tbuckley/cabot-search huggingface dataset:
Abstract A48: Ado-trastuzumab emtansine (T-DM1) controls tumor progression of established HER2-positive breast cancer brain metastases in mice
Authors: Gino B. Ferraro, Vasileios Askoxylakis, David P. Kodack, Mark Badeaux, Dai Fukumura, Jeffrey A. Engelman, Rakesh K. Jain
Journal: Cancer Research (2016)

Abstract Brain metastases represent a major problem in the treatment of HER2-positive breast cancer due to the poor efficacy of HER2-targeted therapies in the brain microenvironment. The antibody drug conjugate ado-trastuzumab emtansine (T-DM1) has shown efficacy in trastuzumab-resistant systemic breast cancer. We tested the hypothesis that T-DM1 could overcome trastuzumab resistance in murine models of brain metastases. Methods: We optimized established animal models of HER2-positive breast cancer brain metastases. We treated mice bearing BT474 (intracranial and intracarotid injections) or MDA-MB-361 (intracranial injection) tumors in the CNS with trastuzumab or T-DM1 at equivalent or equipotent doses. Using intravital imaging, molecular techniques and histological analysis we determined tumor growth, mouse survival, cancer cell apoptosis and proliferation, tumor drug distribution, and HER2 signaling. Results: Treatment with T-DM1 delayed tumor growth in comparison to trastuzumab and control IgG and improved survival. These findings were consistent between HER2-driven and PI3K-driven breast tumors. In BT474 tumors, median survival was 112 days for T-DM1 and 28 days for trastuzumab (p&amp;lt;0.05). Mechanistic studies revealed no difference in HER2 downstream signaling, drug distribution or immune cell enrichment between T-DM1 and trastuzumab treated mice. A significantly increased apoptotic rate was measured for brain metastases treated with the antibody-drug conjugate. Conclusions: T-DM1 can overcome resistance to trastuzumab therapy in HER2-driven or PI3K-driven breast cancer brain lesions due to the cytotoxicity of the DM1 component. The results of our studies indicate that T-DM1 is effective in the brain microenvironment and will directly inform clinical trials in patients with HER2+ breast cancer brain metastases. Citation Format: Gino B. Ferraro, Vasileios Askoxylakis, David P. Kodack, Mark Badeaux, Dai Fukumura, Jeffrey A. Engelman, Rakesh K. Jain. Ado-trastuzumab emtansine (T-DM1) controls tumor progression of established HER2-positive breast cancer brain metastases in mice. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A48.
MLL-AF4 Positive Adult ALL Patients: VH6 Immunoglobulin Gene Rearrangements Predominate While FLT3 Mutations Are Rare.
Authors: Veronique M. Duke, Lena Rai, Jeasmin Mortuza, Giuseppe Saglio, Robert Foa, Elisabeth M. Macintyre, Victor A. Hoffbrand, Panos Kottaridis, Letizia Foroni
Journal: Blood (2004)
PDTB-10. INHIBITION OF RADIATION-INDUCED DNA DAMAGE REPAIR MEDIATED CHROMATIN MODIFICATION BY HISTONE H3 DEMETHYLASE INHIBITOR IN PEDIATRIC BRAINSTEM GLIOMA
Authors: Quanhong Ma, Andrea Plunti, Amanda Saratsis, Rishi Lulla, Jason R Fangusaro, Craig Horbinski, Stewart Goldman, C. David James, Ali Shilatifard, Rintaro Hashizume
Journal: Neuro-Oncology (2016)

Diffuse intrinsic pontine glioma (DIPG) is among the most devastating childhood cancers, and virtually all patients die within two years after diagnosis. Since these tumors occur in the brainstem, there are no surgical options for providing relief to patients, the only therapeutic modality routinely used in the treatment of DIPG is radiation. Radiation often provides transient relief from DIPG symptoms, but cancer recurrence and patient demise is inevitable. Identifying efficacious therapeutics to enhance the radiation effect is desperately needed. We have recently shown that inhibition of the histone H3K27 demethylase JMJD3 acts to restore H3K27 methylation in DIPG harboring H3K27M mutation, while demonstrating potent anti-tumor activity, both in vitro and in vivo. Our expression profiling of K27M DIPG treated with GSKJ4 JMJD3 demethylase inhibitor revealed several decreases in the genes encoded proteins involved with DNA double-strand break (DSB) repair. We investigate the hypothesis that GSKJ4 may inhibits radiation-induced DNA repair by chromatin modification, in association with analysis of therapeutic combination of GSKJ4 and radiation. DNA damage repair is evaluated by western blotting, DNA repair assay, and immunocytochemistry of DSB markers gH2AX and 53BP1. MNase digestion and FAIRE-seq will analyze nucleosome assembly and transcriptional activity in cellular chromatin. Clonogenic survival assays assess the response to radiation in combination with GSKJ4. In vivo response to radiation therapy (RT) and combination of RT + GSKJ4 were measured by bioluminescence imaging and animal survival. GSKJ4 sustained high levels of gH2AX and 53BP1 in irradiated cells treated with GSKJ4 and increase clonogenic death compared to cells exposed to radiation alone. GSKJ4 + RT combination therapy shows further reduction of tumor growth rate and increase of animal survival relative to either monotherapy. We are currently examining the effect of GSKJ4 on chromatin modification in DIPG, which will be reported at the meeting.
MPTH-33. PD-L1 EXPRESSION AND COMBINED PATTERN OF PD-L1/PD-1+TIMC DENSITY PREDICT PROGNOSIS IN GLIOBLASTOMA PATIENTS
Authors: Youn Soo Lee, Jiheun Han, Yong-Kil Hong
Journal: Neuro-Oncology (2016)

Programmed death ligand 1 (PD-L1) on tumor cells is known to promote immune escape of cancer by interaction with programmed cell death (PD-1) on tumor infiltrating immune cells. Immunotherapy targeting these molecules are emerging as new strategies for treatment of glioblastoma (GBM). Understanding of the relationship between PD-L1/PD-1 axis and prognosis in GBM patients may be helpful to predict the effect of the immunotherapy. PD-L1 expression and PD-1+TIMC (Tumor infiltrating mononuclear cell) density were evaluated in tissue microarray (TMA) containing 54 GBM cases by immunohistochemical analysis and evaluate the association with patients’ clinical outcomes. PD-L1 expression and high PD-1+TIMC density in GBM was observed in 31.5% and 50% of cases respectively. High expression of PD-L1 on tumor cells was independent and significant predictive factor for worse overall survival (OS) (HR=4.958, p=0.007) but not significant for disease-free survival (DFS). Meanwhile, PD-1+TIMC density was not correlated with OS and DFS. In analysis by classifying patients based on PD-1 expression and PD-1+TIMC density, patients with PD-L1+/PD-1+TIMC low had the shortest OS (13 months, p=0.0092) and DFS (7 months, p=0.053) and the patients with PD-L1-/PD-1+TIMC low showed longest survival (OS: 41 months, DFS: 14 months). PD-L1 expression in GBM was independent prognostic factor for poor OS. In addition, combined pattern of PD-L1 expression with PD-1+TIMC density also predict patients outcomes, which implies that therapeutic role of PD-1/PD-L1 axis might be considered in context with immunity of GBM.
Akt Inhibitors Induce Apoptosis in Chronic Lymphocytic Leukemia Cells.
Authors: Mercè de Frias, Daniel Iglesias-Serret, Ana M Cosialls, Llorenç Coll-Mulet, Antonio F Santidrián, Diana M González-Gironès, Esmeralda de la Banda, Alberto Fernandez de Sevilla, Gabriel Pons, Joan Gil
Journal: Blood (2009)
Central Nervous System Involvement of Intravascular Large B-Cell Lymphoma on 18F-FDG PET/CT
Authors: Akira Higashiyama, Tsuyoshi Komori, Yuki Inada, Hideto Nakajima, Yoshifumi Narumi
Journal: Clinical Nuclear Medicine (2017)

Intravascular large B-cell lymphoma is a rare subtype of extranodal diffuse large B-cell lymphoma. We present a case of intravascular large B-cell lymphoma with central nervous system involvement that can be detected on F-FDG PET and may be useful for applications in biopsy and diagnosis.
A case of cancer education for high school students who joined the cancer awareness event in a community hospital
Authors: Chihiro Kondoh, Mitsue Tsuihiji, Nagisa Hamajima, Mayumi Amano, Hiromi Ota, Hideyuki Kushihara, Haruka Machii, Michitaka Nagase, Yasuyuki Nakano, Yasutomo Goto, Fumio Nomura
Journal: Annals of Oncology (2016)
Proteinuria
Authors: Jayne Haynes, Richard Haynes
Journal: BMJ (2006)

A 40 year old woman comes to you after she was found to have a reading of 2+ on a dipstick proteinuria test at an insurance company medical examination. She is fit and well with no major medical history or family history of illness. She has no urinary symptoms and no oedema. She is not pregnant.

Proteinuria may be an early indicator of renal disease and increases the risk of renal impairment, hypertension, and cardiovascular disease. Exclude causes of transient proteinuria (box), which does not have these associations. If proteinuria of 1+ or more persists on two subsequent dipstick tests at weekly intervals further investigation is indicated.

History — Ask about symptoms of renal failure and connective tissue diseases (including arthralgia, mouth ulcers, and rashes). Pertinent …
EXTH-31. CONTINUOUS ADMINISTRATION OF VALGANCICLOVIR IMPROVES LENTIVIRAL VECTOR MEDIATED SUICIDE GENE THERAPY FOR GLIOBLASTOMA
Authors: Jubayer Hossain, Lars Ystaas, Krishna Talasila, Kristoffer Riecken, Boris Fehse, Rolf Bjerkvig, Hrvoje Miletic
Journal: Neuro-Oncology (2016)

Previously we have shown that lentiviral vector mediated herpes simplex virus thymidine kinase (HSV-Tk) / ganciclovir (GCV) therapy is a very promising therapeutic option for GBM treatment. By using a patient derived xenograft model we have also reported complete remission on MRI after lentiviral HSV-Tk/GCV therapy. However, tumor recurrence was observed in treated animals and interestingly a fraction of recurrent glioma cells were found to be expressing tk-GFP indicating that some of the transduced cells had survived the 3-week prodrug administration period. We hypothesize that short-term prodrug delivery fails to eliminate a fraction of gliomas cells, which are slow-proliferating; and thus, a longer period of prodrug administration would provide better survival benefit. As long-term prodrug we used valganciclovir (valGCV), which is similar to GCV, but tailored for oral administration. After orthotopic implantation of patient derived glioma spheroids and visible growth on MRI, we intratumorally injected lentiviral vectors expressing HSV-Tk.007-GFP, a highly active mutant of HSV-Tk. Animals were treated with either short-term GCV (3 weeks) or long-term valGCV (3 months). Although both treatment groups showed remission and subsequent tumor recurrence, animals in the valGCV treatment group survived significantly longer and and had a longer recurrence-free time period. Hereby we report that valGCV is a compatible prodrug in the modus operandi of HSV-Tk mediated suicide gene therapy that can effectively cross the blood brain barrier and upon long-term administration results in better therapeutic benefit compared with short-term GCV treatment. We are currently characterizing the recurrent tumors to identify new targets that potentially could lead to further development of the suicide therapy for GBM.
P06.09 Genetic alterations in patients with resection of primary glioblastoma multiforme gr.IV
Authors: R. Trojanec, O. Kalita, M. Megova, Z. Sporikova, J. Vrbkova, M. Vaverka, L. Hrabalek, L. Tuckova, M. Hajduch
Journal: Neuro-Oncology (2016)
US opioid epidemic: it’s harder to get the painkillers I legitimately need
Authors: Kelly Young
Journal: BMJ (2017)

The crackdown on misuse of prescription drugs has had unfortunate consequences for people with legitimate needs in the US. Stricter laws have made access to controlled medications more difficult. Patients wonder whether restricting their access is necessary to reduce illicit drug use when the misconduct of physicians running for-profit “pill mills” has been responsible for most misuse.1

In 2011 my doctor was no longer allowed to order my prescription electronically; instead I had to carry it to the pharmacist. Soon after, my regular drive through pharmacy insisted that I come inside the store with identification. These were minor inconveniences, but everyone acted more cautiously.

The next indication that Florida’s climate had changed was more disturbing. At my sixth appointment for spinal radiofrequency ablation, I …
Prognosis and metastatic potential of colorectal carcinoids compared with adenocarcinomas: Results of a nationwide registry over 15 years
Authors: T. Konishi, T. Watanabe, J. Kishimoto, K. Kotake, T. Muto, H. Nagawa
Journal: Journal of Clinical Oncology (2008)

4054 Background: In the WHO classification, colorectal carcinoids are described as low-grade malignant even in the presence of metastasis. However, it has not been clarified whether colorectal carcinoids are truly “low-grade malignant” because no large series has compared the malignant potential between colorectal carcinoids and carcinomas. This study aims to clarify the prognosis and the metastatic potential of colorectal carcinoids as compared with adenocarcinomas, using a large nationwide database compiled in Japan over 15 years. Methods: All patients diagnosed as colorectal carcinoids from 1984 to 1998 were extracted from a large nationwide database of colorectal cancers, Multi-Institutional Registry of Large-Bowel Cancer in Japan. Size and depth-matched proportion of metastasis and cancer- specific survival were compared between colorectal carcinoids and well- and moderately-differentiated adenocarcinomas registered in the same period. Results: Among 90,057 cases of overall colorectal cancers, a total of 345 cases of carcinoids and 77,957 cases of well- and moderately-differentiated adenocarcinomas were identified, including 247 carcinoids and 69,486 adenocarcinomas that underwent surgery. The size and depth-adjusted risk of lymph node and distant metastasis in colorectal carcinoids was not statistically lower than adenocarcinomas. Notably, even small carcionoids not larger than 10mm and confined within submucosa had 7.7% lymph node metastasis, which was comparable to 7.2% in adenocarconomas (p=0.903, Pearson’s chi-square test). Cancer-specific survival of colorectal carcinoids without metastasis was better than that of adenocarcinomas, showing 100% five-year-survival (p=0.0308, log-rank test). However, the survival of colorectal carcionids with regional or distant metastasis was comparable to that of adenocarcinomas (p=0.9078 and 0.9940, respectively, log-rank test). Conclusions: The metastatic potential of colorectal carcinoids is as high as adenocarcinomas, and the presence of metastasis in colorectal carcinoids could lead to survival that is as poor as in adenocarcinomas. The term “low-grade malignancy” in the WHO classification might be challenged by our results. No significant financial relationships to disclose.
Use of bevacizumab (Bev) in real life for first-line (fl) treatment of ovarian cancer (OC). Part1: the ENCOURAGE cohort of 1158 patients (pts) by GINECO
Authors: D. Berton-Rigaud, F. Selle, A. Floquet, D. Mollon, W. Lescaut, M.-C. Kaminsky, I.L. Ray-Coquard, R. Largillier, A.-M. Savoye, H. Barletta, P. Pautier, H. Orfeuvre, M. Baron, A. Marti, J.-L. Mouysset, J.-B. Paoli, P.-E. Cailleux, C. Cornea, E. Pujade-Lauraine
Journal: Annals of Oncology (2016)
Analytical performance of a new liquid biopsy mutation panel for detection of clinically actionable variants
Authors: C. Svedman, G. Alexander, A. Bergamaschi, J. Han, P.B. Harrington, C.-J. Ku, Y. Ma, W. Gibb, A.i. De Rossi, L. Shen, A.D. Goddard, D.A. Eberhard, K.M. Clark-Langone
Journal: Annals of Oncology (2016)
Prevalence, Predictive Factors Therapy and Outcome of Patients with Follicular Lymphoma Refractory to First Line Immunochemotherapy
Authors: Marc Sorigue, Juan-Manuel Sancho, Santiago Mercadal, Ruben Fernández-Álvarez, Helena Pomares, Olga Garcia, Eva González-Barca, Esther González-García, Miriam Moreno, Cristina Motlló, Montserrat García, Jose-Tomas Navarro, Eva domingo-Domenech, Evarist Feliu, Anna Sureda, Josep-Maria Ribera
Journal: Blood (2015)
Therapeutic Hypothermia After Cardiac Arrest
Authors: Wulfran Bougouin, Florence Dumas, Alain Cariou
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A Retrospective Single Institute Analysis of 127 Lymphoma Patients Who Underwent Allogeneic Stem Cell Transplantation: Impact on Peripheral T-Cell Lymphoma (PTCL) Including ATLL.
Authors: Ryuji Tanosaki, Sung-Won Kim, Satoshi Yamazaki, Takahiro Fukuda, Shin-ichiro Mori, Yuji Heike, Kensei Tobinai, Yoichi Takaue
Journal: Blood (2006)
The New CXCR4 Inhibitor MDX-1338 Exerts Anti-Tumor Activity in Multiple Myeloma
Authors: Aldo M Roccaro, Antonio Sacco, Michelle Kuhne, AbdelKareem Azab, Patricia Maiso, Yong Zhang, Yang Liu, Feda Azab, Ghayas C Issa, Phong Quang, Hai T Ngo, Chin Pan, Lew Choen, Pina M Cardarelli, Irene M. Ghobrial
Journal: Blood (2011)
Molecular, clinical and prognostic characterization of double KRAS/PIK3CA (dKP) mutated metastatic colorectal cancer (mCRC)
Authors: J. Grasselli, E. Elez, G. Argiles Martinez, E. Sanz-Garcia, T. Macarulla, J. Capdevila, M. Alsina, T. Sauri, C. Hierro, H. Verdaguer, I. Matos, A. Garcia, P. Nuciforo, S. Landolfi, H. Garcia Palmer, R. Dienstmann, A. Vivancos, J. Tabernero
Journal: Annals of Oncology (2016)
Pre-Treatment Cytogenetics Predict Complete Remission and Long-Term Outcome in Patients (Pts) ≥60 Years with Acute Myeloid Leukemia (AML): Results from Cancer and Leukemia Group B (CALGB) 8461.
Authors: Sherif S. Farag, Kellie J. Archer, Krzysztof Mrózek, James W. Vardiman, Andrew J. Carroll, Mark J. Pettenati, Bayard L. Powell, Joseph O. Moore, Jonathan E. Kolitz, Maria R. Baer, Sandra H. Bigner, Prasad R. Koduru, Judith Stamberg, Robert J. Mayer, Richard M. Stone, Charles A. Schiffer, Richard A. Larson, Clara D. Bloomfield
Journal: Blood (2004)
PP37. PATIENT EXPERIENCE AND SATISFACTION WITH DEXMEDETOMIDINE IN AWAKE CRANIOTOMY FOR BRAIN TUMOURS
Authors: Ms JOY ROACH, Dr Crispin Weidmann, Dr Richard Chapman, Mr Vasileios Apostolopoulos Apostolopoulos, Ms Victoria Wykes, Mr Paul Grundy
Journal: Neuro-Oncology (2017)

INTRODUCTION: Gross total excision of high and low grade gliomas has been proven beneficial both by prolonging progress free survival and overall survival. In this context awake craniotomies for tumour resections as close as possible to eloquent brain have become popular. Patient experience has improved dramatically with the advent of the electromagnetic navigation which does not require rigid pin fixation of the head and allows conscious sedation throughout the procedure (AAA). Similarly new sedative medications like Dexmedetomidine have become available aiming to achieve the same level of sedation with less respiratory depression. METHODS: In this survey we used Dexmedetomidine intravenously to achieve conscious sedation in 40 consecutive patients who underwent awake craniotomy for an eloquently located brain tumour. After the patients recovered from the operation and were discharged, they were asked to complete a questionnaire that explored the way they experienced the awake craniotomy before, during and after the procedure. Dexmedetomidine use for awake craniotomies is standard practice in North America, but in this work we present the first UK experience of a series of patients. RESULTS: 32/40 responses received. Amongst these 19 patients remember being comfortable during the operation, 6 patients felt some discomfort, and 7 patients were not able to remember and comment on their experience during the operation. From the anaesthetic point of view none of these patients required any intraoperative airway intervention. The satisfaction results are comparable to a previous survey carried out in our unit in 2011 which looked at the level of satisfaction with Propofol and Remifentanil. CONCLUSIONS: The outcome of our survey looking at the use of dexmedetomidine +/- remifentanil matches the previous study in our institution using remifentanil+/-propofol and appears to be as equally as tolerated by patients. The use of dexmedetomidine has the added benefit of little or no respiratory depression. Larger studies are required to explore the true potential of dexmedetomidine further.
Erlotinib Inhibits ABC Transporters of AML Progenitors with Stem Cell Features and Increases Chemosensitivity to Current AML Drugs
Authors: Marie Sebert, Elodie Lainey, Sylvain Thepot, Maximilien Tailler, Lionel Ades, Claude Gardin, Pierre Fenaux, Guido Kroemer, Simone Boehrer
Journal: Blood (2010)
The HLA-DRB1*11 Antigen Is Preferentially Expressed in Hairy Cell Leukemia, Particularly in Patients Who Had Hemolytic Uremic Syndrome with Recombinant Immunotoxin BL22.
Authors: Evgeny Arons, Laura Roth, Sharon Adams, Jeffery Sapolsky, Ira Pastan, Robert J. Kreitman
Journal: Blood (2012)
Overall Survival Benefit for Patients with Relapsed Hodgkin Lymphoma Treated with Brentuximab Vedotin After Autologous Stem Cell Transplant
Authors: Meghan S. Karuturi, Sally Arai, Robert W. Chen, Ajay K. Gopal, Lei Feng, Ying Yuan, Scott E. Smith, Stephen M. Ansell, Joseph D Rosenblatt, Kerry J. Savage, Radhakrishnan Ramchandren, Nancy L Bartlet, Bruce D. Cheson, Andres Forero-Torres, Craig H. Moskowitz, Joseph M. Connors, Michelle A. Fanale, Sven de Vos, Andreas Engert, Tim Illidge, Peter Borchmann, Franck Morschhauser, Sandra J. Horning, Anas Younes
Journal: Blood (2012)