tbuckley/cabot-search huggingface dataset:
Abstract LB-212: XGFR, an Fc-engineered dual signaling inhibitor targeting IGF-1R and EGFR
Authors: Katharina Wartha, Rebecca Croasdale, Juergen Schanzer, Ulrich Brinkmann, Marco H. Hofmann, Carola Ries, Natascha Rieder, Gabriele Hoelzlwimmer, Olivier Freytag, Sylvia Herter, Christian Gerdes, Klaus-Peter Kuenkele, Christian Klein
Journal: Cancer Research (2011)

Abstract Background: Elevated signaling via the receptor tyrosine kinases IGF-1R and EGFR has been identified as common characteristic of multiple cancer type. IGF-1R and EGFR signal predominantly through the PI3K and MAPK signaling pathways and thereby mediate growth and survival signals crucial for the development and progression of cancer. There is strong cross talk on multiple levels between IGF-1R and EGFR dependent signaling pathways. Therefore, targeting IGF-1R and EGFR simultaneously is an attractive way to achieve maximal inhibition of signal transduction and to avoid resistance formation. Methods: Bispecific IGF1R-EGFR antibodies were engineered by linking scFv domains of an EGFR Mab (GA201) via Serine-Glycine linkers to an IgG1 IGF-1R Mab (RG1507). The functional properties of the bispecific antibodies were evaluated in cellular in vitro assays (IGF-1R/EGFR phosphorylation, downregulation, 3D proliferation and ADCC assays) and in in vivo xenograft models for tumor growth inhibition and survival. Results: Bispecific IGF-1R-EGFR antibodies (XGFR2, XGFR3, XGFR4) were successfully generated with yields and stability comparable to conventional IgG1 antibodies. XGFR antibodies effectively inhibited IGF-1R and EGFR phosphorylation and 3D proliferation in H322M tumor cells and induced strong downmodulation of IGF-1R and enhanced EGFR downmodulation compared to the parental EGFR antibody GA201. XGFR antibodies showed strong anti-tumor efficacy comparable to the combination of monospecific IGF-1R and EGFR Mabs in the BxPC3 and H322M xenograft models. To enhance the ADCC properties of XGFR, afucosylated, glycoengineered bispecific antibodies with enhanced affinity for FcγRIIIA were generated using the GlycoMab technology. Glycoengineered bispecific antibodies were shown to have superior ADCC properties in in vitro ADCC assays and XGFR4 significantly prolonged median and overall survival of mice in an ADCC competent in vivo model (A549 i.v.). Conclusions: Bispecific IGF-1R-EGFR antibodies represent an attractive therapeutic strategy to simultaneously target two key components of multiple cancer types (IGF-1R and EGFR), resulting in effective inhibition of the PI3K and MAPK signaling pathway and to avoid the formation of resistance to therapy. Having overcome issues of stability and productivity, bispecific antibodies may become an advantageous way to reduce costs and infusion times in cancer therapy, while at the same time, achieving maximal anti-tumor effects through inhibition of multiple targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-212. doi:10.1158/1538-7445.AM2011-LB-212
BREAST CANCER (Ca) DETECTION WITH Tc-99m- SestaMIBI PRONE IMAGING: ITS CORRELATION WITH MAMMOGRAPHY (MAMM) AND PATHOLOGY
Authors: I Khalkhali, I Mena, E Jouanne, L Diggles, B Jackson, S Klein
Journal: Clinical Nuclear Medicine (1992)

Khalkhali, I.; Mena, I.; Jouanne, E.; Diggles, L.; Jackson, B.; KleiK, S. Author Information
Excess amino acid polymorphism in mitochondrial DNA: contrasts among genes from Drosophila, mice, and humans
Authors: D. M. Rand, L. M. Kann
Journal: Molecular Biology and Evolution (1996)

Recent studies of mitochondrial DNA (mtDNA) variation in mammals and Drosophila have shown an excess of amino acid variation within species (replacement polymorphism) relative to the number of silent and replacement differences fixed between species. To examine further this pattern of nonneutral mtDNA evolution, we present sequence data for the ND3 and ND5 genes from 59 lines of Drosophila melanogaster and 29 lines of D. simulans. Of interest are the frequency spectra of silent and replacement polymorphisms, and potential variation among genes and taxa in the departures from neutral expectations. The Drosophila ND3 and ND5 data show no significant excess of replacement polymorphism using the McDonald-Kreitman test. These data are in contrast to significant departures from neutrality for the ND3 gene in mammals and other genes in Drosophila mtDNA (cytochrome b and ATPase 6). Pooled across genes, however, both Drosophila and human mtDNA show very significant excesses of amino acid polymorphism. Silent polymorphisms at ND5 show a significantly higher variance in frequency than replacement polymorphisms, and the latter show a significant skew toward low frequencies (Tajima's D = -1.954). These patterns are interpreted in light of the nearly neutral theory where mildly deleterious amino acid haplotypes are observed as ephemeral variants within species but do not contribute to divergence. The patterns of polymorphism and divergence at charge-altering amino acid sites are presented for the Drosophila ND5 gene to examine the evolution of functionally distinct mutations. Excess charge-altering polymorphism is observed at the carboxyl terminal and excess charge-altering divergence is detected at the amino terminal. While the mildly deleterious model fits as a net effect in the evolution of nonrecombining mitochondrial genomes, these data suggest that opposing evolutionary pressures may act on different regions of mitochondrial genes and genomes.
Identification of a Steap3 endosomal targeting motif essential for normal iron metabolism
Authors: Teresa Lambe, Robert J. Simpson, Sara Dawson, Tiphaine Bouriez-Jones, Tanya L. Crockford, Michelle Lepherd, Gladys O. Latunde-Dada, Hannah Robinson, Kishor B. Raja, Dean R. Campagna, Guadalupe Villarreal, J. Clive Ellory, Christopher C. Goodnow, Mark D. Fleming, Andrew T. McKie, Richard J. Cornall
Journal: Blood (2008)
Osteomalacia and Weakness From Excessive Antacid Ingestion
Authors: Karl L. Insogna
Journal: JAMA (1980)

A 60-year-old woman was evaluated for bone pain and incapacitating weakness. Initial laboratory studies showed a serum calcium level of 10.1 mg/dL, severe hypophosphatemia (1.1 mg/dL), and an elevated alkaline phosphatase level. X-ray films showed changes consistent with osteomalacia. Further studies revealed hypercalciuria (448 mg/24 hr) but absent urinary phosphorus. These data indicated phosphate malabsorption. Excessive use of an aluminum hydroxide—containing antacid was the cause of this patient's failure to absorb dietary phosphate. The features of this syndrome are reviewed to increase physicians' awareness of this illness, which occurs particularly in the elderly and is easily treated. (<i>JAMA</i>1980;244:2544-2546)
More than happenstance: Creutzfeldt-Jakob disease in farmers and young adults
Authors: S. M Gore
Journal: BMJ (1995)

In 1986, four years after a change in the processing of offals--including those from sheep infected with scrapie--into cattle meal, the first British case of bovine spongiform encephalopathy was confirmed.

Median incubation period in cattle is around four to five years.1 By 14 April 1995, bovine spongiform encephalopathy had been confirmed in 53.3% of dairy herds, 14.7% of beef suckler herds, and 33.8% of all herds with adult breeding cattle; people who work on farms without confirmed cases of bovine spongiform encephalopathy may, however, have worked on farms with infected, but not affected, cattle. The aim of ongoing studies in cattle is to find evidence of direct transmission of bovine spongiform encephalopathy by the two suggested means of transmission of scrapie in sheep: from mother to offspring or between unrelated animals around parturition.

The incubation period of human spongiform encephalopathies--kuru and Creutzfeldt-Jakob disease--is poorly estimated from data2 but is apparently in the range 15-40 years, possibly shorter in people who were young at exposure. The potential for the agent responsible for bovine spongiform encephalopathy to cross species barriers after occupational or dietary exposure--including exposure to cattle meal by ingestion or inhalation--has been a major concern for human health. Whether the agent is pathogenic to humans cannot be known by direct experimentation. Thus, surveillance of cases of sporadic Creutzfeldt-Jakob disease--in terms of occupational distribution, temporal changes in incidence, and dietary correlations--is the only way to get early warning of pathogenesis of bovine spongiform encephalopathy in humans. British surveillance of Creutzfeldt-Jakob disease was therefore reactivated in May 1990,3 and a grant from the European Community in 1993 enabled surveillance projects elsewhere in Europe to share common diagnostic criteria, methodologies, and casecontrol questionnaires. Two observations from …
Activation of the nitric oxide synthase pathway represents a key component of tumor necrosis factor–related apoptosis-inducing ligand–mediated cytotoxicity on hematologic malignancies
Authors: Paola Secchiero, Arianna Gonelli, Claudio Celeghini, Prisco Mirandola, Lia Guidotti, Giuseppe Visani, Silvano Capitani, Giorgio Zauli
Journal: Blood (2001)
Further delineation of chromosomal consensus regions in primary mediastinal B-cell lymphomas: an analysis of 37 tumor samples using high-resolution genomic profiling (array-CGH)
Authors: S Wessendorf, T F E Barth, A Viardot, A Mueller, H A Kestler, H Kohlhammer, P Lichter, M Bentz, H Döhner, P Möller, C Schwaenen
Journal: Leukemia (2007)
1132-160 Restenosis is better associated with change of coronary flow reserve rather than with absolute value of coronary flow reserve
Authors: Se-Joong Rim, Hee-Jung Lee, Jin Mi Kim, Pil-Ki Min, Byoung Eun Park, Young-Guk Ko, Seok-Min Kang, Jong-Won Ha, Donghoong Choi, Yangsoo Jang, Namsik Chung
Journal: Journal of the American College of Cardiology (2004)
Recipient-derived hepatocytes in liver transplants: A rare event in sex-mismatched transplants
Authors: Franz Fogt, Kurt H. Beyser, Christopher Poremba, Robert L. Zimmerman, Urmila Khettry, Josef Ruschoff
Journal: Hepatology (2002)

Bone marrow-derived stem cells have been shown to engraft and populate native tissues during repair and in transplanted animal tissues. Very few studies have been performed in humans to evaluate the possibility of stem cell engraftment in transplanted tissues. In human renal transplants, recipient cells have been demonstrated within vascular and interstitial structures. In a previous study of patients with hepatic transplants, hepatocytes with XY chromosome patterns have been detected in sex-mismatched female to male transplanted livers in a small number of cases. Because of the possibility of Y chromosome microchimerism of females with male offspring, we analyzed the presence of X and Y chromosomes in liver biopsies of 13 patients with sex-mismatched liver transplants (8 female to male, 5 male to female) and long transplant to biopsy intervals (1.2 to 12 years; mean, 4.5 years). We were able to detect recipient-specific sex chromosomal patterns in inflammatory cells by fluorescent in situ hybridization/immunohistochemistry combination within the liver parenchyma but not within hepatocytes. In conclusion, recipient engraftment of stem cells may be an early feature in liver transplant but may be an infrequent persistent feature in long-term grafts.
Control of Genomic Instability and Epithelial Tumor Development by the <i>p53-Fbxw7/Cdc4</i> Pathway
Authors: Jesus Perez-Losada, Jian-Hua Mao, Allan Balmain
Journal: Cancer Research (2005)

Abstract Mouse models of cancer have provided novel insights into the timing of p53 loss during tumorigenesis. We have recently identified Fbxw7/Cdc4 as a downstream target of p53 loss that controls genomic instability and tumor development in epithelial tumors. Although p53-deficient mice primarily develop lymphomas and sarcomas, the additional loss of one copy of the Fbxw7 gene drives tumor development in a range of epithelial tissues. These data highlight the importance of genetic instability at the chromosome level in the development of common cancer types, and further illustrate the value of mouse models in identifying causal genetic events in epithelial tumor formation.
Human Rabies Resistance
Authors: M. J. Friedrich
Journal: JAMA (2012)

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
Ghrelin levels in patients with juvenile idiopathic arthritis: relation to anti–tumor necrosis factor treatment and disease activity
Authors: Thomais Karagiozoglou-Lampoudi, Maria Trachana, Charalampos Agakidis, Polyxeni Pratsidou-Gertsi, Anna Taparkou, Sotiria Lampoudi, Florentia Kanakoudi-Tsakalidou
Journal: Metabolism (2011)
Failure of Conventional Doses of 1α,25-Dihydroxycholecalciferol to Correct Hypocalcemia in a Girl with Idiopathic Hypoparathyroidism
Authors: Russell W. Chesney, Sheldon D. Horowitz, Barbara E. Kream, John A. Eisman, Richard Hong, Hector F. DeLuca
Journal: New England Journal of Medicine (1977)

The candida endocrinopathy syndrome is characterized by chronic mucocutaneous candidiasis, endocrine-organ failure, usually of the parathyroid or adrenal glands, autoantibody formation against various endocrine glands and abnormalities of cell-mediated immunity.1 2 3 Hypoparathyroidism is the most frequent endocrinologic complication.4 The chronic hypocalcemia found cannot be treated with oral calcium since intestinal absorption of calcium in these patients is markedly reduced.5 Oral vitamin D, at a dose of 1.25 to 2.5 mg per day, is the mainstay of therapy,6 but even larger amounts may be required to maintain normal serum calcium concentrations. Patients "resistant" to therapy with vitamin D3, dihydrotachysterol and . . .
An infantile case of pityriasis lichenoides et varioliformis acuta
Authors: D. Hoshina, M. Akiyama, K. Hamasaka, H. Shimizu
Journal: British Journal of Dermatology (2007)

Journal Article An infantile case of pityriasis lichenoides et varioliformis acuta Get access D. Hoshina, D. Hoshina Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita‐ku, Sapporo 060‐8638, Japan *Hamasaka Skin Clinic, Sapporo, Japan E‐mail: hoshina@med.hokudai.ac.jp Search for other works by this author on: Oxford Academic Google Scholar M. Akiyama, M. Akiyama Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita‐ku, Sapporo 060‐8638, Japan *Hamasaka Skin Clinic, Sapporo, Japan E‐mail: hoshina@med.hokudai.ac.jp Search for other works by this author on: Oxford Academic Google Scholar K. Hamasaka, K. Hamasaka Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita‐ku, Sapporo 060‐8638, Japan *Hamasaka Skin Clinic, Sapporo, Japan E‐mail: hoshina@med.hokudai.ac.jp Search for other works by this author on: Oxford Academic Google Scholar H. Shimizu H. Shimizu Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita‐ku, Sapporo 060‐8638, Japan *Hamasaka Skin Clinic, Sapporo, Japan E‐mail: hoshina@med.hokudai.ac.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 157, Issue 1, 1 July 2007, Pages 194–196, https://doi.org/10.1111/j.1365-2133.2007.07931.x Published: 01 July 2007
Effects of histamine on coronary hemodynamics in humans: Role of H1and H2receptors
Authors: Carlo Vigorito, Arturo Giordano, Lorenzo De Caprio, Dino Franco Vitale, Nicola Maurea, Paolo Silvestri, Bernardino Tuccillo, Nicola Ferrara, Gianni Marone, Franco Rengo
Journal: Journal of the American College of Cardiology (1987)
Do Ask, Do Tell
Authors: Jennifer E. Potter
Journal: Annals of Internal Medicine (2002)

As a consequence of bias and ignorance within the medical profession, lesbians and gay men frequently receive suboptimal health care. Knowledge of each patient's sexual orientation and behaviors is critical for the development of a productive therapeutic relationship, accurate risk assessment, and the provision of pertinent preventive counseling. However, clinicians often forget to ask about this information, and many lesbians and gay men are reticent to reveal the truth. I present vignettes from my personal experiences as a lesbian patient and doctor to illustrate the importance of creating an environment in which such disclosure can occur and to portray the challenges and rewards of coming out as a gay physician.
Ketoconazole for Treatment of Disseminated Coccidioidomycosis
Authors: ANTONINO CATANZARO
Journal: Annals of Internal Medicine (1982)

Of 29 selected patients with disseminated coccidioidomycosis, 27 were treated for at least 6 months with ketoconazole, 200 to 600 mg/d. Two patients had progression of coccidioidal disease shortly after starting ketoconazole, and one developed meningitis. Seven of eight patients with synovitis had prompt improvement in symptoms, but four either had recurrent synovial thickening without recoverable Coccidioides immitis or could not remain free of symptoms off the drug. The response of osteomyelitis to ketoconazole was hard to assess; three of eight cases clearly improved and none progressed. Abscess or sinus formation clearly improved in eight of patients; five remained free of disease after the drug was discontinued. Skin lesions improved in six of nine; three lesions remain healed off the drug. Ketoconazole is absorbed readily after oral ingestion and has little toxicity. In the dosages used, it seems to suppress but not eradicate C. immitis. The drug may be able to stabilize the infection while cell-mediated immunity is restored.
Nonoxynol-9 as a Vaginal Microbicide for Prevention of Sexually Transmitted Infections
Authors: Barbra A. Richardson
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
Spleen Tyrosine Kinase Functions as a Tumor Suppressor in Melanoma Cells by Inducing Senescence-like Growth Arrest
Authors: Olivier Bailet, Nina Fenouille, Patricia Abbe, Guillaume Robert, Stéphane Rocchi, Nadège Gonthier, Christophe Denoyelle, Michel Ticchioni, Jean-Paul Ortonne, Robert Ballotti, Marcel Deckert, Sophie Tartare-Deckert
Journal: Cancer Research (2009)

Abstract Loss of tumor-suppressive pathways that control cellular senescence is a crucial step in malignant transformation. Spleen tyrosine kinase (Syk) is a cytoplasmic tyrosine kinase that has been recently implicated in tumor suppression of melanoma, a deadly skin cancer derived from pigment-producing melanocytes. However, the mechanism by which Syk suppresses melanoma growth remains unclear. Here, we report that reexpression of Syk in melanoma cells induces a p53-dependent expression of the cyclin-dependent kinase (cdk) inhibitor p21 and a senescence program. We first observed that Syk expression is lost in a subset of melanoma cell lines, primarily by DNA methylation–mediated gene silencing and restored after treatment with the demethylating agent 5-aza-2-deoxycytidine. We analyzed the significance of epigenetic inactivation of Syk and found that reintroduction of Syk in melanoma cells dramatically reduces clonogenic survival and three-dimensional tumor spheroid growth and invasion. Remarkably, melanoma cells reexpressing Syk display hallmarks of senescent cells, including reduction of proliferative activity and DNA synthesis, large and flattened morphology, senescence-associated β-galactosidase activity, and heterochromatic foci. This phenotype is accompanied by hypophosphorylated retinoblastoma protein (Rb) and accumulation of p21, which depends on functional p53. Our results highlight a new role for Syk tyrosine kinase in regulating cellular senescence and identify Syk-mediated senescence as a novel tumor suppressor pathway the inactivation of which may contribute to melanoma tumorigenicity. [Cancer Res 2009;69(7):2748–56]
Role of teaching hospitals in a developing country.
Authors: O O Akinkugbe
Journal: BMJ (1973)

What role do we envisage for teaching hospitals in this age of tremendous socio-economic transition that most developing nations are witnessing? Practically all developing countries are hopelessly underdoctored, and the problem of maldistribution of the relatively few doctors there are is a real one. Capitals often have more doctors than the rest of the country put to gether, and teaching hospitals contain a substantial percentage of this metropolitan complement. But lest we make the fatal mistake of equating the health needs of a nation with the number of practising physicians, we must emphasize the concept here of health teams as the most crucial units of medical manpower. Traditionally teaching hospitals see their main function as undergraduate and postgraduate teaching, research, and specialist care of the sick and injured. In the setting of a de veloping country one must give due prominence to public health, the central pivot around which most health planning in these localities should rotate.
Challenge test battery in chronic urticaria
Authors: ROBERT P. WARIN, RUTH J. SMITH
Journal: British Journal of Dermatology (1976)

The use of a battery of challenge tests in the routine investigations of patients with chronic urticaria has an important place, demonstrating an exacerbating factor in over half the patients. Diets designed to reduce the ingestion of the substances concerned are associated with clearing or considerable improvements in 75% of the patients treated.