tbuckley/cabot-search huggingface dataset:
Abstract P4-07-04: PARP1/2 inhibition in a subset of triple negative breast cancer (TNBC) patient-derived tumor xenografts (PDX) identifies predictive biomarkers of response
Authors: V Serra, C Cruz, A Bruna, YH Ibrahim, A Vivancos, A Vivancos, P Nuciforo, M Bellet, P Gómez, JM Pérez, C Saura, M Vidal, X Serres, OM Rueda, V Peg, C Caldas, MJ O'Connor, J Baselga, J Cortés
Journal: Cancer Research (2016)

Abstract Background: BRCA1/2 mutation carriers (gBRCA) have a higher risk of breast or ovarian cancer, since BRCA1/2 mutation results in impaired high-fidelity DNA repair by homologous recombination (HR) and subsequently genetic instability. In non-gBRCA TNBC, HR deficiency occurs at the somatic level, by means of BRCA1 mutation, BRCA1 epigenetic loss or mutation in other HR-associated genes. Because PARP1/2 inhibitors (PARPi) are well-tolerated and active anti-cancer agents in the advanced setting of gBRCA tumors, we sought to expand their applicability by identifying response biomarkers in TNBC. Methods: We have assessed the antitumor response of the PARP1/2 inhibitor olaparib as single agent in a panel of 12 primary and advanced TNBC PDX models. On PDXs exhibiting primary sensitivity to olaparib, we have developed models of acquired resistance by continuous exposure to the drug and identifying progression on treatment. We have characterized the models through targeted sequencing and the analysis of the hypermethylation and expression levels of BRCA1 transcript to find potential correlates of drug-sensitivity. Results: Three out of 12 PDXs (25%) treated with single agent olaparib, exhibit tumor regression or disease stabilization. BRCA1 is hypermethylated in two of these PARPi-sensitive TNBC PDX models and is associated with loss of BRCA1 mRNA expression. The third PARPi-sensitive TNBC PDX harbors a frameshift, heterozygous PALB2 mutation, which is no longer detected in the acquired resistance PDX model. Acquired resistance in the hypermethylated PDXs is under study as well as the duration of response compared to gBRCA PDX models. Conclusions: Our study highlights that somatic HR-deficiency is frequent in TNBC and provides the basis of sensitivity to PARPi. Citation Format: Serra V, Cruz C, Bruna A, Ibrahim YH, Vivancos A, Vivancos A, Nuciforo P, Bellet M, Gómez P, Pérez JM, Saura C, Vidal M, Serres X, Rueda OM, Peg V, Caldas C, O'Connor MJ, Baselga J, Cortés J. PARP1/2 inhibition in a subset of triple negative breast cancer (TNBC) patient-derived tumor xenografts (PDX) identifies predictive biomarkers of response. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-07-04.
Exposure to Animals and Risk of Ocular Adnexal Marginal Zone B-Cell Lymphoma
Authors: R. Dolcetti, D. Serraino, G. Dognini, S. Govi, R. Crocchiolo, P. Ghia, E. Pasini, M. Ponzoni, R. Talamini, P. De Paoli, C. Doglioni, A. Ferreri
Journal: Annals of Oncology (2011)
First-in-human uPAR PET: Imaging of Cancer Aggressiveness
Authors: Morten Persson, Dorthe Skovgaard, Malene Brandt-Larsen, Camilla Christensen, Jacob Madsen, Carsten H. Nielsen, Tine Thurison, Thomas Levin Klausen, Søren Holm, Annika Loft, Anne Kiil Berthelsen, Michael Ploug, Helle Pappot, Klaus Brasso, Niels Kroman, Liselotte Højgaard, Andreas Kjaer
Journal: Theranostics (2015)

A first-in-human clinical trial with Positron Emission Tomography (PET) imaging of the urokinase-type plasminogen activator receptor (uPAR) in patients with breast, prostate and bladder cancer, is described. uPAR is expressed in many types of human cancers and the expression is predictive of invasion, metastasis and indicates poor prognosis. uPAR PET imaging therefore holds promise to be a new and innovative method for improved cancer diagnosis, staging and individual risk stratification. The uPAR specific peptide AE105 was conjugated to the macrocyclic chelator DOTA and labeled with (64)Cu for targeted molecular imaging with PET. The safety, pharmacokinetic, biodistribution profile and radiation dosimetry after a single intravenous dose of (64)Cu-DOTA-AE105 were assessed by serial PET and computed tomography (CT) in 4 prostate, 3 breast and 3 bladder cancer patients. Safety assessment with laboratory blood screening tests was performed before and after PET ligand injection. In a subgroup of the patients, the in vivo stability of our targeted PET ligand was determined in collected blood and urine. No adverse or clinically detectable side effects in any of the 10 patients were found. The ligand exhibited good in vivo stability and fast clearance from plasma and tissue compartments by renal excretion. In addition, high uptake in both primary tumor lesions and lymph node metastases was seen and paralleled high uPAR expression in excised tumor tissue. Overall, this first-in-human study therefore provides promising evidence for safe use of (64)Cu-DOTA-AE105 for uPAR PET imaging in cancer patients.
Development lesson
Authors: Trisha Greenhalgh
Journal: BMJ (2008)

I was waiting on a dusty street corner in one of Africa’s poorest countries, with six teenagers. To pass the time, I invited them to give me 10 differences between “third world” and ‘‘first world’’ countries.

“Easy,” said one. “We’re doing this in Geography. GDP.”

“Okay, so people don’t earn much. What’s the impact of that?”

They surveyed the rows of stinking slums. “People can’t afford nice houses. No kitchens or bathrooms. And the roofs sometimes fall off.”

“Why do you think they don’t earn enough money to buy nice houses?”

“I think they might not be able to read. And there probably aren’t enough jobs to go round.”

“Why not?”

Silence while they contemplated where jobs come from.

“Well, they can’t work on a farm because there’re no farms. Nothing grows here.”

This was true. The country was built on rock.

“And no factories either. All the goods are imported.”

“You could build a business, like those call centres they have in India. But I guess they don’t know how.”

We were observing a man arc welding pipes in the middle of the pavement, surrounded by hordes of barefoot children. Car horns drowned the imam’s chant from the nearby mosque.

“They don’t seem to care about safety. Everyone drives really crazy.” We recalled the limbless beggars and the little boy with the missing eye.

“What about health?” I asked.

“I think they would get diseases living so close together and having to poo in the drain.”

“If you didn’t have a job you’d get depressed.”

“They have way more children. I guess because some of them die. The mothers must get really tired.”

“People think it’s cool to smoke”—pointing to an enormous billboard advertising Camel cigarettes.

A man limped by on a disfigured club foot. I explained that this was probably congenital.

“So if you’re born with some problem they can’t fix it like they could in England.”

Our lift was finally pulling up. One final question: “Right, you clever kids, how would you solve all these problems?”

Eventually one of them ventured a solution. “I think,” she said tentatively, “I would start by building a school.”
Undetected HIV infection among acutely ill psychiatric inpatients
Authors: M Sacks, H Dermatis, S Looser-Ott, W Burton, S Perry
Journal: American Journal of Psychiatry (1992)

Serological testing of waste bloods revealed that 25 (7%) of 350 acutely ill psychiatric inpatients had HIV infection. Eight of the 10 HIV-positive patients whose serological status was not recorded on admission were discharged with their status still unrecorded and presumably undetected. Thirty-nine (51%) of the 77 inpatients with HIV-related risk behaviors identified on admission were discharged with no record of their having been serologically tested before or during hospitalization.
Abstract SY30-02: Understanding the proteome through the chaperome: From mechanisms to diagnostics and drugs
Authors: Gabriela Chiosis
Journal: Cancer Research (2015)

Abstract Malignant cellular function is maintained by a functionally altered proteome. Helping the proteome in this context is the chaperome, a network of molecular chaperones and folding enzymes. This talk will discuss how, by using chemical tools that selectively target the stress chaperome, one may perform mechanistic and therapeutic investigations into the tumor proteome. Specifically, using chemical tools as affinity-purification baits or as global perturbers of the altered proteome one may inquire into its nature (i.e., identify and investigate). By attacking specifically the stress chaperome, one may inactivate the altered proteome, and thus revert or slow the disease phenotype (i.e., treat). In summary, I will discuss how by chemically sensing the stress chaperome one may investigate, understand and destabilize the tumor proteome. Citation Format: Gabriela Chiosis. Understanding the proteome through the chaperome: From mechanisms to diagnostics and drugs. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY30-02. doi:10.1158/1538-7445.AM2015-SY30-02
Case 34-1962
Authors: Kenneth T. Bird, Richard B. Cohen
Journal: New England Journal of Medicine (1962)

Presentation of Case First admission. A fifty-three-year-old woman was admitted to the hospital because of a mass in the neck.Six weeks previously a gradually enlarging swelling appeared in the neck below the right ear. It caused only minimal discomfort. An examination twelve days before entry revealed a large, hard mass involving the entire right parotid gland, with fixation to the surrounding tissue. There were no palpable lymph nodes, but a moderate right-sided facial paresis was evident.Physical examination revealed that the orifice of the right parotid duct was pouted and firm; the parotid mass was unchanged. A 2-cm., hard, . . .
Targeting antiapoptotic Bcl-2 family memberswith small molecule inhibitors compliments the activity of the proteasome inhibitors bortezomib and carfilzomib in in vitro models of lymphoproliferative malignancies.
Authors: Luca Paoluzzi, Mithat Gonen, Owen O'Connor
Journal: Clinical Cancer Research (2008)

A33   Over-expression of anti-apoptotic members of the Bcl-2 family have been observed in more that 80% of B-cell lymphomas and contribute to tumor initiation, progression and resistance to therapy. We have recently demonstrated how Carfilzomib (C), the first in a new class of selective proteasome inhibitors, synergizes with AT-101, a small molecule inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-X L  and Mcl-1 in mantle cell lymphoma (MCL). The combination of AT-101 and C has also shown to induce significant decrease of the mitochondrial membrane potential (Δψm, p ≤ 0.008) and apoptosis (p ≤ 0.046) compared to the two drugs given alone.  ABT-737 is small molecule inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-X L  and  Bcl-w. We investigated the cytotoxicity and proapoptotic activity of ABT-737 alone and in combination with the boronic acid derivative bortezomib (B), approved for multiple myeloma and MCL or carfilzomib in a panel of non-Hodgkin lymphoma cell lines that included MCL (HBL-2), T-cell (H9) and diffuse large B-cell (DLBC, RL and SKI) histologies. Cell Titer-Glo assay followed by luminometric acquisition was used for all cytotoxicity assays, JC-1 dye and yopro-1 plus propidium iodide (PI) followed by FACScalibur acquisition was used to assess the Δψm and apoptosis respectively. Drug:drug interactions in terms of synergism, additivity or antagonism were computed using the Calcusyn software (Biosoft, Cambridge, UK) with a combination index (CI)  1 antagonism.  The IC 50  values for ABT-737 alone for 24 hours (h) to 72 h were generally in the low micromolar range across all cell types: 0.03-12.7 µM at 24h, 0.03-9.5 µM at 72h.  The combination of ABT-737 with C or B for 24 h showed a statistically significant increase in cytotoxicity compared to the single drugs and control in MCL (HBL-2, p≤0.0001). In a DLBCL model (RL), the combination of ABT-737 + B was significantly superior to combinations with conventional drugs such as doxorubicin or 4-hydroxycyclophosphamide (p≤0.004). ABT-737 also induced potent mitochondrial membrane depolarization and apoptosis when combined with C and B in MCL and DLBCL compared to the two drugs given alone (p≤0.0001). Animal xenograft studies of ABT-737 plus a proteasome inhibitor will be utilized to identify the most effective schedules of administration of these agents in vivo.
Non-absorption of mepacrine: description of a case.
Authors: J Yudkin
Journal: BMJ (1946)

In a paper published last year (Yudkin, 1945) I suggested that patients with malaria who do not respond well to oral mepacrine therapy might show a low urinary excretion of the drug. In such cases parenteral administration might be of value. Since then I have examined specimens of urine from hundreds of individuals on suppressive or therapeutic mepacrine and had not found one in whomn there was a failure of absorption, nor has it been reported by other workers. In August, 1945, however, such a case was seen in a West African military hospital. The patient was a young European naval rating with malaria who did not respond to large doses of mepacrine orally; he excreted only extremely small quantities of the drug in the Lirine and responded rapidly to a few small doses intramuLscularly.
Money back guarantees for non-reproducible results?
Authors: Eric J Topol
Journal: BMJ (2016)

There are better solutions to the “reproducibility crisis” in research

Money back guarantees are generally unheard of in biomedicine and healthcare. Recently, the US provider Geisenger Health System, in Pennsylvania, started a programme to give patients their money back if they were dissatisfied.1 That came as quite a surprise. Soon thereafter, the chief medical officer at Merck launched an even bigger one, proposing an “incentive-based approach” to non-reproducible results—what he termed a “reproducibility crisis” that “threatens the entire biomedical research enterprise.”2

The problem of irreproducibility in biomedical research is real and has been emphasised in multiple reports.3 4 5 In the same vein, the retraction of academic papers has been rising, attributable, in nearly equal parts, to irreproducible results or data that have been falsified.6

But this problem is not confined to basic science or animal model work from academic laboratories. Clinical trials, the final common pathway for the validation and approval of new drugs, have been plagued with serious drawbacks.

The bad science in clinical trials has been well documented and includes selective publication of …
Heritability of non-HLA genetics in coeliac disease: a population-based study in 107 000 twins
Authors: Ralf Kuja-Halkola, Benjamin Lebwohl, Jonas Halfvarson, Cisca Wijmenga, Patrik K E Magnusson, Jonas F Ludvigsson
Journal: Gut (2016)

Almost 100% individuals with coeliac disease (CD) are carriers of the human leucocyte antigen (HLA) DQ2/DQ8 alleles. Earlier studies have, however, failed to consider the HLA system when estimating heritability in CD, thus violating an underlying assumption of heritability analysis. We examined the heritability of CD in a large population-based sample of twins, considering HLA.In a population-representative sample of 107 912 twins, we identified individuals with CD (equal to villous atrophy) through biopsy reports from all Swedish pathology departments. We calculated concordance rates and tetrachoric correlations for monozygotic (MZ) and dizygotic (DZ) twin pairs. Further, we estimated heritability of CD, first strictly from observed data, and then the non-HLA heritability, representing the heritability of all genetic factors except the HLA locus, using an approach that circumvent the violation of underlying assumptions.We identified 513 twins with a diagnosis of CD (prevalence 0.48%). Concordance rates were higher in MZ pairs (0.49) than in DZ pairs (0.10), as were tetrachoric correlations (0.89 in MZ vs 0.51 in DZ pairs). The heritability of CD was 75% (95% CI 55% to 96%). The non-HLA heritability was slightly attenuated, 68% (95% CI 40% to 96%), with shared (17%) and non-shared (15%) environmental factors explaining the remaining variability of CD.CD is characterised by a high heritability, but our study also suggests that non-shared environmental factors may be of importance to CD development. HLA seems to have only moderate impact on heritability estimates.
Activities of the Field Investigations and Demonstrations Branch
Authors: Raymond F. Kaiser, M.D., Rosalie I. Peterson, M.S.
Journal: JNCI Journal of the National Cancer Institute (1957)

Journal Article Activities of the Field Investigations and Demonstrations Branch Get access Raymond F. Kaiser, M.D., Raymond F. Kaiser, M.D. Chief Nursing Section, Field Investigations and Demonstrations Branch, National Cancer Institute, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Rosalie I. Peterson, M.S. Rosalie I. Peterson, M.S. Head Nursing Section, Field Investigations and Demonstrations Branch, National Cancer Institute, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 19, Issue 2, August 1957, Pages 259–273, https://doi.org/10.1093/jnci/19.2.259 Published: 01 August 1957
The 40–60% Problem
Authors: Guy R. Newell
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article The 40–60% Problem Get access Guy R. Newell, M.D. Guy R. Newell, M.D. Deputy Director NCI Coordinator—Diet, Nutrition, and Cancer Program Office of the Director National Cancer InstituteBethesda, Maryland 20205 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 63, Issue 3, September 1979, Pages 539–540, https://doi.org/10.1093/jnci/63.3.539 Published: 01 September 1979
Development of aphasia, apraxia, and agnosia and decline in Alzheimer's disease
Authors: J A Yesavage, J O Brooks, J Taylor, J Tinklenberg
Journal: American Journal of Psychiatry (1993)

The purpose of this study was to compare the stage and the subtype models of disease progression in Alzheimer's disease. The authors address the issue of whether the overall rate of clinical decline is different in Alzheimer's disease patients with and without early development of aphasia, apraxia, or agnosia.The study was a case series study. Two separate cohorts of Alzheimer's disease patients were used, one from an ongoing single center study at Stanford University (N = 57) and the other from a multicenter project across the state of California (N = 70). Patients were assessed every 6 months in the Stanford study and yearly in the state study. All patients were assessed at least three times. The outcome measure was the average rate of decline on the Mini-Mental State examination.The average rates of decline on the Mini-Mental State were computed for each subject. Subjects were then divided among groups according to whether and when they exhibited aphasia, agnosia, or apraxia. The effects of the presence of aphasia, agnosia, or apraxia were assessed by comparing the average rates of decline on the Mini-Mental State.Alzheimer's disease patients who developed aphasia or apraxia declined more rapidly than those patients who did not develop either sign. These results were not attributable to differences in Mini-Mental State scores at entry into the study. The results suggest the presence of subtypes of Alzheimer's disease in which accelerated decline is associated with the early appearance of certain neurological signs.
Histopathologic Classification, Biologic Characteristics, and Histogenesis of Nasopharyngeal Carcinomas
Authors: P C LIANG, C C CH'EN, C C CHU, Y F HU, H M CHU, Y S TSUNG
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 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
Antigenic Similarity Between Simian Virus 40-lnduced Surface and Fetal Antigens in Hamster Cells2
Authors: Kenzo Kato
Journal: JNCI Journal of the National Cancer Institute (1977)

The tumor-associated cell-surface antigen (TSSA) on simian virus 40 (SV40)-transformed hamster cells was studied serologically by a complement-dependent cytotoxicity test. An antiserum was obtained from guinea pigs inoculated with SV40-transformed hamster cells. The serum was cytotoxic to SV40-transformed hamster cells after absorption with 15-day hamster embryo cells, hamster cells transformed either by polyoma virus or adenovirus 12, various tissues of hamster origin (brainliver, spleen, and kidney), or sheep red blood cells. These results indicated that the major TSSA induced specifically by SV40 was similar or identical to the antigen present during early stages of embryogenesis.
Abstract IA11: Tumor dormancy and recurrence
Authors: Lewis A. Chodosh
Journal: Cancer Research (2016)

Abstract For many types of human cancer, residual tumor cells remain following treatment that are not detected by conventional clinical testing. These cells have the ability to survive in a presumed dormant state within tissues for up to 20 years, either as solitary cells or as micrometastases. Ultimately, residual cells re-emerge from this latent state and resume growth, leading to cancer recurrence. Despite the unrivaled clinical importance of these aspects of breast cancer progression, the mechanisms underlying them are largely unknown. Since dormant residual tumor cells likely constitute the reservoir from which recurrent cancers arise, the lack of therapeutic approaches specifically targeted against these cells as well as our lack of understanding about their biology constitute major obstacles to the successful treatment of human cancers. As such, the development of targeted therapies designed to block pathways on which residual tumor cells depend for survival and growth would represent an attractive approach to preventing cancer recurrence. Consequently, elucidating the pathways that underlie dormant tumor cell survival and recurrence is a critical priority in cancer research. Citation Format: Lewis A. Chodosh. Tumor dormancy and recurrence. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr IA11.