. There was no recurrence after RFA during a mean follow-up period of 28.9 months (range 4.0-89.0, median 20.0 months). The overall recurrence-free survival rate was 100%. There was also a 100% metastasis-free and disease specific survival rate in the cohort. Conclusions: The result of the present study showed percutaneous RFA was a feasible, safe, and promising therapy for the treatment of VHL patients with RCC. No significant financial relationships to disclose.
First line with bevacizumab in combination with paclitaxel (P) and gemcitabine (G) in patients with HER2-negative or recurrent mBC: First PFS analysis.
Authors: J. Salvador, A. Jaen, E. M. Ciruelos, M. Codes, M. Gil, A. Murias, A. Galan, J. R. De la Haba, C. Jara, J. L. Bayo, J. M. Baena, J. Casal, J. R. Mel, I. Blancas, E. Gonzalez, D. Perez, L. Manso
Journal: Journal of Clinical Oncology (2011)

1112 Background: The combination of bevacizumab (B) with taxanes, capecitabine or anthracyclines has shown increased PFS in pts with mBC. The combination with G and P has been evaluated and has demonstrated high response rate and good toxicity profile. The aim of this study is to evaluate the efficacy and toxicity profile of the combination of B with G and P, providing a preliminary analysis of response and PFS in pts include and the toxicity experienced in all pts treated. Methods: A phase II multicenter, national, open-label study in pts diagnosed of recurrent or metastatic HER2 negative BC, treated with first-line B 10 mg/kg, P 150 mg/m2 and G 2000 mg/m2 day 1 and 15 c/28 d until progression disease, unacceptable toxicity or medical decision. This abstract evaluates efficacy by the response rate and PFS and the toxicity profile of the combination of all pts included. The primary end point is PFS and toxicity is evaluated according to NCI CTC v3.0 criteria. Results: From January 2009 to December 2009, 82 evaluable pts were recruited in 23 sites. The characteristic of the all of pts included (90) are: median age 51.5 (26-81), ER + 68%, PR + 59%, triple negative pts 19%, previous chemotherapy (neoadj or adj) 64.4% and > 3 metastatic sites 84% of patients (76). The median cycles administered per pts is 7 (1-21) and the relative median dose intensity is 0.94 for B, 0.90 for P and 0.92 for G. Of the 76 pts with response assessment, the overall response obtained was 71.1% with a clinical benefit of 88.2% (78.71-94.44%) (CR 14.5% (11), PR 56.6% (43), SD 17.1% and PD 11.8%). Of the 82 pts with a median follow up of 12.94 m (0.16- 20.66), the preliminary median PFS for these pts is 10.07 m (8.62-11.22). Toxicity was generally easily controlled. Conclusions: The treatment obtains a high overall response and preliminary PFS and was well tolerated by this pt group (mBC HER2 -). G 1-2 (%) G 3 (%) G 4 (%) Anemia 13.4 1.2 Neutropenia 12.2 6.1 1.2 Febrile neutropenia 1.2 1.2 Thrombocytopenia 6.1 2.4 G 3-4 (%) Vomiting 2.4 Asthenia 4.9 Pyrosis 1.2 Peripheral neuropathy 7.3 Paresthesia 2.4 Infections 4.9 Hypertension 3.7 Acute myocardial infarction 1.2 Palmoplantar erythrodysaesthesia syndrome 1.2
Re-establishing pluripotency in adult cells derived from breast stromal tissue.
Authors: S. M. L. Lim, I. Aksoy, K. G. C. Lim, J. Karuppasamy, U. Divakar, F. J. Ma, F. L. Lam, S. J. N. Remulla, L. W. Stanton
Journal: Journal of Clinical Oncology (2011)

227 Background: Recent advances in pluripotent stem cell biology offer patient-specific disease models to investigate in vitro mechanisms of tumorigenesis. Induced pluripotent stem (iPS) cells were originally derived by reprogramming of human dermal fibroblasts through ectopic expression of pluripotency–associated transcription factors. A limitation to the use of dermal fibroblasts as the starting cell type for reprogramming is that it usually takes weeks to expand cells from a single biopsy, and the efficiency of the process is very low. In contrast, a large number of adipose-derived mesenchymal stromal cells (Ad-MSCs) can be easily obtained from the stroma of human breast tissue, without the time-consuming steps of cell expansion. Here we investigated the ability to induce pluripotency in committed, Ad-MSCs derived from the stroma of breast tissue. Methods: The aim of this study is to investigate the potential of using Ad-MSCs derived from surgically discarded breast stromal tissue to generate human iPS. Discarded tissue during surgical procedures was processed in vitro and Ad-MSCs were derived. These Ad-MSCs were then used to generate iPS cells by ectopic expression of “Yamanaka’s cocktail” containing OCT4, SOX2, KLF4 and c-MYC. Results: The success rate in generating iPS cells from human Ad-MSCs derived from breast stromal tissue is very high compared to the use of dermal fibroblasts. In our study, almost all human Ad-MSC cell lines can be reprogrammed into iPS cells, which share the same characteristics as skin fibroblast-derived iPS cells and human embryonic stem cells in their morphology, gene expression profile and differentiation capacities. Conclusions: We are now optimizing this approach and making it more clinically relevant by adopting an integration-free method to deliver the reprogramming factors. The successful reprogramming of breast stromal-derived Ad-MSCs into iPS cells may provide a valuable source of patient-specific iPS cells to study the mechanism of tumorigenesis in patients with breast cancer.
An expanded population of pathogenic regulatory T cells in giant cell arteritis is abrogated by IL-6 blockade therapy
Authors: Chie Miyabe, Yoshishige Miyabe, Klemen Strle, Nancy D Kim, John H Stone, Andrew D Luster, Sebastian Unizony
Journal: Annals of the Rheumatic Diseases (2016)

Randomised-controlled trials have recently proven the efficacy of the interleukin (IL)-6 receptor antagonist tocilizumab (TCZ) in giant cell arteritis (GCA). However, the mechanism of action of IL-6 blockade in this disease is unknown. Moreover, the role of regulatory T (Treg) cells in the pathogenesis of GCA remains underexplored. Given the plasticity of Tregs and the importance of IL-6 in their biology, we hypothesised that TCZ might modulate the Treg response in GCA. We therefore characterised the Treg compartment of patients with GCA treated with TCZ.We classified 41 patients with GCA into three groups: active disease (aGCA, n=11), disease remission on corticosteroids (rGCA-CS, n=19) and disease remission on TCZ (rGCA-TCZ, n=11). Healthy controls (HCs) were included for comparison. We determined the frequency, phenotype and function of peripheral blood Tregs.Patients with aGCA demonstrated a hypoproliferating Treg compartment enriched in IL-17-secreting Tregs (IL-17+Tregs). Tregs in patients with aGCA disproportionally expressed a hypofunctional isoform of Foxp3 that lacks exon 2 (Foxp3Δ2). Foxp3Δ2-expressing Tregs coexpressed CD161, a marker commonly associated with the Th17 linage, significantly more often than full-length Foxp3-expressing Tregs. Compared with those of HCs, GCA-derived Tregs demonstrated impaired suppressor capacity. Treatment with TCZ, in contrast to CS therapy, corrected the Treg abnormalities observed in aGCA. In addition, TCZ treatment increased the numbers of activated Tregs (CD45RA-Foxp3high) and the Treg expression of markers of trafficking (CCR4) and terminal differentiation (CTLA-4).TCZ may exert its therapeutic effects in GCA by increasing the proliferation and activation of Tregs, and by reverting the pathogenic Treg phenotype seen during active disease.
Phase III study of the efficacy and safety of zibotentan (ZD4054) in patients with bone metastatic castration-resistant prostate cancer (CRPC).
Authors: J. B. Nelson, K. Fizazi, K. Miller, C. S. Higano, J. W. Moul, T. Morris, S. McIntosh, K. Pemberton, M. E. Gleave
Journal: Journal of Clinical Oncology (2011)

117 Background: Endothelin-1 and the endothelin A (ET A ) receptor have been implicated in prostate cancer progression in bone. Zibotentan, a specific ET A receptor antagonist, had a promising signal for prolonged overall survival (OS) in a phase II study of patients with CRPC and bone metastases who were pain free or mildly symptomatic for pain. The aim of this phase III study was to confirm the efficacy and safety of zibotentan in a similar but larger population. Methods: Patients with CRPC and bone metastases were randomized 1:1 to zibotentan 10 mg/day po or placebo, plus standard of care including chemotherapy. The primary endpoint was OS. Secondary endpoints included times to pain progression, chemotherapy use, new bone metastases, and safety. Efficacy endpoints were analyzed using a log-rank test. At least 263 deaths were required for formal analysis. If the true hazard ratio (HR) for zibotentan versus placebo was 0.67, the analysis would have 90% power to demonstrate a statistically significant effect in OS at the 5% level. Results: A total of 594 patients were randomized (299 to zibotentan; 295 to placebo). Baseline group demographics were similar. Mean age was ∼71 yrs, and 64% were Caucasian. Although median OS was longer in zibotentan-treated patients than those receiving placebo (median 24.5 vs 22.5 months), the difference did not reach significance (HR [95.2% confidence interval]; 0.87 [0.69–1.10]: P=0.240). No significant differences were observed for any secondary endpoints. The most commonly reported AEs in the zibotentan group, peripheral edema and headache, were consistent with the pharmacologic action of zibotentan as a vasodilator. Cardiac failure events, actively solicited following a phase II signal, were higher in the zibotentan group (any grade, 5.7%; Common Terminology Criteria for Adverse Events [CTCAE] grade ≥3, 3.0%) than placebo (any grade, 1.7%; CTCAE grade ≥3, 1.0%), but were manageable and reversible. Conclusions: In this placebo-controlled phase III trial treatment with zibotentan 10 mg/day did not lead to a significant improvement in OS in patients with CRPC and bone metastases. Zibotentan had an acceptable safety profile. [Table: see text]
Phase II trial of biweekly gemcitabine, paclitaxel, and bevacizumab as frontline therapy for metastatic breast cancer (MBC).
Authors: Z. A. Nahleh, R. Gupta, J. Abrams, E. M. Gartner, L. Reichle
Journal: Journal of Clinical Oncology (2011)

e11527 Background: Gemcitabine with paclitaxel has been shown to be superior to paclitaxel alone as frontline therapy for MBC. Also adding bevacizumab confers a significant improvement over paclitaxel alone in MBC. The purpose of this study was to evaluate the safety and efficacy of a novel combination and schedule of these three agents. Methods: Phase II single arm, IRB approved. Women with MBC (M1), HER2 negative with no prior chemotherapy for MBC received paclitaxel 150 mg/m², gemcitabine 1,500 mg/ m² and bevacizumab 10 mg/kg, all given on Day 1 every 2 weeks. Response was assessed by RECIST criteria, and toxicitiy by NCI CTCAE version 3.0. The primary endpoint was progression-free survival (PFS) and the trial was designed to detect a 50% improvement in median PFS, from the historical rate of 5.3 months to 8 months. Results: Fourteen women were enrolled between 12/08 and 12/10. Median age 48 years (range 33-72) :10 Caucasians, 3 African Americans, and 1 Middle Eastern; 35% had more than 3 visceral metastatic sites, and 64% had ER/PR positive tumors. Median number of treatment cycles was 9 (range 1-24). Average duration of time on study was 4 months (range 0-11). At a median follow-up of 17 months, median PFS is 11 months (95% CI: 7- NR). The ORR (CR+PR) is 43% (95% CI: 21%-67%). One patient with triple negative MBC, metastatic to lung achieved a CR. Five patients (36%) had stable disease (SD), making the total response rate (ORR+ SD) 79%. Grade 3 or 4 toxicity rate was 57%.The most common toxicities were fatigue, hyperglycemia and nausea (Table). One patient experienced cardiac ischemia and another grade 3 diarrhea. Conclusions: The combination of gemcitabine, paclitaxel and bevacizumab all given every 2 weeks appears to be very effective without unexpected toxicities. The trial closed early primarily as a result of slow accrual. However, we believe that this combination deserves further evaluation possibly at slightly reduced doses of gemcitabine and paclitaxel. Grade 3 or 4 toxicities experienced by > 2 patients. Number of patients (%) Toxicity Grade 6 (43) Pain 3 4 (29) Hyperglycemia 3 3 (21) Dyspnea 3 and 4 3 (21) Anemia 3 2 (14) Fatigue 3 2 (14) Hypertension 3 2 (14) Peripheral neuropathy 3
Human Papillomavirus Type 16 (HPV16) E6/E7-Specific Cytotoxic T Lymphocytes (CTLs) for Immunotherapy of HPV-Associated Malignancies
Authors: Carlos A. Ramos, Neeharika Narala, Ann M. Leen, Ulrike Gerdemann, Matthew L. Anderson, Erich M. Sturgis, Barbara Savoldo, Helen E. Heslop, Malcolm K. Brenner, Cliona M. Rooney
Journal: Blood (2011)
NFκB-Induced Periostin Activates Integrin-β3 Signaling to Promote Renal Injury in GN
Authors: Niki Prakoura, Panagiotis Kavvadas, Raphaёl Kormann, Jean-Claude Dussaule, Christos E. Chadjichristos, Christos Chatziantoniou
Journal: Journal of the American Society of Nephrology (2016)

De novo expression in the kidney of periostin, a protein involved in odontogenesis and osteogenesis, has been suggested as a biomarker of renal disease. In this study, we investigated the mechanism(s) of induction and the role of periostin in renal disease. Using a combination of bioinformatics, reporter assay, and chromatin immunoprecipitation analyses, we found that NF κ B and other proinflammatory transcription factors induce periostin expression in vitro and that binding of these factors on the periostin promoter is enriched in glomeruli during experimental GN. Mice lacking expression of periostin displayed preserved renal function and structure during GN. Furthermore, delayed administration of periostin antisense oligonucleotides in wild-type animals with GN reversed already established proteinuria, diminished tissue inflammation, and improved renal structure. Lack of periostin expression also blunted the de novo renal expression of integrin- β 3 and phosphorylation of focal adhesion kinase and AKT, known mediators of integrin- β 3 signaling that affect cell motility and survival, observed during GN in wild-type animals. In vitro , recombinant periostin increased the expression of integrin- β 3 and the concomitant phosphorylation of focal adhesion kinase and AKT in podocytes. Notably, periostin and integrin- β 3 were highly colocalized in biopsy specimens from patients with inflammatory GN. These results demonstrate that interplay between periostin and renal inflammation orchestrates inflammatory and fibrotic responses, driving podocyte damage through downstream activation of integrin- β 3 signaling. Targeting periostin may be a novel therapeutic strategy for treating CKD.
Safety and Efficacy of Blinatumomab Used in Children with B-Precursor Acute Lymphoblastic Leukemia (ALL) Treated in French Hematological Centers
Authors: Anne-Flore Derache, Fanny Rialland, Gerard Michel, Yves Perel, Virginie Gandemer, Pascale Blouin, Odile Minckes, Arnaud Petit, Andre Baruchel, Benoit Brethon
Journal: Blood (2016)
Global Proteomics in AML: Using SELDI-TOF MS on Diagnostic Samples To Identify Spectra and Protein Biomarkers Indicative of Prognosis.
Authors: Leif Stenke, Maria Pernemalm, Jenny Forshed, Yodi Pawitan, Marita Lagergren-Lindberg, Lena Kanter, Janne Lehtiö
Journal: Blood (2006)
Alfred Wilson McKenzie
Authors: Colin McKenzie
Journal: BMJ (2016)

Alfred Wilson McKenzie (“Freddie”) was a consultant dermatologist of international repute. He was responsible for creating a revolutionary method for assessing and quantifying topical anti-inflammatory activity through the application of steroids to human skin (the McKenzie test).

Freddie was born and spent his childhood in Edinburgh, apart from a year in Burghead as an evacuee. He attended the Royal High School in Edinburgh, where he learnt to play the bagpipes and the violin. The violin was to prove a lifelong love, and he was proud that as a boy he not only performed on the stage of Edinburgh’s Usher Hall but was singled out for praise from the music critic of the Edinburgh Evening News . His love of the bagpipes did not endure, perhaps because he had to practice in the Anderson shelter in the garden to avoid annoying the neighbours.

He finished his national service as a 2nd lieutenant in 1949 and started his medical training at Edinburgh University. As an undergraduate he was awarded the gold medal for medicine, the gold medal of the Royal Victoria Hospital Tuberculosis Trust, and …
An adolescent with disabling abdominal pain
Authors: Marta Minute, Giorgio Cozzi, Egidio Barbi
Journal: BMJ (2016)

A previously healthy teenager was taken to a paediatric emergency department with abdominal pain, nausea, and fatigue. The pain had started four months earlier and had increased in severity and frequency, occurring daily in the past month and resulting in her missing three weeks of school and preventing her from participating in other activities. Painkillers had not helped. The results of repeated diagnostic tests were all normal, including complete blood cell count; blood and faecal inflammatory markers; renal, hepatic, and pancreatic function; urine analysis; and serial abdominal ultrasound scans. Despite repeated medical evaluations, there was no defined diagnosis. The girl reported a dull discomfort in the periumbilical area. She had no fever, vomiting, stool alteration, weight loss, nocturnal pain, or sleep problems. Her parents were concerned that this was a serious illness, given the worsening of symptoms over the past month, the lack of response to drug treatment, and the absence of a clear diagnosis. On examination, the girl appeared well, although she rated her pain 8 out of 10. Vital signs were normal and cardiorespiratory and abdominal examinations were unremarkable.