Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A metastatic colony is the end result of a complex series of steps involving multiple gene products. In some cases, the augmented metastatic potential of certain tumour cells may be due to the increased expression of specific gene products which confer a selective advantage. Transfection of the c-Ha-ras oncogene into suitable recipient cells constitutes a powerful experimental model with which to identify putative gene products augmented in highly metastatic tumour cells compared to their non-metastatic counterparts. Transfection of the activated ras oncogene into 3T3 and 10T1/2 embryo fibroblasts, and adult rat fibroblasts, results in transformants which produce high numbers of spontaneous metastases in nude mice or syngeneic recipients. The ras oncogene will also increase the metastatic aggressiveness of murine tumours with low metastatic potential. However, the ras oncogene will not induce the metastatic phenotype in all recipient cells. Furthermore, specific genes such as adenovirus 2 E1A suppress the ability of ras to induce the metastatic phenotype. Natural 'suppressor' gene products may exist which render certain cells resistant to the induction of metastases by ras. Ras oncogene transfection induces the production of type IV collagenase, motility factors and growth factors. The ras oncogene therefore induces a cascade of gene functions leading to rapid progression to the metastatic phenotype. The mechanism of the induction probably involves complex interactions between the ras p21 product and multiple cellular gene products.
 ...
PMID:Oncogene induction of metastases. 307 39

Less than one in 1000 meningiomas metastasizes. Although the angioblastic and hemangiopericytic tumors are believed by some authors to metastasize with a greater frequency than the other histologic forms of meningioma, most investigators believe that neither the histologic pattern, local aggressiveness, size, nor location of the tumor can be used accurately to predict which tumors will metastasize. Three new cases are presented, bringing the total reported number of metastasizing meningiomas to 113. If the angioblastic meningiomas and hemangiopericytomas are eliminated from this group, 69 reported cases of "benign" metastasizing meningioma remain.
 ...
PMID:"Benign" metastasizing meningiomas. 310 55

Amplification of the c-erbB-2 proto-oncogene was detected in 10% of 122 primary human breast tumors examined. Examination of patients' histories with a post-surgical median follow-up time of 53 months suggested no statistically significant association between the increased copy number of c-erbB-2 proto-oncogene in breast tumors and several oncological disease parameters, such as histopathological grading, ovarian hormonal status, age, number of positive lymph nodes, time to relapse, and survival period. Results of the analysis of matched sets of primary tumors and lymph node metastases were also consistent with the lack of a strong association between increased copy number of c-erbB-2 proto-oncogene and aggressiveness of tumors.
 ...
PMID:Lack of evidence for the prognostic significance of c-erbB-2 amplification in human breast carcinoma. 322 22

In certain experimental tumor models, tumor growth is less pronounced in immune deficient animals. Characteristically, tumors such as the murine B16 melanoma and Lewis lung carcinoma (3LL) are weakly antigenic. We proposed that with such tumors that are weakly antigenic, growth is enhanced by T-cell factors. Young mice were inoculated with irradiated B16 cells in complete Freunds adjuvant (CFA) on three occasions, each separated by 2 weeks. Specific antibody (IgG) to B16 membrane antigens was detected by an enzyme-linked immunosorbent assay (ELISA) after the first injection, and it continued to rise for 6 weeks. B16 growth was compared in 20 mice that had received irradiated B16 in CFA or CFA alone by the same schedule previously. Despite the previous sensitization, the rates of tumor appearance and growth were similar. In an additional experiment involving 23 mice that had received B16 immunization, the period of time in which a palpable tumor developed after the injection of viable B16 cells did not correlate with anti-B16 antibody level. It appeared that detectable antibody to B16 antigens was of little consequence. To explain why B16 primary growth and metastases were reduced in immune deficient hosts, we proposed that lymphocytes might enhance tumor growth. To demonstrate this, splenic lymphocytes from tumor-bearing (B16 or 3LL) or control mice were injected with B16 cells into young, immune competent hosts. Tumors (B16) developed earlier and growth was more rapid in mice that received spleen cells from tumor-bearing (B16) mice. Subsequent cell depletion experiments to determine the mediator of tumor enhancement implicated a T-cell fraction that was neither of T-helper nor T-suppressor cell type phenotypically. Immune deficiency states that are associated with dysfunction of those cells that account for tumor enhancement might explain the reduced tumor aggressiveness that is observed frequently in these conditions.
 ...
PMID:Immunologic enhancement of B16 melanoma growth. 325 40

Twelve cases of squamous cell carcinoma arising in scars of the skin are analyzed. Correlation of tumor aggressiveness, tumor differentiation, intensity of small lymphocyte infiltration, and nature of adjacent collagen tissue to tumor stroma was investigated. All tumors were predominantly well differentiated. Nine patients had no metastasis or recurrence after surgical treatment of the primary tumor. Three patients developed widespread metastases and died less than 2 years after operation. The tumors of these latter patients contained areas of pleomorphic and spindle cells and had minimal infiltrates of small lymphocytes. In contrast, the 9 patients who remained free of tumor had moderate infiltrates of small lymphocytes, and in just 1 of 9 was an area of pleomorphic tumor cells found. Prognosis in scar carcinoma, therefore, may be related to tumor differentiation and the degree of host response with small lymphocytes to the tumor, rather than to the universally poor prognosis recorded in the past.
 ...
PMID:Squamous carcinoma in scars: clinicopathological correlations. 327 10

To determine if the amount of chondroitin sulfate proteoglycan (CSPG) in human colorectal tumor tissue correlates with the tumor's aggressiveness we immunochemically determined the CSPG levels in colorectal carcinomas at different stages. A total of 50 specimens--4 polyps, 15 stage B tumors, 9 stage C tumors, 12 stage D tumors, 7 liver metastases, and 3 lymph node metastases--were examined. Tumor tissues were extracted with 4 M guanidine hydrochloride containing protease inhibitors. The extracts were serially diluted and blotted onto nitrocellulose membranes. Reactivity of a chondroitin sulfate-specific mouse monoclonal antibody (CS-56) was determined by biotinylated goat antimouse Ig and avidin-biotin-peroxidase complex. After comparing tissues from tumors at different stages (classified by the presence or absence of metastasis), we could not find a positive or negative correlation between the amount of CSPG in primary colorectal carcinoma tissues and the tumor's metastatic potential. However, the metastatic foci in the liver or lymph node contained higher amounts of CSPG than the primary tumors did. Immunohistochemical staining of colon carcinoma tissue with CS-56 revealed that CSPG is predominantly localized in fibrotic portions in the tumor tissues. Two-year follow-up studies indicated that a high level of CSPG in primary tumors was not predictive of recurrence.
 ...
PMID:Increased content of chondroitin sulfate proteoglycan in human colorectal carcinoma metastases compared with the primary tumor as determined by an anti-chondroitin-sulfate monoclonal antibody. 328 48

Grading methodology for soft-tissue tumors is not yet unequivocally established. The authors use a system that is an elaboration upon that of the National Cancer Institute: grade 1 or low-grade lesions are malignant lesions with minimal risk of metastases with a tendency for local recurrence if not totally excised, and with a capability for progression to a higher grade with recurrence; grades 2 and 3 are high-grade lesions with a significant risk of metastases; grade 2 are lesions with intermediate aggressiveness, and grade 3 are highly malignant lesions with dissemination early in the course of the disease. Whereas the great majority of grade 3 lesions recur within 24 months of the initial diagnosis, patients with grade 2 lesions may go recurrence-free beyond 36 months. Although more experience is needed in grading soft-tissue sarcomas, it is hoped that grading will continue to contribute to the management of patients with malignant tumors of the soft tissue. It represents an adjunct to histological typing, which is useful in conveying the degree of biological aggressiveness as judged by histological features. Histologically 80% of the lesions can be classified on the basis of hematoxylin and eosin-stained sections and other conventional special stains. In some instances electron microscopy and immunohistochemistry are necessary for histotyping. The most challenging area for histopathological differential diagnosis remains the distinction of tumor-like reactive conditions, and pleomorphic benign tumors from sarcomas.
 ...
PMID:Histological diagnosis and grading of soft-tissue sarcomas. 335 21

Long-term survival rates were correlated with selected clinical features in 479 patients with embryonal carcinoma of the testis and 33 patients with endodermal sinus tumor (infantile embryonal carcinoma, yolk sac tumor). In the period 1977 to 1982 embryonal carcinoma accounted for 26.8% of newly diagnosed germ cell tumors and 43% of nonseminomatous germ cell tumors entered in the Centralized Cancer Patient Data System. Among patients with embryonal carcinoma, over 80% were diagnosed in the 15-to-34 year age group. Seventy-four percent of the patients had metastatic disease at the time of diagnosis, and 50% of these had distant metastases, attesting to the aggressiveness of embryonal carcinoma and its tendency to early hematogenous spread. Despite the highly malignant nature of the tumor, the overall 5-year survival rate with treatments used was an excellent, 88%. Survival was correlated with the extent of disease at the time of diagnosis; the 5-year actuarial survival rates for patients with localized, regional, and distant disease were 98%, 96%, and 74%, respectively. Endodermal sinus tumor was uncommon (1.8% of all testicular germ cell tumors), occurred predominantly in the younger age group (0-24 years), and in 50% of the cases was localized to the testis. The survival rate for the 33 patients with this form of tumor was slightly worse than for the "adult form" of embryonal carcinoma. The authors conclude that survival of patients with embryonal carcinoma has greatly improved over the last decade as a result of improved methods for early detection of metastatic deposits and the effectiveness of newer chemotherapies in the treatment of disseminated disease.
 ...
PMID:Embryonal carcinoma of the testis. 336 62

Many of these observations appear to define a reasonable hypothesis. High-grade or poorly differentiated malignant neoplasms have a shorter tumor-doubling time, are less cohesive, often with irregular borders, and tend to invade by small aggregates and individual tumor cells. The observation of the pattern of invasion provides considerable information on the aggressiveness of the neoplasm. The pattern of invasion appears to correlate with tumor cell cohesiveness, motility, loss of contact inhibition, excretion of enzymes, and other factors associated with aggressiveness in experimental models. It is clear that the pattern of tumor-host interaction indirectly reflects many of these parameters and provides major clues to the biologic potential of human carcinomas. These observations should be used to supplement the histologic and cytologic features commonly used to derive a tumor grade. Aggressive tumors are usually larger and are associated with a greater blood supply. Vascular invasion is more common in this situation and large veins may be invaded by tumor by intravascular growth. Penetration of small lymphatic and blood vessels is associated with a poor prognosis and involvement of large veins with intravascular extensions of tumor have the potential of releasing tumor cell aggregates or emboli into the venous circulation. These large tumor cell aggregates have been demonstrated to be associated with a higher efficiency of metastasis formation and infer a poorer prognosis. Why have I bothered with all this detail about the occurrence of circulating tumor cells and their relation to the development of metastases? It must be stressed that many malignant cells are being released into the circulation of cancer patients and few, if any, ever successfully complete the complex sequence leading to a metastatic focus. This has been termed "metastatic inefficiency." Other investigators have referred to the unique cells that have mastered the intricate sequence of steps required to establish metastases as winners of the metastases decathlon. The observations of vascular (lymphatic or blood) invasion in random tissue sections and their relation to patient prognosis can be best explained by our basic knowledge of cancer biology. The finding of occasional small aggregates of single tumor cells in vascular spaces statistically implies that a considerable number of cells must be entering the vascular compartment.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Tumor-host interactions as prognostic factors in the histologic assessment of carcinomas. 351 Apr 16

The natural history of human cancers can be stimulated assuming an exponential growth pattern. This simple model shows that the duration of the tumor growth during the occult phase is always much shorter than the interval between the carcinogenic stimulus and the clinical emergence of the tumor; this is consistent with the existence of several stages of precancerous lesions which precede the development of the neoplastic clone. Metastatic spread can be simulated and a model of tumor growth can be used to predict the proportion of patients in whom metastatic dissemination can be avoided by an earlier diagnosis. The model predicts also that in the subsets of patients in whom metastatic spread occurs early the occult metastases will be large at the time of the treatment of the primary tumor and therefore adjuvant chemotherapy (CT) will be less effective; this is in keeping with clinical data. The model can also help to understand the relationship between the local control of a tumor and the cure of the patient, and to explain the discrepancy between the great reduction in the local incidence of local recurrence obtained with post-operative radiotherapy and its relatively small impact on survival. However, this simple model is insufficient to explain several features of the course of a human cancer, in particular the heterogeneity of the neoplastic cell population and the inexorable tendency for some cancers to progress towards a more malignant type and to become progressively more resistant to any treatment. Genetic instability appears to be an essential characteristic of human cancers and variations in its degree may be the cause of differences in the aggressiveness and in the severity of the various types of cancers. The recent advances in the molecular biology of cancers has already given to clinicians new and powerful prognostic indicators. These will probably, in the near future help, towards a better understanding of the biology of tumor growth and tumor progression.
 ...
PMID:Klaas Breur Medal lecture 1985. The growth and progression of human tumors: implications for management strategy. 352 54


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