tbuckley/cabot-search huggingface dataset:
P14.13 Incidence of pseudoprogression in high-grade IDH-mutant gliomas
Authors: A SEYVE, S Cartalat, D Meyronet, A D’hombres, M Barritault, E Jouanneau, M Berhouma, J Guyotat, J Honnorat, F Ducray
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Pseudoprogression (PsP) is a well-known concern in IDH-wildtype glioblastomas. The aim of the present study was to describe its incidence in high-grade IDH-mutant gliomas. MATERIAL AND METHODS We retrospectively analyzed the characteristics of a consecutive series of high-grade IDH-mutant gliomas treated with radiotherapy (RT) with or without chemotherapy between March 2009 and September 2017. PsP was defined as a new enhanced lesion that occurred after RT and subsequently disappeared or remained stable during follow-up for a least 6 months. RESULTS The study population consisted of 38 anaplastic IDH-mutant and 1p/19q codeleted oligodendrogliomas, 34 IDH-mutant anaplastic astrocytomas and 18 IDH-mutant glioblastomas. Treatment consisted of radiotherapy alone (n=8, 9%), radiotherapy and PCV chemotherapy (n=63, 70%) and temozolomide radiochemotherapy (n=19, 21%). After a median follow-up of 3.5 years (range 1–8 years), 24 patients (28%) presented a PsP that occurred after a median delay of 10 months after radiotherapy (2 to 32 months). PsP was more frequent in patients treated with RT+PCV than in those treated with RT+TMZ (34% vs 10%, p=0.05). During the first two years after RT completion, 19 patients (21%) presented a PsP and 15 patients (17%) a true progression. At last follow-up, 1 patient (4%) in the PsP group had died compared to 10 patients (16%) in the group of patients without PsP. CONCLUSION PsP is a frequent issue in IDH-mutant high-grade gliomas. Its timing of onset is delayed compared to the timing of PsP onset reported in IDH-wildtype glioblastomas. The association between the use of PCV chemotherapy and PsP requires validation in an independent series.
Consolidative CD8+ Memory T-Cell Donor Lymphocyte Infusion Augments Donor Chimerism with a Low Risk of Gvhd Following Matched Related Donor Hematopoietic Cell Transplantation
Authors: Michael A. Spinner, Lori S. Muffly, Sally Arai, Laura Johnston, Everett H. Meyer, David B. Miklos, Robert S. Negrin, Andrew R. Rezvani, Judith A. Shizuru, Wen-Kai Weng, Samuel Strober, Robert Lowsky
Journal: Blood (2017)
P11.18 Tumor treating fields (TTFields) treatment of spinal cord metastases
Authors: A Kinzel, O Yesharim, A Naveh, Z Bomzon
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Tumor Treating Fields (TTFields) is an anti-mitotic cancer treatment approved for the treatment of Glioblastoma multiforme (GBM) and is currently also investigated in a phase III trial in 1–10 brain metastases from non-small cell lung cancer (METIS). Apart from spread to the brain, some cancer types, such as breast cancer, lung cancer, and melanoma, may lead to metastatic spread to the spinal cord. Previous studies have shown that reported transducer array layouts for the treatment of abdominal/pelvic tumors (e.g. pancreatic cancer), with one pair of arrays positioned on the anterior and posterior of the patient, and the second pair of arrays placed on each side of the thorax, yield therapeutically insufficient field intensities of &lt;1 V/cm in the spinal cord. This finding probably results from the anatomical structure of the spine, consisting of the cerebrospinal fluid as a highly conductive layer, encased by a resistive bone structure that shunts the current delivered across the body by the arrays away from the spine. This simulation-based study aimed at resolving this challenge by identifying novel array layouts on the body that effectively deliver TTFields to the spine. MATERIAL AND METHODS For the simulations of the TTFields delivery to the spine, a human male 34 years old realistic computational model (DUKE v3.1 by ITI’S, Zurich) and the ZMT’s Sim4Life v4.0 electro-quasi-static solver was utilized. TTFields were simulated by imposing an alternating current with a current density of 200 mA/disk and a frequency of 150 kHz on the outer surfaces of the disks of each pair of arrays. RESULTS For one of the tested array layouts, a high electric field was shown to be induced within the spinal cord and surrounding CSF: Our calculations of mean field intensity within the spine and nerves from vertebrae T8-T9 at the top to L3-L4 at the bottom added up to 1.77 V/cm. This layout consisted of the placement of a pair of arrays on the back of the patient, with one array positioned above the section in the spine to which treatment would be delivered, and the other array positioned below the target section. Notably, the resulting electric field is directed along the spine in this setting (ie, vertically). CONCLUSION Our results demonstrate that treatment of the whole spinal cord and nerves in a single direction can be achieved by placing a pair of transducer arrays on the patient’s back: one array on the neck, and one at the bottom of the spine. For the development of an active treatment in the perpendicular direction, further studies need to be conducted.
Bone marrow mesenchymal stromal cells from acute myelogenous leukemia patients demonstrate adipogenic differentiation propensity with implications for leukemia cell support
Authors: Mitra Azadniv, Jason R. Myers, Helene R. McMurray, Naxin Guo, Phil Rock, Myra L. Coppage, John Ashton, Michael W. Becker, Laura M. Calvi, Jane L. Liesveld
Journal: Leukemia (2019)

Bone marrow mesenchymal stromal cells (MSCs) constitute one of the important components of the hematopoietic microenvironmental niche. In vivo studies have shown that depletion of marrow MSCs resulted in reduction of hematopoietic stem cell content, and there is in vitro evidence that marrow MSCs are able to support leukemia progenitor cell proliferation and survival and provide resistance to cytotoxic therapies. How MSCs from leukemia marrow differ from normal counterparts and how they are influenced by the presence of leukemia stem and progenitor cells are still incompletely understood. In this work, we compared normal donor (ND) and acute myelogenous leukemia (AML) derived MSCs and found that AML-MSCs had increased adipogenic potential with improved ability to support survival of leukemia progenitor cells. To identify underlying changes, RNA-Seq analysis was performed. Gene ontology and pathway analysis revealed adipogenesis to be among the set of altered biological pathways dysregulated in AML-MSCs as compared with ND-MSCs. Expression of both SOX9 and EGR2 was decreased in AML-MSCs as compared with ND-MSCs. Increasing expression of SOX9 decreased adipogenic potential of AML-MSCs and decreased their ability to support AML progenitor cells. These findings suggest that AML-MSCs possess adipogenic potential which may enhance support of leukemia progenitor cells.
P14.54 Association of EGFR Expression and Copy Number with Outcome in Depatux-m (ABT-414) Randomized Phase II Study of the EORTC Brain Tumor Group
Authors: M J van den Bent, T Gorlia, Y Sun, R Kular, J Looman, E E Bain, L Robberts-Rapp, P J Ansell, V Golfinopoulos, P French
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Patients with glioblastoma (GBM) have a dismal prognosis and are in desperate need of better therapy than the standard of care (SOC). Epidermal growth factor receptor (EGFR) gene amplification is reported in more than 50% of GBMs as an important target for therapeutic intervention and as a potential predictive biomarker. Depatuxizumab mafodotin (depatux-m, ABT-414) is an antibody-drug conjugate that preferentially binds cells with EGFR active conformation, internalized and releases the cytotoxin, leading to cell death. In the primary analysis we reported a trend (in EORTC 1410; HR: 0.71, 95% CI [0.50–1.02], p = 0.06) at topline analysis which continued to improve with ad hoc follow up (HR of 0.66, 95%CI [0.47–0.93]; p = 0.016) was observed towards improved overall survival (OS) in patients with EGFR amplified (amp) recurrent glioblastoma treated with depatux-m in combination with temozolomide. OS was equivalent in the depatux-m monotherapy and chemotherapy control arms. Here, we evaluate the association of EGFR mRNA expression and EGFR copy number with outcome using the updated efficacy data. METHODS Eligible were patients with centrally confirmed EGFR amp GBM at first recurrence after temozolomide chemo-irradiation. Patients were randomized to either a) depatux-m 1.0–1.25 mg/kg combined with temozolomide 150–200 mg/m2 day 1–5 every 4 weeks, b) depatux-m 1.0–1.25 mg/kg monotherapy or c) either temozolomide or lomustine (TMZ/LOM) depending on the time of relapse. Primary endpoint was OS. Long-term follow-up data (24 months follow-up; 237 events) were utilized for this EGFR analysis. The expression level of EGFR was determined using RT-PCR. The absolute copy number of EGFR was determined using next generation sequencing. EGFR mRNA and EGFR copy number were treated as continuous variables and compared to OS using a generalized additive cox proportional hazards model. RESULTS The outcome of the long-term follow-up was that when used in combination with TMZ, depatux-m addition resulted in improved OS as compared to TMZ/ LOM control regardless of EGFR expression or absolute copy number of EGFR. In contrast, in depatux-m monotherapy, a trend was observed that depatux-m improved the outcome only at highest expression levels and highest absolute EGFR copy number. CONCLUSIONS The long-term follow-up trial results demonstrated that addition of depatux-m to SOC showed a trend to increased survival as compared to SOC alone in EGFR amp patients as determined using Fluorescent in situ hybridization (FISH) analysis. Further retrospective analysis supports this efficacy advantage is observed at all expression and amplification levels. When used in combination with SOC and regardless of the absolute copy number of EGFR, the trend for OS improvement was observed at all expression levels.
P14.98 Improving the targeting of Gamma-Knife radiosurgery for recurrent high-grade gliomas (WHO grades III and IV) with 11C-Methionine PET/CT
Authors: E Chaskis, G Van Simaeys, C Martens, O De Witte, S Goldman, F Lefranc
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The survival of the patients with high-grade gliomas may be improved through a multidisciplinary approach including stereotactic re-irradiation such as Gamma-Knife at recurrence in a selected population. We report our experience in targeting the hypermetabolic areas of high-grade gliomas using 11C-Methionine PET/CT in selected patients. MATERIAL AND METHODS We retrospectively evaluated the local response in patients treated by Gamma-Knife for recurrent high-grade gliomas in our Institution between 2000 and 2018, targeting the hypermetabolic area with Methionine PET/CT. RESULTS We included 25 patients bearing high-grade gliomas (14 female, 11 male) with a median age of 45 years (5–64). There were 11 WHO grade III gliomas (6 astrocytomas, 5 oligodendrogliomas) and 14 glioblastomas. A total number of 33 Gamma-Knife procedures were performed. In all patients, the targeting was based on the hypermetabolic area as defined by Methionine PET/CT. Four patients were treated concomitantly on 2 or more targets. One patient was treated twice on different targets. We observed a positive response in 29 Gamma-Knife procedures, after a median interval of 2 months (1–33) and no response after 4 procedures (4 glioblastomas). In most cases, progression after Gamma-Knife was observed 4 months after irradiation. CONCLUSION Targeting the hypermetabolic areas with Methionine PET/CT was associated with favorable response in most patients treated by Gamma-Knife radiosurgery for local high-grade gliomas recurrence. Our results must be confirmed by a prospective study with regular and homogeneous morphological and metabolic monitoring.
Chidamide, a HDAC Inhibitor, Combined with Cladribine, High Dose Gemcitabine and Busulfan with Autologous Stem Cell Transplantation in Patients with Relapsed/Refractory and Poor-Risk Lymphoma
Authors: Jie Ji, Ting Liu, Pu Kuang, Zhigang Liu, Tian Dong, Jiazhuo Liu
Journal: Blood (2017)
Mitochondrial NIX Promotes Tumor Survival in the Hypoxic Niche of Glioblastoma
Authors: Jinkyu Jung, Ying Zhang, Orieta Celiku, Wei Zhang, Hua Song, Brian J. Williams, Amber J. Giles, Jeremy N. Rich, Roger Abounader, Mark R. Gilbert, Deric M. Park
Journal: Cancer Research (2019)

Abstract Cancer cells rely on mitochondrial functions to regulate key survival and death signals. How cancer cells regulate mitochondrial autophagy (mitophagy) in the tumor microenvironment as well as utilize mitophagy as a survival signal is still not well understood. Here, we elucidate a key survival mechanism of mitochondrial NIX-mediated mitophagy within the hypoxic region of glioblastoma, the most malignant brain tumor. NIX was overexpressed in the pseudopalisading cells that envelop the hypoxic–necrotic regions, and mitochondrial NIX expression was robust in patient-derived glioblastoma tumor tissues and glioblastoma stem cells. NIX was required for hypoxia and oxidative stress–induced mitophagy through NFE2L2/NRF2 transactivation. Silencing NIX impaired mitochondrial reactive oxygen species clearance, cancer stem cell maintenance, and HIF/mTOR/RHEB signaling pathways under hypoxia, resulting in suppression of glioblastoma survival in vitro and in vivo. Clinical significance of these findings was validated by the compelling association between NIX expression and poor outcome for patients with glioblastoma. Taken together, our findings indicate that the NIX-mediated mitophagic pathway may represent a key therapeutic target for solid tumors, including glioblastoma. Significance: NIX-mediated mitophagy regulates tumor survival in the hypoxic niche of glioblastoma microenvironment, providing a potential therapeutic target for glioblastoma.
Development of Murine Systemic Lupus Erythematosus in the Absence of <scp>BAFF</scp>
Authors: William Stohl, Ning Yu, Samantha Chalmers, Chaim Putterman, Chaim O. Jacob
Journal: Arthritis & Rheumatology (2019)

Objective To determine whether systemic lupus erythematosus ( SLE ) can develop in the absence of BAFF in an SLE ‐prone host. Methods Starting with C57 BL /6 mice that express a human BCL 2 transgene (Tg) in their B cells (thereby rendering B cell survival largely independent of BAFF ‐triggered signals), we introgressed this Tg into NZM 2328 mice genetically deficient in BAFF ( NZM . Baff −/− ) to generate NZM . Baff −/− . Bcl2 Tg mice. Expression of human Bcl‐2 and lymphocyte profiles were assessed by fluorescence‐activated cell sorting, and serologic profiles were determined by enzyme‐linked immunosorbent assay. Immunofluorescence and histologic analyses were performed to assess renal immunopathologic features in the mice, and clinical disease was assessed according to the outcomes of severe proteinuria and death. Results In comparison to their non‐Tg NZM . Baff −/− littermates (n ≥ 7), NZM . Baff −/− . Bcl2 Tg mice (n ≥ 8) overexpressed Bcl‐2 in their B cells and developed significantly increased percentages and numbers of B cells and plasma cells, serum levels of IgG autoantibodies, glomerular deposition of IgG and C3, and severity of glomerular and tubulointerstitial inflammation, culminating in severe proteinuria and death (all P &lt; 0.05 versus NZM . Baff −/− littermates). The time course for development of SLE ‐like features in NZM . Baff −/− . Bcl2 Tg mice was more rapid than has been previously observed in NZM 2328 wild‐type mice (median age at death 4.5 months versus 7.5 months). NZM . Baff −/− . Bcl2 Tg mice remained responsive to BAFF , since reintroduction of the Baff gene into these mice further accelerated the course of disease (median age at death 3 months). Conclusion The role of BAFF in the development of SLE ‐like disease may be dispensable as long as B cell survival is preserved via a BAFF ‐independent pathway. This may help explain the limited and variable clinical success with BAFF antagonists in human SLE . Thus, NZM . Baff −/− . Bcl2 Tg mice may serve as a powerful murine model for the study of BAFF ‐independent SLE .
Safety and Efficacy of Nivolumab Monotherapy in Recurrent or Metastatic Cervical, Vaginal, or Vulvar Carcinoma: Results From the Phase I/II CheckMate 358 Trial
Authors: R. Wendel Naumann, Antoine Hollebecque, Tim Meyer, Michael-John Devlin, Ana Oaknin, Joseph Kerger, Jose M. López-Picazo, Jean-Pascal Machiels, Jean-Pierre Delord, Thomas R.J. Evans, Valentina Boni, Emiliano Calvo, Suzanne L. Topalian, Tian Chen, Ibrahima Soumaoro, Bin Li, Junchen Gu, Ricardo Zwirtes, Kathleen N. Moore
Journal: Journal of Clinical Oncology (2019)

Nivolumab was assessed in patients with virus-associated tumors in the phase I/II CheckMate 358 trial (ClinicalTrials.gov identifier: NCT02488759). We report on patients with recurrent/metastatic cervical, vaginal, or vulvar cancers.
Multicenter matched case-control study comparing laparoscopic surgery with open surgery for elderly colon and rectal cancer patients.
Authors: Yasuo Kawaguchi, Takao Hinoi, Minoru Hattori, Masazumi Okajima, Hideki Ohdan, Seiichiro Yamamoto, Hirotoshi Hasegawa, Hisanaga Horie, Kohei Murata, Shigeki Yamaguchi, Kenichi Sugihara, Seiichiro Yamamoto, Masahiko Watanabe
Journal: Journal of Clinical Oncology (2012)

e14091 Background: Laparoscopic surgery for colon cancer has gained acceptance due to advantages, although no clear equivalent evidences exist for the elderly patients. The aim of this study was to compare outcomes of open and laparoscopic colorectal surgery in patients aged 80 and above, and estimate the feasibility of laparoscopic surgery for the elderly patients. Methods: We conducted a matched case-control study using data from 41 hospitals, the member of Japan Society of Laparoscopic Colorectal Surgery. 2014 patients aged 80 and above underwent surgery for colon or rectal cancer between 2003 and 2007. Propensity score method was used to balance covariates between the surgery groups. Covariates included age, sex, BMI, ASA class, performance status, elective or emergency, previous abdominal surgery, tumor size, tumor site, T-stage, N-stage, and TNM stage. For the prediction model, calibration was assessed by the Hosmer-Lemeshow goodness-of-fit test. The primary end point was overall survival (OS). Secondary end points included disease-free survival (DFS), cancer-specific survival (CSS), and postoperative complications. Results: 1526 and 282 patients underwent surgery for colon and rectal cancer, respectively. The distribution of covariates was significantly different between the open surgery (OP) group and the laparoscopic surgery (LAP) group, in colon and rectal cancer. After propensity score matching, all covariates were balanced and no longer had significant differences, except for tumor size in colon cancer cases. There were 804 patients in 402 pairs managed with the OP or the LAP for colon cancer, and 114 patients in 57 pairs for rectal cancer. OS, DFS and CSS did not differ between the groups for either colon cancer (p = 0.916, 0.968 and 0.799 by log-rank test) or for rectal cancer (p = 0.765, 0.519, and 0.950). Overall morbidities were significantly fewer in the LAP group than in the OP group for colon cancer (24.9% vs. 36.3%, p &lt; 0.001), and no difference for rectal cancer (47.4% vs. 40.4%, p = 0.450). Conclusions: The laparoscopic surgery was not inferior to the open procedure, and can be an acceptable alternative to open surgery for elderly patients with colon and rectal cancer.
Concordance of severity scores for photographic assessment of hidradenitis suppurativa
Authors: C. Prouteau, M. Dinulescu, E. Oger, C. Pruvost‐Balland, S. Buche, O. Cogrel, M. Delage, A. Maruani, I. Nicol, E. Sbidian, A. P. Villani, M. Viguier, M. Chastagner, C. Grodner, J. Kaoutar, C. Laurent, S. Leducq, A. Dupuy, C. Droitcourt
Journal: British Journal of Dermatology (2019)

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not.The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Concordance of severity scores assessed on photographs in Hidradenitis suppurativa
Injectable Autoclaved Cryogels: Autoclavable and Injectable Cryogels for Biomedical Applications (Adv. Healthcare Mater. 17/2019)
Authors: Pierre Villard, Mahboobeh Rezaeeyazdi, Thibault Colombani, Kasturi Joshi‐Navare, Devyesh Rana, Adnan Memic, Sidi A. Bencherif
Journal: Advanced Healthcare Materials (2019)

In article number 1900679 by Sidi A. Bencherif and co-workers, a scanning electron micrograph is shown displaying Pseudomonas aeruginosa, rod-shaped bacteria, nested on the polymer walls of a cryogel scaffold. The cryogel is made out of hyaluronic acid, a naturally-occurring biopolymer. To enhance visualization, bacteria are pseudo-colored in blue while elongated flagella are pseudo-colored in yellow. Credit: K. Joshi-Navare, M. Rezaeeyazdi, T. Colombani, and S. A. Bencherif.
Circulating Interferon‐α Measured With a Highly Sensitive Assay as a Biomarker for Juvenile Inflammatory Myositis Activity: Comment on the Article by Mathian et al
Authors: Isabelle Melki, Hervé Devilliers, Cyril Gitiaux, Vincent Bondet, Alexandre Belot, Christine Bodemer, Pierre Quartier, Yanick J. Crow, Darragh Duffy, Mathieu P. Rodero, Brigitte Bader Meunier
Journal: Arthritis & Rheumatology (2019)

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