Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human prostate carcinogenesis has been viewed as a multi-step process involving progression from low histologic grade, small, latent carcinoma to large, higher grade, metastasizing carcinoma. However, recent data suggest that a variety of pathogenetic pathways may exist. The precise etiology and pathogenesis of human prostate cancer remain largely undefined. It is difficult to investigate stages in the development of human prostate cancer, but some animal models provide opportunities in this regard. Short-term treatment of rats with chemical carcinogens produces a low incidence (5-15%) of prostate cancer, provided that prostatic cell proliferation is enhanced during carcinogen exposure. Chronic treatment with testosterone also produces a low prostate carcinoma incidence. A high carcinoma incidence can only be produced by chronic treatment with testosterone following administration of carcinogens such as N-methyl-N-nitrosourea (MNU) and 3,2'-dimethyl-4-aminobiphenyl (DMAB). Testosterone markedly enhances prostate carcinogenesis even at doses that do not measurably increase circulating testosterone. Thus, testosterone is a strong tumor promoter for the rat prostate. All such MNU- or DMAB-initiated and/or testosterone-promoted tumors are adenocarcinomas; most originate from the dorsolateral and anterior, but not ventral, prostate lobes. These tumors share a number of important characteristics with human prostate cancer. A high frequency (70%) of activation of the K-ras gene by a G35 to A mutation occurs in these carcinomas. Another high incidence prostate carcinogenesis model, representing a different pathogenetic pathway, involves chronic administration of estradiol-17 beta to rats in combination with low-dose testosterone. The resulting carcinomas are low-grade and originate exclusively from periurethral ducts of the dorsolateral and anterior prostate. While it is unknown whether testosterone is a tumor promoter in this system, preliminary studies indicate the formation of a DNA adduct in the target tissue, which suggests that estradiol-17 beta acts as a tumor initiating agent in this system. The high incidence models mentioned earlier are adequate for the study of chemoprevention of prostatic carcinogenesis. Analysis of shifts in the relative incidence of metastasizing carcinoma, grossly apparent but not-metastasizing carcinoma, microscopic-size carcinoma, and carcinoma in situ or atypical hyperplasia may allow study of the modifying effects of potential chemopreventive agents on tumor progression in these animal models of prostatic carcinogenesis.
 ...
PMID:Animal models for the study of prostate carcinogenesis. 128 79

We examined 92 patients with epithelial ovarian cancer and 262 patients with benign ovarian diseases undergoing laparotomy. On the basis of a nonparametric method, antigen levels corresponding to prefixed 95% specificity values in a group of 674 women with benign gynecologic diseases were taken as cutoff limits (88.8 U/ml for CA 125 and 13.7 U/ml for CAM 29). Moreover, CA 125 and CAM 29 levels were measured serially during and after chemotherapy in 26 women selected from the patients with advanced epithelial ovarian cancer. At diagnosis, serum CA 125 was as sensitive as serum CAM 29 for nonmucinous tumors, but more sensitive than serum CAM 29 for mucinous tumors. The association of the two markers seemed to give no advantage over the CA 125 assay alone in the diagnosis of epithelial ovarian cancer. In monitoring the response to chemotherapy and follow-up of patients with epithelial ovarian cancer, changes in CA 125 levels correlated with the clinical course of disease better than changes in CAM 29 levels, and the serum CA 125 assay was more reliable than the serum CAM 29 assay in the early detection of tumor progression. In conclusion, serum CAM 29 did not seem to represent a complementary assay to serum CA 125 in the management of patients with epithelial ovarian cancer.
Tumour Biol 1992
PMID:Combined evaluation of serum CA 125 and CAM 29 in patients with epithelial ovarian cancer. 129 26

In tumor progression, populations of cancer cells with different patterns of growth and invasion arise within the same tissue and within individual neoplasms. We tested the hypothesis that, even in histologically undifferentiated carcinomas, such diversity may be influenced by differentiation-dependent adhesive mechanisms. We used as prototypes two cell lines that originated in the same clone of a poorly differentiated cervical carcinoma, but express strikingly different phenotypes. Cells of line C-4I express select characteristics of the spinous stage of stratified squamous epithelial differentiation while cells of line C-4II resemble basal cells. C-4I cells form rapidly expanding compact tumors in vivo and multilayered cohesive colonies in culture, while C-4II cells form slow-growing infiltrating tumors in vivo and dispersed, monolayered colonies in culture. In suspension culture which prevented any cell-substratum interactions, C-4I cells formed aggregates that were significantly larger and more compact than those formed by C-4II. Thus, greater intercellular adhesion between the 'spinous' C-4I cells contributed significantly to the phenotypic divergence of the lines. Upon disruption of intercellular adhesion with the glutamine analogue 6-diazo-4-oxo-norleucine (DON), C-4I cultures on plastic and in suspension assumed forms resembling C-4II. On plastic, single 'basal' C-4II cells adhered more rapidly and migrated more slowly than C-4I cells, in keeping with the capacity of C-4II, but not C-4I, to secrete fibronectin (FN) substrata. However, on exogenous FN matrices, migration and cell dispersion were accelerated in both lines. Both lines expressed similar integrin profiles. Thus, the lines had diverged in extracellular matrix production, but not in the receptors for extracellular matrix components. The properties of the C-4 lines mimic those of specific cell types in normal stratified squamous epithelia, where intercellular adhesion increases but FN secretion diminishes with progression from the basal to the spinous stage of differentiation. Our results demonstrate a direct influence of differentiation-associated adhesive mechanisms on growth patterns and suggest that similar mechanisms may be responsible for variations in invasiveness among neoplastic clonal subpopulations. An awareness of these correlations may help to interpret the modes of local invasion by poorly differentiated carcinomas in terms of specific, well-defined cell properties.
Tumour Biol 1992
PMID:Divergence in patterns of invasion among subpopulations derived from a human carcinoma clone: roles of intercellular contacts and of cell-substratum adhesion. 129 33

The successful growth of metastatic tumor cells is due to their responses to local paracrine growth factors and inhibitors and their production and responses to autocrine growth factors. At early stages of metastatic progression, there is a tendency for many common malignancies to metastasize and grow preferentially at particular sites, suggesting that paracrine growth mechanisms may dominate the growth signals affecting metastatic cells. At later stages of metastatic progression, where widespread dissemination to various tissues and organs occurs, autocrine growth mechanisms may dominate the growth signals affecting metastatic cells. The progression of malignant cells to completely autonomous (acrine) states can ultimately occur, and at this stage of metastatic progression cell growth can be completely independent of growth factors or inhibitors. Various strategies have been developed to treat cancer that are based on the responses of malignant cells to growth factor or inhibitor analogs, anti-receptor antibodies, or antibody- or growth factor-toxin conjugates. Since the responses and expression of growth factor receptors can change during malignant progression, the development of cancer treatments using analogs of specific growth inhibitors or antagonists of growth factors, such as monoclonal antibodies or other agents, to block growth signaling mechanisms may only be useful at the early stages of malignant cancer progression before widespread metastasis of acrine cells occurs.
 ...
PMID:Paracrine/autocrine growth mechanisms in tumor metastasis. 129 54

The results of a double blind prospective study comparing the chemoprophylactic effects of adriamycin and mitomycin C and two modes of instillation (early: 6 hours following transurethral resection; late: 7-14 days later) for superficial carcinoma of the bladder are presented herein. Since the minimum follow up is over 5 years, the effects on tumor progression and mortality achieved by each of the 4 arms of the protocol were also evaluated. Concerning tumor recurrence, early instillation of mitomycin and overall early instillation therapy achieved significantly better results (p < 0.01). No differences, however, were observed relative to tumor progression or mortality.
 ...
PMID:[Results of a randomized, double blind prospective study of intravesical chemoprophylaxis with 2 drugs: adriamycin and mitomycin; and 2 ways of initiating the instillations: early and late. Effect on recurrence and progression]. 129 28

MHC class I antigens participate in the immune response by presenting peptides to CD8+ cytotoxic T cells. Decreased expression of these antigens in tumor cells may contribute to an evasion of immune system and consequently to enhanced tumor growth. However, not all tumors expressing low levels of HLA antigens show increased malignancy, probably as a result of the differential activity of the oncogenes involved in malignant transformation. The ras family of cellular oncogenes is one of the most frequently detected families of transformation-inducing genes in human solid tumors. The aim of this work is to study the expression of MHC antigens and the ras oncogene product, p21ras, in 60 primary breast tumors in order to define its clinical significance in tumor progression. HLA antigen expression and p21ras levels were measured on breast tumors using immunohistochemistry methods and enzymoimmunoassay, respectively. The results demonstrate that more invasive tumors have both a decreased expression of HLA class I antigens and higher levels of p21ras protein expression than less aggressive tumors. These findings indicate that the capacity of breast cancers to grow and metastasize is related to low levels of MHC class I antigens and enhanced p21ras expression, thus supporting the involvement of MHC and ras oncogenes in breast tumor malignancy.
 ...
PMID:MHC class I antigen expression is inversely related with tumor malignancy and ras oncogene product (p21ras) levels in human breast tumors. 129 32

Nuclear DNA content was measured in 72 colorectal carcinomas using single-cell microspectrophotometry on Feulgen-stained smears. Four samples were analyzed from each tumor. Patients were followed for 41-65 months (average, 53). DNA heterogeneity (both aneuploid and nonaneuploid patterns) was present in 44% of the cases. Sixty-eight percent of the tumors showed an aneuploid DNA pattern in at least one of the samples. Patients with nonaneuploid tumors tended to have a survival advantage over patients with homogeneously aneuploid tumors and demonstrated a significantly longer disease-free survival. The DNA ploidy pattern is of potential value in conjunction with histopathologic prognostic parameters in colorectal carcinoma. Since colorectal tumors exhibit pronounced DNA heterogeneity, multiple samples are required from each tumor to permit a proper evaluation of its DNA pattern. The DNA heterogeneity may represent tumor progression and can partly explain the conflicting results reported concerning DNA pattern and prognosis in colorectal carcinoma.
 ...
PMID:Colorectal carcinoma. DNA ploidy pattern and prognosis with reference to tumor DNA heterogeneity. 129 27

Mitotic regimen of tumor was studied in 75 male and 50 female patients with breast cancer. Mitotic index (9.7 and 14.3%, respectively) and number of pathologic mitoses (28 and 25%) did not differ significantly between the two groups. However, retardation of chromosome movement in meta-, ana- and telophase was 3 times more frequent in males. This suggests that breast carcinoma in males tends to become more aneuploid than in females. The latter reflects the rate of tumor progression. Clinically, breast cancer in males is characterized by rapid growth, early dissemination and resistance to treatment.
 ...
PMID:[The mitotic regimen of breast cancer in men]. 130 Jul 69

The level of relative accumulation of a 32P radionuclide was measured in 180 tumor samples obtained from 148 patients with stage I--IV breast cancer. Mean initial relative accumulation level (IRAL) was 1477 +/- 174% whereas that following effective conservative treatment (posttreatment) (PRAL)--486 +/- 81% (P < 0.01). The prognostic value of IRAL was established: in a group of stage III breast cancer, those with a high IRAL survived 2 years with no evidence of disease in 55.1 +/- 12.1% whereas those with a low IRAL--in 94.1 +/- 5.7% (P < 0.02). In patients undergoing conservative treatment, low PRAL proved predictive of complete response while high PRAL--of tumor progression. In patients with stage III breast cancer who had responded to preoperative treatment and had had a low PRAL, two-year locoregional recurrence rate was only 13% as compared to 68% in a similar group of patients with high PRAL (P < 0.02).
 ...
PMID:[The practical use of the determination of relative 32P accumulation in the tumor in breast cancer]. 130 Aug 11

The term cancer chemoprevention refers to the prevention or prolongation of carcinogenesis by intervention with drugs prior to the malignant (i.e., invasive) stage. The development of chemopreventive drugs is the major objective of the Chemoprevention Branch of the National Cancer Institute. Neoplastic lesions of the urinary bladder present a unique opportunity for evaluating chemopreventive agents because of (1) the accessibility of the lesions to observation and biopsy, and (2) those patients who have been successfully treated for a primary lesion represent a population at unusually high risk for recurrence and/or progression. Although 70-80% of bladder cancers initially present as superficial, papillary transitional cell neoplasms with limited potential for invasion, the incidence of recurrence is high after resection (60-75%). Recurrent tumors are highly unpredictable, and may be of higher grade or stage (progression). Although recurrence is responsible for high treatment-related morbidity, progression represents the greatest potential for mortality. Thus, potential chemopreventive agents considered here would modulate bladder carcinogenesis from initiation of normal-appearing tissue through progression of superficial tumors. Clinical trials of chemopreventive drugs involve healthy target populations, and the endpoints are reduced cancer incidence or mortality, reduced/eliminated precancerous lesions or increased latency, with none to minimal toxicity. Since cancers may not appear for 20-30 years, two of the most difficult aspects of testing these drugs in intervention trials are the long observation periods and large study populations required to measure cancer incidence reduction. However, observing the regression or recurrence of superficial bladder lesions (TIS, T1, Ta) requires relatively short time periods. Thus, these lesions lend themselves to the investigation of intermediate biomarkers, defined as morphologic and/or molecular alterations in tissue between initiation and tumor invasion. It is hypothesized that modulation of one or more biomarkers would interrupt carcinogenesis and result in a decrease in cancer incidence. Thus, evaluation of biomarkers as surrogate endpoints would allow bladder trials to be of even shorter duration, use fewer subjects and be lower in cost. In addition, intermediate biomarkers could predict which superficial lesions (or normal-appearing tissue) have the greatest potential for neoplastic progression. Development of strategies for the design of intervention trials for bladder cancer and review of the current status of intermediate biomarkers in the bladder, and methods for their validation, are major objectives of this workshop.
 ...
PMID:Development of chemopreventive agents for bladder cancer. 130 71


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