tbuckley/cabot-search huggingface dataset:
Abstract 3878: Newly identified p53-pathway restoring small molecule, CB002 analog #4 induces apoptosis and appears non-toxic <i>in vivo</i>
Authors: Liz J. Hernandez Borrero, Avital Lev, Lanlan Zhou, David T. Dicker, Wafik S. El-Deiry
Journal: Cancer Research (2019)

Abstract The transcription factor encoding TP53 tumor suppressor gene is mutated in more than half of human cancers. TP53 accounts for therapy resistance and poor patient survival in colorectal and other cancers. Upon cellular stress, p53 protein determines cell fate through the regulation of cell senescence, cell cycle arrest, and apoptosis pathways. Distinct from other tumor-suppressors, mutated p53 can acquire a gain-of-function activity, leading to chemotherapy resistance and a more aggressive tumor phenotype. Direct therapeutic targeting of transcription factors is challenging especially when reactivation is needed; thus, to date, there are no FDA approved drugs for p53 functional restoration in tumors harboring p53 mutations. To overcome this, we have screened for small molecules capable of restoring wild-type p53 pathway signaling rather than direct physical restoration of its function. We identified a small molecule, CB002 analog #4 capable of restoring the p53 pathway in HCT116, SW480 and DLD-1 colorectal cancer cell lines as indicated by the increased expression of p53-target genes NOXA, p21 and DR5, and apoptotic markers upon treatment. We found that analog #4 enhances ethidium homodimer staining of dead cells and decreases the number of positive Ki67 staining cells in colorectal cancer patient organoids. Sub-G1 analysis demonstrated that analog #4 does not induce apoptosis in normal human fibroblasts and preliminary in vivo studies indicate that it can be safely administered to mice. We are investigating the in vivo efficacy of analog #4 in addition to its mechanism of action through micro-array experiments. Our data supports the concept that small molecules can restore the p53-pathway as a therapeutic strategy that can be translated into a clinical setting. Citation Format: Liz J. Hernandez Borrero, Avital Lev, Lanlan Zhou, David T. Dicker, Wafik S. El-Deiry. Newly identified p53-pathway restoring small molecule, CB002 analog #4 induces apoptosis and appears non-toxic in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3878.
American Surgeon, Baltimore
Journal: JAMA (1964)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Revised (1972-1973) bivalent influenza vaccine. Serum and nasal antibody responses to parenteral vaccination
Authors: R. P. Wenzel
Journal: JAMA (1973)

A new (1972-1973), more potent inactivated influenza vaccine was evaluated for acceptability and effectiveness in stimulating serum and nasal antibodies. The vaccine contained 700 chick cell agglutination (CCA) units of A<sub>2</sub>Hong Kong antigen and 300 CCA units of B antigen (B/Mass/71). Injection of the vaccine into 100 middle-aged and elderly volunteers was well tolerated and effective in stimulating serum hemagglutination inhibition (HI) and nasal neutralizing antibody to the A<sub>2</sub>component. All men with undetectable serum HI titers of &lt;10 and 62% of men with serum HI titers of ≤ 160 had serum antibody responses. A direct correlation between serum HI antibody titers and nasal neutralizing antibody titers was demonstrated. All men with ≥ 16-fold serum rise had ≥ 4-fold nasal antibody rises. Since both serum and nasal antibodies may have protective roles, influenza vaccines should induce high titers of both systemic and local antibodies.
A Novel Combination of the mTORC1 Inhibitor Everolimus and the Immunomodulatory (IMiD) Drug Lenalidomide Produces Durable Responses in Patients with Heavily Pretreated Relapsed Lymphoma
Authors: Brenda Ernst, Amylou Constance Dueck, Angela Toro, Patrick B. Johnston, Thomas Haberman, Jose F. Leis, Joseph R. Mikhael, Grzegorz S. Nowakowski, Joseph P. Colgan, Luis F. Porrata, James L Slack, Stephen M. Ansell, Thomas E. Witzig, Craig B. Reeder
Journal: Blood (2014)
Early immune reconstitution and abrogation of GvHD after infusion of HSV-TK engineered donor lymphocytes after haplo-identical hemopoietic stem cell transplantation
Authors: F. Ciceri, C. Bonini, A. Bondanza, Z. Magnani, M. Bernardi, J. Peccatori, F. Crippa, C. Gallo Stampino, M. Bregni, C. Bordignon
Journal: Journal of Clinical Oncology (2004)

6515
Factor VIII/protein C and not ADAMTS13/VWF:Ag ratio is a prognostic risk factor for patients with cirrhosis and low MELD score
Authors: Niccolò Bitto, Giulia Tosetti, Armando Tripodi, Ilaria Mancini, Luciano Baronciani, Carla Valsecchi, Pietro Lampertico, Flora Peyvandi, Massimo Primignani, Vincenzo La Mura
Journal: Journal of Hepatology (2020)
Correction
Journal: BMJ (1894)

cent. were injected into the gums, and the patient died a few minutes after the teeth had been extracted.-TheBoston Medical and Surgical Journal of June 21st relates the following sad case of a medical man who seems to have fallen a victim to the abuse of drugs.The practitioner, who was 35 years of age, is said to have long been a great sufferer from rheum- atism, and in order to relieve the pain he used morphine freely, and thus became addicted to the opium habit.After a time he also took large quantities of chloral, paraldehyde, and other hypnotics, and a few days before his death he is said to have swallowed about an ounce and a-quarter of paraldehyde in a single dose, yet the next day he had re- covered from the effects of the drug sufficiently to go out.It was at first supposed that he had died from morphine poisoning, but the coroner's inquiry showed that death was in reality due to septiceemia resulting from the excessive use of the hypodermic syringe.Both arms, from the shoulders to the wrists, were in a state of violent inflammation. MEDICAL VACANCIES.The following vacancies are announced:
Brittle asthma
Authors: J. G Ayres, J. F Miles, P. J Barnes
Journal: Thorax (1998)

The term "brittle asthma" was first used in 1977 to describe patients with asthma who maintained a wide variation in peak expiratory flow (PEF) despite high doses of inhaled steroids. 1It was coined at a time when patterns of PEF variability were beginning to be described with respect to clinical patterns of disease, such as the morning dip in PEF 1 2 and the "double dip" pattern of morning and evening dips 3 seen in patients with less well controlled asthma.The brittle asthmatic PEF pattern of variability was identified as a separate group, being described as chaotic showing no such obvious repeating pattern.The significance of the brittle pattern was not completely clear at that time, although the inference was that these patients had more severe asthma that was, by definition, more difficult to control.Three papers published shortly afterwards showed that this chaotic pattern of PEF could lead to death from an acute severe attack 4-6 and the authors raised the possibility that these patients tended to be poorly compliant with treatment.Nevertheless, not all non-compliant patients showed this chaotic pattern, so clearly other factors were important.However, it is not clear how these patients would fit into a classification of severe asthma which would include all those patients at risk of death or repeated hospital admissions.Some physicians are unhappy with brittle asthma being classified as a separate asthma phenotype, regarding these patients as simply the severe end of the spectrum.However, it is our belief that definition of diVering asthma phenotypes is important, so what follows represents our view that brittle asthma should be considered as a specific asthma phenotype.We suggest how further study of patients of this type may help in unravelling the pathogenesis and treatment of at risk asthma.
Proc Soc Exper Biol &amp;amp; Medicine, New York
Journal: JAMA (1964)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
From the editors
Authors: Nicola Mccarthy, Sarah Seton-Rogers, Gemma Alderton, Meera Swami, Catriona Rodwell, Isobel Barry, Craig Nicholson, Man Tse, Gillian Young, Lara Crow Art Controller, Susanne Harris, Vicky Summersby, Patrick Morgan, Judith Shadwell, Simon Fenwick, Natalie Smith, Laura Firman, Jacques Smit, Deborah Anthony, Tim Redding, Leah Rodriguez
Journal: Nature reviews. Cancer (2009)
Society Proceedings
Journal: JAMA (1928)

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
Transverse Fracture of the Temporal Bone
Journal: JAMA (1963)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Highlights
Journal: JAMA (2016)

Dexmedetomidine in ICU Patients With Delirium 1460Agitated delirium is particularly problematic among patients receiving mechanical ventilation.In a randomized trial involving 74 adult patients in the intensive care unit (ICU) considered ineligible for extubation because of the severity of agitation and delirium, Reade and colleagues examined the eff ect of dexmedetomidine added to standard care on ventilator-free time.The authors report that compared with standard care alone, the addition of dexmedetomidine resulted in more ventilator-free hours in the 7 days after randomization.In an Editorial, Ely and Pandharipande discuss evolving treatment of brain dysfunction in critically ill patients.
THE PHYSICIAN'S CAREER
Journal: JAMA (1967)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 novel translocation, t(2;5)(p23;q35), in childhood phagocytic large T- cell lymphoma mimicking malignant histiocytosis
Authors: Y Kaneko, G Frizzera, S Edamura, N Maseki, M Sakurai, Y Komada, M Sakurai, H Tanaka, M Sasaki, T Suchi
Journal: Blood (1989)
A phase II study of M6620 in combination with carboplatin compared with docetaxel in combination with carboplatin in metastatic castration-resistant prostate cancer.
Authors: Atish Dipankar Choudhury, Wanling Xie, Mamta Parikh, Daniel Lee, Elizabeth R. Kessler, David Johnson Einstein, Bose Kochupurakkal, Kent William Mouw, Eliezer Mendel Van Allen, L. Austin Doyle, Alan D. D'Andrea, Mary-Ellen Taplin, Geoffrey Shapiro
Journal: Journal of Clinical Oncology (2020)

TPS252 Background: Alterations in DNA damage repair genes are common in metastatic castration-resistant prostate cancer (mCRPC), and are implicated in responses to carboplatin, PARP inhibitors and immunotherapeutics. The ATR kinase is involved in the DNA damage response, and ATR inhibitors have been demonstrated in preclinical models to have synergistic activity with platinum compounds due to induction of replication stress. Methods: This is a randomized open-label Phase 2 study of the ATR inhibitor M6620 + carboplatin vs. docetaxel + carboplatin in mCRPC. Patients (pts) previously treated with at least one secondary hormonal therapy and taxane-based chemotherapy undergo mandatory pre-treatment biopsy and are randomized 1:1 to receive Arm A (docetaxel 60 mg/m2 day 1 + carboplatin AUC 4 day 1) or Arm B (M6620 90 mg/m2 days 2,9 + carboplatin AUC 5 day 1) every 21 days. Pts randomized to Arm A who are not candidates for docetaxel receive carboplatin AUC 5 monotherapy. Stratification factors are 1) prior PARP inhibitor (yes vs. no) and 2) evaluable disease by RECIST 1.1 (yes vs. no). Pts on Arm A crossover to Arm B (M6620+carboplatin) at the earlier of PSA or radiographic progression. For the primary endpoint of overall response rate (ORR; PSA reduction by ≥ 50% or radiographic response by RECIST 1.1), with 65 pts on each arm (total N = 130), there will be 80% power to distinguish ORR of 40% vs. 20% using a chi-square test (one sided α = 0.05). 136 pts will be enrolled to account for 5% dropout. Secondary endpoints include time to PSA progression, radiographic PFS, PFS by PCWG3 criteria, safety and adverse events in each arm. Biomarker studies include whole exome sequencing, RAD51 focus formation, and ATM IHC from tumor specimens. Circulating cell-free DNA from pre-treatment and progression plasma specimens will undergo ultra-low pass whole genome sequencing and deep targeted sequencing. The goal of this study is to expand therapeutic options in mCRPC through a novel approach to targeting the DNA damage response, and to identify biomarkers associating with response and resistance to both standard and trial therapy. Enrollment began June 2019 (NCI/ETCTN #10191). Clinical trial information: NCT03517969.
Local Committee on Arrangements
Journal: JAMA (1964)

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
Hippocampal Volume, PTSD, and Alcoholism in Combat Veterans
Authors: Steven Woodward
Journal: American Journal of Psychiatry (2006)

Studies imposing rigorous control over lifetime alcohol intake have usually not found smaller hippocampal volumes in persons with posttraumatic stress disorder. Because the majority of negative studies have used adolescent samples, it has been suggested that chronicity is a necessary condition for such findings. To test the hypothesis that a smaller hippocampus in PTSD is unrelated to comorbid alcoholism or to chronicity, this study estimated hippocampal volume in a relatively large group (N=99) of combat veterans in which PTSD, lifetime alcohol abuse/dependence, and Vietnam versus Gulf War service were crossed. In subjects with histories of alcoholism, unadjusted hippocampal volume was 9% smaller in persons with PTSD than in those without PTSD. In nonalcoholic subjects, the PTSD-related difference in hippocampal volume was 3%. The failure to observe a strong association between PTSD and hippocampal volume in nonalcoholic subjects was not ascribable to younger age, reduced PTSD chronicity, or lower PTSD symptom severity. The possibility that smaller hippocampal volume is limited to groups in which PTSD is compounded by comorbid alcoholism is not necessarily incompatible with results suggesting a smaller hippocampus is predispositional to PTSD. Further examination of the role of alcoholism and other comorbid conditions in studies of brain structure and function in PTSD appears warranted.
Ultrasound May Markedly Improve Cancer Detection in Dense Breasts
Authors: T. C. Jefferson
Journal: JAMA (1999)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
NEW LIFE MEMBERS
Journal: Annals of Internal Medicine (1954)

College News Notes1 August 1954NEW LIFE MEMBERSAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-41-2-392 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt is a pleasure for the College to announce that the following Fellows have become Life Members since the publication of the last list in the May issue of this journal:Dr. James M. Moss, Alexandria, Va.Dr. Roy E. Kinsey, Peekskill, N. Y.Dr. Melvin H. Stich, Brooklyn, N. Y.Dr. George G. Reader, New York, N. Y.Dr. Ira L. Rubin, New York, N. Y.Dr. Charles P. Archambeault, Washington, D. C.Dr. Phillip Thomas Knies, Columbus, OhioDr. Herbert Koteen, Pleasantville, N. Y.Dr. Kelso Adair Carroll, Washington, D. C.GIFTS TO COLLEGE LIBRARY OF PUBLICATIONS BY This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1954Volume 41, Issue 2Page: 392-418 ePublished: 1 December 2008 Issue Published: 1 August 1954 PDF downloadLoading ...