Surviving Mesothelioma a Patients Guide
 
 

Texas Mesothelioma Fact Sheet

While mesothelioma is a problem in all states, the specific incident rate for Texas is 0.9 / 100,000. This is below the average rate of 1.1 / 100,000. Click on the tabs below to find mesothelioma and asbestos research in TX, recent TX mesothelioma-related court cases, mesothelioma specialists in TX and potential asbestos hotspots in Texas.


Texas Mesothelioma Info


By clicking on the above tabs, you will find information on mesothelioma specific to the state of Texas


Texas Research and Clinical Trials
This is a partial list of scientific or medical grants in your state for research into mesothelioma and related illnesses.

Texas Doctors and Hospitals
This is a partial list of hospitals and physicians that reportedly treat mesothelioma patients in your state.

Texas Cases
This is a partial list of relevant court cases on mesothelioma in your state.

Disclaimer: Inclusion on this directory does not constitute endorsement by Cancer Monthly, Inc. All physicians who appear in this section do so based on their own expression of interest in the fields of mesothelioma treatment. Cancer Monthly, Inc. has not verified the competence, professional credentials, business practices or validity of the expressed interests of these physicians. Cancer Monthly makes no recommendation of any physician on this list and makes no suggestion that any such physician will cure or prevent any disease. Those consulting a physician on this list should approach the consultation exactly as they would with any other unknown physician.
In re E.I. du Pont de Nemours & Co.
NO. 08-0625, SUPREME COURT OF TEXAS, July 3, 2009, Opinion Delivered
In re GE Co.
NO. 07-0195, SUPREME COURT OF TEXAS, November 14, 2007, Argued, December 5, 2008, Opinion Delivered
In re Global Sante Fe Corp.
No. 07-0040, SUPREME COURT OF TEXAS, January 16, 2008, Argued, December 5, 2008, Opinion Delivered
Borg-Warner Corp. v. Flores
NO. 05-0189, SUPREME COURT OF TEXAS, September 29, 2006, Argued , June 8, 2007, Opinion Delivered
Hallco Tex., Inc. v. McMullen County
NO. 02-1176 , SUPREME COURT OF TEXAS, January 4, 2005, Argued , December 29, 2006, Opinion Delivered
In re Van Waters & Rogers, Inc.
NO. 03-0777 , SUPREME COURT OF TEXAS, September 3, 2004, Delivered
Pustejovsky v. Rapid-American Corp.
NO. 98-1128, SUPREME COURT OF TEXAS, September 8, 1999, Argued , November 30, 2000, Opinion Issued
Todd Shipyards Corp. v. Perez
NO. 99-0697, SUPREME COURT OF TEXAS, May 18, 2000, Delivered
Temple-Inland Prods. Corp. v. Carter
No. 97-0592, SUPREME COURT OF TEXAS, October 21, 1998, Argued , April 29, 1999, Delivered
Union Carbide Corp. v. Smith
NO. 01-08-00641-CV, COURT OF APPEALS OF TEXAS, FIRST DISTRICT, HOUSTON, October 1, 2009, Opinion Issued
Hospitals and Cancer Centers

University of Texas-MD Anderson Cancer Center
1515 Holcombe Blvd Unit 432
Houston, TX
713.792.6363

Physicians

Department Of Clinical Investigation
University of Texas, MD Anderson Cancer Center
1515 Holcombe Blvd., P.O. Box 39
Houston, TX 77030
(713) 792-7959

Paul Mansfield, M.D.
M.D. Anderson Cancer Center
1515 Holcombe Blvd Ste 444
Houston, TX 77030
(713) 792-6161
CitySite
Celotex Corp
Abilene Abilene Hospital
Dyess Air force Base
Alvin Amoco Chocolate Bayou
Amarillo Amarillo City Barn
Amarillo Helium
Amarillo Incinerator
Amarillo Public Schools
Amarillo Smelter
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American Lead & Zinc
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Asarco
Harrington Station
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Smelter Plant
St Anthony
Sulphur Plant
Texaco Refinery
Andrews Williams Electric
Angleton Right Motor Company
Arlington Quality Inn
Six Flags Mall
ARP Baker Tank-ARP
Aurora Texas Gulf Chemical Plant
Austin Wight Engineering
Bastrop International Paper Company
Bay City Celanese Plant
Chemical Plant
Cornet Rice Mill
Nuclear Plant
Bayport Oxyrene Chemical Plant
Retszlof Chemical
Baytown Aamco
Brown & Rood
Cedar Bayou Power Plant
Chevron Chemical
Chevron Oil
Chevron Gulf
Baytown Esso Refinery
Exxon Chemical
Baytown Gulf Oil Refinery
Humble Exxon
Mobay Chemical
PH Robinson Power Plant
Shell Oil
Standard Oil
Beaumont Beaumont Works
Bethlehem Steel
Dupont Chemical
Gulf Oil
Magnolia Petroleum
Mobil Oil
Shell Oil
Sinclair Oil
Sun Oil
Union 76 Refinery
Big Spring Carbon Plant
Big Spring Cosden Oil & Chemical
Cosden Petrofina Refinery
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Big Springs High School
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Bishop Celanese Chemical
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Borger Carbon Black Co
Co-Polymer Rubber & Chemical
Phil Tex
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Standard Asbestos
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Marathon Oil
Union Carbide
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Byer City Phillips North Plant
Cactus Phillips Petroleum
Calvert City BF Goodrich
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Center Parker Brothers Car Dealership
Channelview Arco Chemical Plant
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Chevron Oil Refinery
Cherry Point Standard Oil
Chocolate Bayou American Oil Refinery
Amoco Chemical
Dow Chemical
Monsanto Chemical
Phillips Petroleum
Clarksville Clarksville Base
Clarksville Hospital
Clear Lake NASA
Cleveland Diamond Shamrock
Clute Ross Motor Company
College Station Texas A&M University
Comanche Nabisco
Commerce Talley Automotive
Commerce City Total Petroleum Refinery
Conroe Texaco Refinery
Cordell Whitco
Corpus Christi Bedford Construction Company
C.C. Plumbing & Heating
CCPC
Celanese Chemical
Central Power and Light Dispatching
Chevron Oil Refinery
Coastal States Refinery
Corn Products Co. Intl.
Corpus Christi Plumbing & Heating
Corpus Christi Shipyard
Hoechst Celanese
Nueces Bay Power Station
Reynolds Corpus
Southern Alkale
Southwest Oil Refinery
Sun Tide Refinery
Valeo
Water Street Station
Crane Phillips Petroleum
Crockett Firestone
Cypress Daniel Valve
Daingerfield Lone Star Steel
Dalhart Phillips Helium Plant
Dallas Armored Motor Co
AT&T Dallas Works Plant
Austin Bridge
Baker Hotel
Baylor Hospital
City Of Dallas
Citywide Heating and Air
Cooks Machinery
Dallas ISD
Dallas Morning News
Dallas Plumbing
DFW Airport
Frymire Engineering
General Electric
Mobil Building
Mrs. Bairds
North Lake Plant
Owens Corning Ware
Painters Union #53
Palace Theatre
Parkdale Plant
Parkland Hospital
Presbyterian Hospital
Quality Inn
Redmond Plaza
Republic Bank Building
Reunion Arena
Reunion Hotel
Sheraton
SMU
St Paul Hosp
State Farm
Tempo Heating & Air
Travelers Insurance Company
United Industries Company
United Tile Company
VAMC
Verson All Steel Mfg co
Ward Bros Plumbing
Deer Park Big Three Gas
Brown & Root
Celanese Chemical
Crown Chemical
Diamond Shamrock Refinery
Dupont Chemical
Ethel Corp
Hoechst Celanese
Occidental Chemical
Phillips Refinery
Quantium
Rohm & Haas
Sam Berton Power Plant
Sam Berton Power Plant
Shell Chemical
Shell Oil & Refinery
Shell Refinery
Union Carbide
Upjohn chemical
US Industries
Denison Johns-Manville
Denton Chick Spec. Co
Texas Women's University
University of North Texas
Denver City Shell Oil
Shell Plant
Desoto Cory-Joslins Macnsons
Dimmitt Anstart
EL Cor Chemical
Good Pasture Fertilizer Plant
Dumas American Zinc Smelter
Diamond Shamrock Refinery
Natural Gas Pipeline
Phillips Petroleum
Phillips Refinery
Phillips Refinery
Shamrock
Eagle Lake Arco Chemical Plant
Earth Plant X
Edna B&R Compressor Station
El Paso Airway Blvd
Art Craft Tile Co
Asarco
Chevron Refinery
Darbyshire Steel
El Paso Electric Co
El Paso Gas
Newman Power House
Pecos HS
Phelps Dodge
Providence Hospital
Rio Grande Power
Standard Chemical Refinery
Standard Oil
Sun Power Hospital
Texaco Refinery
Thomas Hospital
Elk Trading House Power Plant
Elsa Elsa Canning
Ennis Southern Pacific Railroad
Evadale East TX Paper Mill
Evandale Owens Illinois Paper Company
Fairfield Fairfield Powerhouse
Flower Bluff CP&L Power Plant
Flower Bluff Power Station
Fort Bliss Fort Bliss
Fort Hood Civil Service
Fort Worth Carswell AFB
Freeport BASE
Dow Chemical
Dupont Chemical
Ethel Corp
Monsanto Chemical
Rhone Pulene
Shintech
Ft. Worth Commerce Building
Dixon Jenkins Plant
General Dynamics
Gainesville Armco Plant
Galveston Gulf Oil
King Boilerworks
Naval Shipyard
Standard Dredging Co
Todd Shipyard
Glen Rose Brown & Root
Glen Rose Squaw Valley Plant
Gonzales Marathon Oil
Texaco Refinery
Grand Prairie Chance Voight Aircraft
Green Bayou B & R Pipe Mill
Greenville Auto Care by Jerry
Auto Doc
Caldwell Covering
City of Greenville
Crawford Smith Repair
Firestone
Judson Textile Mill
Toyota House
Gulf Port VA Hospital
Hamlin Celotex Manufacturing Plant
Harbor Island Texaco Refinery
Harlingen Air Force Base-Harlingen
Sun Valley Mall
Valley Baptist Hospital
Henderson Martin Lake Plant
Spencer Chemical-Gulf Oil Plant
Hereford Ford Motor Company
Hillsboro Keasbey & Mattison Plant
Houston Amoco Chemical
Amoco Oil Refinery
Anchor Packing
AO Smith Pipe Plant
Anheuser Busch Brewery
Arco Refinery
Arco Sinclair
Armco Sheffield Steel
Armco Sheffield Steel
Astrodome Stadium
Bear Creek Golf Course Clubhouse
Brown & Root
Brown & Root
Brown & Todd Shipyard
Brown Shipyard
Buck Jones Sandblasting
Budweiser Brewery
Burbank Elementary
Campbell Roofing
Cameron Iron
Carnation Plant
Cashmere Garden High School
Celanese
Champion Simpson Paper Mill
Charter Oil
Chevron Oil Refinery ( Green Bayou)
Chicago Bridge & Iron
Citizen's Bank
Cleco Air Tools
Consolidated Chemical
Continental Airport
Crown Chemical
Daniel Valve
Diamond Shamrock Refinery
Dixel Manufacturing
Dow Chemical
Dupont Chemical
Eagle Insulation
Exxon Refinery
Fiberglass Insulations
Gavis St. Power Plant
Goodyear Plant
Green Bayou Power
Gulf Oil Refinery
Hewitt Machine
Houston Power & Light
Humble Bldg
Intercontinental Airport
Johnson Space Center
Lone Star Heat
Maxwell House Plant
Monsanto Chemical
Mrs. Bairds
M and J Valve
Nabisco
NASA
Palm Center
Pennzoil Building
Penwalt Chemical
Petrotex
Houston Phillips 66
Houston Phillips Refinery
R&P Machine Shop
R&P Machine Shop
Rice University
Roman Hause Chemical
Sam Houston High School
Seing Loin Roofing
Sheffield Steel Mill
Shell building
Shell Refinery
Shelter W Green
Shortcut to Sun Tide Refinery
Signal Oil
Sinclair Copper
Southland Paper Mill
Stauffer Chemical
Sun Tide Refinery
T.H. Wharton Power Plant
Tennaco Refinery
Tennessee Gas Building
Tetrahydrofuran Plant
Texaco Refinery
Texas Children's Hospital
Texas Petrochem
Todd Shipyard
Tony Marin Body Shop
Union Carbide
Water Treatment Plant
West Printing Co
White Motor Company
Yard & Bloodworth
Huntsville Sam Houston University
Ingleside Reynolds Metal
Kennedy CNR Lease Service
Seaboard Oil co
Kermit Burns Electric
Kermit Gulf Oil
Shell Oil
Kerrville Ramada Inn
Killeen Fort Hood
Kingsville Communications Bldg
Hoechst Celanese
LaGrange Calloway Textile Mill
LaPorte Air Products
Bayport Chemical Complex
Big 3 Oxygen & Nitrogen Plant
Dupont Chemical
Dupont Chemical
Retszlof Chemical
Rohm & Haas
Shell Oil Refinery
Tennaco Refinery
Union Carbide
Upjohn Dow Chemical
US Industries
Laredo Laredo Power Plant
US Air Force Base
League City Webster Power Plant
Lone Star Lone Star Steel
Long view Standard Tool
Longview ADV Ross-Roy Green
Combustion Eng.
Eastman Kodak
International Paper Company
R.G. Letourneau
Trinity Industries
Lubbock Reese Air Force Base
Sound Photo
Southwestern Power Service
SPS
Texas Tech University
Lufkin Champion International
Marshall B. W. Karbo Pipeline
Texas & Pacific Railroad
Maryneal Chemical Plant
Meade-Kingsport Rust Engineering
Mesquite Dallas Works Plant
TU Electric
Midland Bank Building Midland
Cosland Gas Refinery
Paragon Midland
Safety Building
Twin Tower Bank Building
Monahans Sealey Smith Plant
Monahans Texas Utilities
Monahans TU Electric
Mount Pleasant American Petro Fina
Monticello Plant
Nacogdoches SFA University
Nederland Pure Oil Refinery
Sun Oil Refinery
Odessa A & B Plumbing
Bowie Junior High
Burns Electric
Butane Diane Plant
El Paso Chemical
Foreman Electric
Odessa College
Odessa School District
Portland Cement Plant
Ref Chem Corp
Rexall Plant
Rexene Plastics
Rexene Polymor
Rubber Plant
Shell Oil
Shell Refinery
Star Insulation
StarAdair Insulation
Texas Instruments
University of Texas
University of Texas
University of Texas Permian Basin
Webb Woodworks
Old Ocean Pan American-Aroco Product Plant
Pan American-Aroco Product Plant
Old Ocean Phillips 66
Old Ocean Phillips Refinery
Orange American Bridge
Atlantic Reserve Fleet
BF Goodrich
Chevron Gulf
Consolidated Shipyard
Dupont Chemical
Echo Plant
Fina Refinery
Firestone
Levingston Shipyard
OI Paper Mill
Owens Illinois Paper Company
Phillips Carbon
Sabine Industries
Shell Oil Refinery
Spencer Chemical-Gulf Oil Plant
Owentown Pittsburgh Corning
Roadmaster
Pampa Cabot Plant
Celanese
Phillips Petroleum
Panhandle Pan-Tex Plant
Paris Babcock & Wilcox
Campbell's Soup Plant
Pasadena A.G. Monday Plastic Plant
Air Products
Al Wheeler
Arco Refinery
Arco Refinery
Arco Sinclair
Bayshore Hospital
Celanese Chemical
Champion Simpson Paper Mill
Crown Chemical Refinery
Crown Chemical Petroleum
Crown-Central Refinery
Deerwater Power Plant
Diamond Shamrock
Dixie Chemical
Dupont Chemical
Ethel Corp
Exxon Refinery
Goodyear Plant
Hoechst Celanese
Humble Exxon
Marathon Oil
Mobil Chemical
Parson Construction
Pasadena School District
Phillips 66
Phillips 66
Phillips Petroleum
Rohm & Haas
Rohm- Haas
Shell Oil
Sol-Tex
Tennaco
Pasadena-Deer Park Texas All-Kyls
Pecos Brandon Hotel
Phillips Phillips Petroleum Rice Plant
Plains Plains Plant
Point Comfort Alcoa Plant
Formosa Plastics
Port Angeles Texaco
Port Aransas Pass Stillman Trans
Port Arthur Atlantic Refinery
Carbon Black Plant
Chevron
Continental Can Co
Fina Refinery
Great Lakes Carbon
Gulf Oil Power Plant
St Mary's Hospital
Texaco Chemical Plant
Texaco Refinery
Port Lavaca Alcoa
Atar Facility
Dechert Exxon
Joslin Power Station
Union Carbide
Port Neches Dupont Chemical
Independent Refinery
Jefferson Chemical
Neches Butane Products
Petro Gas Port Neches
Pure Oil Refinery
Texaco Chemical Plant
Texaco Refinery
Texas US Chemical
Port Nueces BF Goodrich
Powerhouse University of Texas At Austin
Premont Petrochemical Plant
Refugio B&R Compressor Station
Compressor Station
Richardson Texas Instruments
TI Manufacturer
Rio Grande City Rincon Gas Compression Station
Rockdale Alcoa Plant
Rusk Rusk State Hospital
San Angelo Goodfellow AFB
Johnson & Johnson
San Angelo School District
Shannon Hospital
San Antonio Beckwith Eng.
C5 Building
Calaveras Power Plant
City Public Service
JT Deeley Power Plant
Lackland Air Force Base
Lackland Power Plant
Leon Creek Power Plant
Mission Road Power Plant
Pearl Brewing
San Antonio Power Plant
Southern Ice & cold Storage
Texaco Oil Refinery
Texas Culture Building
Tutle Power
US AA building
US Hospital
Victor Bauning Power Plant
Water Power Division
WB Tuttle Power Plant
San Patrick Reynolds Metals Company
Sanford Phillips Petroleum
Seadrift Brown & Root
Union Carbide
Vistron
Senora Trentham Corp
Sequin AT&T Building
Sheldon Southland Paper Mill
Sherman Capital Product
Kaiser Aluminum
Texas Instruments
Wilson Jones Hospital
Sherman-Denison RSI
Skelleytown Cabot Plant
Slaton Santa Fe Railroad
Sugarland Nalco Chemical
Sulphur Springs Price Ford Motor
Sundown Arco Chemical Plant
Sunray Shamrock Refinery
Sweeney Amoco Refinery
Phillips Petroleum
Phillips Refinery
Sweetwater Sweetwater School District
United States Gypsum
Taylor Bahan Textile
Texarkana Cooper Tire & Rubber Company
Globe Union Johnson Control
Red River Army Depot
Texas City Amoco Texas City
American Oil
Amoco Chemical
Amoco Refinery
Arthur G. McKee Construction
Bechtel Refinery
Bethel
GAF Plant
Marathon Oil
Monsanto Chemical
Pan American Refinery
Philbra
Republic Oil Texas City
Sterling Chemical
Tin Processing Corp
Union Carbide
Union Republic Plant
Weftner Power Plant
White Coast
Tomball S-R Wintergreen
Wessell Manufacturing
Tyler Block Metal
General Electric Trine Plant
Kelly Springfield Tire
Southern Aluminum
Sterling Faucet
Tyler Lee HS
Tyler Pipe
Western Foundry
Van Horn EL Cor Chemical
Vicksburg Spencer Chemical-Gulf Oil Plant
Victoria CP&L Electric Plant
Dupont Chemical
Powerhouse
Town Plaza mall
Union Carbide
Victoria Works
Vidor Champion Paper Mill
Owens Illinois Paper Company
Waco Libby Owens Ford Glass Plant
Owens Illinois
Trading House Creek Power Plant
Weatherford 3M Plant
Webster Webster Power Plant
Weimar Utex
White Oak Cherokee Street
Wichita Falls City National Bank
Fina Refinery
Ponds Laundry
Sheppard AFB
Wichita Falls Auditorium
YMCA
Winnsboro Getty Oil Refinery
Woodville S&T Fabricating
Research
Smythe, W Roy. Targeting Bcl-xl Expression In Mesothelioma
Grant: 1R01CA098545-01A1
Abstract: DESCRIPTION (provided by applicant): Malignant mesothelioma is an example of a solid tumor extremely unresponsive to conventional therapy, with few patients surviving for more than 12 months regardless of treatment. We postulate that this treatment unresponsiveness is due to apoptosis resistance. BCL-XL is an anti-apoptotic member of the BCL-2 protein family, and is over-expressed in mesothelioma. Attenuated expression of other anti-apoptotic proteins and normal pro-apoptotic protein expression is noted in this tumor. Data from our laboratory suggests that constitutive transcriptional activation of the bcl-xl gene is responsible for protein over-expression. We have demonstrated bcl-xl down-regulation in human mesothelioma cells at the protein and mRNA level by both antisense oligonucleotide and full-length adenoviral antisense constructs leads to apoptotic human cell death in vitro. Down-regulation of bcl-xl also sensitizes mesothelioma cells to subsequent in vitro chemotherapy exposure leading to additive or synergistic cellular death. Pilot studies evaluating in vivo down-regulation of bcl-xl utilizing an adenoviral vector antisense construct or antisense oligonucleotides demonstrate inhibition of mesothelioma tumor growth. These experimental results suggest the following hypotheses: (1) bcl-xl expression is abnormal in mesothelioma due to up-regulation of constitutive transcriptional activity, (2) bcl-xl over-expression is in part responsible for mesothelioma clinical treatment resistance, (3) down-regulation of bcl-xl expression will lead to a bcl-2 family protein "imbalance" favoring apoptosis, (4) in vivo administration of bcl-xl antisense oligonucleotides will lead to BCL-XL down-regulation and apoptotic death of mesothelioma tumor cells, and (5) down-regulation of BCL-XL expression in vivo will sensitize mesothelioma tumor cells to conventional treatments such as chemotherapy and ionizing radiation. We will test the hypotheses regarding constitutive transcriptional activation by evaluation of the known transcriptional pathways and promoter function for bcl-xl. In vivo treatment hypotheses will be tested by use of established animal xenograft treatment models of mesothelioma. Our goals are to understand the mechanism of transcriptional up-regulation of the bcl-xl gene in this tumor, and to find a more effective clinical treatment for malignant mesothelioma. A more complete knowledge of bcl-xl constitutive up-regulation mechanisms could be of therapeutic import for a number of solid tumors that have a similar bcl-2 family phenotype. Upstream targets regulating bcl-xl expression for use in future therapeutic paradigms may be identified.

Tags: Bcl2 Gene /protein, Apoptosis, Gene Expression, Genetic Transcription, Mesothelioma Genetic Regulation, Neoplasm /cancer Genetics, Neoplastic Growth, Oligonucleotide Clinical Research, Gel Mobility Shift Assay, Human Tissue, Immunocytochemistry, Laboratory Mouse, Polymerase Chain Reaction, Tissue /cell Culture, Western Blotting

  • Followup Grant: 7R01CA098545-02
  • Followup Grant: 5R01CA098545-03
  • Followup Grant: 5R01CA098545-04
Walker, Cheryl L. Wilm's Tumor Suppressor Gene In Masothelioma
Grant: 1R01ES006658-01
Abstract: Mesothelioma is an asbestos associated tumor arising from mesothelial cells that line the body cavities. Although the etiology of asbestos induced mesothelioma has been well described, very little is known about the molecular alterations that cause these tumors. Our lack of knowledge regarding the molecular events that cause mesothelioma has hampered efforts to identify alternative fibers that can be used as safe asbestos substitutes and has contributed to a diagnostic dilemma in the identification of these tumors. The long range goal of this research is to understand how asbestos fibers transform mesothelial cells. To achieve this goal, the general approach is to identify molecular alterations that occur in transformed mesothelial cells and elucidate the mechanism by which asbestos fibers caused these alterations. The proposed studies are designed to determine the role of the Wilms' tumor (WT-1) suppressor gene in normal and malignant mesothelial cells. Specific Aims are to 1) Determine the expression pattern of the WT 1 gene in normal and transformed rat mesothelial cells. The expression of the 4 splice variants of WT-1 in normal and transformed mesothelial cells will be examined by PCR to identify differences in gene processing between normal and transformed cells. Using in situ hybridization, WT-1 expression patterns will be correlated with histological subtypes (epithelial, fibrous, mixed) of mesotheliomas to determine if gene expression is regulated by cell differentiation. 2) Identify alterations in the WT-1 gene in transformed rat mesothelial cells. Mutations at the WT-1 gene locus will be identified in cell lines isolated from transformed rat mesothelial cells (spontaneous and asbestos-induced) using direct sequencing of PCR amplified CDNA. To gain information regarding the function of WT-1 in transformed cells, rat mesothelioma cell lines will be transfected with wild type WT-1 to determine the ability of this gene to suppress the transformed phenotype. 3) Establish the similarity or difference in WT-1 alterations between rat and human mesothelioma. Data obtained from the rat cell lines will be expanded to primary rat tumors induced by asbestos and human mesotheliomas to determine if WT-1 is a putative target gene for asbestos. The usefulness of this gene as a biomarker to discriminate between mesothelioma and parenchymal lung tumors will be determined by examining the pattern of expression/alterations in the WT-1 gene in other types of human lung cancer. Information resulting from this research will yield new diagnostic strategies for the identification of mesothelioma and yield mechanistic insights on the role of the WT-1 suppressor gene as a putative gene target for asbestos in mesothelioma development. In addition, these studies will contribute to our knowledge regarding the WT-1 locus by elucidating the function of this gene in an extra-renal neoplasm.


Tags: Wilms' Tumor, Asbestos, Environment Related Neoplasm /cancer, Mesothelioma, Tumor Suppressor Gene Biomarker, Cell Differentiation, Cell Transformation, Gene Mutation, Genetic Marker, Lung Neoplasm, Molecular Oncology, Neoplasm /cancer Diagnosis, Neoplasm /cancer Genetics, Nucleic Acid Sequence Human Tissue, In Situ Hybridization, Laboratory Mouse, Laboratory Rat, Polymerase Chain Reaction, Tissue /cell Culture

Walker, Cheryl L. Wilm's Tumor Suppressor Gene In Mesothelioma
Grant: 5R01ES006658-02
Abstract: Mesothelioma is an asbestos associated tumor arising from mesothelial cells that line the body cavities. Although the etiology of asbestos induced mesothelioma has been well described, very little is known about the molecular alterations that cause these tumors. Our lack of knowledge regarding the molecular events that cause mesothelioma has hampered efforts to identify alternative fibers that can be used as safe asbestos substitutes and has contributed to a diagnostic dilemma in the identification of these tumors. The long range goal of this research is to understand how asbestos fibers transform mesothelial cells. To achieve this goal, the general approach is to identify molecular alterations that occur in transformed mesothelial cells and elucidate the mechanism by which asbestos fibers caused these alterations. The proposed studies are designed to determine the role of the Wilms' tumor (WT-1) suppressor gene in normal and malignant mesothelial cells. Specific Aims are to 1) Determine the expression pattern of the WT 1 gene in normal and transformed rat mesothelial cells. The expression of the 4 splice variants of WT-1 in normal and transformed mesothelial cells will be examined by PCR to identify differences in gene processing between normal and transformed cells. Using in situ hybridization, WT-1 expression patterns will be correlated with histological subtypes (epithelial, fibrous, mixed) of mesotheliomas to determine if gene expression is regulated by cell differentiation. 2) Identify alterations in the WT-1 gene in transformed rat mesothelial cells. Mutations at the WT-1 gene locus will be identified in cell lines isolated from transformed rat mesothelial cells (spontaneous and asbestos-induced) using direct sequencing of PCR amplified CDNA. To gain information regarding the function of WT-1 in transformed cells, rat mesothelioma cell lines will be transfected with wild type WT-1 to determine the ability of this gene to suppress the transformed phenotype. 3) Establish the similarity or difference in WT-1 alterations between rat and human mesothelioma. Data obtained from the rat cell lines will be expanded to primary rat tumors induced by asbestos and human mesotheliomas to determine if WT-1 is a putative target gene for asbestos. The usefulness of this gene as a biomarker to discriminate between mesothelioma and parenchymal lung tumors will be determined by examining the pattern of expression/alterations in the WT-1 gene in other types of human lung cancer. Information resulting from this research will yield new diagnostic strategies for the identification of mesothelioma and yield mechanistic insights on the role of the WT-1 suppressor gene as a putative gene target for asbestos in mesothelioma development. In addition, these studies will contribute to our knowledge regarding the WT-1 locus by elucidating the function of this gene in an extra-renal neoplasm.

Tags: Wilms' Tumor, Asbestos, Environment Related Neoplasm /cancer, Mesothelioma, Tumor Suppressor Gene Biomarker, Cell Differentiation, Cell Transformation, Gene Mutation, Genetic Marker, Lung Neoplasm, Molecular Oncology, Neoplasm /cancer Diagnosis, Neoplasm /cancer Genetics, Nucleic Acid Sequence Gene Targeting, Human Tissue, In Situ Hybridization, Laboratory Mouse, Laboratory Rat, Polymerase Chain Reaction, Tissue /cell Culture

  • Followup Grant: 5R01ES006658-04
  • Followup Grant: 5R01ES006658-03
Bright, Robert K. T Cell Focused Cancer Vaccines In Murine Tumor Models
Grant: 7R29CA077351-06
Abstract: DESCRIPTION: (Applicant's Abstract) One in six people will die of cancer. the systemic nature, recall ability and exquisite specificity of the immune system makes immunotherapy an attractive prospect for cancer treatment. Hepatocellular carcinoma, cervical carcinoma, various leukemias and lymphomas all have proposed viral etiologies. Viral encoded tumor specific antigens make viral associated tumors strong candidates for immunotherapy. Recent studies have described the presence of simian virus 40 (SV40)-like gene sequences and proteins (specifically the large tumor antigen: SV40 Tag) in human osteosarcomas, glioblastomas, ependymomas and malignant pleural mesotheliomas (MPM), demonstrating SV40 association with certain human malignancies. To facilitate the development of human clinical protocols for the immunotherapy of SV40 associated human malignancies, the proposed study will employ an SV40 murine tumor system to evaluate the efficacy of CTL transfer therapies and peptide based vaccines designed to target an immune response to SV40 Tag expressing tumors in vivo. Briefly, SV40 Tag specific CTL will be generated by immunization of Balb/c mice with SV40 Tag gene constructs and the epitope specificity determined by using selected H-2d restricted synthetic peptides representing potential CTL epitopes on SV40 Tag. These CTL will be utilized to examine the ability of adoptively transferred T cells to protect against tumor challenge in syngeneic mice. Further, selected synthetic peptides will be examined for the ability to actively induce protective tumor immunity in vivo. Completion of this study will provide valuable information on the active induction of tumor destructive immunity involving SV40 Tag-epitope specific CTL in vivo. Moreover, the information generated using the murine SV40 tumor model will expedite the development of reagents and clinical trials designed to examine SV40 Tag specific immunotherapies for SV40 associated human malignancies.


Tags: Cytotoxic T Lymphocyte, Neoplasm /cancer Immunology, Neoplasm /cancer Immunotherapy, Neoplasm /cancer Vaccine, Nonhuman Therapy Evaluation, Simian Virus 40, Tumor Antigen Mhc Class I Antigen, Astrocytoma, Disease /disorder Model, Drug Screening /evaluation, Ependymoma, Immunogenetics, Mesothelioma, Neoplastic Cell, Neoplastic Transformation, Osteosarcoma, Synthetic Peptide, Virus Antigen, Virus Genetics, Virus Protein, Virus Related Neoplasm /cancer Active Immunization, Laboratory Mouse

Coltman, Charles A. Southwest Oncology Group--operations Office
Grant: 2U10CA032102-08
Abstract: The Southwest Oncology Group is a major multidisease, multidisciplinary cooperative therapeutic research organization with 29 Member Institutions, 22 Community Clinical Oncology Programs (CCOPs) and 148 Cooperative Group Outreach Program (CGOP) Centers throughout the country. The scientific thrust of the Group is through multidisciplinary disease oriented committees which develop important, testable hypotheses in the management of each tumor category. The Group is a powerful tool in the design and conduct of innovative therapeutic research. The long-term objective is improved treatment and potential cure of many currently incurable malignancies. This Competative Renewal Application differs from past applications in that the Southwest Oncology Group has developed a series of new initiatives designed to enhance urological cancer research, and melanoma research as well as to extend the scientific thrust of the Group from the basic science standpoint in leukemia, lymphoma and flow cytometry of many tumor categories.

Tags: Blood And Re System, Bone Marrow Transplantation, Neoplasms Of Blood And Re System, Leukemia Acute, Neoplasms Of Blood And Re System, Lymphoma, Neoplasms Of Body Regions, Head And Neck, Neoplasms Of Reproductive System, Breast Neoplasms, Neoplasms Of Respiratory System, Lung Neoplasms, Neoplasms Of Skin, Melanoma, Neoplasms, Pediatric, Neoplastic Therapy, Cancer Chemotherapy, Neoplastic Therapy, Cancer Radiotherapy Adrenal Cortex Hormones Analogs, Dexamethasone, Adrenal Cortex Hormones Analogs, Prednisone, Alkaloids, Vincristine, Antibiotics, Anthracyclines, Daunomycin, Antibiotics, Mithramycin, Antibiotics, Mitomycin C, Antineoplastic Agents, Antineoplastic Agents, Biological Response Modifiers, Aziridines, Bacteria, Actinomycetales, Bacillus Calmette-guerin, Benzo-alpha-pyrones, Cell Sorting, Laser, Children, Congenital Abnormalities, Skin, Nevus, Drugs Adverse Effects, Drugs Resistance, Drugs, Chemotherapy, Drugs Combination, Estratriene Series, Estrogens, Genetics, Cytogenetics, Genetics, Genes, Gene Amplification, Genetics, Genes, Gene Expression, Genetics, Genes, Proto-oncogenes, Genetics, Mutation, Chromosome Mutation, Chromosome Translocations, Guanidines, Cimetidine, Haloalkylamines, Bcnu, Haloalkylamines, Cyclophosphamide, Halopyrimidines, Halouracil, Fluorouracil, Immunity, Cytokines, Lymphokines, Interferons, Immunity, Cytokines, Lymphokines, Interleukin 2, Information Gathering (data Collection), Metals, Heavy Metals, Platinum (compounds), Cis Platinum Compounds, Neoplasms Classification And Staging, Neoplasms Diagnosis, Immunodiagnosis Of Neoplasms, Neoplasms Immunization (immunotherapy), Neoplasms Immunology, Tumor Antigens, Neoplasms Of Blood And Re System, Bone Marrow Neoplasms, Multiple Myeloma, Neoplasms Of Blood And Re System, Leukemia Chronic, Neoplasms Of Blood And Re System, Leukemia Lymphocytic, Neoplasms Of Blood And Re System, Leukemia Myeloid, Neoplasms Of Blood And Re System, Leukemia, Hairy T-cell Leukemia, Neoplasms Of Body Cavities, Mesothelioma, Neoplasms Of Brain, Neoplasms Of Gastrointestinal System, Neoplasms Of Nervous System, Glioma, Astrocytoma, Neoplasms Of Reproductive System Female, Neoplasms Of Reproductive System Female, Ovary Neoplasms, Neoplasms Of Reproductive System Female, Uterus Neoplasms, Neoplasms Of Reproductive System Female, Uterus Neoplasms, Cervix Neoplasms, Neoplasms Of Reproductive System Male, Prostate Neoplasms, Neoplasms Of Reproductive System Male, Testis Neoplasms, Neoplasms Of Skeletal System, Osteogenic Sarcoma, Neoplasms Of Urinary Tract, Kidney Neoplasms, Neoplasms Of Urinary Tract, Urinary Bladder Neoplasms, Neoplasms Surgery, Neoplasms, Sarcoma, Neoplastic Therapy, Combination Antineoplastic Therapy, Nucleic Acids, Mrna, Nursing, Nursing Care, Oncology Nursing, Pyrimidine Nucleosides, Cytosine Nucleosides, Cytosine Arabinoside, Radiation Therapy, Extracorporeal Radiation, Reproductive System Disorders Male, Penile Disorders, Therapy Evaluation, Human, Tissue (cell) Culture, Clone Cells, Tissue Compatibility-transplant, Transplantation Autologous, Cooperative Study Human, Clinical, Nucleic Acids, Nucleic Acid Probes

  • Followup Grant: 5U10CA032102-09
  • Followup Grant: 5U10CA032102-10
Coltman, Charles A. Southwest Oncology Group - Operations Office
Grant: 5U10CA032102-11
Abstract: The Southwest Oncology Group is a major multidisease, multidisciplinary cooperative therapeutic research organization with 29 Member Institutions, 22 Community Clinical Oncology Programs (CCOPs) and 148 Cooperative Group Outreach Program (CGOP) Centers throughout the country. The scientific thrust of the Group is through multidisciplinary disease oriented committees which develop important, testable hypotheses in the management of each tumor category. The Group is a powerful tool in the design and conduct of innovative therapeutic research. The long-term objective is improved treatment and potential cure of many currently incurable malignancies. This Competative Renewal Application differs from past applications in that the Southwest Oncology Group has developed a series of new initiatives designed to enhance urological cancer research, and melanoma research as well as to extend the scientific thrust of the Group from the basic science standpoint in leukemia, lymphoma and flow cytometry of many tumor categories.

Tags: Acute Leukemia, Acute Lymphoblastic Leukemia, Bone Marrow Transplantation, Breast Neoplasm, Head /neck Neoplasm, Lung Neoplasm, Lymphoma, Melanoma, Neoplasm /cancer Chemotherapy, Neoplasm /cancer Radiation Therapy, Pediatric Neoplasm /cancer Bacillus Calmette Guerin, Alpha Benzopyrone, Antineoplastic, Astrocytoma, Autologous Transplantation, Aziridine, Biological Response Modifier, Bladder Neoplasm, Brain Neoplasm, Carmustine, Cervix Neoplasm, Child (0-20), Chromosome Translocation, Chronic Leukemia, Cimetidine, Cis Platinum Compound, Clone Cell, Combination Antineoplastic Therapy, Combination Chemotherapy, Cooperative Study, Cyclophosphamide, Cytogenetics, Cytosine Arabinoside, Data Collection, Daunorubicin, Dexamethasone, Drug Adverse Effect, Drug Resistance, Estrogen, Extracorporeal Radiation, Female Reproductive System Neoplasm, Fluorescence Activated Cell Sorter, Fluorouracil, Gastrointestinal Neoplasm, Gene Amplification, Gene Expression, Hairy T Cell Leukemia, Human Therapy Evaluation, Interferon, Interleukin 2, Kidney Neoplasm, Lymphocytic Leukemia, Mesothelioma, Messenger Rna, Mithramycin, Mitomycin C, Multiple Myeloma, Myeloid Leukemia, Neoplasm /cancer Classification /staging, Neoplasm /cancer Immunodiagnosis, Neoplasm /cancer Immunotherapy, Neoplasm /cancer Surgery, Nevus, Oncology Nursing, Osteogenic Sarcoma, Ovary Neoplasm, Penis Disorder, Prednisone, Prostate Neoplasm, Protooncogene, Sarcoma, Testis Neoplasm, Tumor Antigen, Uterus Neoplasm, Vincristine Human Clinical Subject, Nucleic Acid Probe

    Coltman, Charles A. Southwest Oncology Group--ccop Research Base
    Grant: 2U10CA037429-07
    Abstract: The Southwest Oncology Group is a major multi-disease, multi-disciplinary cooperative group organization, which includes 36 Member Institutions, 25 Community Clinical Oncology Programs (CCOPs), and 265 Cooperative Group Outreach Program affiliates (CGOPs) centered throughout the United States and Canada. New program initiatives have brought on 25 Urologic Cancer Oncology Program (UCOP) affiliates and 34 High Priority participants to add to the Group's total annual accrual of approximately 7000 patients. this Competitive Renewal Application is submitted to fund the Southwest Oncology Group as a research base for the current and proposed Community Clinical Oncology Program participants. Significant components of this application include a major emphasis of this cooperative group to increase minority participation in clinical trials through the addition of seven Minority- based CCOPs and the formation of a Minorities Subcommittee in the Cancer Control Research Committee. The Southwest Oncology Group also continues to promote and strengthen its internationally-known expertise in cancer control and prevention research through the efforts of the Cancer Control Research Committee, particularly in the areas of quality of life and chemoprevention.

    Tags: Cancer Information System, Cancer Prevention, Cancer Rehabilitation /care, Community Health Service, Health Science Research Analysis /evaluation, Human Therapy Evaluation, Neoplasm /cancer Education, Neoplasm /cancer Therapy, Patient Care Planning 13 Cis Retinoate, Cns Neoplasm, Acute Leukemia, Acute Lymphoblastic Leukemia, Acute Myelogenous Leukemia, Androgen Inhibitor, Antineoplastic, Autologous Transplantation, Bladder Neoplasm, Bleomycin, Bone Marrow Transplantation, Breast Neoplasm, Cancer Registry /resource, Carcinogenesis Inhibitor, Carmustine, Cervix Neoplasm, Chronic Leukemia, Cis Platinum Compound, Clinical Study /trial, Colon Neoplasm, Colorectal Neoplasm, Combination Antineoplastic Therapy, Combination Chemotherapy, Continuing Education, Cooperative Study, Cyclophosphamide, Cytosine Arabinoside, Diaziquone, Doxorubicin, Estrogen Receptor, Etoposide, Fluorouracil, Folate, Germ Cell Neoplasm, Glioma, Hairy T Cell Leukemia, Head /neck Neoplasm, Homologous Transplantation, Ifosfamide, Interferon, Interleukin 2, Isoquinoline, Kidney Neoplasm, Lomustine, Lung Neoplasm, Lymphoma, Male Reproductive System Neoplasm, Mechlorethamine, Melanoma, Mesothelioma, Metastasis, Methotrexate, Multiple Myeloma, Mycosis Fungoides Lymphoma, Neoplasm /cancer Chemotherapy, Neoplasm /cancer Hormone Therapy, Neoplasm /cancer Immunotherapy, Neoplasm /cancer Nutrition Therapy, Neoplasm /cancer Radiation Therapy, Oat Cell Carcinoma, Ovary Neoplasm, Pancreas Neoplasm, Patient /disease Registry, Peptide Hormone Analog, Platinum, Prednisone, Procarbazine, Prostate Neoplasm, Quality Of Life, Reproductive System Neoplasm, Tamoxifen, Testis Neoplasm, Tumor Necrosis Factor Alpha, Uterus Neoplasm, Vincristine Human Clinical Subject

    • Followup Grant: 5U10CA037429-08
    Coltman, Charles A. Southwest Oncology Group-ccop Research Base
    Grant: 5U10CA037429-09
    Abstract: The Southwest Oncology Group is a major multi-disease, multi-disciplinary cooperative group organization, which includes 36 Member Institutions, 25 Community Clinical Oncology Programs (CCOPs), and 265 Cooperative Group Outreach Program affiliates (CGOPs) centered throughout the United States and Canada. New program initiatives have brought on 25 Urologic Cancer Oncology Program (UCOP) affiliates and 34 High Priority participants to add to the Group's total annual accrual of approximately 7000 patients. this Competitive Renewal Application is submitted to fund the Southwest Oncology Group as a research base for the current and proposed Community Clinical Oncology Program participants. Significant components of this application include a major emphasis of this cooperative group to increase minority participation in clinical trials through the addition of seven Minority- based CCOPs and the formation of a Minorities Subcommittee in the Cancer Control Research Committee. The Southwest Oncology Group also continues to promote and strengthen its internationally-known expertise in cancer control and prevention research through the efforts of the Cancer Control Research Committee, particularly in the areas of quality of life and chemoprevention.


    Tags: Cancer Information System, Cancer Rehabilitation /care, Community Health Service, Health Science Research Analysis /evaluation, Human Therapy Evaluation, Neoplasm /cancer Education, Neoplasm /cancer Therapy, Patient Care Planning 13 Cis Retinoate, Cns Neoplasm, Acute Leukemia, Acute Lymphocytic Leukemia, Acute Myelogenous Leukemia, Androgen Inhibitor, Antineoplastic, Autologous Transplantation, Bladder Neoplasm, Bleomycin, Bone Marrow Transplantation, Breast Neoplasm, Cancer Registry /resource, Carcinogenesis Inhibitor, Carmustine, Cervix Neoplasm, Chemoprevention, Chronic Leukemia, Cis Platinum Compound, Clinical Study /trial, Colon Neoplasm, Colorectal Neoplasm, Combination Antineoplastic Therapy, Combination Chemotherapy, Continuing Education, Cooperative Study, Cyclophosphamide, Cytosine Arabinoside, Diaziquone, Doxorubicin, Estrogen Receptor, Etoposide, Fluorouracil, Folate, Germ Cell Neoplasm, Glioma, Hairy T Cell Leukemia, Head /neck Neoplasm, Homologous Transplantation, Hormone Therapy, Ifosfamide, Interferon, Interleukin 2, Isoquinoline, Kidney Neoplasm, Lomustine, Lung Neoplasm, Lymphoma, Male Reproductive System Neoplasm, Mechlorethamine, Melanoma, Mesothelioma, Metastasis, Methotrexate, Multiple Myeloma, Mycosis Fungoides Lymphoma, Neoplasm /cancer Chemotherapy, Neoplasm /cancer Immunotherapy, Neoplasm /cancer Nutrition Therapy, Neoplasm /cancer Radiation Therapy, Ovary Neoplasm, Pancreas Neoplasm, Patient /disease Registry, Peptide Hormone Analog, Platinum, Prednisone, Procarbazine, Prostate Neoplasm, Quality Of Life, Reproductive System Neoplasm, Small Cell Carcinoma Of Lung, Tamoxifen, Testis Neoplasm, Tumor Necrosis Factor Alpha, Uterus Neoplasm, Vincristine Human Subject, Nutrition Related Tag

    Coltman, Charles A. Southwest Oncology Group Coop Research Base
    Grant: 5U10CA037429-10
    Abstract: The Southwest Oncology Group is a major multi-disease, multi-disciplinary cooperative group organization, which includes 36 Member Institutions, 25 Community Clinical Oncology Programs (CCOPs), and 265 Cooperative Group Outreach Program affiliates (CGOPs) centered throughout the United States and Canada. New program initiatives have brought on 25 Urologic Cancer Oncology Program (UCOP) affiliates and 34 High Priority participants to add to the Group's total annual accrual of approximately 7000 patients. this Competitive Renewal Application is submitted to fund the Southwest Oncology Group as a research base for the current and proposed Community Clinical Oncology Program participants. Significant components of this application include a major emphasis of this cooperative group to increase minority participation in clinical trials through the addition of seven Minority- based CCOPs and the formation of a Minorities Subcommittee in the Cancer Control Research Committee. The Southwest Oncology Group also continues to promote and strengthen its internationally-known expertise in cancer control and prevention research through the efforts of the Cancer Control Research Committee, particularly in the areas of quality of life and chemoprevention.


    Tags: Cancer Information System, Cancer Rehabilitation /care, Community Health Service, Health Science Research Analysis /evaluation, Human Therapy Evaluation, Neoplasm /cancer Education, Neoplasm /cancer Therapy, Patient Care Planning 13 Cis Retinoate, Cns Neoplasm, Acute Leukemia, Acute Lymphocytic Leukemia, Acute Myelogenous Leukemia, Androgen Inhibitor, Antineoplastic, Autologous Transplantation, Bladder Neoplasm, Bleomycin, Bone Marrow Transplantation, Breast Neoplasm, Cancer Registry /resource, Carcinogenesis Inhibitor, Carmustine, Cervix Neoplasm, Chemoprevention, Chronic Leukemia, Cis Platinum Compound, Clinical Trial, Colon Neoplasm, Colorectal Neoplasm, Combination Antineoplastic Therapy, Combination Chemotherapy, Continuing Education, Cooperative Study, Cyclophosphamide, Cytosine Arabinoside, Diaziquone, Doxorubicin, Estrogen Receptor, Etoposide, Fluorouracil, Folate, Germ Cell Neoplasm, Glioma, Hairy T Cell Leukemia, Head /neck Neoplasm, Homologous Transplantation, Hormone Therapy, Ifosfamide, Interferon, Interleukin 2, Isoquinoline, Kidney Neoplasm, Lomustine, Lung Neoplasm, Lymphoma, Male Reproductive System Neoplasm, Mechlorethamine, Melanoma, Mesothelioma, Metastasis, Methotrexate, Multiple Myeloma, Mycosis Fungoides Lymphoma, Neoplasm /cancer Chemotherapy, Neoplasm /cancer Immunotherapy, Neoplasm /cancer Nutrition Therapy, Neoplasm /cancer Radiation Therapy, Ovary Neoplasm, Pancreas Neoplasm, Patient /disease Registry, Peptide Hormone Analog, Platinum, Prednisone, Procarbazine, Prostate Neoplasm, Quality Of Life, Reproductive System Neoplasm, Small Cell Carcinoma Of Lung, Tamoxifen, Testis Neoplasm, Tumor Necrosis Factor Alpha, Uterus Neoplasm, Vincristine Human Subject, Nutrition Related Tag

    Idell, Steven Control Of Fibrin Turnover In Pleural Disease
    Grant: 1P01HL076406-01A10001
    Abstract: Disordered fibrin turnover has been implicated in the pathogenesis of pleural inflammation and repair. We hypothesize that deranged regulation of plasminogen activator inhibitor-1 (PAI-1) and of the urokinase receptor (uPAR) in pleural mesothelial cells are critical determinants of locally impaired fibrinolysis and intrapleural remodeling after asbestos exposure or in fibrosing pleuritis. Mechanisms that regulate expression of these proteins in mesothelial cells are now poorly understood. We will extend work done in previous funding cycles to address these important gaps. We will achieve this objective in four closely integrated specific aims. In Aim 1, we will determine mechanisms that regulate the expression of PAI-1 and uPAR in mesothelial cells exposed to asbestos or mediators of fibrosing pleural injury. In Aims 2 and 3, we will elucidate mechanism(s) by which PAI-1 is regulated by pleural mesothelial cells at the posttranscriptional level and will determine how control at this level influences pathophysiologic responses of these cells. In Aim 4, we will further test a novel interventional approach; intrapleural administration of single-chain uPA (scuPA) to prevent pleural loculation. We will use our established rabbit models of tetracycline- or P. multocida induced pleural injury in these studies. To accomplish the work, we will use a wide range of molecular, biochemical and histologic techniques, all of which are well-established in our laboratory. These studies will foster better understanding of the role of the mesothelial cell in the regulation of the PAI-1-uPA-uPAR system and will increase our understanding of how these cells contribute to pleural remodeling after injury. The project will also facilitate the development of novel, clinically applicable non-surgical approaches to prevent intrapleural loculation and its associated morbidity.

    Tags: Fibrin, Fibrinolysis, Lung Disorder, Pathologic Process, Plasminogen Activator Inhibitor, Pleural Cavity Effusion Rna Binding Protein, Mesothelioma, Posttranscriptional Rna Processing, Protein Binding, Protein Biosynthesis, Protein Protein Interaction, Receptor Expression, Urokinase Cell Line, Human Tissue, Immunocytochemistry

    • Followup Grant: 5P01HL076406-020001
    • Followup Grant: 5P01HL076406-030001
    • Followup Grant: 5P01HL076406-040001
    Okayasu, Ryuichi Role Of Dna Repair In Asbestos Toxicity
    Grant: 5R03CA071438-02
    Abstract: DESCRIPTION: (Applicant's Abstract) Although asbestos exposure causes human disease such as asbestosis, lung carcinoma, and mesothelioma, the mechanism of toxicity is not clearly understood. Abundant evidence suggests that free radicals mediate its toxicity, the target of which, however, is not clearly defined. The goal of this proposal is to further clarify the cellular and molecular mechanisms of asbestos toxicity and define a basis for the prevention of asbestos-related diseases. This will be attained by an in vitro model system using a unique DNA repair deficient mutant cell line. Two hypotheses to be tested are 1) DNA double strand breaks (DSBs) produced by free radicals play a critical role in asbestos induced toxicity; if DNA DSBs are not repaired or misrepaired, cells are killed. 2) Reduction in initial DNA damage by an antioxidant agent in asbestos treated cells results in reduction of cytotoxicity. The following specific aims are proposed to test these hypotheses. i) To investigate the effect of DNA DSB and repair on cell survival using a DNA DSB repair deficient mutant of CHO cells (xrs-5 cells) treated with asbestos fibers. Colony formation assay will be employed in xrs-5 and CHO cells exposed to asbestos. ii) To directly measure the degree of DNA DSBs in asbestos treated CHO and xrs-5 cells by a pulsed-field gel electrophoresis. The premature chromosome condensation technique which can detect interphase chromosome breaks will be applied to further clarify the sequence of events from DNA damage to cell death. iii) To examine the effect of an anti-oxidant in asbestos induced cell killing and DNA DSBs using CHO cells. The cell survival assay will be employed but with combined treatments of asbestos and ascorbic acid. DNA DSBs will be examined with samples of the combined treatments as in ii). All of these studies will be conducted with chrysotile and crocidolite fibers (with higher iron content) to examine the catalytic power of iron in crocidolites. The results from these studies shall clarify the role of DNA damage/repair, specifically DNA DSBs, in asbestos induced toxicity, and may provide a useful basis for reducing the toxicity.


    Tags: Dna Damage, Dna Repair, Asbestos, Cytotoxicity, Environmental Toxicology Antioxidant, Ascorbate, Free Radical Oxygen, Iron, Oxidative Stress Cho Cell, Mutant, Pulsed Field Gel Electrophoresis, Tissue /cell Culture

    Van Houten, Bennett Asbestos Induced Oxidative Dna Damage And Repair
    Grant: 1R01ES007038-01
    Abstract: There is no text on file for this abstract.

    Tags: Dna Damage, Dna Repair, Asbestos, Chemical Carcinogenesis, Free Radical Oxygen Adduct, Antioxidant, Chemical Carcinogen, Fibroblast, Hypoxanthine Phosphoribosyltransferase, Mesothelioma, Mitochondrial Dna, Neoplasm /cancer Genetics, Nucleic Acid Sequence, Tumor Suppressor Gene, Xeroderma Pigmentosum Gas Chromatography Mass Spectrometry, High Performance Liquid Chromatography, Polymerase Chain Reaction

    • Followup Grant: 5R01ES007038-02
    • Followup Grant: 5R01ES007038-04
    • Followup Grant: 5R01ES007038-05
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    Intervention: Drug: cediranib maleate
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    Intervention: Drug: everolimus
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    Intervention: Biological: bevacizumab;   Drug: cisplatin;   Drug: gemcitabine hydrochloride
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    Intervention: Biological: recombinant interleukin-12
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    Intervention: Drug: Cisplatin;   Drug: Imatinib Mesylate;   Drug: Pemetrexed
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    Intervention: Drug: pemetrexed, cisplatin and CBP501;   Drug: pemetrexed and cisplatin
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    Intervention: Drug: antineoplaston A10;   Drug: antineoplaston AS2-1
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    Intervention: Drug: LBH589
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    Intervention: Drug: pemetrexed;   Drug: cisplatin
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    Intervention: Other: biologic sample preservation procedure
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    Intervention: Drug: fentanyl sublingual spray;   Other: questionnaire administration
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    Intervention: Drug: CBP501 + Cisplatin + Pemetrexed;   Drug: Cisplatin + Pemetrexed
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    Mesothelioma Info