Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anti-idiotypic antibodies (Ab2) that functionally mimic epitopes associated with human cancer cells are the most specific cancer vaccines currently available. Ab2 can induce specific humoral anti-tumor immunity in cancer patients. However, the potential of Ab2 for inducing cellular immunity in cancer patients still requires demonstration. Clonotypic antibodies directed against the combining site for tumor Ag on human T-cell clones may provide highly effective reagents for inducing protective T-cell immunity against human cancer. A new generation of cancer vaccines, molecularly cloned tumor-associated antigens (Ag), has recently been developed. Recombinant Ag have been successfully expressed in vectors allowing large scale production of Ag for immunization of cancer patients. Recombinant tumor Ag was shown to induce specific and protective immunity in experimental animals. In contrast to Ab2, which may mimic a single cancer-associated epitope, recombinant Ag express multiple epitopes that are potentially immunogenic. Ag vaccines, therefore, may be more effective in arresting tumor growth than single epitope (Ab2) vaccines because tumor destruction by antibodies is dependent on antibody density on tumor cell surfaces. In light of the important roles that both B and T cells play in the control of tumor growth, the demonstration of induction of specific B and T cell-immunity by recombinant tumor Ag and Ab2 in experimental animals is encouraging. Ultimately, the immunomodulatory role of both types of vaccines has to be compared in cancer patients who are immunologically tolerant to many Ag/epitopes expressed by their growing tumors. The development of both Ab2 and recombinant Ag for single antigenic systems provides the first step towards this goal.
 ...
PMID:Epitope- and antigen-specific cancer vaccines. 177 73

We use a method of relative potency comparisons to rank the potential strength of 44 compounds being tested in rodent carcinogenicity bioassays. All of our previous hazard evaluations have been for human conditions where great numbers of simultaneous and serial exposures may act in combination to produce a neoplasm comprised of 2(20) to 2(30) cells commonly expected to derive from a single precancerous cell. For human exposures, we have always assumed an initiated target tissue containing at least one transformed but subcarcinogenic cell per organ. Thus, for man we have focused on empirical correspondences that may help to index the monoclonal growth of a particular cell lineage during cancer expansion. In contrast to humans, initiation of target tissues in animals subjected to National Toxicity Program (NTP) bioassays may not be a given condition, because of extensive precautions taken to minimize exposures to contaminates in food, water and cage environments. For this evaluation, we used categorical assignments of 'unlikely', 'possible' and 'probable' carcinogens adapted from NTP tests. Our rank ordering, of compounds according to maximum doses tested in male mice and male rats, is coded accordingly to the three outcomes taken from the NTP tests, but the magnitude of potency depend completely upon our particular method of comparing toxicological data. We have attempted to demonstrate that a relative potency based analysis of a diversity of toxicological data may be useful for rank ordering potentially hazardous compounds to be tested by the NTP and for range-finding of their effective test doses to be administered during chronic test protocols.
 ...
PMID:On the rodent bioassays currently being conducted on 44 chemicals: a RASH analysis to predict test results from the National Toxicology Program. 180 Aug 99

A series of 61 consecutive procedures of chest wall resection and reconstruction in 58 patients during the period between August, 1986 and December, 1990 is reported. The ages ranged between 6-77 years. The chest wall resection was indicated for malignant affections in 54 cases. Among these, there were 24 patients with bronchial carcinoma invading the chest wall, 17 patients with primary or metastatic sarcoma, 11 patients with recurrent breast cancer and 3 with cancer metastases of varying origin. Pulmonary resection included pneumonectomy in 8 cases, lobectomy in 19, segmental and wedge resections in 26. In the majority of resections, the reconstruction was accomplished without implants. In cases with full thickness removal of the chest wall, the plane of the rib cage and/or the sternum was reconstructed using Vicryl mesh (n = 7), PTFE soft tissue patch (n = 11), marlex-mesh (n = 1), or methyl-methacrylate (n = 3). There was one case of hospital mortality, 6 weeks postoperatively, due to neurological failure from an independent preoperatively undiagnosed brain tumor. There were 4 reoperations: one early and one late (4 months) infection, one case of limited superficial necrosis of a flap and one with chronic lymphous drainage from a large myocutaneous flap. In no instance was primary postoperative ventilation therapy necessary. Mechanical ventilation was instituted only on day 8 in the patient who accounts for the mortality in this series. In the presence of primary infection, the greater omentum was used for the restoration of the integument.
 ...
PMID:Reconstruction of chest wall defects. 180 37

The advent of hybridoma technology and the availability of virtually unlimited amounts of specific high affinity monoclonal antibodies to desired antigens have ushered in a new revolution in immunoassay methodology. An ever increasing number of monoclonal antibody-based immunoassays are replacing those employing polyclonal antisera. A host of hitherto unknown tumor-associated antigens have also been identified due to the development of unique monoclonal antibodies. The exquisite specificities and affinities of monoclonals has led to the development of sensitive and reproducible immunoassays for various analytes, especially tumor-associated antigens. Most tumor-associated antigens are glycoconjugates and among these many are blood group antigens and their derivatives, found both as glycoproteins and glycolipids. The development and clinical applications of new immunoassays for cancer-associated carbohydrate antigens in the last decade has had a major positive impact on the management of cancer patients.
Semin Cancer Biol 1991 Dec
PMID:Immunoassays for cancer-associated carbohydrate antigens. 181 Apr 66

Although mucins have been studied at the biochemical and biophysical level for some time, attempts to define their structures in detail were only partially successful because of their size and complexity. The advent of monoclonal antibodies reactive with these molecules introduced a new approach to structural studies by defining antigenic epitopes, by allowing purification of the mucin molecules by affinity chromatography, and by providing a means to clone genes coding for the core proteins. By their profile of reactivity with the normal and cancer-associated mucin in a particular tissue, the antibodies also defined a difference in the mucin derived from the two sources. It is now clear that this difference lies in the carbohydrate side chains, as the core proteins are identical. Because the mucins are tumor-associated antigens and the cancer mucins can express epitopes that are relatively tumor specific, this family of molecules is now being intensively studied. There is also considerable interest in elucidating the normal function of the mucin and in determining whether, through an altered structure, this function is subverted in malignancy. In the next few years we should expect that the structure of other mucins will be defined in the same detail as the product of the MUC1 gene. We should also expect to see the continued application of mucin-reactive antibodies in the clinic and the investigation of mucins as agents for immunotherapy of some cancers. As to the function(s) of these molecules, perhaps we will learn enough in the future to make a critical reappraisal of the name.
 ...
PMID:Structure and biology of a carcinoma-associated mucin, MUC1. 189 26

Nude mice were inoculated with CHO/IFN-gamma cells, a line of Chinese hamster ovary tumor cells, that had been genetically engineered to produce murine IFN-gamma. Severe cachexia, as evident from body weight loss and reduced food intake, occurred in these mice, but not in those injected with CHO/control cells, i.e. the original, non-IFN-gamma-producing line. The essential role of IFN-gamma in the pathogenesis of cachexia was confirmed by the demonstration that monoclonal antibodies (MAbs) against IFN-gamma, given prior to injection of the tumor cells, prevented cachexia. In addition to IFN-gamma, the presence of the tumor cells was also required for cachexia to develop. As evident from pair-feeding experiments, reduced food intake could only partially account for the rapid and extensive body-weight loss. Cachexia was characterized by a marked reduction in the amount of interscapular fat tissue. Injected tumor cells exclusively invaded intraperitoneal adipose tissue and elicited an inflammatory cell infiltrate, indicating that interscapular fat loss was due to humoral factors. Our data suggest that, among the humoral factors responsible for cancer-associated cachexia, IFN-gamma plays a prominent role.
Int J Cancer 1991 Aug 19
PMID:Severe cachexia in mice inoculated with interferon-gamma-producing tumor cells. 190 42

Immunohistochemical assays have been employed to study the expression of ER, PgR, EGFR and Ki67 immunostaining in normal breast tissue (n = 76). The expression of ER and PgR was highly variable in both pre and postmenopausal women and was characterised by large numbers of apparently negative cells. This was most evident for ER-ICA staining in tissues removed from premenopausal women. PgR levels were highest in the ducts of premenopausal women, while EGFR expression was elevated in both ducts and lobules. Ki67 expression was observed in less than 10% of all normal cells and was suppressed by the menopause in lobular tissue. Tamoxifen therapy (40 mg d-1) did not influence the expression of PgR, EGFR or Ki67 immunostaining in cancer associated normal tissue (n = 17). A significant increase, however, was observed in the mean percentage ER positivity in ductal tissue. No effect of duration of tamoxifen therapy was observed on the expression of the antigens studied.
Br J Cancer 1991 Oct
PMID:Influence of the antioestrogen tamoxifen on normal breast tissue. 191 Dec 27

Our studies provide evidence that thiols, such as N-acetyl-L-cysteine, inhibit both spontaneous mutations and induced mutations in bacteria, prevent the in vivo formation of carcinogen-DNA adducts, and suppress or delay the development of tumors or preneoplastic lesions in rodents. N-Acetylcysteine and other thiols exert antioxidant activity toward superoxide anion, hydrogen peroxide, and singlet oxygen, assessed in bacterial genotoxicity models. In addition, several other mechanisms were shown to contribute to their antimutagenic and anticarcinogenic activities, in the extracellular environment and in nontarget or target cells. These mechanisms include blocking of electrophilic metabolites and of direct-acting compounds, either of endogenous or exogenous source, modulation of several xenobiotic-metabolizing pathways, and protection of DNA-dependent nuclear enzymes. Chemoprevention of mutation and cancer by thiols is particularly useful under conditions of reduced glutathione (GSH) depletion due to toxic agents or to cancer-associated viral diseases, such as acquired immunodeficiency syndrome (AIDS) or viral hepatitis B.
 ...
PMID:Antioxidant activity and other mechanisms of thiols involved in chemoprevention of mutation and cancer. 192 3

Observation of genetic alterations that appear consistently in specific types and stages of cancer provides a strong impetus to cancer geneticists to focus their investigations on the exploration of such volatile regions of the human genome. Introduction of powerful molecular cytogenetic and molecular genetic methods in recent years permits more detailed analysis, which will help researchers in their efforts to determine if such areas of the human genome have a functional role in the initiation and progressive development of leukemias and solid tumors. This discussion will focus on several provocative molecular cytogenetic tools that are currently available to localize potential cancer-associated genes and on how these methods are being used in conjunction with the current modes of analysis, including cytogenetics and somatic cell genetics. In addition, we will explore how these methods will help to isolate and dissect recently discovered cancer-associated genes within the human genome. All of these methods used in combination with each other will provide essential DNA markers for future diagnostic and prognostic evaluation of cancer.
Cancer Genet Cytogenet 1991 Sep
PMID:Gene mapping in cancer. 193 14

The UM-E7 monoclonal antibody raised against the UM-SCC-I human squamous cell carcinoma (SCC) cell line identifies a cell surface antigen that is strongly expressed in normal tissues. The locus (MICI) controlling the expression of E7 and related cell surface antigens has been mapped to chromosome band 11p13. This band has been identified as a region of cancer-associated aberrations and as the probable locus of a tumor suppressor gene. Although E7 antigen expression is strong in normal keratinocytes, it varies among squamous carcinoma cell lines. Some SCC lines (12/26) exhibit weak expression of the E7 antigen, whereas other SCC cell lines (14/26) and 21 cell lines from other tumor types express the antigen strongly. On the basis of these observations and of mapping data, we postulated that low E7 antigen expression in a subset of SCC cell lines might be associated with chromosomal rearrangement or deletion involving the E7 locus on 11p. Fully evaluable karyotypes were prepared from 19 SCC cell lines, including 11 with weak and eight with strong E7 expression. Eight of the 11 lines with weak E7 expression had 11p abnormalities. Four of these contained 11p deletions, and four others had a breakpoint in 11p. In contrast, none of the cell lines in the group with strong E7 expression had an 11p deletion, although one had a rearrangement with an 11p breakpoint. In the four tumors with visible 11p deletions, the smallest region of overlap corresponded to the 11p13-p14 region. The mean log10 50% endpoint E7 titer in the group with 11p deletions or breakpoints was nearly two orders of magnitude lower than that of the lines with no 11p abnormality (1.95 +/- 0.53) (P less than 0.02). Our results indicate that the UM-E7 antibody identifies tumors with 11p13-p14 deletions and other 11p rearrangements and that the 11p region is a site of nonrandom chromosome rearrangement in a subset of human squamous cancers. The strong association of loss of antigen expression with visible 11p deletion or rearrangement in some tumors suggests that other tumors with this phenotype may contain submicroscopic lesions of 11p13-p14.
Genes Chromosomes Cancer 1991 Jul
PMID:11p deletions and breakpoints in squamous cell carcinoma: association with altered reactivity with the UM-E7 antibody. 195 93


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>