Kettering University

About: Kettering University is a education organization based out in Flint, Michigan, United States. It is known for research contribution in the topics: RNA & Antigen. The organization has 6842 authors who have published 7689 publications receiving 337503 citations. The organization is also known as: GMI Engineering & Management Institute & General Motors Institute.

Adaptation of orbital bleeding technic to rapid serial blood studies.

Abstract: SummaryAdaptation of orbital bleeding procedure to rapid, serial blood sampling of mice and other small laboratory animals has been made. Blood (0.2 ml) is collected in disposable, heparinized micropipettes by rupturing the fragile opthalmic venous plexus with tip of blood collection tube. The tube may be sealed and centrifuged for hematocrit determination and plasma separation for enzyme or other biochemical studies. Bleeding procedure for a mouse requires less than 30 seconds, and 100 mice can be bled and processed by a technician in about 1I/2 hours. Appropriate illustrations demonstrate technical details of procedure.

From the Laboratory to the Clinic: A Retrospective on Fully Synthetic Carbohydrate‐Based Anticancer Vaccines

Abstract: This review provides an account of our explorations into oligosaccharide and glycoconjugate construction for the creation and evaluation of vaccines based on carbohydrate-centered tumor antigens. Our starting point was the known tendency of transformed cells to express selective carbohydrate motifs in the form of glycoproteins or glycolipids. Anticancer vaccines derived from carbohydrate-based antigens could be effective targets for immune recognition and attack. Obtaining significant quantities of such structures from natural sources is, however, extremely difficult. With the total synthesis of tumor-associated carbohydrate antigens accomplished, we began to evaluate at the clinical level whether the human immune system can respond to such fully synthetic antigens in a focused and useful way. Toward this goal, we have merged the resources of chemistry and immunology in an attack on the problem. The synthesis and immunoconjugation of various tumor-associated carbohydrate antigens and the results of such constructs in mice vaccinations will be described. For fashioning an effective vaccine, conjugation to a suitable immunogenic carrier was necessary and conjugates of KLH (keyhole limpet cyanin) have consistently demonstrated the relevant immunogenicity. Preclinical and clinical studies with synthetic conjugate carbohydrate vaccines show induction of IgM- and IgG-antibody responses. Another approach to anticancer vaccines involves the use of clustered glycopeptides as targets for immune attack. Initial attention has been directed to mucin related O-linked glycopeptides. Synthetic trimeric clusters of glycoepitopes derived from the Tn-, TF- and Lewis(y)-antigens, appropriately bioconjugated, have been demonstrated to be immunogenic. The hope is that patients immunized in an adjuvant manner with synthetic carbohydrate vaccines would produce antibodies reactive with cancer cells and that the production of such antibodies would mitigate against tumor spread, thereby enabling a more favorable survival and "quality of life" prognosis.

Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST).

Abstract: BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most frequent sarcoma of the intestinal tract and often shows constitutive activation of either the KIT or PDGFRA receptor tyrosine kinases because of gain-of-function mutation Although the efficacy of tyrosine kinase inhibitors in metastatic GIST depends on tumor mutation status, there have been conflicting reports on the prognostic importance of KIT mutation in primary GIST METHODS: A total of 127 patients were studied who presented to our institution from 1983 to 2002 with localized primary GIST and underwent complete gross surgical resection of disease The majority of tumors originated in the stomach (58%) or small intestine (28%) By using polymerase chain reaction (PCR) and direct sequencing, a KIT mutation was found in 71% of patients and a PDGFRA mutation in 6% RESULTS: After a median follow-up of 47 years, recurrence-free survival was 83%, 75%, and 63% at 1, 2, and 5 years, respectively On multivariate analysis recurrence was predicted by > or =5 mitoses/50 high-power fields, tumor size > or =10 cm, and tumor location (with patients having small bowel GIST doing the worst) In particular, a high mitotic rate conferred a hazard rate of 146 (95% confidence interval, 65-324) Specific KIT mutations had prognostic importance by univariate but not multivariate analysis Patients with KIT exon 11 point mutations and insertions had a favorable prognosis Those with KIT exon 9 mutations or KIT exon 11 deletions involving amino acid W557 and/or K558 had a higher rate of recurrence, whereas patients without a tyrosine kinase mutation had intermediate outcome CONCLUSIONS: In the absence of therapy with tyrosine kinase inhibitors, recurrence in completely resected primary GIST is independently predicted by mitotic rate, tumor size, and tumor location

Inducible in vivo genome editing with CRISPR-Cas9

Abstract: CRISPR-Cas9-based genome editing enables the rapid genetic manipulation of any genomic locus without the need for gene targeting by homologous recombination. Here we describe a conditional transgenic approach that allows temporal control of CRISPR-Cas9 activity for inducible genome editing in adult mice. We show that doxycycline-regulated Cas9 induction enables widespread gene disruption in multiple tissues and that limiting the duration of Cas9 expression or using a Cas9(D10A) (Cas9n) variant can regulate the frequency and size of target gene modifications, respectively. Further, we show that this inducible CRISPR (iCRISPR) system can be used effectively to create biallelic mutation in multiple target loci and, thus, provides a flexible and fast platform to study loss-of-function phenotypes in vivo.