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3. Statins In Intracerbral Hemorrhage (SATURN)

Author

NINDS Stroke Trials Network (StrokeNet), Canadian Stroke Consortium (CSC), University of Cincinnati, Medical University of South Carolina, Yale University, MetroHealth Medical Center, UH, Cleveland Medical Center, Spectrum Health Hospitals, West Virginia University, Columbia University, Weill Medical College of Cornell University, New York Presbyterian Brooklyn Methodist Hospital, Buffalo General Medical Center, State University of New York - Upstate Medical University, St. Joseph's Regional Medical Center, New Jersey, Tufts Medical Center, Massachusetts General Hospital, UMASS Memorial Medical Center, Brigham and Women's Hospital, Baystate Medical Center, University of Vermont Medical Center, Lahey Hospital & Medical Center, Augusta University Medical Center, Prisma Health-Upstate, The Moses H. Cone Memorial Hospital, University of Virginia, George Washington University, University of Maryland, Baltimore, Mount Sinai Hospital, New York, NYU Langone Medical Center - Tisch Hospital, Montefiore Medical Center, NYU Langone Hospital - Brooklyn, Froedtert Hospital, Central DuPage Hospital, Rush University Medical Center, Loyola University, Stanford University, Mercy San Juan Medical Center, Oregon Health and Science University, Kaiser Permanente, University of Southern California, Cedars-Sinai Medical Center, University of New Mexico, Long Beach Memorial Medical Center, Kaiser Permanente Fontana, University of California, Irvine, Arrowhead Regional Medical Center, Huntington Memorial Hospital, Scripps Health, University of California, San Diego, Ochsner Health System, St. Joseph's Hospital and Medical Center, Phoenix, Desert Care Network, Eden Medical Center, San Francisco General Hospital, University of California, San Francisco, University of Louisville, Ohio State University, University of Iowa, Sanford Medical Center Fargo, University of Nebraska, Tampa General Hospital, University of Florida, Jackson Health System, Mayo Clinic, Baptist Medical Center Jacksonville, Wayne State University, University of Michigan, Mercy Health Saint Mary Grand Rapids, Metro Health, Michigan, University of Kentucky, McLaren Health Care, Regions Hospital, Allina Health System, University of Kansas, University of Minnesota, St. Cloud Hospital, Milton S. Hershey Medical Center, Abington Memorial Hospital, Temple University, University of Pennsylvania, Lehigh Valley Hospital, York Hospital, York, PA, Thomas Jefferson University, University of Pittsburgh, St. David's HealthCare, Baylor College of Medicine, Tulane Medical Center, The University of Texas Health Science Center at San Antonio, OU Medical Center, University of Utah, Swedish Medical Center, St. Mary's Medical Center, Banner University Medical Center, Intermountain Medical Center, Legacy Emanuel Medical Center, Sacred Heart Medical Center Springfield, Harborview Injury Prevention and Research Center, University of Wisconsin, Madison, Aurora BayCare Medical Center, Wake Forest University Health Sciences, University of Alabama at Birmingham, University of South Alabama, Carolinas Medical Center, Barnes-Jewish Hospital, St. Luke's Hospital, Kansas City, Missouri, University of Arkansas, OSF Healthcare System, Cox Medical Center South, North Shore University Hospital, Rhode Island Hospital, Hartford Hospital, Staten Island University Hospital, Johns Hopkins University, University of North Carolina, Chapel Hill, University of Alberta, The Ottawa Hospital, London Health Sciences Centre, Hamilton General Hospital, Hopital de l'Enfant-Jesus, Montreal Neurological Institute and Hospital, Foothills Medical Centre, University Health Network, Toronto, Health Sciences Centre, Winnipeg, Manitoba, Thunder Bay Regional Health Sciences Centre, Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre, Fraser Health, Hopital de Chicoutimi, Université de Sherbrooke, and Magdy H Selim, MD, PhD, Professor of Neurology

Published
2024

7. Chronic Hypertension and Pregnancy (CHAP) Project (CHAP)

Author

Columbia University, Drexel University College of Medicine, Rutgers, The State University of New Jersey, Lehigh Valley Hospital, Saint Peters University Hospital, Christiana Care Health Services, Washington University School of Medicine, Duke University, University of Texas Southwestern Medical Center, The University of Texas Health Science Center, Houston, Stanford University, University of Pennsylvania, The University of Texas Medical Branch, Galveston, University of Utah, Intermountain Health Care, Inc., University of California, San Francisco, Johns Hopkins University, University of Pittsburgh, Ochsner Health System, University of North Carolina, Chapel Hill, National Heart, Lung, and Blood Institute (NHLBI), WakeMed Health and Hospitals, San Francisco General Hospital, McKay-Dee Hospital, Winthrop University Hospital, New York Hospital Queens, Latter Day Saints Hospital, Lyndon B Johnson General Hospital, Virtua Medical Group, Bayview Medical Center, Duke Regional Hospital, Utah Valley Regional Medical Center, Northwestern, Brown (WIHRI), Baylor College of Medicine, Case Western/Metro Health, Ohio State University, University of Iowa, University of California, San Diego, Indiana University, Unity Point Health-Meriter Hospital WI, Weill Medical College of Cornell University, University of Oklahoma, Medical University of South Carolina, Beaumont Hospital, University of Colorado, Denver, University of Kansas Medical Center, Denver Health and Hospital Authority, Gundersen Health System, Wake Forest University Health Sciences, Oregon Health and Science University, Medical College of Wisconsin, Temple University, New Jersey Medical School, University of South Alabama, Vanderbilt University, University of Arkansas, Emory University, St. Luke's Hospital and Health Network, Pennsylvania, Cleveland Clinic Fairview Hospital, University of Tennessee, TriHealth Inc., Cleveland Clinic Hillcrest Hospital, Tulane University, Yale University, Arrowhead Regional Medical Center, Geisinger Clinic, Premier Health Miami Valley Hospital, and Alan Tita, Principal Investigator

Published
2023

9. Trial Evaluating Endoscopy Competence Among Gastroenterology Trainees in the Era of the Next Accreditation System. (EnCompAS)

Author

University of California, Los Angeles, University of California, Irvine, Drexel University College of Medicine, University of South Alabama, The University of Texas Health Science Center at San Antonio, Northwestern University, University Hospitals Cleveland Medical Center, Advocate Lutheran General Hospital, Washington University School of Medicine, Emory University, Rush University, Ochsner Health System, St. John Providence Health System, University of Wisconsin, Madison, State University of New York - Downstate Medical Center, University of North Carolina, University of Miami, and New York Medical College

Published
2021

11. Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea (TWiTCH)

Author

National Heart, Lung, and Blood Institute (NHLBI), Boston Children's Hospital, University of Texas Southwestern Medical Center, Children's Healthcare of Atlanta, Children's Hospital of Philadelphia, The Hospital for Sick Children, Children's National Research Institute, Columbia University, St. Jude Children's Research Hospital, University Hospitals Cleveland Medical Center, University of South Alabama, Medical University of South Carolina, University of Alabama at Birmingham, University of Miami, University of Mississippi Medical Center, Wayne State University, Children's Hospital of The King's Daughters, Nemours Children's Clinic, Duke University, East Carolina University, Children's Hospitals and Clinics of Minnesota, Ann & Robert H Lurie Children's Hospital of Chicago, Baylor College of Medicine, State University of New York - Downstate Medical Center, and Steven and Alexandra Cohen Children's Medical Center

Published
2020

18. Tools for the 21st Century. Southwest Alabama Cooperative Literacy Project. Final Evaluation.

Author

University of South Alabama, Mobile., Lipscomb, Judith D., and Cronin, C. Hines

Abstract

The Southwest Alabama Cooperative Literacy Project was a workplace literacy program involving the University of South Alabama and seven manufacturing plants in the LeMoyne Industrial Complex in southwestern Alabama. The project's primary objective was to increase job productivity by teaching both conventional and functional literacy skills in reading and mathematics. During the project, 26 employees participated in 1 or more sessions of reading classes, and 35 employees took 1 or more sessions of math classes. Of the 39 participants who completed one or more sessions in reading, math, or both, 27 were black males, 2 were black females, and 10 were white males. All were between the ages of 35 and 60. The participants held diverse positions at their respective plants, such as:--welder, storeroom worker, pulp handler, operator, millwright, loader, and foreman. Fifteen of the 24 participants who completed the reading sessions and 21 of the 27 participants who completed the math sessions scored 80% or higher on their end-of-session competency tests. Follow-up evaluations of the participants' job productivity were slated for the coming months. Information about the project was disseminated through various conferences and publications. (Also included are the project's final performance report and nine tables summarizing the characteristics of participants in the various project classes.) (MN)

Published
1994

19. Learning Successive and Coordinate Concepts: A Synthesis.

Author

University of South Alabama, Mobile. and Dempsey, John V.

Abstract

This paper introduces successive and coordinate intellectual thinking skills, using concepts as a best case example. The attributes and optimal presentation requirements of successive and coordinate concepts are reviewed, and types of errors commonly associated with successive and coordinate skills are delineated. The effects of both of these skills on the transfer of learning and training are also considered. Finally, a model structure is proposed that accommodates successive and coordinate relationships. Successive concepts are defined as having clearly distinguishable critical and variable attributes, whereas coordinate concepts have multiple, common critical and variable attributes. It is noted that learners, in classifying a concept, can either generalize to instances or discriminate non-instances. Two arguments are presented: successive concept learning should focus on generalization skill development, or the use of examples-only as an instructional strategy; and, since coordinate concepts emphasize both generalization and discrimination, they are better learned through the use of matched sets of examples and nonexamples. It is concluded that a matrix is a useful model structure that could provide for increasing discrimination along one axis and increasing generalization along the other axis. (32 references) (Author/DB)

Published
1990

23. Research on SACS: Does Accreditation Really Matter?

Author

University of South Alabama, Mobile. and Isom, Bess A.

Abstract

Two types of research--informal interviews and a questionnaire survey--were conducted by the Southern Association of Colleges and Schools (SACS) to assess teacher perceptions of regional school accreditation by SACS and to aid in SACS consultations and schools' staff development programs. The questionnaire survey compared teacher expectations of school or program change before the SACS accreditation process with their perceptions of actual change after SACS. A total of 741 teachers (279 in the preaccreditation survey and 462 in the postaccreditation survey) in a large southern school district were asked about changes in instructional programs or materials, facilities, pupil services, administration, community interaction, and personal growth. Findings are presented in 16 text tables, 5 graphs, and 33 appendix tables. Among the findings are that perceived changes did not meet teachers' expectations of change and that teachers anticipated greatest change in the areas where SACS guidelines were most explicit. The findings support three recommended changes in SACS processes and a proposed model for school staff development. In the informal interviews, conducted in the same district as the survey, five principals and six teachers indicated they considered the SACS accreditation process was worth the effort. Copies of the survey questionnaire are appended. (RW)

Published
1982

24. The Effects of a Structured Language Training Program with Moderately Retarded Children.

Author

University of South Alabama, Mobile. and Grill, J. Jeffrey

Abstract

Evaluated was the effectiveness of daily 10-minute sessions in a structured language training program (Teaching the American Language to Kids) with 72 moderately retarded students ages 5- to 13-years. Lee's Developmental Sentence Scoring of free speech samples was used as the pre- and posttest. Gain scores of 17 experimental Ss (students who had met the test's minimum sentence production requirement) were significantly higher than scores of 12 control subjects, and comparison of pre- and posttest measures within the experimental group also indicated a significant gain. (CL)

Published
1974

25. University of South Alabama Faculty Handbook.

Author

University of South Alabama, Mobile.

Abstract

Concerned primarily with policies, procedures, regulations, channels of communication, and benefits for the faculty, the 1974 faculty handbook of the University of South Alabama discusses: (1) organization and administration; (2) colleges, divisions, departments, and programs; (3) university facilities and services; (4) student-related information; and (5) general faculty personnel policies. Appendices cover: (1) academic freedom and tenure; (2) faculty dismissal proceedings; (3) research; and (4) inventions, discoveries, patents, and copyrights. (KE)

Published
1974

26. The Classroom Chefs: A Children's Picture Cookbook for Nutrition Education. Teachers Manual.

Author

University of South Alabama, Mobile. Head Start State Training Office. and Minter, Margaret

Abstract

This teacher's manual presents lesson plans and recipes designed for use with preschool children, discusses the need for early nutrition education, and offers suggestions for conducting cooking activities in the classroom. Specific ideas are provided to involve handicapped children in cooking experiences. Nutrition education in the preschool is emphasized as a good way to help children form good food habits and healthy attitudes toward different kinds of foods early in life. Preferred locations for the cooking center in the preschool as well as suggestions about necessary furniture, equipment, and utensils are given. A list of children's books that can be related to cooking experiences is included. Nine illustrated recipes are provided, including recipes for chili, succotash, and Chinese egg drop soup. Each recipe lists ingredients, materials, procedure, and preparatory tasks for the teacher. Lesson plans accompany each recipe include: (1) basic developmental concepts involved (e.g., counting and measuring, fine motor coordination); (2) lists of words and phrases to use during preparation (e.g., ingredient); (3) ways to introduce and prepare the recipes; (4) suggested expansion activities (e.g., discovering the sources and uses of heat); and (5) forms for evaluating each cooking experience. (BRT)

Published
1975

27. Retrospective Conversion Manual: University Library Recon Project.

Author

University of South Alabama, Mobile. and Ramage, Pat

Abstract

This manual provides a brief description of the procedures employed by the University of South Alabama in converting their library records from print to computerized cataloging. A description of the procedure is followed by detailed instructions and examples. Rules for NOTIS-LCCN Conversion Records, OCLC--Telex Transfer, and Conversion of Telex-Transferred Records are briefly presented. Sample forms for maintaining statistics, a key to color-coding signals in the shelf list, and examples of procedures for several different potential situations are outlined. (THC)

Published
1985

28. A Curriculum Model for Teaching Telecommunications to Middle and Secondary School Students.

Author

University of South Alabama, Mobile. Coll. of Education. and Daughenbaugh, Richard L.

Abstract

This curriculum guide is intended for use in teaching a unit on telecommunications to students with a basic understanding of computing. Introductory materials spell out the purpose of the unit--to provide an introduction to the sending and receiving of electronic information using a personal computer system and the telephone communications system--together with behavioral objectives and information on the timeline and the materials and equipment needed for the unit. Plans are then presented for four lessons, which require a minimum of seven 50-minute class periods: (1) Introduction to the Telecommunications Unit; (2) Data Transmission; (3) Electronic Bulletin Board System Procedures and Operations; and (4) Types of Networks. Each lesson includes a set of objectives for the lesson; a 10- to 15-item vocabulary list; an estimated time line; an overview of materials preparation; the content to be presented; a detailed description of classroom procedures; suggestions for additional classroom activities; and student worksheets. A glossary containing 59 key phrases is appended as well as a printout of messages produced by the public domain electronic bulletin board; lists of online networks (including connect and subscription costs) and communications software; masters for overhead transparencies designed for use in presenting the content of the lessons; and vocabulary word puzzles. (SD)

Published
1989

29. Evaluation of the University of South Alabama College of Education Teacher Training Program by Analyses of Its Alumni, 1969.

Author

University of South Alabama, Mobile. and Johnson, Granville B.

Abstract

To improve selection and training at both Bachelor's and Master's levels, an evaluation study of the alumni of the College of Education was undertaken. Alumni were sent questionnaires to ascertain their feelings about their training, and a rating scale was sent to the principals of schools where alumni were teaching (see TM 001 301 for sample). Details of results are given. (A related document is ED 060 650.) (MB)

Published
1969

30. Evaluation of the University of South Alabama College of Education Teacher Training Program by Analyses of its Alumni, II - 1971.

Author

University of South Alabama, Mobile. and Johnson, Granville B.

Abstract

To ascertain the effectiveness of a training program, an evaluation of its effect on trainees must be obtained. In a teacher training program, sources of feedback exist which may prove significant in the development of improved training techniques. Two of these are: How the alumni feel about their own training experience and how their principals feel about their qualifications as teachers. One major purpose of this study is to evaluate the alumni of the College of Education with the aim of improving selection and training techniques at both the Bachelor's and Master's degree levels. A second major purpose of this survey is to note any directional trends by comparing the current results with those obtained in 1969. (Author)

Published
1971

31. Evaluation of Leadership and Crossover Teacher Institutes Concerned with Problems of Desegregation.

Author

Auburn Univ., AL., University of South Alabama, Mobile., Irvine, La Verne F., and Brierley, Norman R.

Abstract

During 1969, groups of Southeast Alabama elementary and secondary school administrators, teachers, and supervisors participated in a series of eight training institutes concerning problems relating to school desegregation. Through the use of questionnaires, information was obtained relative to participants' motivation and expectations, participants' satisfactions and derived benefits from programs, and concerning participants' attitudes about race and desegregation. Responses toward the institutes were generally favorable and, in addition, reflected a positive approach in attempting to resolve problems regarding school desegregation. However, some negative views concerning both school desegregation and the institutes were evident. Recommendations are suggested for planning future institutes. (Author/JW)

Published
1970

32. University of South Alabama Dialect Tape Center: Audio Tape Resources.

Author

University of South Alabama, Mobile. and Mele, Joseph C.

Abstract

Intended for use by teachers, actors, linguists, sociologists, and others interested in dialect study, this catalog lists the holdings of the Dialect Tape Center at the University of South Alabama (Mobile), an organization that was founded to provide ready access to tape recordings of representative American English as it is currently spoken throughout the country. In addition, the catalogue provides a limited listing of tapes of non-American speaking English in 23 foreign countries. The tapes listed were recorded from individuals selected as typical of the local population of speakers, and each tape generally consists of two parts: an impromptu monologue and a 44-sentence sequence highlighting each American phoneme. The catalog is divided alphabetically according to state and then to city, county, or region. Each of the more than 300 entries also provides information concerning the age and sex of the speaker and the date the recording was made. An ordering code number is provided for each tape. (FL)

Published
1980

33. Evaluation for Teaching.

Author

University of South Alabama, Mobile. and Johnson, Granville B.

Abstract

This teacher rating scale was sent to principals of alumni. The first six variables concern personality; the next 10 are directly associated with teaching. A factor analysis is being made. No statistical test of validity was made due to lack of a criterion measure. However, rater bias and test unreliability lower validity. (See TM 001 300 for information on complete evaluation study.) (MS)

Published
1969

34. Label-free quantitative proteomics and SAINT analysis enable interactome mapping for the human Ser/Thr protein phosphatase 5

Author

Department of Pathology, University of Michigan, Ann Arbor, MI, USA, Department of Pathology, University of Michigan, Ann Arbor, MI, USA ; Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA, Department of Biochemistry and Molecular Biology, University of South Alabama, Mobile, AL, USA ; These authors have contributed equally to this study., Centre for Systems Biology, Samuel Lunenfeld Research Institute at Mount Sinai Hospital, Toronto, Ontario, Canada, Centre for Systems Biology, Samuel Lunenfeld Research Institute at Mount Sinai Hospital, Toronto, Ontario, Canada ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada, Department of Biochemistry and Molecular Biology, University of South Alabama, Mobile, AL, USA ; Department of Clinical Science and Education, Karolinska Institute, Stockholm, Sweden ; Department of Biochemistry and Molecular Biology, University of South Alabama, 307 University BLVD N, Mobile, AL 36688, USA Fax: +1-251-460-6850, Skarra, Dana V., Goudreault, Marilyn, Choi, Hyungwon, Mullin, Michael, Nesvizhskii, Alexey I., Gingras, Anne-Claude, Honkanen, Richard E., Department of Pathology, University of Michigan, Ann Arbor, MI, USA, Department of Pathology, University of Michigan, Ann Arbor, MI, USA ; Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA, Department of Biochemistry and Molecular Biology, University of South Alabama, Mobile, AL, USA ; These authors have contributed equally to this study., Centre for Systems Biology, Samuel Lunenfeld Research Institute at Mount Sinai Hospital, Toronto, Ontario, Canada, Centre for Systems Biology, Samuel Lunenfeld Research Institute at Mount Sinai Hospital, Toronto, Ontario, Canada ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada, Department of Biochemistry and Molecular Biology, University of South Alabama, Mobile, AL, USA ; Department of Clinical Science and Education, Karolinska Institute, Stockholm, Sweden ; Department of Biochemistry and Molecular Biology, University of South Alabama, 307 University BLVD N, Mobile, AL 36688, USA Fax: +1-251-460-6850, Skarra, Dana V., Goudreault, Marilyn, Choi, Hyungwon, Mullin, Michael, Nesvizhskii, Alexey I., Gingras, Anne-Claude, and Honkanen, Richard E.

Abstract

Affinity purification coupled to mass spectrometry (AP-MS) represents a powerful and proven approach for the analysis of protein???protein interactions. However, the detection of true interactions for proteins that are commonly considered background contaminants is currently a limitation of AP-MS. Here using spectral counts and the new statistical tool, Significance Analysis of INTeractome (SAINT), true interaction between the serine/threonine protein phosphatase 5 (PP5) and a chaperonin, heat shock protein 90 (Hsp90), is discerned. Furthermore, we report and validate a new interaction between PP5 and an Hsp90 adaptor protein, stress-induced phosphoprotein 1 (STIP1; HOP). Mutation of PP5, replacing key basic amino acids (K97A and R101A) in the tetratricopeptide repeat (TPR) region known to be necessary for the interactions with Hsp90, abolished both the known interaction of PP5 with cell division cycle 37 homolog and the novel interaction of PP5 with stress-induced phosphoprotein 1. Taken together, the results presented demonstrate the usefulness of label-free quantitative proteomics and statistical tools to discriminate between noise and true interactions, even for proteins normally considered as background contaminants.

Published
2011

35. FINAL PROJECT REPORT: WOODLAND SEASONALITY ON THE NORTHERN COAST OF THE GULF OF MEXICO

Author

Reitz, Elizabeth, AUTHOR (University Of Georgia), Hadden, Carla, AUTHOR (Center For Applied Isotope Studies), Little, Maran E., AUTHOR (University Of Georgia), Waselkov, Gregory A., AUTHOR (University Of South Alabama), Andrus, C. Fred, AUTHOR (Department Of Geological Sciences, University Of Alabama), and Peacock, Evan, AUTHOR (Mississippi State University)

Published
2013
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40. Protein Phosphatase 2A Signaling in Human Prostate Cancer

Author

UNIVERSITY OF SOUTH ALABAMA MOBILE, Singh, Ajay, UNIVERSITY OF SOUTH ALABAMA MOBILE, and Singh, Ajay

Abstract

Advanced prostate cancers (PCa) treated with first line androgen-deprivation therapy (ADT) eventually relapse in a hormone refractory or castration-resistant (CR) form. Relapsed disease is highly aggressive and poses an increased risk of morbidity and death. Previously, we demonstrated that PPP2CA, which encodes the catalytic-subunit (alpha-isoform) of the protein phosphatase 2A (PP2AC ), is downregulated in CR PCa. The level of PP2AC was decreased in majority of CR PCa cell lines and cancer lesions as compared to the adjacent normal/benign tumor tissues. Under this project, we have utilized multiple approaches to demonstrate a functional role of PP2A in human prostate cancer progression. We have shown that PP2A downregulation promotes growth, androgen depletion-resistance and aggressive behavior of prostate cancer cells. We have also developed in vivo experimental support for a suppressor role of PP2A in prostate cancer progression using orthotopic mouse model. Furthermore, we delineated the molecular mechanisms involved in the PP2A-mediated growth and aggressive phenotypes of PCa cells. We observed PP2A downregulation facilitates castration-resistant growth of PCa cells in both androgen receptor (AR)- dependent and independent manners in AR expressing (LNCaP and C4-2) cells. Moreover, we identified that PPP2CA downregulation favors EMT, migration and invasion of PCa cells through Akt-dependent activation of -catenin and NF- B pathway. Our data strongly suggest that downregulation of PP2A is associated with human prostate cancer progression and restoration of PP2A activity may be an effective approach for the treatment of the advanced disease., The original document contains color images.

Published
2014

41. Exploring a Novel Mechanism of Docetaxel Resistance in Prostate Cancer

Author

UNIVERSITY OF SOUTH ALABAMA MOBILE, Singh, Ajay, UNIVERSITY OF SOUTH ALABAMA MOBILE, and Singh, Ajay

Abstract

Docetaxel (DTX), a semi-synthetic analog of paclitaxel, has emerged as the standard of care for chemotherapy of hormone-resistant prostate cancer (PCa). However, most patients treated with DTX ultimately develop resistance to the drug and succumb to the disease. Therefore, understanding the mechanisms underlying DTX resistance is a priority area in PCa research. Increasingly, it is being suggested that cancer cells may use common pathways for disease aggressiveness/metastatic spread and chemotherapeutic resistance. Therefore, we investigated the role of CXCL12/CXCR4 signaling, which is known to promote invasion and metastasis, in DTX-resistance of PCa cells. Our data demonstrated that CXCL12 treatment rescued the PCa cells from DTX-induced cytotoxicity and G2/M mitotic arrest. Furthermore, the cytoprotective effect of CXCL12 was abolished upon pretreatment of PCa cells with AMD3100 (a small molecule antagonist of CXCR4) or siRNA-mediated silencing of CXCR4, thus confirming the role of CXCR4 in DTX-resistance. Immunofluorescence analyses revealed enhanced polymerization of microtubules in DTX-treated PCa cells. In accordance with this, immunoblot analyses demonstrated increased levels of detyrosinated (glu-) and acetylated (ace-) tubulins, specific markers of the polymerized tubulin, in PCa cells treated with DTX. Cotreatment of CXCL12 abrogated DTX-induced stabilization of microtubules in the PCa cells, an effect that was diminished when the cells were pre-treated with AMD3100. Data from our mechanistic studies suggest the role of PAK4-dependent LIMK1 activation in the CXCL12- induced resistance to docetaxel toxicity and microtubule destabilization. Altogether, our findings demonstrate the role of CXCL12/CXCR4 signaling axis in DTX-resistance of PCa cells and thus could be an attractive target for therapeutic enhancement of DTX.

Published
2014

42. Protein Phosphatase 2A Signaling in Human Prostate Cancer

Author

UNIVERSITY OF SOUTH ALABAMA MOBILE, Singh, Ajay, UNIVERSITY OF SOUTH ALABAMA MOBILE, and Singh, Ajay

Abstract

Advanced prostate cancers (PCa) treated with first line androgen-deprivation therapy (ADT) eventually relapse in a hormone refractory or castration-resistant (CR) form. Relapsed disease is highly aggressive and poses an increased risk of morbidity and death. Previously, we demonstrated that PPP2CA, which encodes the catalytic-subunit (alpha-isoform) of the protein phosphatase 2A (PP2AC ), is downregulated in CR PCa. The level of PP2AC was decreased in majority of CR PCa cell lines and cancer lesions as compared to the adjacent normal/benign tumor tissues. Under this project, we have utilized multiple approaches to demonstrate a functional role of PP2A in human prostate cancer progression. We have shown that PP2A downregulation promotes growth, androgen depletion-resistance and aggressive behavior of prostate cancer cells. We have also developed in vivo experimental support for a suppressor role of PP2A in prostate cancer progression using orthotopic mouse model. Furthermore, we delineated the molecular mechanisms involved in the PP2A-mediated growth and aggressive phenotypes of PCa cells. We observed PP2A downregulation facilitates castration-resistant growth of PCa cells in both androgen receptor (AR)- dependent and independent manners in AR expressing (LNCaP and C4-2) cells. Moreover, we identified that PPP2CA downregulation favors EMT, migration and invasion of PCa cells through Akt-dependent activation of -catenin and NF- B pathway. Our data strongly suggest that downregulation of PP2A is associated with human prostate cancer progression and restoration of PP2A activity may be an effective approach for the treatment of the advanced disease., The original document contains color images.

Published
2013

43. Exploring a Novel Mechanism of Docetaxel Resistance in Prostate Cancer

Author

UNIVERSITY OF SOUTH ALABAMA MOBILE, Singh, Ajay, UNIVERSITY OF SOUTH ALABAMA MOBILE, and Singh, Ajay

Abstract

Docetaxel (DTX), a semi-synthetic analog of paclitaxel, has emerged as the standard of care for chemotherapy of hormone-resistant prostate cancer. Docetaxel confers its anti-neoplastic activity by inhibiting microtubule depolymerization, which leads to G2/M mitotic arrest and subsequent apoptosis (1). However, most patients treated with DTX ultimately develop resistance to the drug and succumb to the disease (2). Therefore, understanding the mechanisms underlying DTX resistance is a priority area in prostate cancer research. Previously, it was reported that CXCL12/CXCR4 signaling play an important role in microtubule organization in immune cells (3) and its inhibition induced mitotic catastrophe (G2/M arrest) in ovarian cancer cells (4). Based on these earlier observations, we hypothesized that CXCL12-CXCR4 signaling axis would promote docetaxel resistance by counteracting the microtubule stabilizing action of docetaxel., The original document contains color images.

Published
2013

44. Protein Phosphatase 2A Signaling in Human Prostate Cancer

Author

UNIVERSITY OF SOUTH ALABAMA MOBILE, Singh, Ajay, UNIVERSITY OF SOUTH ALABAMA MOBILE, and Singh, Ajay

Abstract

Advanced prostate cancers (PCa) treated with first line androgen-deprivation therapy (ADT) eventually relapse in a hormone refractory or castration-resistant (CR) form. Relapsed disease is highly aggressive and poses an increased risk of morbidity and death. Previously, we demonstrated that PPP2CA, which encodes the catalytic-subunit (alpha-isoform) of the protein phosphatase 2A (PP2AC ), is downregulated in CR PCa. The level of PP2AC was decreased in majority of CR PCa cell lines and cancer lesions as compared to the adjacent normal/benign tumor tissues. Under this project, we have utilized multiple approaches to demonstrate a functional role of PP2A in human prostate cancer progression. Specifically, we have generated and characterized stable PPP2CA overexpression (C4-2 and PC3) and knockdown (LNCaP) transfectants and obtained experimental evidence (in vitro) for the role of PP2A downregulation in growth, androgen depletion- resistance and aggressive behavior of prostate cancer cells. We have also developed in vivo experimental support for a suppressor role of PP2A in prostate cancer progression using orthotopic mouse model. Our data strongly suggest that downregulation of PP2A is associated with human prostate cancer progression and restoration of PP2A activity may be an effective approach for the treatment of the advanced disease., The original document contains color images.

Published
2012

46. Protein Phosphatase 2A Signaling in Human Prostate Cancer

Author

UNIVERSITY OF SOUTH ALABAMA MOBILE, Singh, Ajay, UNIVERSITY OF SOUTH ALABAMA MOBILE, and Singh, Ajay

Abstract

To determine the role of PP2A, a serine/threonine phosphatase, in human prostate cancer (PCa) progression, we have conducted a series of experiments. Specifically, we have investigated the effect of PP2A activity modulation on androgen-independent (AI) growth of prostate cancer cells and defined underlying mechanisms. Our data show that the downregulation of PP2A activity by pharmacological inhibition or siRNA-mediated PPP2CA silencing sustains the growth of AD PCa (LNCaP) cells under androgen-deprived condition by relieving the androgen-deprivation-induced cell cycle arrest and preventing apoptosis. Immunoblot analysis revealed enhanced phosphorylation of Akt, ERK, BAD, increased expression of cyclins (cyclin A1 and cyclin D1) and decreased expression of cyclin inhibitor (p27) upon PP2A downregulation. Furthermore, our data show that PP2A inhibition partially maintains AR signaling through its increased expression and ligand-independent phosphorylation, which is also supported by AR transcriptional activity assay and its target gene, KLK3, expression. Pharmacological inhibition of Akt, ERK and AR confirmed a role of these signaling pathways in facilitating the AI growth of LNCaP cells. These findings are further supported by the effect of ceramide, a potent PP2A activator, on AI PCa (C4-2) prostate cancer cells. Ceramide suppresses AI growth of C4-2 cells, which could be rescued by pre-treatment with PP2A inhibitor. Altogether, these initial findings identify a novel PP2A-mediated signaling mechanism that support AI growth of prostate cancer cells., The original document contains color images.

Published
2011

47. Burkholderia mallei Cluster 1 Type VI Secretion Mutants Exhibit Growth and Actin Polymerization Defects in RAW 264.7 Murine Macrophages

Author

UNIVERSITY OF SOUTH ALABAMA MOBILE DEPT OF MICROBIOLOGY AND IMMUNOLOGY, Burtnick, Mary N., DeShazer, David, Nair, Vinod, Gherardini, Frank C., Brett, Paul J., UNIVERSITY OF SOUTH ALABAMA MOBILE DEPT OF MICROBIOLOGY AND IMMUNOLOGY, Burtnick, Mary N., DeShazer, David, Nair, Vinod, Gherardini, Frank C., and Brett, Paul J.

Abstract

Burkholderia mallei is a facultative intracellular pathogen that causes severe disease in animals and humans. Recent studies have shown that the cluster 1 type VI secretion system (T6SS-1) expressed by this organism is essential for survival in a hamster model of glanders. To better understand the role of T6SS-1 in the pathogenesis of disease, studies were initiated to examine the interactions of B. mallei tssE mutants with RAW 264.7 murine macrophages. Results obtained by utilizing modified gentamicin protection assays indicated that although the tssE mutants were able to survive within RAW 264.7 cells, significant growth defects were observed in comparison to controls. In addition, analysis of infected monolayers by differential interference contrast and fluorescence microscopy demonstrated that the tssE mutants lacked the ability to induce multinucleated giant cell formation. Via the use of fluorescence microscopy, tssE mutants were shown to undergo escape from lysosome-associated membrane protein 1-positive vacuoles. Curiously, however, following entry into the cytosol, the mutants exhibited actin polymerization defects resulting in inefficient intra- and intercellular spread characteristics. Importantly, all mutant phenotypes observed in this study could be restored by complementation. Based upon these findings, it appears that T6SS-1 plays a critical role in growth and actin-based motility following uptake of B. mallei by RAW 264.7 cells., The original document contains color images. Pub. in Infection and Immunity, v78 n1, p88-99, Jan 2010.

Published
2010

49. Crosstalk Between Cancer Cells and Bones Via the Hedgehog Pathway Determines Bone Metastasis of Breast Cancer

Author

UNIVERSITY OF SOUTH ALABAMA MOBILE, Shevde-Samant, Lalita, UNIVERSITY OF SOUTH ALABAMA MOBILE, and Shevde-Samant, Lalita

Abstract

The Hh pathway has been extensively studied in development and recently has also been shown to be activated in a variety of cancer types thus making it a putative therapeutic target. Our preliminary data indicated that OPN is a transcriptional target of Gli1 = Gli1 is a transcription factor of the Hedgehog (Hh) pathway. Research in our laboratory indicates that OPN is under direct control of the Hh pathway as seen by the effect of agonistic Hh pathway ligands and the Hh pathway inhibitor cyclopamine. Moreover we find that the Hh ligands Shh and lhh can stimulate differentiation of osteoblasts. The OPN-containing conditioned medium from the MDA-MB-435 cells is also able to potentiate differentiation of osteoblasts., The original document contains color images.

Published
2008

50. Mechanisms of cardiac dysfunction and changes in sarcolemmal Na+- K+-ATPase activity in hearts subjected to ischemia reperfusion injury

Author

Singal, Pawan K. (Physiology) Freed, Darren H. (Surgery) Jassal, Davinder S. (Physiology) Schaffer, Stephen (University of South Alabama), Dhalla, Naranjan S. (Physiology), Singh, Raja Balraj, Singal, Pawan K. (Physiology) Freed, Darren H. (Surgery) Jassal, Davinder S. (Physiology) Schaffer, Stephen (University of South Alabama), Dhalla, Naranjan S. (Physiology), and Singh, Raja Balraj

Abstract

To understand the mechanisms underlying cardiac dysfunction during ischemia reperfusion (I/R) injury, we tested the hypothesis that oxidative stress and defects in endothelium play a critical role in the activation of calpain and matrix metalloproteinases (MMP), inhibition of sarcolemmal (SL) Na+-K+-ATPase, and induction of cardiac dysfunction during I/R injury. It was observed that I/R induced depression in cardiac function and SL Na+-K+-ATPase activity was greater in hearts perfused at constant flow than in hearts perfused at constant pressure. Such a difference was associated with increased calpain activity as well as decreased endothelial nitric oxide synthase protein content and in nitric oxide production. The depression in Na+-K+-ATPase activity and decrease in protein content of Na+-K+-ATPase isoforms in I/R hearts were associated with an increase in calpain activity and translocation of calpain isoforms (I and II) from the cytosol to SL membrane as well as changes in the distribution of calpastatin. I/R induced alterations were Ca2+-dependent and were prevented by treatment with calpain inhibitors, MDL28170 and Leupeptin (Leu). These results suggest that depressions in cardiac function and SL Na+-K+-ATPase activity in the I/R hearts may be due to endothelial dysfunction as well as changes in the activity and translocation of calpain. In another set of experiments, we examined the role of oxidative stress in activation of calpain during I/R and its association with changes in the activity of MMP. Our results show depression of cardiac function and Na+-K+-ATPase activity in I/R hearts were associated with increased calpain and MMP activities. These alterations due to I/R were attenuated by ischemic preconditioning as well as treatment with antioxidant, N-acetylcysteine (NAC) and mercaptopropionylglycine (MPG). Treatment of I/R hearts with MMP inhibitor doxycycline (Dox) improved I/R-induced changes in cardiac function and Na+-K+-ATPase activity withou

Published
2008

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