tbuckley/cabot-search huggingface dataset:
The basal subtype to predict clinical benefit from neoadjuvant chemotherapy: Final results from a phase II clinical trial of DDMVAC + bevacizumab.
Authors: Arlene O. Siefker-Radtke, Woonyoung Choi, Sima Porten, Yu Shen, Ashish M. Kamat, Surena F. Matin, Randall E. Millikan, Colin P. N. Dinney, Bogdan Czerniak, David James McConkey
Journal: Journal of Clinical Oncology (2015)

4531 Background: Gene expression profiling (GEP) suggests 3 main subtypes of urothelial cancer: basal, which historically has the worst prognosis with high proliferation and HIF-1 expression; p53-like, with decreased proliferation and increased markers of extracellular matrix (ECM); and luminal which has increased proliferation compared to p53-like tumors. We hypothesized that GEP of transurethral resections (TUR) and cystectomy specimens from patients on a neoadjuvant trial would predict benefit from chemotherapy Methods: Sixty patients enrolled on a neoadjuvant trial of DDMVAC+B. TUR and cystectomy specimens were available for gene expression profiling in 39 and 33 patients, respectively, with matched specimens in 23 patients. The validation set consisted of 49 patients treated with perioperative MVAC on a previously published clinical trial Results: Chemotherapy was quite active with pT0N0 and ≤ pT1N0 down-staging rates of 38% and 53%, respectively. Basal tumors had improved survival compared to luminal and p53-like (5-year OS 91%, 73% and 36%, p = 0.015). A validation cohort of patients treated with perioperative MVAC confirmed this survival benefit (5-year OS basal, luminal, and p53-like 77%, 57%, and 57%, respectively, p = 0.027). The use of bevacizumab in basal tumors did not confirm evidence of significant benefit in these small numbers of patients (5-year OS bevacizumab: 91% vs MVAC: 77%, p = 0.68) Bone metastases within 2 years associated exclusively with the p53-like subtype (p53-like: 100%, luminal: 0%, basal 0%, p ≤ 0.001). The p53-like subtype was enriched at cystectomy (basal to p53-like in 3/5 (60%), luminal to p53-like in 5/7 (71%), suggesting chemo-resistance in p53-like tumors Conclusions: In contrast to historical expectations, the basal subtype was predictive of clinical outcomes from neoadjuvant chemotherapy, reflecting the impact of chemotherapy on highly proliferative tumors. Bone metastases were associated with the p53-like subtype which is enriched for ECM. We can no longer think of urothelial cancer as one disease; subtyping should be considered for all tumors, and may have implications on selecting therapy Clinical trial information: NCT00506155.
Diagnosis and treatment of aphasia. Part II
Authors: M. L. Albert
Journal: JAMA (1988)

IN PART I of this article, published in the previous issue, we reviewed the classification of aphasic syndromes, described key clinical features of each syndrome, and discussed neurodiagnostic techniques developed to improve clinical diagnosis and facilitate our understanding of brain-language relationships. We emphasized that although gross clinicoanatomic correlations can be useful, there is no one-to-one correspondence between specific parts of the brain and specific components of language. A comprehensive neurological theory of language must involve both hemispheres and subcortical structures as well. In part II we focus on diagnostic aphasia tests and developments in therapy for aphasia. <h3>APHASIA TESTS</h3> Much of what we know about clinical features of aphasia comes from informal, but thorough, bedside examinations of individual patients. This form of evaluation, although highly informative when conducted by an experienced aphasiologist, is by its nature nonstandardized. A few short clinical tests, such as Marie's 3-Paper Test,<sup>126</sup>have long
The "Urban Factor" and Lung Cancer: Cigarette Smoking or Air Pollution?
Authors: Bertram W. Carnow
Journal: Environmental Health Perspectives (1978)

Data are presented which suggest that cigarette smoking, and to a lesser degree, urban pollution as indexed by benzo[a]pyrene are etiologic factors in the causation of lung cancer. The dose--response relationship to benzo[a]pyrene to lung cancer death rate in the urban community was estimated by using data on lung cancer deaths among coke oven workers. It appears to be an excess of 2--5 mumg/m3 of benzo[a]pyrene per 100,000 population, suggesting that a lifetime community exposure to benzo[a]pyrene on a continuing basis may have a greater impact on lung deaths in the community than that considered by the Royal College of Physicians.
Tired of taking the blame, AIDS drug regulator Ellen Cooper quits
Journal: JAMA (1991)

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
Recovery
Authors: Lee Passarella
Journal: JAMA (1993)

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
Aortic aneurysms.
Journal: BMJ (1971)

graduate training.Furthermore, doctors often continue to work or are re-employed im the service after the customary retiring age of 65, and so are hit by the pensions abatement rule.There is also the problem of non-recognition of doctors' pre-1948 service.The abortive Crossman pension proposals3 prompted widespread discussion about the effectiveness of state pensions,
Fracture Figures Transposed
Journal: JAMA (1964)

taken at the time the cast was removed (Fig 1 bottom left ), the fracture line was no longer visible.A film taken one year later did not reveal any sign of avascular necrosis (Fig 1 bottom right).She regained full function of the hip, and was fully active until the age of 18 when pain and spasm began in the region of the right hip and knee.These symptoms were mild and inconstant, but recurred and increased with each of her three pregnancies.
MECHANICAL THERAPEUTIC AGENCIES.THE SALT OF THE EARTH.
Journal: JAMA (2002)

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
Effect of bromocriptine on pituitary tumors
Authors: B. Ambrosi
Journal: JAMA (1982)

<h3>To the Editor.—</h3> We read with interest the article by Spark and co-workers (1982;247:311) about the effects of bromocriptine on the size of prolactin-secreting, human-growth-hormone-secreting and nonsecretory pituitary tumors and would like to make a comment about some of the issues raised therein. During the past five years, we administered bromocriptine (2.5 to 15 mg/day) for two to 46 months to 26 patients (12 females and 14 males) with prolactin-secreting pituitary macroadenomas with computed tomographic (CT) scan controls before, during, and after bromocriptine therapy. Eighteen of them had previously undergone pituitary surgery (by transsphenoidal or transfrontal route), telecobaltotherapy, or both, while eight had never been treated before. In our experience, the normalization of prolactin levels was not always related to the reduction of the tumor mass: in fact, bromocriptine normalized serum prolactin concentration in 19 cases (73%), while a shrinkage of the adenoma was documented at CT scan in only
Consumption of seafood and preterm delivery
Journal: BMJ (2002)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Consumption of seafood and preterm delivery Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Abstract 3574: Identification of long non-coding RNAs involved in chromosomal instability in a cellular model of prostate cancer
Authors: Rogelio Montiel Manriquez
Journal: Cancer Research (2019)

Abstract Most of the human genome is transcribed into RNA, but only 2% encodes proteins, leading to a large group of non-coding RNA which, without constitutive RNA, is divided into 2 groups: small (sncRNA) and long (lncRNAs) non-coding RNAs. In this study we used RNA-seq data to identify new lncRNAs which could be involved in chromosomal instability (CIN) in prostate cancer (PCa). Our aim is to study their molecular mechanism and potential role as prognostic biomarkers in this disease. Using RNA-seq data from two prostate cell lines, neoplastic (LNCaP) and non-neoplastic (PrEC), we have identified an unannotated long lncRNA adjacent to CEP55 (centrosomal protein 55), a gene associated with CIN. We have named this 1.6 kb transcript as lncRNA- CEP55. qPCR experiments showed it is downregulated in the neoplastic cell line, in contrast to the adjacent coding gene, CEP55, which is upregulated in the same cell line and downregulated in PrEC. Our data suggest this new lncRNA might be a possible repressor for CEP55. Changes in expression of CEP55 have been associated to CIN in other cancer cell lines. LINC02043 is an annotated lncRNA. We identified a differential expression between PrEC and LNCaP using RNA-seq data. LINC02043 is adjacent to the protein-coding gene RFC4; this gene is associated with CIN in different human cancers. We performed qPCR experiments and found LINC02043 to be downregulated in LNCaP, whereas the adjacent coding gene RFC4 is upregulated; the opposite is found in PrEC cell line. Our findings suggest LINC02043 could have a possible repressor role in RFC4. This protein-coding gene is related to mismatch repair and DNA double-strand break repair, abnormalities in this coding gene have been associated with CIN in other cancer cell lines. LINC02043 could play an important role in the cis-regulation of RFC4. lncRNA-CEP55 and LINC02043 are important targets of study, these lncRNAs could play an essential role in regulating the expression of adjacent genes related to CIN, an enabling characteristic that facilitates the development of the hallmarks of cancer. Further analysis is needed to validate their mechanisms of action and their potential use as prognostic biomarkers in PCa. Particularly in PCa, CIN has lately been related to cancer progression. The role of lncRNAs as drivers of CIN in PCa is a promising field in order to understand PCa progression and may play a potential role as biomarkers in this disease. Citation Format: Rogelio Montiel Manriquez. Identification of long non-coding RNAs involved in chromosomal instability in a cellular model of prostate cancer [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 3574.
Abstract 2559: Functional characterization of a RECQL4 mutation in Rothmund Thomson Syndrome
Authors: Tianyi Wu, Robert L. Walker, Marbin Pineda, MiYoung Lee, Yuelin Zhu, Ashok R. Venkitaraman, Paul S. Meltzer
Journal: Cancer Research (2019)

Abstract Osteosarcoma (OS) is the most common malignancy of the bone, typically diagnosed during the adolescent years. Despite early advances in treatment, OS survival rates have not improved in recent times. Targeted treatment remains elusive because OS is a genetically complex and heterogeneous disease and the low incidence of sporadic OS presents a challenge in dissecting the causes and drivers of tumor development. Type II Rothmund-Thomson Syndrome (RTS), a cancer predisposition disorder, presents a potential model for studying OS pathogenesis as roughly 30% of Type II RTS patients are eventually diagnosed with OS. Type II RTS is associated with germline mutations of the DNA helicase RECQL4 that exclusively target the C-terminal helicase domain thought to be involved in various cellular mechanisms of DNA repair. The N-terminal SLD2-homology domain, required for the assembly of the CMG complex at origins of replication, is spared. We used CRISPR/Cas9 gene editing to generate cell lines containing a common RECQL4 mutation identified in Type II RTS patients to further study its effects. Unexpectedly, a mutation previously reported as a nonsense mutation instead upregulates the activation of a known cryptic splice site in exon 14. This splice variant results in the in-frame deletion of the final 66 amino acids of exon 14. Our cell lines exhibit a mildly increased sensitivity to the DNA double-strand break inducing agent neocarzinostatin consistent with RECQL4’s reported functions in DNA damage repair. We will use next generation sequencing techniques to further characterize DNA damage repair signatures in RTS RECQL4 mutant cell lines. Citation Format: Tianyi Wu, Robert L. Walker, Marbin Pineda, MiYoung Lee, Yuelin Zhu, Ashok R. Venkitaraman, Paul S. Meltzer. Functional characterization of a RECQL4 mutation in Rothmund Thomson Syndrome [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 2559.
Australian Rheumatism Association: Fourth Annual Report, 1960
Authors: N Wing, S Nelson, R Strang, G Burnison, B Haynes, I Ferguson, R Robinson
Journal: Annals of the Rheumatic Diseases (1960)

Round maintained the clinical tradition established by predecessors, and consisted of the presentation of eight patients who suffered either from a rare rheumatic complaint or who had been referred to Hospital with an unusual presentation ofa rheumatic condition.The presentation was both lively and witty and was acknowledged by the Society with hearty applause.
Abstract 2967: Activity of G-quadruplex stabilizing small molecule that downregulates MYC and synergizes with Navitoclax in acute myeloid leukemia cells
Authors: Justin J. Montoya, Megan A. Turnidge, Daniel H. Wai, David W. Lee, Apruvi Patel, Vijay Gokhale, Laurence J. Hurley, David O. Azorsa
Journal: Cancer Research (2019)

Abstract Acute Myeloid Leukemia (AML) is a malignancy of myeloid precursor cells that can occur when genomic changes alter expression of key genes, causing cells to resume an undifferentiated state and proliferate. Ongoing efforts have focused on developing therapies that specifically target the protein products of aberrantly expressed genes. However, many of the identified proteins are difficult to target because of structural challenges, protein overexpression, or mutations that confer resistance to therapy. A type of therapy that circumvents these issues is the use of small molecules that stabilize DNA secondary structures called G-quadruplexes, which are present in the promoters of many potential oncogenes, and have regulatory roles in their transcription. This study analyzes the activity of G-quadruplex stabilizing small molecule GQC-05 that has been shown to down-regulate MYC, which is commonly misregulated in AML. Treatment of MYC-expressing AML cell lines KG-1a, CMK and TF-1 with GQC-05 resulted in decreased expression of MYC mRNA and protein, with the effect more pronounced in KG-1a cells. GQC-05 treatment of the AML cells decreased cell viability, while increasing apoptosis and DNA damage. Combinational drug screening was performed to identify compounds that potentiated the anti-proliferative effects of GQC-05. Results from the screen identified the BCL-2 inhibitor Navitoclax as a compound that potentiated GQC-05 activity. Co-treatment with GQC-05 and Navitoclax showed synergistic effect on cell viability of AML cells as determined by Chou-Talalay analysis. Furthermore, co-treatment with Navitoclax did not affect the downregulation of MYC by GQC-05, but did increase apoptosis and DNA damage leading to rapid cytotoxicity. These results indicate that the G-quadruplex stabilizing small molecule GQC-05 may function more as a DNA damaging agent in AML cells and that combining GQC-05 with a Bcl-2/Bcl-XLinhibitor such as Navitoclax can result in increased cytotoxic activity. Citation Format: Justin J. Montoya, Megan A. Turnidge, Daniel H. Wai, David W. Lee, Apruvi Patel, Vijay Gokhale, Laurence J. Hurley, David O. Azorsa. Activity of G-quadruplex stabilizing small molecule that downregulates MYC and synergizes with Navitoclax in acute myeloid leukemia cells [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 2967.
Molecular Mechanisms of DNA Damage Initiated by a,b-Unsaturated Carbonyl Compounds As Criteria for Genotoxicity and Mutagenicity
Authors: Erwin Eder, Christian Hoffman, Heinz Bastian, Christoph Deininger, Sabine Scheckenbach
Journal: Environmental Health Perspectives (1990)

OL,,-Unsaturated carbonyl compounds are important not only from a theoretical but also a practical standpoint.These ubiquitous compounds can interact with DNA through various mechanisms.The pre- dominant interaction is the formation of cyclic 1,N2-deoxyguanosine adducts; 7,8-cyclic guanine adducts are also found.We have synthesized and characterized the stereoisomers of adducts formed by about 20 a,ID-unsaturated carbonyl compounds.The different types of adducts and the mutagenic and genotoxic response can be explained by the molecular structures of the agents.Compounds forming saturated cyclic adducts are mutagenic in S. typhimurium strain TA100 and to a lesser extent in TA1535.Substances with a leaving group at the C-3 position form unsaturated conjugated cyclic adducts and are mutagenic only in the His D3052 frameshift strains with an intact excision repair system (no urvA mutation).Metabolic epoxidation of the double bond and other metabolic activation, e.g., activation of the nitrogroups via nitroreductases, were also found to contribute to genotoxic and mutagenic activities.Our results have further elucidated the genotoxic mechanisms of these compounds; however, additional investigations are required for a complete understanding of the genotoxic activity of this class of compounds.
Filanesib (ARRY-520) Demonstrates Potent and Rapid Activity in Preclinical Models of MM, Dependent on Bcl-2 Family Expression, and Synergistic with Dexamethasone and IMiDs
Authors: Susana Hernández-García, Laura San-Segundo, Lorena González-Méndez, Teresa Paíno, Ana Alicia López-Iglesias, Montserrat Martín-Sánchez, Mercedes Garayoa, Michael J Humphries, Brian Tunquist, Maria-Victoria Mateos, Enrique M Ocio
Journal: Blood (2014)
International collaboration is feasible in trials for rare conditions: The EURAMOS experience
Authors: N. Marina, S. Bielack, M. Sydes, M. Bernstein, T. Butterfass-Bahloul, S. Smeland, A. Holiday, J. Whelan
Journal: Journal of Clinical Oncology (2007)

20501 Background: Osteosarcoma is rare and the outcome for patients has plateaued following the introduction of multi-agent chemotherapy. To demonstrate further improvements would likely require large numbers of patients, only achievable in this setting via International collaboration. Therefore, in October 2001, 4 multinational groups - Children's Oncology Group (COG), Cooperative Osteosarcoma Study Group (COSS), European Osteosarcoma Intergroup (EOI) and Scandinavian Sarcoma Group (SSG) - agreed on the merits of collaboration to determine whether altering post-operative therapy based on histological response improved outcome. Following a number of practical and regulatory hurdles the trial opened to accrual in April 2005. Methods: Eligibility criteria include: new diagnosis with resectable osteosarcoma; age &lt;40 years; normal organ function. Standard therapy includes 29 weeks of cisplatin, doxorubicin and high-dose methotrexate (MAP). Following two cycles of cisplatin/doxorubicin and 2–6 cycles of high-dose methotrexate, patients undergo resection. Post-operative therapy is dependent on histological response. Good histological responders (&gt;90% necrosis) are randomized to continuing MAP or MAP with maintenance pegylated interferon. Poor histological responders are randomized to MAP or MAP plus ifosfamide and etoposide. Results: All groups are recruiting and accrual is ahead of schedule: 373 patients have been enrolled (159 COG, 108 COSS, 83 EOI, 23 SSG) and 160 patients randomized: 87 (54%) good responders (46 MAP), 73 (46%) poor responders (39 MAP). Conclusions: International collaboration is feasible and results in rapid accrual of large number of patients. The implementation of such trials is difficult and time consuming due to the complexity of multinational regulatory issues. However, the effort is worthwhile to potentially improve outcomes for patients with rare diseases. No significant financial relationships to disclose.