Massachusetts Mesothelioma and MA Asbestos Research, Clinical Trials, and Attorney Data Sheet

Massachusetts Mesothelioma Fact Sheet

While mesothelioma is a problem in all states, the specific incident rate for Massachusetts is 1.3 / 100,000. This is above the average rate of 1.1 / 100,000. Click on the tabs below to find mesothelioma and asbestos research in MA, recent MA mesothelioma-related court cases, mesothelioma specialists in MA and potential asbestos hotspots in Massachusetts.

Massachusetts Mesothelioma Info

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

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

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

Massachusetts 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.

Matsuyama v. Birnbaum
SJC-09964, SUPREME JUDICIAL COURT OF MASSACHUSETTS, March 4, 2008, Argued, July 23, 2008, Decided

Sullivan v. Chief Justice for Admin. & Mgmt. of the Trial Court
SJC-09739 , SUPREME JUDICIAL COURT OF MASSACHUSETTS, September 7, 2006, Argued , December 15, 2006, Decided

Letteney's Case
SJC-07898, SUPREME JUDICIAL COURT OF MASSACHUSETTS, March 5, 1999, Argued , April 5, 1999, Decided

Germain v. Girard
No. 07-P-811., APPEALS COURT OF MASSACHUSETTS, April 17, 2008, Argued, August 21, 2008, Decided

Commonwealth v. Bechtel Corp.
Docket Number: 06-4933-BLS1, SUPERIOR COURT OF MASSACHUSETTS, AT SUFFOLK, May 21, 2008, Decided, May 22, 2008, Filed

Hathaway v. Raytheon Eng'rs & Constructors, Inc.
Docket Number: 99-0208, SUPERIOR COURT OF MASSACHUSETTS, AT SUFFOLK, April 13, 2007, Decided

Hospitals and Cancer Centers

Dana Farber Cancer Center Institute
44 Binney St.
Boston, MA
617.632.3470

Physicians

Richard Kraiden, M.D.
Pulmonary Pathologist
Massachusetts General Hospital
Boston, MA 02114

David Sugarbaker, M.D.
Dana Farber Cancer Institute & Brighams & Womens Hospital
75 Francis St.
Boston, MA 02115

City	Site

	Otis Air Force Base
Boston	Bethlehem Steel Shipyard Bingham Memorial Hospital Boston ISD Boston Naval Shipyard Brayton Point-Falls River Power Plant Harvard University Logan Airport Peter Bentbrigham Hospital Port Smith Quincy Market Center State House
Boston	Taun Man Power Plant
Boston	Whidden Memorial Hospital
Cambridge	Cambridge Electric Light Company
Charleston	Boston Naval Shipyard
Chelsea	Call Burglar Alarm Co
Holyoke	Worthington Pump Corporation
Hopewell	Chesapeake Paper Mill
Newport	Boston Naval Shipyard
Ruston	Grambling University
Salem	Salem Hospital

Research

Fletcher, Jonathan A. Tumor Suppressor Loci In Mesothelioma
Grant: 5R01CA068376-02

Abstract: DESCRIPTION: (adapted from the investigator's abstract) Malignant mesothelioma is an asbestos-associated neoplasm which is a growing public health concern and which poses tremendous diagnostic and therapeutic challenges. At least 65% of mesotheliomas have deletion of the mid- portion of the chromosome 6 long arm, and it is notable that this same region is deleted nonrandomly in breast cancer, leukemia, non-Hodgkin's lymphoma, osteosarcoma, and prostate cancer. Dr. Fletcher and coworkers hypothesize that a tumor suppressor gene in the 6q16.3-q21 region is deleted and/or mutated in the majority of mesotheliomas, and they also hypothesize that this gene has broad relevance in non-mesothelioma tumorigenesis. Dr. Fletcher will address these hypotheses by fine mapping of the 6q deletion region, by mapping, isolating, and characterizing balanced cytogenetic rearrangements that interrupt this region, and by evaluating candidate tumor suppressor genes in mesotheliomas and in non- mesothelioma tumors with 6q deletions. Mapping will be performed in two phases. Initially, Dr. Fletcher will map a broad region of the chromosome 6 long arm in 30 primary mesotheliomas in cell lines using an established 10-member FISH panel of mega-YACs spaced at 2-10 megabase intervals. This phase of mapping will define the critical deletion region while simultaneously evaluating the possibility of additional deletion regions. In the second phase Dr. Fletcher will re-evaluate the same group of mesotheliomas using a bacterial artificial chromosome (BAC) FISH panel spanning the critical deletion region at 500 kb intervals. These studies may reveal cytogenetically in apparent heterozygous and homozygous deletions which will further narrow the critical deletion region. The deletion mapping will be coordinated with mega-YAC FISH mapping and cloning of breakpoints for balanced cytogenetic rearrangements within the consensus deletion region. Screening for candidate tumor suppressor genes will then be accomplished by direct cDNA selection using 100-250 kb BAC DNA sequences containing the critical deletion region and a cytogenetic breakpoint. Candidate tumor suppressor genes will be evaluated with a respect to copy number (FISH), inactivating point mutations (SSCP/sequencing), and expression (Northern blotting) in primary mesotheliomas, mesothelioma cell lines, and in non- mesothelioma cancers with known 6q deletions. Long-term objectives include evaluation of the 6q tumor suppressor gene as a potential diagnostic marker in mesothelioma and evaluation of the biological elements of this gene through functional studies.

Tags: Gene Deletion Mutation, Genetic Mapping, Mesothelioma, Neoplasm /cancer Genetics, Tumor Suppressor Gene Chromosome Walking, Cytogenetics, Molecular Oncology, Nucleic Acid Sequence Artificial Chromosome, Bacteria, Clinical Research, Complementary Dna, Fluorescent In Situ Hybridization, Human Subject, Human Tissue, Northern Blotting

Followup Grant: 5R01CA068376-03
Followup Grant: 1R01CA068376-01A1

Wolinsky, Jesse B. Functional Vectors For Treatment Of Mesothelioma
Grant: 1R43CA128278-01A1

Abstract: DESCRIPTION (provided by applicant): Gene therapy offers the potential to cure or prevent diseases by delivering a therapeutic gene into a host. Gene delivery can effectively stimulate the body's immune response and prevent or control infection. Consequently, gene therapy is under investigation for mesothelioma and other cancer. In this SBIR Phase I proposal, Fifth Base proposes to evaluate and develop a novel charge-reversal amphiphile as carrier of genetic material for mesothelioma cancer cells. We hypothesize that a change in electrostatic interaction between the carrier and DNA will translate to enhanced transfection efficiency and provide a mechanism to deliver the Herpes Simples Virus Thymadine Kinase (HSV-tk) gene. Accordingly, our three specific aims are: SPECIFIC AIM 1: Characterize the charge-reversal amphiphiles and amphiphile/HSV-tk gene supramolecular assemblies. SPECIFIC AIM 2: Evaluate functional interactions amphiphile/DNA supramolecular assemblies with the cells in vitro and delivery of the HSV-tk gene to mesothelioma cancer cells. SPECIFIC AIM 3: Large scale synthesis, sterilization, shelf-live/storage, and initial cytotoxic/toxicology studies. The results from successful completion of these studies will be: (1) the identification of one or two charge-reversal amphiphiles that can deliver the HSV-tk gene to cells; (2) demonstration of a new approach that is a conceptual departure from current gene delivery vectors; and (3) the establishment of commercialization criteria for production and use of material in a Phase II proposal which will focus on evaluation of the charge-reversal amphiphile and HSV-tk gene in an in vivo animal mode. Project Narrative: Patients with Malignant Pleural Mesothelioma (MPM) confront a dismal prognosis. The median survival of patients with mesothelioma is 9-12 months, with extremely low long-term survival over five years regardless of treatment modality. With the use of combination chemotherapy consisting of cisplatin and pemetrexed, the median survival rate is increased by 3-4 months; Most patients are not viable candidates for surgical intervention, and those that elect to have surgery experience mainly palliative benefits. Despite recent advances in surgery, radiotherapy, and chemotherapy, there is no reliably curative treatment for MPM and long-term patient survival is rarely realized. We propose to develop a charge-reversal amphiphile as carrier of genetic material for mesothelioma cancer cells, which may offer the best long-term solution for adults combating this cancer.

Tags: There Are No Thesaurus Terms On File For This Project.

Rheinwald, James G. Cell Culture Analysis Of Human Epithelial Neoplasia
Grant: 2R01CA026656-08

Abstract: Mesothelioma is rare except among the many miners, shipbuilders, and insulation workers and their families who had a large exposure to asbestos within the period from 1940 to the early 1960's, when this link was found and occupational inhalation was reduced. This cancer first becomes detectable twenty to forty years after the exposure. Thus its incidence has been increasing and will continue to be responsible for 2 to 3,000 death per year until at least the end of the century. Mesothelioma does not respond to current types of treatment. Very little is known about its biology, nor is the mechanism of asbestos-induced transformation or the reason for the long latency period for tumor growth understood. I have recently identified the specific requirements of normal human mesothelial cells for rapid, long-term growth in culture, and have discovered that these cells can undergo an extraordinary, but reversible dedifferentiation during rapid growth. Surprisingly, most mesotheliomas do not grow in the culture conditions optimal for normal mesothelial cells. I propose a three-pronged approach to understanding malignant transformation of mesothelial cells: 1) experimental carcinogenesis of normal human cells with asbestos or with X-rays, selecting for growth factor-independent variants, 2) study of the tumorigenicity of cell lines cultured from normal or asbestos-treated rats, and 3) identification of additional substratum components required by mesothelioma cells for growth in culture. In order to assess the malignant or premalignant behavior of experimental transformants and natural mesotheliomas, we will inoculate cells intraperitoneally into nude mice and assess the ability of the cells to replace the resident mouse mesothelial cell population and/or to invade the underlying stroma. Our results will provide specific information about this human cancer, and, more generally, about the role of EGF- and hydrocortisone-sensitive systems in the regulation of epithelial cell growth.

Tags: Neoplasms Characteristics, Cellular Level Studies (general), Neoplasms Of Body Cavities, Mesothelioma, Occupational Health, Occupational Diseases, Pathology B Study Section Cell Dedifferentiation, Fibrous Proteins, Keratin, Growth Factors (incl. Anabolics), Epidermal Growth Factor, Neoplasms Related Interest, Preneoplastic Conditions, Neoplasms, Radiation Induced, Neoplastic Transformation, Carcinogenesis, Chemical, Toxicology, Environmental, Cell Differentiation, Neoplastic Growth Genetics, Mutation, Mutants, Human, Tissues, Fluids Etc. From Non-related Sources Outside Immediate Project, Mammals, Rodents, Myomorpha, Athymic Mice (nude), Neoplasms Transplantation, Physical Separation, Electrophoresis, Gel

Followup Grant: 5R01CA026656-09
Followup Grant: 5R01CA026656-10
Followup Grant: 2R01CA026656-11
Followup Grant: 5R01CA026656-12
Followup Grant: 5R01CA026656-07

Bueno, Raphael Validation Of Prognostic And Diagnostic Molecular Tests In Mesothelioma
Grant: 1R01CA120528-01

Abstract: DESCRIPTION (provided by applicant): Malignant pleural mesothelioma (MPM) is a highly lethal cancer for which effective therapy is lacking. Even the basic elements to treatment for this malignancy such as expedient diagnosis and accurate prognosis remain challenging and aggressive surgical extirpation is required for definitive staging and prognosis. We have previously described a novel technique using gene expression ratios to translate whole genome expression studies into clinically relevant tests that can accurately predict many clinical parameters such as diagnosis and prognosis in cancers. Specifically, we developed a test to distinguish between MPM and lung cancer and another test to predict outcome in MPM patients undergoing surgery. These ratio-based tests require small amounts of tumor RNA, to predict in a statistically significant manner diagnosis as well as clinical outcome for patients undergoing surgery for MPM. We propose to expand the diagnostic capability of these tests by identifying additional genes to make the correct diagnosis whenever MPM is suspected. This methodology can serve as a template for a genomic. Differential diagnosis algorithm to be an adjunct for pathology. We will then refine and validate these tests on additional specimens. We also propose to refine and develop the methodology so that specimens obtained minimally invasively or while using image-guided fine needle aspiration can be appropriately tested. To bring the prognostic and diagnostic tests to bedside they need to be made relevant to actual patient management, be standardized and be validated, preferably in a multi-center setting. We propose to prospectively validate the prognostic tests both with fine needle aspiration and minimally invasive biopsies in additional patients enrolled prospectively in clinical trials at our institution and in a multi center study. The proposed work will capitalize on new technology that can measure the expression (RNA) of the entire tumor genome to develop new tests that can be easily applied to patients. In addition to providing new tests that will alter the management of MPM patients--by eventually making surgery for diagnosis unnecessary and save certain patients from unnecessary major surgery-- this work will allow us to develop a diagnostic, prognostic and treatment directing platform that can be ultimately used for other cancers and human diseases to allow individual genome directed therapy for cancer and other diseases.

Tags: Diagnosis, Gene, Mesothelioma Biopsy, Neoplasm /cancer, Prognosis, Surgery Clinical Research

Followup Grant: 5R01CA120528-02
Followup Grant: 5R01CA120528-03
Followup Grant: 5R01CA120528-04

Bueno, Raphael Gene Ratio Based Prognosis In Mesothelioma
Grant: 1R21CA100315-01A1

Abstract: DESCRIPTION (provided by applicant) Malignant pleural mesothelioma (MPM) is a lethal malignancy of the pleura for which there is little effective therapy and overall survival remains dismal. This cancer affects approximately 3,000 Americans per year and its incidence is rising. Classification and staging is difficult because there are four different staging systems and the correct histological subtype of MPM is often difficult to diagnose. In addition, there are no known diagnostic or prognostic markers for MPM and limited knowledge of gene expression in this malignancy. In preliminary experiments, we have used oligonucleotide-based microarrays to evaluate gene expression in MPM and confirmed the results using real time quantitative PCR. We have developed a new gene ratio based model that correlates with outcome after surgical resection for MPM independently from stage, histologic subtype and any other known clinical predictor. We have demonstrated that this simple test can be performed by quantitative real time RT-PCR and correctly classified two cohorts of MPM specimens based on outcome. The goal of this proposal is to first confirm and refine the prognostic gene-ratio test that we discovered for MPM by comparing it to several others such tests. We will then determine the reproducibility, precision and variability of this test. We will demonstrate the feasibility of obtaining the samples for this test with minimally invasive methods. Finally we will validate the refined gene ratio prognostic test in an independent cohort of MPM patients from whom tumor and outcome data will be collected prospectively. We will determine the accuracy of this test in predicting outcome as defined by survival and tumor progression.

Tags: Diagnosis Design /evaluation, Diagnostic Test, Mesothelioma, Neoplasm /cancer Diagnosis, Neoplasm /cancer Genetics, Pleural Neoplasm, Prognosis Rna, Diagnosis Quality /standard, Gene Expression, Neoplasm /cancer Classification /staging, Pleural Cavity, Pneumonectomy, Tumor Progression Biopsy, Clinical Research, Human Tissue, Microarray Technology, Polymerase Chain Reaction

Followup Grant: 4R33CA100315-02
Followup Grant: 5R33CA100315-03
Followup Grant: 5R33CA100315-04

Kriebel, David Lung Cancer And Exposure To Chrysotile And Amphiboles
Grant: 1R03CA075605-01

Abstract: Considerable controversy surrounds the question of whether the two different ytpes of asbestos -- amphilboles and chrysotile -- have different carcinogenic potencies. The "amphibole hypothesis" holds that chrysotile is less likely to cause lung cancer and mesothelioma than are the amphiboles. The abiolity to clarify this question is limited by a lack of quantitative data with which to estimate separate dose-response curves for the two fiber types. This proposal seeks funds to study lung cancer and mesothelimoma risks in a Sovenian cement asbestos plant in which excellent historical exposure data are available, distinguishing the two broad classes of asbestos fibers. The small Grant Investigator, an occupatinal physician and epidemiology doctoral student, would conduct a detailed historical exposure reconstruction and case control studies of lung cancer and mesothelimoma. The cohort of workers employed in the cement asbestos manufacturing plant of salonit Anhovo, Slovenia will be constructed from existing detailed wage lists which date from the 1940s. Cases will be all incident cases of primary lung cancer or mesothelioma from 1964 to 1994 in those who were hired after 1959 and who worked at least one month between 1964 and 1994. They will be identified using data from the slovenian National Cancer Registry, one of the oldest national registries in Europe. Exposure measurements are available for most exposed jobs begining in 1961. Three different methods of measurement were used: konimeter measuring particles/cm3, a gravimetric method measuring milligrams/m3, and membrane filter measuring fibers/cm3. Regression analyses will be used to calculate operation-specific conversion factors among these methods. Cumulative lifetime exposure to amphilboles and to chrysotile will be estimated sparately for all cases and controls. Logistic regression models will be used to estimate separate exposure-resonse curves for the two fiber types controlling for smoking (smoking history data available on each worker from medical records).

Tags: Asbestos, Environmental Toxicology, Lung Neoplasm, Mesothelioma, Neoplasm /cancer Epidemiology Disease /disorder Etiology Human Data

Followup Grant: 5R03CA075605-02

Bueno, Raphael Gene Ratios For Lung Cancer Detection And Prognosis
Grant: 1R21CA098501-01A1

Abstract: DESCRIPTION (provided by applicant): Lung cancer is the number one cancer killer in the US for both men and women. Almost 156,000 (85%) of patients who present with lung cancer die from the disease within 5 years of presentation. There are several reasons for these stark mortality figures including non-existing screening, and ineffective therapeutic options for most patients. Even patients with stage I lung cancer who are treated surgically with intent to cure have a 30% five-year mortality due to metastatic disease. Early efforts to screen patients with spiral chest CT are being undertaken in the US but are limited by the large number of benign nodules discovered. We recently described a new method to translate data obtained from gene profiling with microarrays into simple clinically usable tests utilizing gene ratios. In preliminary work we developed models to detect lung cancer in minute specimens of lung nodules, and distinguish between different types of cancers that may affect the lung. We also developed a model to predict patient outcome after surgery for early lung cancer in a way that adds to current staging techniques. All of these tests utilize gene expression profiling data that can be acquired with microarrays or quantitative RT-PCR. We propose to extend our preliminary findings in order to determine if our gene ratio tests can 1. Distinguish between lung adenocarcinoma, mesothelioma and adenocarcinoma metastatic from breast origin to the lung using tumor bank specimens. 2. Accurately predict outcome using a set of specimens obtained from patients who underwent surgery for lung adenocarcinoma and linked with outcomes database. 3. Allow detection of lung cancer using fine needle aspirations obtained from lung nodules. We envision that our methodology will be adaptable to a future clinical scenario where each suspicious nodule would be evaluated by fine needle aspiration determining the diagnosis and best therapeutic options for the patients.

Tags: Gene Expression, Lung Neoplasm, Neoplasm /cancer Classification /staging, Neoplasm /cancer Diagnosis, Prognosis Adenocarcinoma, Mesothelioma, Metastasis, Neoplasm /cancer Genetics Clinical Research, Fine Needle Aspiration, Gene Expression Profiling, Human Subject, Human Tissue, Microarray Technology, Polymerase Chain Reaction

Followup Grant: 5R21CA098501-02

Bullock, Peter A. A Chemical Genetic Approach To Inhibiting T-ag Assembly On The Viral Origin
Grant: 1R03AI069100-01A2

Abstract: DESCRIPTION (provided by applicant): One of the critical events during the replication of many DNA viruses is the binding of "initiator proteins" to origins of replication. Once bound to the origins of replication, the virally encoded initiator proteins frequently assemble into higher oligomeric complexes. Our long-term goal is to develop a systematic approach for the isolation of inhibitors that will selectively block the assembly of viral initiators on origins of replication. These inhibitors will serve as useful reagents for exploring biological activity and as lead compounds for drug design. The systematic approach that we will utilize is an extension of recently described chemical genetics methods. A critical component of this technique is the use of split intein based vectors to generate diverse cyclic-peptide libraries in E. coli cells. This is a very cost effective method for generating complex, but very stable, libraries. Using straightforward genetic screens, the libraries will be searched for members that are able to disrupt the assembly of a prototype viral initiator termed Simian Virus 40 T-antigen. The advantages of selecting cyclic peptide inhibitors that block T-antigen oligomerization include the fact that much of T-ag's structure has been determined and T-ag's interaction with the Simian Virus 40 origin is understood in great detail. Furthermore, inhibitors of T-ag oligomerization are clinically relevant. For example, SV40 T-ag may be a human health issue; although interpretations remain uncertain, data have linked it to a variety of human cancers including mesothelioma and non-Hodgkin's lymphomas (reviewed in Vilchez and Butel (2004) Clinical Microbiology Reviews 17: 495-508). Furthermore, SV40 virus is closely related to two human viruses, BK and JC virus. These viruses induce a number of diseases in humans, including cancer. In addition, JC virus induces progressive multifocal leukoencephalopathy (PML); a disease that occurs in patients whose cellular immunity has been impaired. Indeed, approximately 5% of patients with AIDS have PML. Therefore, the approach that we propose to use to isolate inhibitors of T-ag assembly may identify lead compounds against BK and JC viruses. More importantly, these experiments will serve to demonstrate that the chemical genetic approach that we describe is a general method for the isolation of inhibitors against viral initiators. Once the feasibility of the approach is demonstrated, similar experiments will be conducted with the viral initiators encoded by other DNA viruses, such as those encoded by Herpes simplex virus and different strains of human papillomavirus. Thus, the approach described herein might facilitate the isolation of compounds with broad clinical relevance. 1 DNA viruses are a significant health risk; however, there are currently few options for treating these pathogens. Describe herein is a proposal for a chemical genetics approach for the isolation of inhibitors against DNA tumor viruses. Thus the proposal is likely to have broad clinical significance.

Tags: Chemical Genetics, Cyclic Peptide Aids, Alphaherpesvirinae, Dna, Dna Replication, Dna Virus, Polyomavirus Hominis 2, Antigen, Base, Binding Protein, Biotransformation, Cell, Cellular Immunity, Chemical, Drug Design /synthesis /production, Genetic Library, Genetic Screening, Genetics, Health, Human, Human Papillomavirus, Intein, Intracellular, Lead, Library, Literature Survey, Lymphoma, Mesothelioma, Microbiology, Molecular Weight, Motivation, Neoplasm /cancer, Nucleic Acid Sequence, Peptide, Peptide Library, Progressive Multifocal Leukoencephalopathy, Protein, Protein Binding, Quality Of Life, Sectioning, Simian Virus 40, Virus, Virus Dna

Raso, Victor A. Model To Test The Therapeutic Value Of Toxin Conjugates
Grant: 2R01CA049254-04A1

Abstract: Aspirations to harness the lethal potency of plant and bacterial toxins for beneficial use in medicine have yet to be fully realized. Various toxins have been chemically or genetically linked with specific antibody and ligand carriers to focus their action exclusively on cancer cells. These new derivative toxins provide very potent and highly selective cell kill in vitro but their performance as therapeutic agents in animal models has continued to fall far short of expectation. Substantial deficiencies have persisted despite years of intensive effort to refine the technology for producing toxin conjugates. This continuing study has therefore been designed to identify the key factors underlying in vivo effectiveness and to furnish unique insights into tumoricidal mechanisms. It addresses this critical problem from a novel perspective by deploying a model system of advanced neoplastic disease which is curable using selective toxin therapy. Valuable information regarding the fundamentals of toxin-based therapeutics is being obtained which should facilitate the design of agents with optimal clinical effectiveness and utility. A model of human malignant mesothelioma in athymic and SCID mice is being used, since the natural resistance of murine cells allows diphtheria toxin to selectively kill the human cancer target cells and cure these mice. Thus this study will encompass patterns of malignancy which involve mainly the peritoneal cavity as well as more disseminated forms of disease. Special in vivo tumor labeling and autoradiographic techniques have been developed to measure the time course, location and extent of native toxin versus immunotoxin action on tumors in situ. Essential features are thereby being revealed which explain how a single microgram dose of native toxin can kill a billion or more cancer cells and eradicate established solid tumors weighing 1-3 gm. A new, diphtheria toxin-based hybridoma screening agent has been designed to identify the most suitable monoclonal antibodies for making potent anti-tumor cell immunotoxins. Experiments are being performed to determine the pertinent distinctions which explain discrepancies in the action of toxin conjugates and diphtheria toxin in this model. Various antibodies, antibody fragments and ligands will be linked to diphtheria toxin to determine if such modifications curtail its access to tumor cells and diminish its effectiveness. The therapeutic model will provide a frame of reference to judge the performance of modified toxins and to improve those which fail to achieve cures. This system offers a means for directly testing which structural changes obstruct the curative properties of a toxin and which are permissible.

Tags: Antineoplastic, Chemical Conjugate, Disease Model, Drug Screening /evaluation, Immunotoxicity, Neoplasm /cancer Chemotherapy, Toxin Cytotoxicity, Diphtheria Toxin, Hybridoma, Immunoglobulin G, Immunoglobulin Structure, Ligand, Mesothelioma, Monoclonal Antibody, Peritoneal Cavity, Point Mutation, Ricin, Severe Combined Immunodeficiency Athymic Mouse, Autoradiography, Iodine, Laboratory Mouse, Selenium, Tissue /cell Culture

Followup Grant: 5R01CA049254-05
Followup Grant: 5R01CA049254-06
Followup Grant: 1R01CA049254-01
Followup Grant: 5R01CA049254-02
Followup Grant: 5R01CA049254-03

Raso, Victor A. Targeting Toxins With Acid-triggered Hybrid Antibodies
Grant: 1R01CA049856-01A1

Abstract: The long-term objective of this project is to harness the lethal potency of plant and bacterial toxins for beneficial use in medicine. To accomplish this goal we have designed a novel mechanism which combines the accurate targeting of antibody-bound toxin to cells with a precise means of triggering its release and full activity once it has reached its intracellular destination. Certain toxic proteins such as diphtheria toxin and Pseudomonas exotoxin, undergo an acid (pH 4-5) dependent conformational change within endosomal compartments inside the cell. This denaturation is critical to the passage of toxin out of these vesicles and into the cytosol where it acts to kill the cell. The aim of this project is to generate murine and human monoclonal antibodies which will tightly bind toxin at physiological pH levels (pH 6-8) but efficiently release this toxin when it undergoes its conformational transition at pH 4-5. Such antibodies will be covalently linked to a second cell-reactive antibody or receptor ligand to form a hybrid molecule with dual specificity. This hybrid will carry and attach antibody-bound toxin to the surface of only those cells bearing chosen target sites. Toxin will be released in its lethal form when the hybrid-toxin complex is taken into cells and is exposed to the low pH in endosomes. This approach is very flexible since antibodies or ligands to virtually any membrane site can be easily coupled with the toxin-bearing antibody to form a variety of highly specific cytotoxic agents. The binding of hybrid-antibody to toxin would also block the indiscriminate attachment of toxin to cells and prevent the neutralization of hybrid-delivered toxin by any circulating endogenous antibodies. The hybrid-antibody system will be especially useful for delivering toxin fragments or genetically modified toxins with improved characteristics. A monoclonal antibody to the human transferrin receptor has been coupled to an acid-releasable monoclonal antibody directed against diphtheria toxin. This hybrid will serve to evaluate the release strategy since its receptor internalization pathway involves entry into acidified cellular compartments. Ensuing therapeutic studies with this reagent will allow us to judge its in vivo effectiveness. An athymic mouse model of early and advanced stage human malignant mesothelioma will be used to test tumoricidal action and to monitor the biodistribution of hybrid-delivered diphtheria toxin and toxin analogs.

Tags: Drugs Synthesis, Design And Production, Drugs Vehicles, Immunological Preparations, Hybrid Designed Antibodies, Immunological Preparations, Monoclonal Antibodies, Toxins Acids-bases, Hydrogen-ion Concentration, Cell Components, Cytoplasm, Cell Hybrids, Hybridomas, Chemical Structure, Stereochemistry, Conformations, Immunology, Antigens Bacterial, Bacterial Toxins, Immunology, Antigens Bacterial, Diphtheria Toxin, Immunology, Antigens Bacterial, Exotoxins, Metal Complexes, Ligands, Models, Disease Models, Neoplasms Of Blood And Re System, Bone Marrow Neoplasms, Multiple Myeloma, Neoplasms Of Body Cavities, Mesothelioma, Neoplastic Cells, Protein (peptide) Sequence, Receptors, Transferrin Receptors, Therapy Evaluation, Non-human, Toxicology, Plant Poisons Animals, Chordates, Mammals, Rodents, Hystricomorpha, Guinea Pigs, Animals, Chordates, Mammals, Rodents, Myomorpha, Athymic Mice (nude), Bacteria, Pseudomonadales, Pseudomonas, Human, Clinical, Thiols

Followup Grant: 5R01CA049856-02
Followup Grant: 5R01CA049856-03
Followup Grant: 5R01CA049856-04
Followup Grant: 5R01CA049856-05

Rheinwald, James G. An Autocrine Basis Epithelial Growth And Neoplasia
Grant: 5R01CA026656-14

Abstract: Our long-term objective is to understand how growth and differentiation are regulated in epithelia and to identify the mechanisms by which cells escape normal controls and behave malignantly. We are studying human mesothelial cells (HM) - the simple squamous epithelial cell type that lines the inner body cavities - and human keratinocytes (HK) - the cell type that forms stratified squamous epithelia such as that of the epidermis, oral cavity, esophagus, and exocervix. The mechanisms responsible for the maintenance of normal tissue homeostasis, the rapid but transient division and migration during wound repair, and the dysplasia and invasiveness of malignant cells are yet unknown for mesothelial cells and keratinocytes, which are among the most abundant cells in the body. Mesothelioma and oral and esophageal squamous cell carcinoma are important clinically because they are usually diagnosed at a stage too far advanced to permit complete surgical resection and radiation/chemotherapy are almost never curative. Recently, we and others have recognized that FGF, a polypeptide mitogen which has long been studied for its role in angiogenesis, may be the central character in normal HM and HK regulation and may also be involved in the uncontrolled growth exhibited by their malignant forms. We propose to characterize an FGF-like factor which we have found to be secreted by many naturally and experimentally transformed HM and HK cell lines. We will determine whether its expression and autocrine action is essential for mitogenic stimulation of normal cells by interfering with its expression with antisense oligo- nucleotides. We will introduce a constitutively expressed FGF gene into normal HK, graft the cells to the dermis of athymic mice, and assess the consequences of autocrine FGF in vivo on commitment to and expression of terminal differentiation by immunohistological evaluation of the tissue formed. Lastly, we will seek to identify genes that trans-activate FGF gene expression as a step in the process of malignant transformation in HM and HK cells by retroviral insertional mutagenesis of normal HM cells and by isolating tumor-derived genes that confer FGF-independence upon NIH3T3 cells.

Tags: Cell Differentiation, Keratinocyte, Neoplastic Cell, Protein, Somatic Cell Transformation, Transforming Growth Factor Cell Division, Cellular Oncology, Genetic Repressor /activator, Mesothelioma, Neoplastic Growth, Protein Sequence Athymic Mouse, Blocking Antibody, Gel Electrophoresis, Human Tissue From Nonrelated Source, Molecular Cloning, Mutant, Tissue /cell Culture, Transfection

Sprince, Nancy L. T-cells And Alveolar Macrophages In Asbestos Exposure
Grant: 1R01ES003301-01A1

Abstract: Asbestos-related diseases are a major public health problem in the United States. An estimated 14 million individuals have been exposed to asbestos during their working lives. Asbestos has been causally linked to interstitial lung disease, pleural fibrosis, lung cancer, mesothelioma and cancers of the gastrointestinal tract, larynx and possibly kidney. Preliminary studies suggest that altered immunoregulation may play a role in the pathogenesis of asbestos-related diseases. Preliminary findings of increased OKT4+/OKT8+ ratio in peripheral blood of patients with pleural plaques or asbestosis of the lung and increased OKT8+ in lung tissue of patients with idiopathic pulmonary fibrosis suggest compartmental shifts of circulating T8 bearing lymphocytes into tissue. Preliminary findings of decreased natural killer activity in peripheral blood of subjects with asbestos exposure suggest decreased immune surveillance which may be related to carcinogenicity of asbestos. The aim of this prospective exposure control study is to evaluate further the prevalence of abnormalities of the cellular immune system in asbestos workers and to relate those abnormalities to extent of asbestos exposure and to the presence of asbestos-related diseases. Subjects with low and moderate to high asbestos exposure and normal controls will be evaluated. The investigation will characterize lymphocytes and macrophages by virtue of their reactivity with monoclonal antibodies and by measurements of cell function. With respect to lymphocytes, in vitro natural killer activity will be assessed as will immunoglubin production. With respect to macrophages, assessment of phagocytosis, fibronectin and secretion of soluble mediators will be performed in lung lavage fluid. As an index of asbestos exposure, ferruginous body and asbestos fiber counts will be performed on lung lavage fluid. Fibers will be characterized by elemental analysis and scanning electron microscopy to elucidate fiber type and composition. Serial changes in the immune findings will be correlated with extent of exposure and with clinical manifestations and progression of disease. Statistical methods to be used are one-way analysis of variance, contingency table analysis, multiple linear regression, and longitudinal multivariate analysis. This study will test the validity of measurements of immunity as an index of severity of clinical disease and extent of asbestos exposure.

Tags: Blood Cells, T Lymphocytes, Immunity, Cellular Immunity (general), Immunity, Immunoregulation, Respiratory Disorders, Environmental Pollutants Associated, Respiratory Disorders, Pulmonary Fibrosis And Granulomas, Respiratory System, Alveolar Macrophages, Silicates, Asbestos, Toxicology Study Section Blood Cells, Lymphocytes, Killer Cells, Blood Coagulation, Lysokinase, Cell Ingestion, Phagocytosis, Diseases, Cellular Level Studies (general), Diseases, Pathologic Processes (not Classified Elsewhere), Dosage And Route, Rate And Duration Of Administration, Fatty Acids, Unsaturated, Prostaglandins, Globulins, Gamma Globulins, Immunoglobulin Biosynthesis, Glycoproteins, Fibronectin, Neoplasms Of Body Cavities, Mesothelioma, Neoplasms Of Respiratory System, Lung Neoplasms, Occupational Health, Occupational Diseases, Population Studies Human, Longitudinal Study, Respiratory Disorders Diagnosis, Respiratory Disorders, Pneumoconiosis, Respiratory Disorders, Respiratory System Toxins Biomedical Systems Automated, Computer Processing Of Clinical Data, Cell Sorting, Laser, Chemistry, Analytical Methods, Spectrometry, X-ray, Human Subjects, Volunteers, Human, Clinical, Immunological Preparations, Monoclonal Antibodies, Immunology, Antibody Specificity, Information Gathering (data Collection), Questionnaires, Mathematics, Statistics (including Biometry), Optics, Microscopy, Electron Scanning, Optics, Microscopy, Fluorescence, Optics, Microscopy, Phase, Physical Separation, Chromatography, Affinity, Physical Separation, Ultracentrifugation, Density Gradient, Radioassay, Scintillation Spectrometry, Respiratory Disorders Diagnosis, Lavage And Aspiration, Respiratory Visualization, Lung Scanning, Radiography, Respiratory Function

Followup Grant: 5R01ES003301-03
Followup Grant: 5R01ES003301-04
Followup Grant: 5R01ES003301-05

Talcott, James A. Clinical And Classical Epidemiology In Oncology
Grant: 1K08CA001418-01A1

Abstract: Cancer epidemiology has been identified as a critical area for further progress in the control of cancer. The value of classical epidemiology for insights into etiology and for preventive oncology is well recognized. The application of biostatistical and epidemiological techniques to patients care problems, called clinical epidemiology, has also led to very interesting and useful results. The proposed research program has been design to demonstrate methodological breadth in these two fields. One project is a classical epidemiological case control study of asbestos-containing cigarettes as a risk factor for the development of malignant mesothelioma. This proposal is abased on a recently completed cohort study showing very high mortality in men who made the filters for the cigarettes, which contained crocidolite asbestos. Two projects apply clinical epidemiology techniques, collectively known as risk stratification, to separate clinical problems in cancer. Using these techniques, patients are separated into subgroups at distinctly different risks of an important outcome or disease state. This requires a systematic approach, from hypothesizing potential risk factors, collecting risk factor and outcome data in one patient population, modelling mathematical relationships between risk factors and outcomes using multivariate techniques, and testing these models in additional populations. Only after this process is completed can altered treatment strategies using this verified prognostic information be devised and tested. The current study applies these techniques to cancer patient populations: those with fever and neutropenia and those with suspected spinal cord compression. The proposed studies of patients with fever and neutropenia build on a retrospective study which identified powerfully-predictive prospective risk factors for medical emergencies. The studies of patients with suspected spinal cord compression are more exploratory, based upon the published literature, possibly relevant results of the study of fever and neutropenia and theoretical factors. At the same time, the principal investigator will obtain degree the Master of Science Degree in Clinical Biostatistics at the Harvard School of Public Health, which was specifically designed to give quantitative research skills to clinical researchers. In summary, the proposed research program will promote the training of clinical investigator through an integrated program of classroom training and clinical research. The research plan includes three separate investigations, diverse in their subject matter, which will apply the quantitative material learned in the classroom to significant patient care problems. The end result of this program will be a well-trained clinician, prepared for an independent academic career in clinical cancer research.

Tags: Neoplasms Of Body Cavities, Mesothelioma, Neoplastic Disease Epidemiology-statistics, Neoplastic Disease Epidemiology-statistics, Cancer Risk, Silicates, Asbestos Blood Cells, Leukocytes, Neutrophils, Drugs Abuse, Smoking, Neoplastic Transformation, Carcinogenesis, Chemical, Temperature (body), Fever Blood And Re Disorders, Blood Disorders, Human, Clinical, Models, Mathematical, Nervous Disorders Central, Spinal Cord Disorders

Followup Grant: 5K08CA001418-02
Followup Grant: 5K08CA001418-03

Cannistra, Stephen A. Adhesion Protein And Ovarian Cancer Implantation
Grant: 1R01CA060670-01

Abstract: Ovarian cancer is a highly lethal neoplasm due to its ability to form tumor implants on the peritoneal mesothelial surface of the abdominal cavity and bowel serosa. The mechanism by which ovarian cancer cells bind to peritoneal mesothelium most likely involves cell-cell recognition through specific adhesion molecules. In order to study this phenomenon, we have developed methods to isolate normal and malignant ovarian epithelial cells and have used an in vitro adhesion assay to quantitate the binding of these cells to peritoneal mesothelium. We have determined that the CD44 adhesion molecule is partly responsible for ovarian cancer cell binding through recognition of mesothelial-associated hyaluronate, a known ligand for CD44. In addition, we have found that ovarian cancer cells also bind through a CD44-independent mechanism which is not related to known adhesion proteins such as integrins or selectins. The first specific aim of this proposal is to determine the in vivo relevance of CD44 in the process of ovarian cancer cell implantation. By using a well-established nude mouse model, we will determine the effects of interfering with CD44 function (with neutralizing antibody or with soluble CD44 protein) on the implantation of CD44-positive ovarian cancer cells in vivo. We will also use a CD44-negative, implantation- incompetent ovarian cancer cell line to determine the effects of CD44 expression (by transfection) on in vivo implantation. In the second specific aim, the regulation of CD44 expression and function will be investigated in normal and malignant ovarian epithelial cells at the gene level using Southern and Northern analyses, and at the protein level using pulse-chase techniques. The third specific aim is to identify additional adhesion molecules which mediate the CD44-independent binding of ovarian cancer cells to peritoneal mesothelium. By using either ovarian cancer cells or mesothelial cells as immunogens, monoclonal antibodies will be generated and screened for their ability to neutralize binding. These neutralizing antibodies will provide useful tools for identifying potentially novel adhesion molecules expressed by either malignant ovarian epithelium or by peritoneal mesothelial cells. These studies should lead to a better understanding of the role of adhesion molecules in the process of ovarian cancer cell implantation. A complete characterization of these structures may eventually permit the design of adhesion antagonists capable of interfering with or reversing the intraabdominal spread of ovarian cancer.

Tags: Cell Adhesion, Cell Adhesion Molecule, Epithelium, Neoplasm /cancer Invasiveness, Ovary Neoplasm, Protein Cd Antigen, Disease Model, Gene Expression, Hyaluronate, Ligand, Mesothelioma, Neoplastic Growth, Neutralizing Antibody, Peritoneum Neoplasm Athymic Mouse, Clone Cell, Human Subject, Laboratory Mouse, Northern Blotting, Protein Purification, Southern Blotting, Transfection

Followup Grant: 5R01CA060670-02
Followup Grant: 5R01CA060670-03

Doucette-stamm, Lynn P53 Mutation Screening By Multiplex Sequencing
Grant: 1R43CA065204-01

Abstract: The goal of this project is to develop a rapid, cost-effective screening method for detecting all mutations in the p53 gene. The goal of Phase I is to optimize conditions for direct genomic sequencing of PCR products from human tumor cell lines. Both malignant mesotheliomas and sarcomas have been shown to be induced by different chemical carcinogens. Forty malignant mesothelioma and sarcoma cell lines, for which mutations have previously been detected, will be studied. These samples will allow the determination of the efficiency and applicability of multiplex sequencing for scanning genomic DNA for point mutations. Phase II will involve the study of large numbers of malignant mesotheliomas. These experiments will determine if specific codons or exons in p53 are mutated in malignant mesotheliomas and if there is any correlation between the site of mutation and the clinical outcome. Overall, this research will demonstrate the feasibility of using a multiplex sequencing approach for mutation scanning in human clinical samples. While the specific aims of this project are to determine the location of p53 mutations in malignant mesotheliomas, the methods developed will allow one to screen other forms of cancer for mutations in p53 as well as in other genes.

Tags: There Are No Thesaurus Terms On File For This Project.

Griffin, Thomas W. Intraperitoneal Immunotoxins
Grant: 2R01CA039748-03

Abstract: The objective of this study is the development and evaluation of anti-tumor immunotoxins (IT's) for intraperitoneal therapy of advanced intraperitoneal malignancy. Immunotoxins (monoclonal antibody-ricin A chain conjugates) directed against carcinoembronic antigen and human transferrin receptor will be used. The anti- tumor effects of these IT's will be evaluated in human tumor xenografts established as intraperitoneal tumors in nude mice. Alternate methods of immunotoxin construction will be evaluation, to optimize anti-tumor efficacy in these models. Further enhancement of anti-tumor effect of the IT's will be sought, by the in vivo use of modified forms of the IT potentiator monensin (monensin linoleate, monensin in emulsion, and liposomal monensin.) Augmentation of IT anti-tumor effect by combination with radioimmunotherapy (90 Yttrium antibody or 90 Yttrium-IT) will also be examined. A limited clinical trial of i.p. IT's in refractory intraperitoneal malignancy will be performed. This trial will investigate toxicity and efficacy of i.p. IT's, and the biodistribution of 111 Indium-IT's after i.p. infusion will be determined by external scanning and tissue biopsy. These studies should yield important information regarding development of IT's as clinical anti-cancer agents.

Tags: Biological Transport, Ion Exchange And Transport, Ion Carriers (ionophores), Immunology, Antigens Carcinoembryonal, Immunology, Antitoxins, Immunology, Toxic Reactions And Mechanisms In Immunology Antibiotics, Anthracyclines, Adriamycin, Antineoplastic Agents, Drugs Adverse Effects, Drugs, Pharmacology, Biochemical, Globulins, Gamma Globulins, Immunoglobulin A, Haloalkylamines, Cyclophosphamide, Immunological Preparations, Monoclonal Antibodies, Immunology, Antigens, Surface Antigens, Metalloproteins, Transferrin, Neoplasms Immunization (immunotherapy), Neoplasms Of Body Cavities, Mesothelioma, Neoplasms Of Gastrointestinal System, Colon Growths, Neoplastic Therapy, Cancer Chemotherapy, Neoplastic Therapy, Cancer Radiotherapy, Neoplastic Therapy, Combination Antineoplastic Therapy, Receptors, Antigen Receptors, Tissue Compatibility-transplant, Transplantation Heterologous, Toxicology, Cytotoxicity, Toxicology, Plant Poisons, Toxalbumins (plant) Animals, Chordates, Mammals, Rodents, Myomorpha, Athymic Mice (nude), Drugs, Chemotherapy, Drugs Combination, Models, Disease Models, Radiotracers

Followup Grant: 5R01CA039748-04
Followup Grant: 5R01CA039748-05

Rheinwald, James G. Cell Culture Analysis Of Human Epithelial Neoplasi
Grant: 5R01CA026656-06

Abstract: We began this project with a study of squamous cell carcinoma of the oral cavity and epidermis in humans, finding defective differentiation in these cells. Our identification of the 40 kilodalton keratin in SCC cells then led us to study other epithelial cell types in culture and disclosed the expression of: (1)\cell-type-specific subsets of a large family of keratins and (2)\cell-type-specific growth requirements by mesothelial cells, urothelial cells, and kidney tubule epithelial cells. In addition to defining culture conditions for long-term, clonal growth of these cell types, we have begun to study the nature of dedifferentiation in mesoderm-derived epithelial cell types. We have found that normal mesothelial cells dedifferentiate reversibly during rapid growth in culture and that this process, which includes a morphological change to fibroblastoid appearance and the expression of vimentin intermediate filaments, occurs also in mesothelioma. We are now seeking to identify and characterize the various cell types that grow in culture from normal human kidney cortex. We have also substantially improved conditions for keratinocyte growth in culture and have optimized conditions for identifying and isolating rare, induced mutants from these feeder layer-dependent cells, thus setting the stage for seeking chemical-induced transformation events in cultured populations of normal human keratinocytes. (M)

Tags: Cell Biology Study Section, Neoplasms Characteristics, Cellular Level Studies (general), Neoplasms Of Skin, Tissue (cell) Culture, Tissue, Epithelium Neoplasms Related Interest, Preneoplastic Conditions, Neoplasms, Carcinoma Basosquamous, Neoplastic Transformation, Carcinogenesis (general), Cell Differentiation, Cell Growth Regulation Connective Tissue Cells, Fibroblasts, Diagnostic Tests, Biopsy, Human, Tissues, Fluids Etc. From Non-related Sources Outside Immediate Project, Mammals, Lagomorphs, Mammals, Rodents, Myomorpha, Athymic Mice (nude), Mammals, Rodents, Myomorpha, Mice (laboratory), Physical Separation, Electrophoresis, Gel

Wang, Zhao-yi Regulation Of Cell Growth By The Wilms Tumor Gene
Grant: 1R29CA076632-01A1

Abstract: DESCRIPTION: (Adapted from investigator's abstract) The Wilms' tumor suppressor gene, wt1, encodes a zinc finger transcription factor, WT1. A number of mutations to the wt1 gene have been identified in subsets of Wilms tumor, mesothelioma, ovarian tumor and acute myeloid leukemia, suggesting that dysfunction of WT1 may be important in many tumors. However, effectively nothing is known about the endogenous genes regulated by WT1, and thus the signaling pathways triggered by WT1 and how mutated WT1 influences these pathways to result in Wilms' tumor remain to be discovered. The long-term objective of the investigator's research is to characterize the normal functions of WT1 during development and the dysfunctions of mutated WT1 that lead to the genesis of Wilms' tumor. The investigators recently cloned a gene whose expression is over tenfold greater in cells expressing WT1 than in cells with undetectable levels of WT1. The gene was identified as retinoblastoma (Rb) suppressor associated protein (AP) (RbAp46), a nuclear protein that physically interacts with Rb. The investigators have recently cloned and expressed the full-length cDNA of RbAp46, and analyzed its effect on tumor cells. Remarkably, expression of exogenous RbAp46 suppressed growth in four out of four tumor cell lines, suggesting that RbAp46 itself has growth inhibitory activity. The investigators now plan to establish the positive correlation between the levels of WT1 and RbAp46 expression in different tumor cells and in mouse tissues from different stages of development using Northern and in situ hybridization analysis. They plan to analyze the promoter region of RbAp46 to determine whether WT1 directly regulates the expression of RbAp46. They plan to explore the possible roles of RbAp46 as a mediator of WT1 function by expressing exogenous RbAp46 or by down-regulating RbAp46 in cells. The investigators plan to probe the mechanisms by which RbAp46 functions as a growth inhibitor by analyzing its impact on the cell cycle and its influence on the ras signaling pathway. The investigators plan to perform structure and function analysis to identify the domain(s) of RbAp46 required for its function. The investigators plan to identify the proteins which interact with RbAp46 by co-immunoprecipitation and an in vivo GST capture assay and, if necessary, by a yeast two-hybrid strategy. It is hoped that these studies will lay the foundation of therapeutic intervention for the Wilms' tumor and other tumors as well.

Tags: Wilms' Tumor, Cell Growth Regulation, Gene Expression, Neoplasm /cancer Genetics, Retinoblastoma Protein, Transcription Factor, Tumor Suppressor Gene, Tumor Suppressor Protein Cell Differentiation, Developmental Genetics, Gene Interaction, Genetic Promoter Element, Growth Inhibitor, Neoplastic Transformation, Protein Structure /function, Regulatory Gene 3t3 Cell, Athymic Mouse, Cell Line, Immunoprecipitation, In Situ Hybridization, Neoplastic Cell, Northern Blotting

Followup Grant: 5R29CA076632-02
Followup Grant: 5R29CA076632-03
Followup Grant: 5R29CA076632-04
Followup Grant: 5R29CA076632-05

Clinical Trials

Active, not recruiting Bevacizumab (Avastin) and Erlotinib (Tarceva) in Previously Treated Mesothelioma

Condition: Mesothelioma
Intervention: Drug: Erlotinib; Drug: Bevacizumab
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Active, not recruiting Sorafenib in Treating Patients With Malignant Mesothelioma

Condition: Malignant Mesothelioma
Intervention: Drug: sorafenib tosylate
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Completed Ecteinascidin 743 in Treating Patients With Malignant Mesothelioma

Condition: Malignant Mesothelioma
Intervention: Drug: trabectedin
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Completed Gefitinib in Treating Patients With Malignant Mesothelioma

Condition: Malignant Mesothelioma
Intervention: Drug: gefitinib
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Active, not recruiting Dasatinib in Treating Patients With Previously Treated Malignant Mesothelioma

Condition: Malignant Mesothelioma
Intervention: Drug: dasatinib; Other: immunoenzyme technique; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis
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Active, not recruiting Capecitabine in Treating Patients With Malignant Mesothelioma

Condition: Malignant Mesothelioma
Intervention: Drug: capecitabine
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Active, not recruiting Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Malignant Mesothelioma

Condition: Malignant Mesothelioma
Intervention: Biological: bevacizumab; Drug: cisplatin; Drug: gemcitabine hydrochloride
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Active, not recruiting PTK787/ZK 222584 in Treating Patients With Unresectable Malignant Mesothelioma

Condition: Malignant Mesothelioma
Intervention: Drug: vatalanib
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Completed Erlotinib in Treating Patients With Malignant Mesothelioma of the Lung

Condition: Malignant Mesothelioma
Intervention: Drug: erlotinib hydrochloride
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Active, not recruiting AZD2171 in Treating Patients With Malignant Pleural Mesothelioma That Cannot Be Removed By Surgery

Condition: Malignant Mesothelioma
Intervention: Drug: cediranib maleate
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Active, not recruiting Gemcitabine Plus Cisplatin in Treating Patients With Malignant Mesothelioma of the Pleura That Cannot Be Removed by Surgery

Condition: Malignant Mesothelioma
Intervention: Drug: cisplatin; Drug: gemcitabine hydrochloride
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Active, not recruiting Pleurectomy/Decortication Followed by Intrathoracic/Intraperitoneal Heated Cisplatin for Malignant Pleural Mesothelioma

Condition: Pleural Mesothelioma; Malignant Pleural Mesothelioma
Intervention: Drug: Cisplatin; Drug: Sodium Thiosulfate
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Active, not recruiting Extrapleural Pneumonectomy With Intraoperative Intrathoracic/Intraperitoneal Heated Cisplatin With Amifostine and Sodium Thiosulfate

Condition: Pleural Mesothelioma; Malignant Pleural Mesothelioma
Intervention: Drug: Cisplatin; Drug: Sodium Thiosulfate
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Recruiting Pleurectomy/Decortication With Intraoperative Intrathoracic/Intraperitoneal Heated Cisplatin With Sodium Thiosulfate

Condition: Pleural Mesothelioma; Malignant Pleural Mesothelioma
Intervention: Drug: Cisplatin; Drug: Sodium Thiosulfate; Drug: ALIMTA
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Recruiting Extrapleural Pneumonectomy /Pleurectomy Decortication, IHOC Cisplatin and Gemcitabine With Amifostine and Sodium Thiosulfate Cytoprotection for Resectable Malignant Pleural Mesothelioma

Condition: Malignant Pleural Mesothelioma
Intervention: Procedure: Extrapleural pneumonectomy (EPP), Pleurectomy/Decortication; Drug: cisplatin; Drug: gemcitabine; Drug: amifostine; Drug: sodium thiosulfate
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Completed Pemetrexed Plus Gemcitabine as Front-Line Chemotherapy for Patients With Malignant Pleural or Peritoneal Mesothelioma

Condition: Mesothelioma
Intervention: Drug: Pemetrexed; Drug: Gemcitabine
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Active, not recruiting Neoadjuvant Pemetrexed Disodium and Cisplatin Followed by Surgery and Radiation Therapy in Treating Patients With Pleural Mesothelioma

Condition: Malignant Mesothelioma
Intervention: Drug: cisplatin; Drug: pemetrexed disodium; Procedure: conventional surgery; Procedure: neoadjuvant therapy; Radiation: radiation therapy
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Suspended Flavopiridol in Treating Patients With Metastatic or Unresectable Refractory Solid Tumors or Hematologic Malignancies

Condition: Breast Cancer; Head and Neck Cancer; Intraocular Melanoma; Kidney Cancer; Leukemia; Lung Cancer; Lymphoma; Malignant Mesothelioma; Melanoma (Skin); Multiple Myeloma and Plasma Cell Neoplasm; Sarcoma; Small Intestine Cancer
Intervention: Drug: alvocidib
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Completed Completed

Condition:
Intervention:
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Phase II Trial of Neo-Adjuvant Pemetrexed Plus Cisplatin Followed by Surgery and Radiation for Pleural Mesothelioma

Condition: Pleural Neoplasms
Intervention: Drug: pemetrexed; Drug: cisplatin
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Recruiting Collecting Tumor Samples From Patients With Gynecological Tumors

Condition: Cancer
Intervention: Other: biologic sample preservation procedure
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