Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histaminase has been shown to be associated with several types of human cancer. In the present study, we examined the activity of histaminase and its relationship with Regan isoenzyme of alkaline phosphatase in ascitic fluids obtained from patients with ovarian and several other types of cancer. We have found that about 44% of the ovarian cancer patients had elevated levels of histaminase in the ascitic fluid, whereas a less frequent incidence was observed in fluids obtained from other types of cancer. There was concurrence in the elevation of histaminase activity with the appearance of Regan isoenzyme in most of the samples examined. Of the 10 patients who showed elevated histaminase, 9 had high Regan isoenzyme activity; whereas in 9 patients with normal levels of histaminase, all except 1 had low or moderate levels of Regan isoenzyme activity. These results, therefore, confirm the observation of an association of histaminase with human cancer and suggest the possibility for the utilization of histaminase, in conjunction with Regan isoenzyme and cancer-associated proteins, for cancer diagnosis and clinical evaluation of tumor progression and regression during therapy.
 ...
PMID:Elevation of histaminase and its concurrence with Regan isoenzyme in ovarian cancer. 80 68

The relationship of abnormal nuclear morphology to molecular genetic alterations that are important in colorectal tumorigenesis is unknown. Therefore, Feulgen-stained isolated nuclei from 22 adenomas and 42 carcinomas that had been analyzed for ras gene mutations and allelic deletions on chromosomes 5q, 18q, and 17p were characterized by computerized image analysis. Both nuclear area and the nuclear shape factor representing irregularity correlated with adenoma-carcinoma progression (r = 0.57 and r = 0.52, P < 0.0001), whereas standard nuclear texture, a parameter of chromatin homogeneity, was inversely correlated with progression (r = -0.80, P < 0.0001). The nuclear parameters were strongly interrelated (P < 0.0005). In multivariate analysis, the nuclear parameters were predominantly associated with adenoma-carcinoma progression (P < or = 0.0001) and were not influenced significantly by the individual molecular genetic alterations. Nuclear texture, however, was inversely correlated with fractional allelic loss, a global measure of genetic changes, in carcinomas (r = -0.39, P = 0.011). The findings indicate that nuclear morphology in colorectal neoplasms is strongly related to tumor progression. Nuclear morphology and biologic behavior appear to be influenced by accumulated alterations in cancer-associated genes.
 ...
PMID:The relationship of quantitative nuclear morphology to molecular genetic alterations in the adenoma-carcinoma sequence of the large bowel. 135 73

The cancer stroma is made of cellular and non cellular formations which grow along with cancer cells to build up a tumor. It comes from inflammatory cells and mesenchymal tissue which are mobilized and modified by factors released by cancer cells which bring about inflammatory cell accumulation, angiogenesis, fibroblast mitosis and extracellular matrix production. The extracellular matrix is altogether a barrier against and supporting to cancer cells. The extracellular matrix is also involved in the storage of growth factors which are bound to glycosaminoglycans. Although they are antinomic in vitro, peptidic factors released by tumor cells seem to have an enhancing effect on tumor growth in vivo. The cancer invasion is mediated through diverse enzyme activities, particularly proteases, which degrade the matrix whose degradation products can facilitate the tumor progression. The anti-cancer activity which is exhibited in vitro by macrophages and lymphocytes is expressed at a low level by tumor-macrophages and lymphocytes in vivo. The cancer associated inflammation has no particular feature which could help to screening or to follow up patients. Several elements of the cancer stroma could be selected as targets for investigative cancer therapy.
 ...
PMID:[Cancer stroma]. 176 34

Karyotypic abnormalities have been described in more than 10,000 human neoplasms analyzed by means of chromosome banding. These aberrations are of three different kinds: primary abnormalities, which are essential in establishing the tumor; secondary abnormalities, which develop only after the neoplasm is established but which nevertheless may be important in tumor progression; and cytogenetic noise, which is the background level of nonconsequential aberrations. These latter changes are, in contrast to the primary and secondary aberrations, randomly distributed throughout the genome. The primary abnormalities, of which more than 100 have been identified, are strictly correlated with particular neoplastic disorders and even with histopathological subgroups within a given tumor type. To these purely cytogenetic data implicating specific genetic changes in carcinogenesis may now be added the growing evidence of molecular specificity emerging from recombinant DNA studies. It appears that both currently known classes of directly cancer-relevant genes, the dominant oncogenes and the recessive anti-oncogenes, are located at precisely those genomic sites that are visibly involved in neoplasia-associated chromosomal rearrangements. The molecular genetic data thus support the cytogenetic conclusion that the distribution of consistently cancer-associated breakpoints reflects the genomic position of genes that, either directly or through the control function they exert, are essential in the proliferation and differentiation of human cells.
 ...
PMID:Chromosome abnormalities in cancer. 222 17

Asbestos has been described as a physical carcinogen in that long thin fibers are generally more carcinogenic than shorter thicker ones. It has been hypothesized that long thin fibers disrupt chromosome behavior during mitosis, causing chromosome abnormalities which lead to cell transformation and neoplastic progression. Using high-resolution time lapse video-enhanced light microscopy and the uniquely suited lung epithelial cells of the newt Taricha granulosa, we have characterized for the first time the behavior of crocidolite asbestos fibers, and their interactions with chromosomes, during mitosis in living cells. We found that the keratin cage surrounding the mitotic spindle inhibited fiber migration, resulting in spindles with few fibers. As in interphase, fibers displayed microtubule-mediated saltatory movements. Fiber position was only slightly affected by the ejection forces of the spindle asters. Physical interactions between crocidolite fibers and chromosomes occurred randomly within the spindle and along its edge. Crocidolite fibers showed no affinity toward chromatin and most encounters ended with the fiber passively yielding to the chromosome. In a few encounters along the spindle edge the chromosome yielded to the fiber, which remained stationary as if anchored to the keratin cage. We suggest that fibers thin enough to be caught in the keratin cage and long enough to protrude into the spindle are those fibers with the ability to snag or block moving chromosomes.
 ...
PMID:Behavior of crocidolite asbestos during mitosis in living vertebrate lung epithelial cells. 785 Jul 91

A new approach is proposed that has the potential to be a successful therapy for most disseminated cancers because it can circumvent the problems posed by three characteristics which are universally expressed by cancer cells: heterogeneity, plasticity, and the lack of a cancer specific or cancer associated characteristic which is not also shared by some normal cells. Analysis shows that almost all current and research approaches for treating disseminated cancers have the same fundamental strategy: they rely on an agent interacting individually and effectively with each cancer cell. We call all these approaches "lock and key" strategies to emphasize the need for this individual agent to cell interaction. The three characteristics preclude current approaches from successfully treating most disseminated cancers because they operate by a "lock and key" strategy which (a) only kills cancer cells expressing a single particular trait, (b) allows other cancer cells to adapt and survive the treatment, and (c) also kills the normal cells which express the same particular trait. The heterogeneity and plasticity of cancer cells can only be circumvented by an attack which is microregional (not cell by cell) and destructive (not killed by conventional endogenous or exogenous cytotoxic agents). All cells in each microregion must be destroyed, including those which do not express an exploitable trait. The proposed approach can achieve such microregional destruction by the delivery to, and long term immobilization of, a large number of radio-isotopes. The proposed approach exploits the additive contribution of multiple mechanisms to enhance tumor specificity of the microregions. Given that all targeting and killing agents are "imperfect", this is the only way specificity can be enhanced. The biological basis of these specificity enhancing mechanisms are well-known. However, they are ignored by current therapies because most of them can only be exploited in the context of the proposed approach. Some of the mechanisms reflect characteristics, such as heterogeneity, genetic instability, and tumor progression which are the result of the micro-evolutionary process of tumor development. These are virtually always present in, and virtually specific to, cancer. Others reflect the somewhat "imperfect" cancer associated characteristics of structures, including cancer cells, extracellular structures, and non-malignant cells within the tumor mass. The additive contribution of the multiple mechanisms gives the process the potential to destroy all the cancer cells with minimal non-tumor toxicity. The cornerstone of the proposed approach is a novel class of soluble chemicals. They can be administered intravenously to subjects, circulate throughout body fluids and are enzymatically converted into an insoluble material when the chemicals reach targeted sites. In this paper, these chemicals are called "soluble precipitable reagents" (SPR) to describe their ability to be converted from a soluble to an insoluble material. The insoluble material is called platform to indicate that it has the ability to bind various agents. The SPR chemicals enable a three-step process to be constructed which can deliver and retain a large number of radio-isotope atoms in tumor tissue. In step 1, a binary reagent comprised of an SPR attached to an imperfect cancer targeting agent is administered. The binary reagent is endocytosed and transported into lysosomes where the targeting agent moiety is digested and the detached SPR is converted by natural intracellular lysosomal enzymes into a platform. As will be discussed, a very large number of platform molecules can be made to accumulate inside targeted cells. In step 2, a supersensitive fraction of the cancer cells, including some which had accumulated platform in step 1, are killed by the administration of a very low dose of an anti-cancer agent. Very few, if any, normal cells will be killed by the very low dose. The death of the ce
 ...
PMID:A proposal for a new direction to treat cancer. 980 54

Based on the multistage and multifocal nature of colorectal carcinogenesis, it is likely that reduction of cancer mortality through early detection and identification of new prognostic markers is an attainable goal. Well-documented changes occur in mucin glycoconjugates during neoplastic progression in the colon, and the nonneoplastic colonic mucosa in colon cancer patients is morphologically and histochemically abnormal. In this retrospective study, 152 archival colorectal tissues from 49 patients were studied for changes in mucin secretions as detected by the galactose oxidase-Schiff's (GOS) sequence. Intensity of the stain was evaluated in histological sections by semiquantitative analysis, and the area percentage of epithelium stained was quantified by image cytometry. The correlation between gender or tumor size, location and reactivity with peanut agglutinin and quantitative expression of GOS-reactive mucins was determined as well as intratumor and inter individual variability. Reactivity with GOS: (a) decreased during neoplastic progression and malignant conversion in the neoplasm; (b) increased in the normal colonic mucosa of patients with progressively more advanced disease; and (c) was of prognostic significance for patient survival or recurrence both in the normal colon of cancer patients and in invasive neoplasms. These data are consistent with the conclusion that GOS reactivity in the normal colonic mucosa is a dosimeter of exposure to environmental/lifestyle colorectal carcinogens rather than a marker for an oncodevelopmental cancer-associated antigen.
 ...
PMID:Validation of the galactose oxidase-Schiff's reagent sequence for early detection and prognosis in human colorectal adenocarcinoma. 981 34

Defects in apoptosis signaling pathways are common in cancer cells. Such defects may play an important role in tumor initiation because apoptosis normally eliminates cells with damaged DNA or dysregulated cell cycle, i.e., cells with increased malignant potential. Moreover, impaired apoptosis may enhance tumor progression and promote metastasis by enabling tumor cells to survive the transit in the bloodstream and to grow in ectopic tissue sites lacking the otherwise required survival factors. Finally, raised apoptosis threshold may have deleterious consequences by rendering cancer cells resistant to various forms of therapy. The intensive apoptosis research during the past decade has resulted in the identification of several proteins which may promote tumorigenesis by inhibiting apoptosis. Of special relevance in human cancer are those commonly expressed in primary tumors and functioning at the common part of the signaling pathway leading to apoptosis. Proteins fulfilling these criteria include antiapoptotic members of the Bcl-2 protein family, heat shock proteins, Hsp70 and Hsp27, as well as survivin, the novel cancer-associated member of the inhibitor of apoptosis protein family. Understanding the molecular mechanisms of action of these proteins may offer novel modes of rationally and selectively manipulating the sensitivity of cancer cells to therapy.
 ...
PMID:Escaping cell death: survival proteins in cancer. 1009 11

The introduction of therapeutic genes into proliferating tumor cells in vivo by direct intralesional injection of retroviral vectors can provide an effective and valuable approach for the treatment of a variety of solid tumor types. Efficient transduction of tumor cells in situ by direct injection was demonstrated using a retroviral vector containing the beta-galactosidase (beta-gal) gene. Ablation therapy in vivo was demonstrated using a retroviral vector containing the Herpes simplex virus thymidine kinase gene (HSV-TK) to deliver the TK gene into the murine colorectal tumor cell line CT26. Ablation of CT26 tumor cells in situ was achieved by directly injecting high-titer HSV-TK retroviral vector preparations into the site of tumor cell inoculation followed by intraperitoneal (i.p.) delivery of ganciclovir (GCV). This gene therapy strategy demonstrated a markedly lower rate of tumor progression, with several complete regressions, compared to animals in control groups. We also demonstrated that resistance to subsequent challenges with unmodified CT26 cells and an enhanced cellular immune response is associated with tumor regression in immunocompetent animals. Our results demonstrate the feasibility of direct in situ administration of HSV-TK retroviral vectors for the treatment of cancer and suggest that a cellular immune response may be elicited by this therapy.
 ...
PMID:Ablation of tumor cells in vivo by direct injection of HSV-thymidine kinase retroviral vector and ganciclovir therapy. 1041 79

MUC1 mucin is a target protein for many monoclonal antibodies. Human MUC1 detected by a murine anti-KL-6 monoclonal antibody that recognizes a sialylated carbohydrate chain has been designated KL-6/MUC1. Given the heterogeneous antigenicity of KL-6/MUC1, we established a new murine monoclonal antibody, H9, that reacts with epitope DTRP (Asp-Thr-Arg-Pro) peptides within the immunodominant region of the tandem repeat of MUC1 mucin. The reactivity of the H9 antibody differs from that of other previously reported antibodies that recognize the tandem repeat region of MUC1. Immunohistochemical experiments indicate that the reactivity of the H9 antibody is similar to that of other antibodies directed against MUC1 core proteins. A new cancer-associated protein detected by a sandwich assay using the H9 antibody as a catcher and the KL-6 antibody as a tracer is designated HK9. Serum HK9 levels showed a high expression level in lung cancer: 51% (19/37 cases) for adenocarcinoma, 39% (11/28 cases) for squamous cell carcinoma, and 67% (10/15 cases) for small cell carcinoma. The HK9 expression in lung cancer increased with cancer progression. These findings suggest monoclonal antibody H9 to be a novel antibody that reacts with an epitope within the tandem repeat region of MUC1, and that the cancer-associated antigen HK9 may have useful tumor-associated properties.
 ...
PMID:A novel monoclonal antibody, H9, directed against the core protein of MUC1 mucin. 1067 62


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