tbuckley/cabot-search huggingface dataset:
Abstract 2662: Site specific ADC generation using SMARTag technology with programmable payload placement
Authors: David Rabuka
Journal: Cancer Research (2014)

Abstract Antibody-drug conjugates (ADCs) are an exciting, new therapeutic option for cancer treatment. ADCs offer the promise of targeted drug delivery with increased efficacy and safety. Currently approved ADCs are heterogeneous mixtures resulting from nonselective ligation of drug to either cysteine or lysine residues. This heterogeneity complicates the pharmacokinetics and pharmacodynamics of these drugs. Redwood Bioscience, Inc. has developed the SMARTagTM technology platform that enables precise, programmable, site-selective chemical protein modification and stable bioconjugate generation. Leveraging the target sequence of Formylglycine Generating Enzyme (FGE), proteins are chemoenzymatically modified to generate a precisely placed aldehyde functionality that can be chemically elaborated. Subsequently, novel ligation chemistry is employed that exploits this “aldehyde tag” site. This new reaction, the hydrazino-iso-Pictet-Spengler (HIPS) ligation, possesses two distinct advantages over current carbonyl ligations. First, the HIPS ligation proceeds quickly at near neutral pH in the absence of catalysts, allowing for one-step labeling of aldehyde-functionalized proteins under mild conditions. Second, HIPS ligation products are very stable in human plasma relative to an oxime-linked conjugates. Thus, the HIPS ligation exhibits a combination of stability and speed at near neutral pH that is unmatched by current carbonyl bioconjugation chemistries. We will present our novel protein modification platform and its application to generating ADCs, including our new conjugation chemistries and linker libraries. These technologies have been applied to the generation of a panel of site-specifically modified bioconjugates. Data from preclinical tumor models and PK studies highlighting the efficacy and safety of these ADCs and how these results are impacted by payload placement to the antibody will be presented. Citation Format: David Rabuka. Site specific ADC generation using SMARTag technology with programmable payload placement. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2662. doi:10.1158/1538-7445.AM2014-2662
Abstract 74: Activation of Akt1 accelerates carcinogen-induced tumorigenesis in mammary gland of virgin and post-lactating transgenic mice
Authors: Yanyuan Wu, Juri Kim, Yayha Elshimali, Jaydutt V. Vadgama
Journal: Cancer Research (2014)

Abstract Introduction The data from in vivo and in vitro studies suggest that activation of Akt regulates cell survival signaling and plays a key role in tumorigenesis. To explore oncogenic role of Akt1 in the development of mammary tumor, transgenic mice were created. Methods The transgenic mice were generated by expressing myristoylated-Akt1 (myr-Akt1) under the control of MMTV-LTR promoter. The carcinogen 7, 12 dimethyl-1,2-benzanthracene (DMBA) was used for inducing tumor formation. Results The MMTV driven myr-Akt1 transgene expression was detected primarily in mammary glands, uterus, and ovaries and the expression level increased significantly in lactating mice, suggesting the response was hormone dependent. The total expression level of Akt in the mammary gland was also high in these lactating mice. Interestingly, the expression of MMTVmyr-Akt1 in ovary of transgenic mice caused significant increase in circulating estrogen levels, even at post-lactating stage. Expression of myr-Akt1 in mammary glands alone did not increase tumor formation frequency. However, an increased susceptibility to the induction of mammary tumors by DMBA was observed in transgenic mice, especially in post-lactating mice. DMBA induced 42.9% of mammary tumors in post-lactating transgenic mice within 34 weeks, but none in post-lactating wild-type mice. The myr-Akt1 driven mammary tumors induced by DMBA had increased phosphorylated-Akt1 and showed strong expression of estrogen receptor (ERα) and EGFR. Cyclin D1 was more frequently up-regulated in mammary tumors from transgenic mice compared to tumors from wild-type mice. Overexpression of Cyclin D1, however, was not completely dependent on activated Akt1. Interestingly, mammary tumors that had metastasized to secondary sites had increased expression of twist and slug, but showed low expression of Cyclin D1. Conclusions In summary, activation of Akt1 in mammary gland accelerated carcinogen-induced tumorigenesis, especially in post-lactating mice. Citation Format: Yanyuan Wu, Juri Kim, Yayha Elshimali, Jaydutt V. Vadgama. Activation of Akt1 accelerates carcinogen-induced tumorigenesis in mammary gland of virgin and post-lactating transgenic mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 74. doi:10.1158/1538-7445.AM2014-74
Pediatric Transcatheter Valve Replacement
Authors: Christopher J. Petit
Journal: Circulation (2015)

T ransformative advances in medical technology rarely occur in isolation, but rather may be indirectly informed, if not accelerated, by advances in related fields.Bonhoeffer et al 1 introduced the first transcatheter valve in 2000, implanting it in a 12-year-old boy with tetralogy of Fallot.The report of the transcatheter aortic valve by Cribier a mere 2 years later suggests the interdependence of investigators on breakthroughs in related fields. 2 The advancements in cardiac devices are shared among pediatric and adult cardiologists, with benefits ideally befalling both patient populations when a breakthrough occurs, whether that technology was initially introduced for adults or children.
CLINICAL NOTES ON AN EPIDEMIC OF POLIOMYELITIS
Authors: N M SHUTKIN
Journal: Annals of Internal Medicine (1951)

Article1 March 1951CLINICAL NOTES ON AN EPIDEMIC OF POLIOMYELITISNED M. SHUTKIN, M.D.NED M. SHUTKIN, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-34-3-655 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe epidemic of anterior poliomyelitis in North Carolina during the summer months of 1948 was unprecedented both as to the number of cases and also as to the percentage of the bulbar and/or respiratory cases. The unusual incidence of the latter so taxed the facilities of the poliomyelitis unit set up at the North Carolina Orthopedic Hospital that, for the most part, we were obliged to admit only those patients with bulbar and/or respiratory symptoms and those with evidence of high spinal cord involvement, so frequently the precursor of respiratory or bulbar paralysis.In the course of handling 362 acute...Bibliography1. Bodian D: Poliomyelitis, neuropathological observations in relation to motor symptoms, J. A. M. A. 134: 1148, 1947. CrossrefMedlineGoogle Scholar2. McCarter JC: The brain stem in acute poliomyelitis, Quart. Bull., Northwestern Univ. M. School 22: 264, 1948. Google Scholar3. BestTaylor CHNB: Physiological basis of medical practice, ed. 4, 1945, Williams & Wilkins Co., Baltimore. Google Scholar4. Hart VK: Personal communication. Google Scholar5. Saphir O: Visceral lesions in poliomyelitis, Am. J. Path. 21: 99, 1945. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Gastonia, North Carolina*Received for publication June 9, 1949.From the North Carolina Orthopedic Hospital, Gastonia, North Carolina.†National Foundation for Infantile Paralysis Fellow, Duke University School of Medicine, Durham, N. C. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byMyokarditis und weitere MyokardiopathienCardiovascular Disturbances in PoliomyelitisCardiorespiratory Problems in Severe Poliomyelitis Observed during the Recent Epidemic 1 March 1951Volume 34, Issue 3Page: 655-668KeywordsHospitalsOrthopedicsParalysisPoliomyelitisSpinal cord ePublished: 1 December 2008 Issue Published: 1 March 1951 PDF downloadLoading ...
Abstract 20013: The Alpha-Arrestin Arrdc3 Regulates Obesity in Mice and Humans
Authors: Parth Patwari, Valur Emilsson, Eric E Schadt, William A Chutkow, Loren G Fong, Stephen G Young, Richard T Lee
Journal: Circulation (2010)

Obesity, a major contributor to cardiovascular disease, has a significant genetic component, yet few genes are known to contribute to the risk of obesity. A genome-wide linkage scan for high body mass index (BMI) in 3893 males and 4445 females identified a linkage peak on chromosome 5q13-15. Positional cloning revealed an association of a rare haplotype to high BMI in males (P=0.000006) but not females, with an odds ratio of 3.8. The risk locus contains a single gene named “arrestin domain containing 3” (ARRDC3), an uncharacterized alpha-arrestin. Alpha-arrestins are related to the visual and beta-arrestins that regulate receptor signaling, but little is known about alpha-arrestin function. We investigated ARRDC3 expression by Northern analysis and detected prominent expression in non-neural tissues, especially adipose and muscle. Analysis of gene expression in human omental fat biopsies showed significant correlation of ARRDC3 mRNA with BMI in males but not females, supporting the male-specific linkage t...
The Influence of Estrogens on the Incidence of Tumors in Foster Nursed Mice
Authors: John J. Bittner
Journal: Cancer Research (1941)

315 mice of inbred A C3H(Z) and C57 black (B) strains were injected with crystalline estrogens to determine whether the incidence of the resulting breast carcinoma would be similar to the incidence of spontaneous tumors observed in breeding females of inbred stocks and hybrid generations.  Pellets of estone (average weight 2 mg) or estradiol benzoate (average weight 1.5-2.0 mg) were implanted subcutaneously when the mice were aged 4-6 weeks.  Induced tumors occurred in some mice of inbred strains (except males of the C3H strain) nursed by females of strains having a high incidence of spontaneous mammary tumors.  None of the estrogen-treated mice nursed by females of stocks with a low incidence of spontaneous tumors developed tumors regardless of their genetic constitution.  In males of the ABF1 generation receiving estradiol benzoate animals which died before 9 months of age had a high incidence of tumors while mice which survived longer than 9 months were free from the tumors.  It is concluded that estrogen administration may induce mammary tumors in mice which have an inherited susceptibility for spontaneous tumors and an active milk influence and an active milk influence without an inherited susceptibility for the development of spontaneous tumors.
Allogeneic blood stem cell transplantation: peripheralization and yield of donor-derived primitive hematopoietic progenitor cells (CD34+ Thy- 1dim) and lymphoid subsets, and possible predictors of engraftment and graft-versus-host disease
Authors: M Korbling, YO Huh, A Durett, N Mirza, P Miller, H Engel, P Anderlini, K van Besien, M Andreeff, D Przepiorka
Journal: Blood (1995)
The mechanisms of mTOR inhibitor overcoming cisplatin resistance.
Authors: Chunjing Wu, Medhi Wangpaichitr, Lynn Feun, Theodore Lampidis, Marcus T. Kuo, Carlos Robles, Niramol Savaraj
Journal: Cancer Research (2006)

5434  We have previously shown that mTOR inhibitor (CCI-779) can restore cisplatin sensitivity in cisplatin resistant small cell lung cancer cell (SCLC) line (Mol. Cancer 4:25, 2005). However, not all cisplatin resistant cell lines are sensitive to mTOR inhibitor. In this report, we have investigated the molecular differences in these cisplatin resistant lung cancer cell lines and determined whether reversal of cisplatin resistance is by inhibition of mTOR. Two pairs of lung cancer cell lines and their resistant variants were used: SCLC1/SR-2 and MSCLCS/MSCLCSC. SR-2 exhibits 20 fold resistance to cisplatin and can be completely reversed with 30 ng/ml of CCI-779 whereas MSCLCSC exhibits 7 fold resistance to cisplatin and cannot be reversed with the same dosage. To confirm that the reversal effect is due to inhibition of mTOR, we have used SiRNA to knock down mTOR. Two SiRNA were used with similar result. The maximal effect occurs at 48 hrs. with 80% inhibition and lasts for 72hr. The ID50 of cisplatin was also decreased from 2.5 to 0.2ug/ml in the transfected cell lines which is similar to using CCI-779. The amount of phosphor-4E-BP was also decreased with maximal effect seen at 72 hr. Thus, our results further confirm that inhibition of mTOR can restore cisplatin sensitivity. Since SR-2 expressed higher levels of several genes including elongation factor alpha, hTERT, cyclin D3, Cyclin B replication A protein, RAD 52, RAD51, and Ku80, we determined whether these proteins decrease after addition of CCI-779. Our results show that Elongation factor alpha, hTERT, CyclinD3, Cyclin B, Replication A protein were decreased whereas RAD 52, RAD51 and Ku80 showed no changes. SR-2 cell lines also possess higher levels of pAKT and PDK1 which indicates activation of PI3, a growth stimulatory pathway upstream of mTOR. Thus, by inhibiting mTOR, the survival pathway of cisplatin resistant cells is inhibited. In contrast, MSCLCSC has minute amounts of pAKT as well as phosphor mTOR (cannot be detected by westernblot).In addition, by gene specific array analysis, MSCLCSC only showed increase in elongation factor alpha which can be inhibited by mTOR, whereas RAD51, 52, Ku80 are not affected by mTOR inhibitor. The remaining genes are being investigated. Thus, it is likely that mTOR inhibitor will restore cisplatin resistance in cell lines which have activated PI3 survival pathway and which possess high levels of replication proteins whose translation is controlled by mTOR. Supported by VA Research fund.
Abstract 3006: Serum insulin growth factor/insulin growth factor receptor1 (IGF-I, IGF-I-1R) and VEGF-A as prognostic factors and surrogate biomarkers in triple negative breast cancer patients (TNBC)
Authors: Abdel-Rahman N. Zekri, Abeer Bahnassy
Journal: Cancer Research (2014)

Abstract Background: We evaluated the prognostic and predictive values of serum IGF-I, IGF-I-1R, VEGF and TGF-β1 in triple-negative and non-triple-negative breast cancer (TNBC&amp;NTNBC) patients through correlation with standard prognostic factors and survival. Methods: serum expression of VEGF-A, TGF-β1, IGF-I and IGF-I-1R proteins was measured in of 43 TNBC, 53 NTNBC and 20 normal control (NC) by quantitative enzyme linked immune-sorbant assay (ELISA). Results were correlated to patients’ characteristics, disease free and overall survival (DFS&amp;OS). Results: The cutoff points that discriminate between TNBC and NTNBC were: 10.09 ng/ml, 412.54 pg/ml and 106.96 ng/ml for IGF-I-1R, VEGF-A, and IGF-I. VEGF, IGF-I and IGF-I-1R differed significantly between groups (p &amp;lt;0.001) whereas TGF-β1 differed significantly between NC and the other groups (p&amp;lt;0.001). TNBC was associated with positive lymph nodes (p&amp;lt;0.001), relapse and metastasis (p&amp;lt;0.001). Response rate (RR) was significantly lower in TNBC patients (p&amp;lt;0.001) with high serum VEGF-A, IGF-I-I/IGF-I-IR (p= 0.004, 0.001/0.003). Reduced DFS associated with high tumor grade, high VEGF-A (p&amp;lt;0.001), high IGF-I/ IGF-I-IR (P&amp;lt;0.001/ p&amp;lt;0.001). Reduced OS associated with relapse (p&amp;lt;0.001), high VEGF-A (p=0.001) and high IGF-I/ IGF-I-IR (p= 0.012/p= 0.02). in multivariate analysis positive nodes (P&amp;lt; 0.001), high VEGF-A (P = 0.02) and IGF-I/ IGF-I-1R (P= 0.03, P= 0.01) were independent factor for disease recurrence. Conclusions: TNBC represents an aggressive subset of breast tumors. IGF-I, IGF-I-IR, VEGF-A could be used as surrogate biomarkers for TNBC, as prognostic marker since their expression level correlates with reduced OS and high incidence of relapse. They also represent promising candidates for targeted therapy in TNBC patients. Citation Format: Abdel-Rahman N. Zekri, Abeer Bahnassy. Serum insulin growth factor/insulin growth factor receptor1 (IGF-I, IGF-I-1R) and VEGF-A as prognostic factors and surrogate biomarkers in triple negative breast cancer patients (TNBC). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3006. doi:10.1158/1538-7445.AM2014-3006
Personality test scores as predictors of alcoholism almost a decade later
Authors: M A Schuckit, J Klein, G Twitchell, T Smith
Journal: American Journal of Psychiatry (1994)

Comparisons of alcoholic and control subjects have revealed potential differences on a variety of personality tests. However, these results are difficult to interpret because subgroups of alcoholic subjects with antisocial personality disorder were often included in the overall analyses, and because testing was usually carried out while alcoholic subjects were in withdrawal. This article evaluates whether individuals' personality test scores at approximately age 20 predict their risk of subsequent development of alcohol abuse or dependence by about age 30.As part of a larger prospective study of sons of alcoholic and control subjects, subsets of up to 78 subjects (39 matched pairs) out of a sample of 223 men took various personality tests that included the Eysenck Personality Inventory, subtests of the MMPI, and evaluations of locus of control and anxiety. An average of more than 9 years later, the incidence of alcohol abuse or dependence in these 223 subjects was determined by structured interviews.The 55 men who subsequently went on to develop alcohol abuse or dependence did not differ on any of the personality tests from the 168 men who did not develop alcoholism.These data are consistent with prospective studies indicating that except for antisocial personality disorder, it is difficult to identify a reliable personality profile associated with an individual's risk of alcoholism.
UVEOPAROTITIS; CASE REPORT
Authors: Marie L. Carns
Journal: Annals of Internal Medicine (1942)

Case Reports1 June 1942UVEOPAROTITIS; CASE REPORTMARIE L. CARNS, M.D., F.A.C.P.MARIE L. CARNS, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-16-6-1239 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptUveoparotitis (uveo-parotid fever or Heerfordt's syndrome) is a comparatively rare condition. Approximately 100 cases have been reported in the literature, the majority in Scandinavian and German journals of ophthalmology. No previous case has been so diagnosed at the Wisconsin General Hospital. The essential features are bilateral inflammatory lesions of the uveal tract and bilateral parotitis, often associated with paralyses of the cranial nerves, usually the peripheral portion of the seventh. The parotitis is of a chronic almost painless type, with a tendency to progress to resolution without suppuration. A low grade fever is generally present. The ocular manifestations commonly follow...References1. HEERFORDT CF: Über eine "Febris uveo-parotidea subchronica," Arch. Ophth., 1909, lxx, 254-273. Google Scholar2. GARLANDTHOMSON HGJG: Uveo-parotid tuberculosis, Quart. Jr. Med., 1933, xxvi, 157-177. Google Scholar3. PINNER M: Non caseating tuberculosis, Am. Rev. Tuberc., 1937, xxxvi, 706-709; 1938, xxxvii, 690-728; 1939, xxxix, 186-203. Google Scholar4. MICHELSON HE: Uveoparotitis, Arch. Dermat. and Syph., 1939, xxxix, 329-344. CrossrefGoogle Scholar5. FOLGER HP: Uveoparotitis, Arch. Ophth., 1936, xv, 1098-1116. CrossrefGoogle Scholar6. ARBUSEMADONICK DM: Uveo-parotid fever (Heerfordt's syndrome); neurologic manifestations; report of two cases, Am. Jr. Med. Sci., 1938, cxcvi, 222-232. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Madison, Wisconsin*Received for publication July 26, 1940.From the Department of Medicine, University of Wisconsin. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1942Volume 16, Issue 6Page: 1239-1244KeywordsCranial nervesFeversLesionsOphthalmologyParalysisParotitis ePublished: 1 December 2008 Issue Published: 1 June 1942 PDF downloadLoading ...
Obesity, insulin resistance and the prevalence of atopy and asthma in US adults
Authors: J. Ma, L. Xiao, S. B. Knowles
Journal: Allergy (2010)

The roles of obesity and insulin resistance in asthma and atopy are not well understood. We investigated whether there is an association of obesity and insulin resistance with asthma and atopy prevalence in US adults.Data from the 2005-2006 National Health and Nutrition Examination Survey were analyzed by multivariate logistic regression, controlling for sex, age, ethnicity, income, and smoking status. Obesity was measured by body mass index (BMI) and waist circumference, and insulin resistance by the homeostasis model assessment. Asthma was defined by self-report of ever receiving a diagnosis and still having asthma currently, and atopy by any positive specific serum IgE responses to a panel of aeroallergens.Neither obesity measure nor insulin resistance was associated with atopy. Obesity was positively associated with asthma overall (odds ratio [OR] for obese vs normal BMI = 2.28, 95% CI: 1.76, 2.96; OR for obese vs normal waist circumference = 1.75; 95% CI: 1.22, 2.51) but insulin resistance was not (OR = 1.26; 95% CI: 0.80, 1.98). Obesity was also associated with nonatopic asthma (OR for obese vs normal BMI = 2.5; 95% CI: 1.2, 5.2; OR for obese vs normal waist circumference = 2.07, 95% CI: 1.21, 3.54), while obese BMI was also associated with atopic asthma (OR = 2.04, 95% CI: 1.37, 3.03). Obesity remained independently associated with all asthma outcomes after controlling for insulin resistance.Obesity was independently associated with asthma, and atopic and nonatopic asthma, after controlling for insulin resistance and socio-demographic factors. There was no evidence that insulin resistance was associated with atopy or asthma.
Late Results of Percutaneous Balloon Mitral Valvuloplasty: The Chinese Experience
Authors: Tsung O. Cheng, Chuan Rong Chen
Journal: Circulation (2000)

To the Editor:We are writing in support of the conclusions reached by Iung et al 1 concerning the late results of percutaneous balloon mitral valvuloplasty (PBMV).The French experience confirmed the Chinese experience that was reported earlier with a larger number of patients, namely, a PBMV can be performed with good late results in a variety of patient subsets. 2,3The Inoue balloon technique, which the Chinese investigators have used since November 1985 4 and the French investigators began using more recently, is the procedure of choice for the treatment of mitral stenosis. 5e also found that a hemodynamic evaluation did not provide any information additional to that from clinical and echocardiographic examinations.For this reason and to simplify the procedure to make its use more widespread, the Chinese physicians have not performed systematic hemodynamic measurements before or after PBMV for the last several years.In China, Ͼ18 000 PBMVs have been performed to date.