tbuckley/cabot-search huggingface dataset:
P014/O04 Phenotypic heterogeneity of regulatory T cells in rheumatoid arthritis
Authors: Y El Ahmadi, M Cren, Y-M Pers, E Dufourq-Lopez, C Jorgensen, R Fereirra, P Louis-Plence
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> Rheumatoid arthritis (RA) is the most frequent chronic inflammatory rheumatism characterized by infiltration of many immune cells into the synovial tissue leading to cartilage and bone degradation over time. The working hypothesis of our team is to use immunomodulatory properties of regulatory T (Treg) cells to restore immune homeostasis in RA. These approaches are based on a better knowledge of the cell populations present in the inflamed tissue and in particular the sub-populations of Treg cells. Heterogeneity of Treg cells is well known however most Treg studies in RA have focused on CD25+FoxP3+ Treg cells in the peripheral blood of patients. <h3>Objectives</h3> In this project using innovative approaches such as 18-colors cytometric analyses our project aims to better characterize the Treg subsets to unravel the heterogeneity of the Treg cell subsets in RA. <h3>Methods</h3> The phenotypic analyses will be performed using 18-colors conjugated antibodies, analyzed on the LSR II, to allow the simultaneous characterization of CD25+FoxP3+ Tregs, Tr1 cells and CD8<sup>+</sup> Tregs within the T lymphocytes. Activation status of the various subsets will be also investigated using various activation markers. The phenotypic characterization will be performed on the synovial fluid (SF) and peripheral blood (PB) from RA and Osteoarthritis patients used as controls. <h3>Results</h3> The preliminary results showed that the frequency of CD25+FoxP3+ is higher in the SF compare with PB in both pathologies. Furthermore, the phenotype and activation status of CD25+FoxP3+ Treg cells is different between both fluids with an accumulation of effector activated CD25+FoxP3+ Treg cells in the SF. Interestingly, whereas Tr1 cells are barely detectable in the peripheral blood, the Tr1 subset seems to be enriched in the synovial fluid in both pathologies. <h3>Conclusions</h3> This study confirm the presence of activated CD25+FoxP3+ Treg cells in the SF of RA and provide evidence for the presence of other Treg subsets in SF. A better characterization of the suppressive activity of the various Treg subsets need to be investigated and particularly in inflammatory conditions. A better understanding of the suppressive function of the various Treg subsets will thus provide identification of new therapeutic targets in RA patients. <h3>Disclosure of Interest</h3> None declared.
Cystic transformation of focal lesions after therapy is associated with remission but adverse outcome in myeloma
Authors: Maximilian Merz, Thomas Hielscher, Elias Karl Mai, Anja Seckinger, Dirk Hose, Anna Jauch, Sandra Sauer, Steffen Luntz, Uta Bertsch, Marc S. Raab, Kai Neben, Hans Salwender, Igor W. Blau, Hans-Walter Lindemann, Jan Dürig, Christof Scheid, Mathias Haenel, Katja Weisel, Tim Weber, Stefan Delorme, Hartmut Goldschmidt, Jens Hillengass
Journal: Blood Cancer Journal (2019)
Mutant calreticulin interacts with MPL in the secretion pathway for activation on the cell surface
Authors: Nami Masubuchi, Marito Araki, Yinjie Yang, Erina Hayashi, Misa Imai, Yoko Edahiro, Yumi Hironaka, Yoshihisa Mizukami, Yoshihiko Kihara, Hiraku Takei, Mai Nudejima, Masato Koike, Akimichi Ohsaka, Norio Komatsu
Journal: Leukemia (2019)
Cancer cell reprogramming: a promising therapy converting malignancy to benignity
Authors: Lanqi Gong, Qian Yan, Yu Zhang, Xiaona Fang, Beilei Liu, Xinyuan Guan
Journal: Cancer Communications (2019)

Abstract In the past decade, remarkable progress has been made in reprogramming terminally differentiated somatic cells and cancer cells into induced pluripotent cells and cancer cells with benign phenotypes. Recent studies have explored various approaches to induce reprogramming from one cell type to another, including lineage‐specific transcription factors‐, combinatorial small molecules‐, microRNAs‐ and embryonic microenvironment‐derived exosome‐mediated reprogramming. These reprogramming approaches have been proven to be technically feasible and versatile to enable re‐activation of sequestered epigenetic regions, thus driving fate decisions of differentiated cells. One of the significant utilities of cancer cell reprogramming is the therapeutic potential of retrieving normal cell functions from various malignancies. However, there are several major obstacles to overcome in cancer cell reprogramming before clinical translation, including characterization of reprogramming mechanisms, improvement of reprogramming efficiency and safety, and development of delivery methods. Recently, several insights in reprogramming mechanism have been proposed, and determining progress has been achieved to promote reprogramming efficiency and feasibility, allowing it to emerge as a promising therapy against cancer in the near future. This review aims to discuss recent applications in cancer cell reprogramming, with a focus on the clinical significance and limitations of different reprogramming approaches, while summarizing vital roles played by transcription factors, small molecules, microRNAs and exosomes during the reprogramming process.
Real-World Outcomes for Maintenance Treatment Sequencing after Receiving Lenalidomide, Bortezomib, and Dexamethasone Induction in Patients with Newly Diagnosed Multiple Myeloma (NDMM) Followed By Autologous Stem Cell Transplant (ASCT)
Authors: Rafael Fonseca, Kejal Parikh, Brian Ung, Quanhong Ni, Safiya Abouzaid, Amit Agarwal
Journal: Blood (2017)
10-year follow-up results of perioperative chemotherapy with doxorubicin (DXR) and ifosfamide (IFM) for high-grade soft tissue sarcomas (STS) in the extremities: Japan Clinical Oncology Group study JCOG0304.
Authors: Kazuhiro Tanaka, Junki Mizusawa, Norifumi Naka, Akira Kawai, Hirohisa Katagiri, Toru Hiruma, Yoshihiro Matsumoto, Hiroyuki Tsuchiya, Robert Nakayama, Hiroshi Hatano, Makoto Emori, Masami Hosaka, Yukihiro Yoshida, Takeshi Okamoto, Satoshi Abe, Kunihiro Asanuma, Ryohei Yokoyama, Haruhiko Fukuda, Toshifumi Ozaki, Yukihide Iwamoto
Journal: Journal of Clinical Oncology (2019)

e22533 Background: STS are rare malignant tumors and relatively resistant against chemotherapy. We have previously reported 3-year follow-up on the efficacy results of perioperative chemotherapy with DXR and IFM for STS in the extremities (JCOG0304) in ASCO 2011 (abstract ID:#10078). In the present report, we analyzed 10-year follow-up results of JCOG0304. Methods: Patients with operable, FNCLCC grade 2/3 STS (T2bN0M0, AJCC 6th edition) in the extremities were treated with 3 courses of preoperative and 2 courses of postoperative chemotherapy consisted of DXR 60 mg/m 2 plus IFM 10 g/m 2 in 3-week interval. Primary endpoint was progression-free survival (PFS). Prognostic factors were evaluated by log-rank test. Results: A total of 72 patients were enrolled between March 2004 and September 2008, and 70 patients were eligible. Median follow-up period was 10.0 years for all eligible cases. The local recurrence and distant metastasis were observed in 5 and 19 patients, respectively. Ten-year progression-free survival (PFS) was 65.7% (95% CI, 53.4%-75.5%) with no PFS event within last 5-year of follow-up. Ten-year overall survival (OS) was 78.1% (95% CI, 66.3%-86.2%). Subgroup analysis demonstrated no significant difference in PFS and OS regarding age, sex, histological grade, and histology. Secondary malignancy occurred in 6 patients. Conclusions: Only a few long-term results of clinical trials of perioperative chemotherapy for STS have been reported. Our results demonstrated that the 10-year outcome of JCOG0304 for the patients with operable, high-grade STS in the extremities was stable and remained favorable. Clinical trial information: C000000096.
Abstract 2259: Risk of Death and Beneficial Effects of Statins in Acute Coronary Syndromes Related to Inflammatory Markers in the MIRACL Study
Authors: Scott Kinlay, Gregory G Schwartz, Anders G Olsson, Nader Rifai, Michael Szarek, Peter Libby, Peter Ganz
Journal: Circulation (2006)

Objective: To assess the relationships of inflammatory markers C-reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL6) to prognosis after an acute coronary syndrome (ACS) and their...
Outcome research: Ambulatory intraperitoneal chemotherapy in stage IIIC ovarian cancer.
Authors: Carlos Garcia Gerardi, Javier Vidaurreta, Ernesto Gil Deza, Nelson Kohen, Claudio Levit, Eduardo L. Morgenfeld, Sebastian Alessandria, Edgardo G. J. Rivarola, Felipe G. Gercovich
Journal: Journal of Clinical Oncology (2012)

e15507 Background: Intraperitoneal chemotherapy in stage III ovarian cancer is indicated following the results of the GOG 172 study but the ambulatory application of the scheme in 24 hours continuous infusion is not feasible. Following expert recommendations (Walker, ASCO 2009 Educational Book), we evaluated the feasibility of administrating a modified GOG 172 regime in an ambulatory form. Methods: Between September 2009 and October 2010, ten patients diagnosed with stage IIIC ovarian cancer and optimal cytoreduction received the following treatment in ambulatory form: IV paclitaxel (135mg/m 2 /3hrs Day 1), followed by IP cisplatin (60-75mg/m 2 Day 2), plus IP paclitaxel (60mg/m 2 Day 8). Cycles were administered every 21 days, up to a maximum of six cycles. The tolerance for this treatment was evaluated according to the CTC for Adverse Event 3.0. Results: Population Characteristics: Mean age (47 years; range 26-64). PS (0: 4 pt; 1: 6 pt). Pathology (Papillary: 7 Pts; Mucinous, Endometroid and Poorly Differentiated: 1 pt each). N-positives: 4 pt; N-negatives: 6 pt. Intestinal resection: 1pt. In all cases, treatment was applied according to the specified parameters. Total number of cycles administered: 37 (mean cycles per pt 3 range 2-6). The average time of treatment application was 3 hours per day (9 hours total). Toxicity (G3-4): Leukopenia (2 pts). Toxicity (G1-2): Alopecia (10 pts), Anemia (9 pts), Myalgia (8 pts), Neurologic (7 pts), Fatigue (6 pts), Nausea and vomiting (6pt), Renal (2 pts), Allergy (1 pt), Pain at Catheter site (1 pt). With an average follow up time of 16 months (Range: 9-26), none of the patients have died. Three patients have progressed after the Intraperitoneal chemotherapy, while seven are alive without evidence of disease after the treatment. Conclusions: 1) The modified GOG 172 scheme can be safely applied in an ambulatory form. 2) The time required for applying the treatment is similar to that of other frequently used treatments (BEP, paclitaxel – trastuzumab, R-CHOP, b-FOL). 3) Patient tolerance was very good. 4) With an average follow-up of 16 months, all 10 patients are alive and 7 of them remain free of disease.
PD-L1 expression is a predictive biomarker for CIK cell-based immunotherapy in postoperative patients with breast cancer
Authors: Zi-Qi Zhou, Jing-Jing Zhao, Qiu-Zhong Pan, Chang-Long Chen, Yuan Liu, Yan Tang, Qian Zhu, De-Sheng Weng, Jian-Chuan Xia
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> A sequential combination of radiochemotherapy/endocrinotherapy and cytokine-induced killer cell (CIK) infusion has been shown to be an effective therapy for post-mastectomy breast cancer based on statistical analysis of the patient population. However, whether an individual could obtain an improved prognosis from CIK cell-based treatment remains unknown. In the present study, we focused on immune microenvironment regulation and specifically investigated the relationship between PD-L1 expression and survival benefit from CIK immunotherapy in breast cancer. <h3>Methods</h3> A total of 310 postoperative breast cancer patients who received comprehensive treatment were enrolled in this retrospective study, including 160 patients in the control group (received chemotherapy/radiotherapy/endocrinotherapy) and 150 patients in the CIK cell treatment group (received chemotherapy/radiotherapy/ endocrinotherapy and subsequent CIK infusion). <h3>Results</h3> We found that overall survival (OS) and recurrence-free survival (RFS) were significantly better in the CIK group than that in the control group. PD-L1 expression in tumor tissue sections was showed to be an independent prognostic factor for patients in the CIK treatment group using multivariate survival analysis. Further survival analysis in the CIK group showed that patients with PD-L1 tumor expression exhibited longer OS and RFS. In addition, among all patients who were enrolled in this study, only the patients with PD-L1 expression experienced survival benefits from CIK treatment. <h3>Conclusions</h3> Our study showed the relationship between PD-L1 expression and CIK therapy and revealed that PD-L1 expression in the tumor is as an indicator of adjuvant CIK therapy for postoperative breast cancer.
Plasmonic gold nanoparticles: Optical manipulation, imaging, drug delivery and therapy
Authors: Majid Sharifi, Farnoosh Attar, Ali Akbar Saboury, Keivan Akhtari, Nasrin Hooshmand, Anwarul Hasan, Mostafa A. El-Sayed, Mojtaba Falahati
Journal: Journal of Controlled Release (2019)
Predictive biomarkers of response to cetuximab in Chinese patients with metastatic colorectal cancer.
Authors: Brigette Ma, Herbert Loong, Giok Siong Liem, Frankie Mo, Joanna Tong, SC Cesar Wong, Anthony T. C. Chan, Ka Fai To
Journal: Journal of Clinical Oncology (2012)

e14085 Background: The paraffin-embedded tumor samples of 183 Chinese patients (pts) with metastatic colorectal cancer (mCRC) who had chemotherapy (chemo) over a period of 3.3 years were analyzed for the presence of KRAS, PIK3CA and BRAF mutations. Methods: PCR-direct sequencing was performed in micro-dissected tumor cells. The relationship between mutation and survival was evaluated using the Proportional Hazard Model, and relationship with drug response was evaluated with logistic regression. Multivariate analysis was used to adjust for the influence of age, sex, prior lines of chemo, use of bevacizumab (Bev) and the number of sites of metastases. Results: The median age was 58 yrs, over 50% of pts had &gt; 2 lines of chemo and 50% had cetuximab. The prevalence of KRAS, BRAF and PI3KCA mutations were: 55%, 5%, 20% respectively. The prevalence of each KRAS mutation subtype was: G12D (36%), G12V (22%) and G13D (16%). KRAS mutation and prior use of Bev were independent prognostic factors with respective hazard ratios (HR) of 1.5 (95% CI = 1.05-2.16, p = 0.03) and 0.51 (95% CI = 0.3-0.87, p = 0.01). In the subgroup of patients who received cetuximab and chemotherapy in the first-line setting, KRAS mutation was associated with a lack of response to chemo with odd ratio (OR) of 0.1 (95% CI = 0.01-0.79, p=0.03). There was no correlation between the presence of BRAF and/ or PIK3CA mutations and OS or drug response. Five pts had co-expression of KRAS and PIK3CA mutations and none of them responded to cetuximab. Of the 14 pts who had complete response or prolonged disease stabilization to cetuximab-chemo, 4 had KRAS mutation, 1 had PIK3CA mutation and none had BRAF mutations. Conclusions: The prevalence of KRAS, BRAF and PIK3CA mutations reported in this Chinese cohort is consistent with reports from other non-Asian populations. KRAS mutation is an independent negative prognostic factor in chemo-treated pts with mCRC. KRAS mutation was associated with poorer response to 1 st line cetuximab-based chemo.
miR-378a influences vascularization in skeletal muscles
Authors: Bart Krist, Paulina Podkalicka, Olga Mucha, Mateusz Mendel, Aleksandra Sępioł, Olga Martyna Rusiecka, Ewelina Józefczuk, Karolina Bukowska-Strakova, Anna Grochot-Przęczek, Mateusz Tomczyk, Damian Klóska, Mauro Giacca, Paweł Maga, Rafał Niżankowski, Alicja Józkowicz, Agnieszka Łoboda, Józef Dulak, Urszula Florczyk-Soluch
Journal: Cardiovascular Research (2019)

MicroRNA-378a, highly expressed in skeletal muscles, was demonstrated to affect myoblasts differentiation and to promote tumour angiogenesis. We hypothesized that miR-378a could play a pro-angiogenic role in skeletal muscle and may be involved in regeneration after ischaemic injury in mice.Silencing of miR-378a in murine C2C12 myoblasts did not affect differentiation but impaired their secretory angiogenic potential towards endothelial cells. miR-378a knockout (miR-378a-/-) in mice resulted in a decreased number of CD31-positive blood vessels and arterioles in gastrocnemius muscle. In addition, diminished endothelial sprouting from miR-378a-/- aortic rings was shown. Interestingly, although fibroblast growth factor 1 (Fgf1) expression was decreased in miR-378a-/- muscles, this growth factor did not mediate the angiogenic effects exerted by miR-378a. In vivo, miR-378a knockout did not affect the revascularization of the ischaemic muscles in both normo- and hyperglycaemic mice subjected to femoral artery ligation (FAL). No difference in regenerating muscle fibres was detected between miR-378a-/- and miR-378+/+ mice. miR-378a expression temporarily declined in ischaemic skeletal muscles of miR-378+/+ mice already on Day 3 after FAL. At the same time, in the plasma, the level of miR-378a-3p was enhanced. Similar elevation of miR-378a-3p was reported in the plasma of patients with intermittent claudication in comparison to healthy donors. Local adeno-associated viral vectors-based miR-378a overexpression was enough to improve the revascularization of the ischaemic limb of wild-type mice on Day 7 after FAL, what was not reported after systemic delivery of vectors. In addition, the number of infiltrating CD45+ cells and macrophages (CD45+ CD11b+ F4/80+ Ly6G-) was higher in the ischaemic muscles of miR-378a-/- mice, suggesting an anti-inflammatory action of miR-378a.Data indicate miR-378a role in the pro-angiogenic effect of myoblasts and vascularization of skeletal muscle. After the ischaemic insult, the anti-angiogenic effect of miR-378a deficiency might be compensated by enhanced inflammation.
R N Jackson
Authors: Ben Essex
Journal: BMJ (2019)

R N Jackson (“Nevil”) was in the Royal Air Force during the second world war and qualified in 1947. In 1952 he became a singlehanded general practitioner, but in 1959 he joined Michael and Ida Fisher, and Charlie Benn in a group practice in Sydenham. They set up the first patient participation group where each street …
The Prevalence of Wilson’s Disease: An Update
Authors: Thomas Damgaard Sandahl, Tea Lund Laursen, Ditte Emilie Munk, Hendrik Vilstrup, Karl Heinz Weiss, Peter Ott
Journal: Hepatology (2019)

Background and Aims In 1984, Scheinberg and Sternlieb estimated the prevalence of Wilson’s disease to be 1:30,000 based on the limited available data. This suggested a large number of overlooked cases with potentially fatal consequences. The “Scheinberg‐Sternlieb Estimate” is still widely used, although more recent clinical and genetic studies of higher quality are now available. In the present study, we included these data to update the prevalence estimate. Approach and Results A MEDLINE Ovid, Science Citation Index Expanded, and PubMed systematic search for all relevant studies on the prevalence of Wilson’s disease was conducted. In total, 59 studies (50 clinical and 9 population‐based genetic) were included in the final analysis. We identified 4 recent clinical studies based on nationwide databases of high quality, providing prevalence estimates from 1:29,000 to 1:40,000. Higher frequency populations do exist because of frequent first‐cousin marriages and/or a higher mutation frequency. When calculating prevalence from the incidence related to number of births, estimates were 1:40,000‐1:50,000. Clinical screening studies, including examination for Kayser‐Fleischer rings or ceruloplasmin, did not improve these estimates because of insufficient sample size or selection biases. Population‐based genetic studies in US and UK populations were not in disagreement with the clinically based estimates. At the same time, studies from France and Sardinia suggested that the genetic prevalence may be 3‐4 times higher than the clinical disease prevalence. This raises the question whether the penetrance is indeed 100% as generally assumed. Conclusions The original prevalence estimate from 1984 of 1:30,000‐1:50,000 still appears valid, at least for the United States, Europe, and Asia. In some population‐based studies, the genetic prevalence was 3‐4 times higher than clinically based estimates. The question of penetrance needs further evaluation.
Cumulative burden of new-onset chronic health conditions (CHCs) among older cancer survivors.
Authors: Kelly Kenzik, Grant R. Williams, Nickhill Bhakta, Leslie L. Robison, Smita Bhatia
Journal: Journal of Clinical Oncology (2019)

11528 Background: In the US there are an estimated 11 million survivors of cancer diagnosed at ≥65y of age. Description of the morbidity in these survivors has been limited to single complications or to prevalence of comorbidities. The cumulative burden of CHCs remains unstudied, and is critically needed to inform healthcare delivery in this burgeoning population. Methods: Using SEER-Medicare, we identified 300,082 patients with breast (34%), prostate (33%), colorectal (16%), non-small cell lung (NSCLC 10%) or non-Hodgkin lymphoma (NHL 7%) diagnosed between 2000 and 2011 at age &gt; 65y (mean age at diagnosis: 75y; 47% males, 88% non-Hispanic whites). An age-, race-, and sex-similar non-cancer cohort (n = 97,842) was assembled. New-onset non-malignant health conditions (n = 109) were consolidated into 10 organ-specific CHCs. Inpatient CHC visits were used to describe severe CHCs. The cumulative incidence (CI) and cumulative burden (CB) of CHCs was described up to 10y from cancer diagnosis and by attained age – up to six months prior to death or until 12/31/2013. Subsequent malignant neoplasms (SMNs) were described 10y from primary cancer diagnosis. Results: The 10y CI of any CHC and severe CHC was 98% (95% CI 98-99%) and 73% (72-73%) in cancer patients and 92% (91-92%) and 55% (54-55%) in non-cancer controls (hazard ratio [HR 10y ]: 1.65, 95% CI 1.64-1.66). Cardiovascular conditions were the largest contributor to severe non-malignant CHCs (10y CI: 49%-69%). Prostate cancer survivors had the highest 10y CI for SMNs (19.4%). The CI for severe CHCs was 44% by age 80y and 85% by age 90y, compared to 34% and 54% in controls (p &lt; 0.001). The 10y CB of CHCs was highest among NSCLC (42 CHCs/survivor) and NHL (41 CHCs/survivor) survivors; in comparison, the 10y CB was 31 CHCs/individual in controls. Colorectal cancer survivors had greatest overall burden at age 80y (27 CHCs/survivor) and 90y (36 CHCs/survivor), compared to 13 and 16 CHCs/individual in controls. Conclusions: The cumulative burden of new-onset multimorbidity among older cancer survivors is substantially greater than that of their non-cancer counterparts, providing quantifiable evidence that survivor-adapted healthcare management policies and risk-based interventions are needed.