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

E-cadherin is a Ca(2+)-dependent cell adhesion molecule which plays an important role in normal growth and development via mediation of homotypic, homophilic cell-cell interaction. Recent studies suggest that E-cadherin may be important in neoplastic progression as well, particularly as a suppressor of invasion. We have previously demonstrated that the invasive phenotype of rat prostate cancer cells is associated with the decreased expression of E-cadherin (M. J. G. Bussemakers, R. J. A. Van Moorselaar, L. A. Giroldi, T. Ichikawa, J. T. Isaacs, F. M. J. Debruyne, and J. A. Schalken, Cancer Res., 52:2916-2922, 1992). This is of particular interest, since the locus to which the human E-cadherin gene is mapped is frequently involved in allelic loss in prostate cancer (B. S. Carter, C. M. Ewing, W. S. Ward, B. F. Treiger, T. W. Aalders, J. A. Schalken, J. I. Epstein, and W. B. Isaacs, Proc. Natl. Acad. Sci. USA, 87:8751-8755, 1990; U. S. Bergerheim, K. Kunimi, V. P. Collins, and P. Ekman, Genes, Chromosomes Cancer, 3: 215-220, 1991). Impaired E-cadherin function is likely to be associated with aberrant expression of the protein. We therefore analyzed E-cadherin expression in situ by immunohistochemistry in nonmalignant and malignant specimens of human prostatic tissue. Of 92 tumor samples of either primary or metastatic deposits of prostate cancer, 46 had reduced or absent E-cadherin staining when compared to nomalignant prostate, which uniformly stained strongly positive. There was a statistically significant correlation between the decreased expression of E-cadherin and loss of tumor differentiation. Additionally, certain tumors within a histologically similar group could be distinguished by the presence of mixed populations of E-cadherin-negative and -positive cells. The percentage of tumors with aberrant E-cadherin staining increased when clinically localized tumors were compared to either tumors with extensive local progression or metastatic deposits of prostate cancer, suggesting a correlation between loss of E-cadherin and tumor progression. Taken together, these findings suggest that further exploration of E-cadherin as a candidate invasion suppressor molecule in human prostate cancer is warranted.
Cancer Res 1992 Sep 15
PMID:Expression of the cellular adhesion molecule E-cadherin is reduced or absent in high-grade prostate cancer. 151 67

One hundred fifteen gastroenteropancreatic (GEP) patients with malignant endocrine tumors entered a prospective multicenter trial (12 patients with gastrinoma, 53 with carcinoid syndrome, 45 with nonfunctioning tumors, and five with other endocrine GEP tumors) to determine the efficacy of 200 micrograms Sandostatin three times a day in the control of tumor growth. This interim report describes the results in 85 patients. Thirty-four patients died, 14 before and 20 after the first follow-up investigation, indicating a "negative" selection of patients included in the trial and suggesting that Sandostatin cannot prevent disease progress when it is far advanced. In the evaluation of 68 patients monitored for at least 3 months, partial regression was observed in 4.4%, stable disease in 50%, and tumor progression in 45%. However, an initially favorable response frequently occurred with a decrease in response later: 54.4% at 3 months to 38% at 12 months for the whole group of patients. Proven inhibition of tumor growth was mirrored by suppression of serum and urine hormone parameters. It is concluded that Sandostatin exerts a beneficial effect on tumor growth in patients with metastatic endocrine GEP tumors. This beneficial effect decreases with time and is as yet unpredictable in the individual patient.
Metabolism 1992 Sep
PMID:Gastroenteropancreatic endocrine tumors: effect of Sandostatin on tumor growth. The German Sandostatin Study Group. 151 29

Loss of cell cycle control and acquisition of chromosomal rearrangements such as gene amplification often occur during tumor progression, suggesting that they may be correlated. We show here that the wild-type p53 allele is lost when fibroblasts from patients with the Li-Fraumeni syndrome (LFS) are passaged in vitro. Normal and LFS cells containing wild-type p53 arrested in G1 when challenged with the uridine biosynthesis inhibitor PALA and did not undergo PALA-selected gene amplification. The converse occurred in cells lacking wild-type p53 expression. Expression of wild-type p53 in transformants of immortal and tumor cells containing mutant p53 alleles restored G1 control and reduced the frequency of gene amplification to undetectable levels. These studies reveal that p53 contributes to a metabolically regulated G1 check-point, and they provide a model for understanding how abnormal cell cycle progression leads to the genetic rearrangements involved in tumor progression.
Cell 1992 Sep 18
PMID:Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles. 152 30

Substantial experimental evidence accumulated over the past 8 years has indicated an etiological role for specific human papillomavirus (HPV) types in anogenital cancer and its premalignant precursors. Virus infection and viral gene expression emerge as necessary but obviously not sufficient factors for cancer induction. Additional modifications of host cell genes appear to be required for malignant progression of infected cells. The expression of viral oncoproteins in cells infected by "high-risk" types (e.g., HPV 16, HPV 18), in contrast to "low-risk" types (e.g., HPV 6, HPV 11), results in chromosomal instability and apparently in accumulation of mutational events. These "endogenous" modifications seem to be most important in the pathogenesis of premalignant lesions and tumor progression. Exogenous mutagens should act as additional cofactors.
Virology 1991 Sep
PMID:Human papillomaviruses in the pathogenesis of anogenital cancer. 165 7

The Moolgavkar-Venzon-Knudson (M-V-K) two-stage model for carcinogenesis was used to estimate the risk-specific dose (RsD) based on the incidence of tumors reported by Kociba et al. (1978) for Sprague-Dawley rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD; dioxin). The results from the recently completed (1990) reevaluation of the Kociba et al. study, which used the current National Toxicology Program (NTP) pathology criteria, were also evaluated. Time-to-tumor information for each rat was incorporated into the analysis. Model parameters for the approximate form of the hazard function of the two-stage M-V-K model were determined by maximum likelihood estimation. This simplification was significant but necessary, because laboratory data on the intermediate cell growth rate and the transition rates have not been determined. Estimates of the RsD (10(-6) risk) (based on the original 1978 histopathology results) were 10 fg/kg/d when carcinomas and hyperplastic nodules were combined and 150 fg/kg/d when only carcinomas were considered. In contrast, using the 1990 histopathology data, the RsD (10(-6) risk) was 80 fg/kg/d when adenomas and carcinomas were combined and 25,000 fg/kg/d when only hepatocellular carcinomas were considered. Since the two-stage M-V-K model is intended to predict the occurrence of malignant tumors, the mathematically appropriate RsD is 25,000 fg/kg/d (10(-6) risk). Because the model does not account for pharmacokinetics or the possibility of other toxic effects, the appropriate RsD (10(-6) risk) for humans should be much smaller. Using the carcinoma data only, a sensitivity analysis of key parameters in the model was conducted. Results indicated that the ranges of plausible values for the RsD (10(-6) risk) for the original 1978 and the 1990 reevaluation data were 70-2600 fg/kg/d and 120-50,000 fg/kg/d, respectively. The lowest plausible RsD is, therefore, approximately 10-fold greater than the current U.S. EPA RsD (10(-6) risk) of 6.4 fg/kg/d [which is based on the linearized multistage (LMS) model]. Even though these results must be considered preliminary until some of the values for the model parameters are experimentally determined and a complete physiologically based or receptor-based model is developed, this analysis shows that nearly any plausible laboratory data on tumor progression will yield a much higher RsD than currently embraced by the U.S. EPA.
J Toxicol Environ Health 1991 Sep
PMID:Risk assessment of 2,3,7,8-TCDD using a biologically based cancer model: a reevaluation of the Kociba et al. bioassay using 1978 and 1990 histopathology criteria. 165 56

We have shown in previous studies that metastatically-competent variant subpopulations (B5, C1) derived from a non-metastatic murine mammary adenocarcinoma (SP1) have a pronounced growth advantage over their non-metastatic tumor cell counterparts in primary tumors. As a result, primary tumors can be progressively overgrown by cells having the competence to spread elsewhere in the body. This occurs despite any evidence to indicate an intrinsic in vivo growth rate advantage of the metastatic cells when grown as isolated populations. This suggested that cell-cell interactions between metastatic and non-metastatic tumor populations may be involved in the metastatic cell growth dominance process. Evidence was therefore sought for growth factors released by SP1 cells which could preferentially stimulate the B5 or C1 variants and thereby mediate this cell-cell interaction process. We found that cocultures of SP1 and C1 or B5 cells with irradiated C1, B5, or SP1 "feeder" cells showed significant stimulation of C1 and B5 by SP1 "feeder" cells. Cell growth stimulation in response to EGF, TGF-alpha, TGF-beta 1, bFGF, PDGF, NGF, IGF-1, or IGF-2 demonstrated that only TGF-beta 1 could duplicate this effect. A repeat of the coculture experiment in the presence of specific neutralizing anti-TGF-beta antibodies was therefore undertaken and this was found to markedly reduce the stimulation of C1 or B5 cells by irradiated SP1 cells. Conditioned media from the SP1 and C1 cell lines was quantitated for TGF-beta activity and contained 4.5 ng/ml and 2.0 ng/ml, respectively. However, the majority of the TGF-beta released by SP1 cells was found to be spontaneously active, whereas 70% of the TGF-beta released by C1 cells was in its latent form. Scatchard analysis revealed approximately four times the number of TGF-beta receptors, of similar type and affinity, present on C1 as compared with SP1 cells. The in vitro results support the hypothesis that active TGF-beta released by SP1 cells may stimulate the proliferation of metastatic variant cells in a paracrine like fashion. In vivo evidence for this was obtained by showing that coinjection of irradiated SP1 cells could selectively stimulate tumor growth of viable C1 cells and this effect was markedly diminished by neutralizing polyclonal anti-TGF-beta antibodies. Taken together, the results suggest a novel role for TGF-beta in clonal evolution of malignant tumor growth and as a molecular mediator of tumor cell-tumor cell interactions involved in facilitating tumor progression.
J Cell Physiol 1991 Sep
PMID:Reduction of TGF-beta activity abrogates growth promoting tumor cell-cell interactions in vivo. 165 15

Advanced steps of tumor progression are generally characterized by an increased growth fraction within the neoplastic cell population. The presence of a relevant growth fraction is also related to widely accepted prognostic parameters in some human malignancies. Our aims were to evaluate the presence of a growth fraction with Ki67 monoclonal antibody (MoAb), and to correlate it with tumor progression and HLA-DR antigen expression in 88 melanocytic lesions. The lesions were 19 acquired melanocytic nevi, 58 primary melanomas [divided into 26 superficial spreading melanomas (SSM), 24 superficial spreading melanomas with nodular areas (SS + NM), and five nodular melanomas (NM)], and 11 metastases from malignant melanomas. Ki67 MoAb stained 16%, 19%, 71%, 100%, and 82% of nevi, SSM, SS + NM, NM, and metastases, respectively. Among primary melanomas, Ki67 MoAb stained 12%, 28%, 50%, and 70% of tumors less than 0.75, 0.75-1.49, 1.5-2.9, and greater than or equal to 3 mm thick, respectively. A concordant reactivity pattern for Ki67 and HLA-DR antigens was found in 72% of lesions (p less than 0.0001). We have shown that a representative growth fraction (ie, Ki67 reactivity) is present in melanocytic lesions only in advanced steps of tumor progression and correlates with HLA-DR antigen expression. Despite the different biologic values of Ki67 and HLA-DR antigens, we suggest the joint evaluation of both antigens as a useful marker of aggressive behavior in melanoma.
J Invest Dermatol 1990 Sep
PMID:Ki67 antigen expression correlates with tumor progression and HLA-DR antigen expression in melanocytic lesions. 169 3

In the treatment of vulvar malignancy surgery, chemotherapy, irradiation therapy and so on can be used. Actually, it was rarely performed only by a single method. For treatment by the stage of cancer progression, the superficial cancer was treated by wide local resection for the patients except old women who were done simple vulvectomy. For the invasive cancer, stage 1 or 2, the pre-operative bleomycin (BLM) was administered to reduce the tumor mass, thereafter, radical vulvectomy with inguinal lymph node resection was performed. If inguinal lymph nodes metastasis was found, area of resection was extended to pelvic lymph nodes. Recently, micro-invasive carcinoma was defined that the foci was below 2 cm and interstitial invasion below 1 mm. In this condition, it was needless to remove the lymph nodes. For the stage of 3 or 4 which was inoperable, chemotherapy (mainly BLM) combined with irradiation therapy was done. In the cases of good general condition, it was chosen by super-radical vulvectomy.
Gan To Kagaku Ryoho 1990 Sep
PMID:[Management of vulvar cancer]. 169 52

We present six patients with intracranial nongerminomatous germ cell tumors that produced alpha-fetoprotein (AFP). Their ages ranged from 8 to 20 years (average, 11.5 years old); two were male and four were female. Four of the tumors originated in the pineal region and two in the suprachiasmatic region. One patient treated with only radiation therapy died within 3 months of admission as a result of intraperitoneal metastasis via a ventriculoperitoneal shunt. Another patient, treated with radiation therapy and intrathecal administration of neocarzinostatin, died after 12 months because of tumor progression and subarachnoid dissemination. Two patients who received radiation and combination therapy with cisplatin, vinblastine, and bleomycin died after 13 and 25 months. The remaining two patients treated with radiation therapy and adjuvant chemotherapy (cisplatin and etoposide) are now alive without recurrence after 16 and 19 months from admission. Adjuvant chemotherapy with cisplatin and etoposide appears to be efficacious in the treatment of intracranial nongerminomatous germ cell tumor.
Neurosurgery 1990 Sep
PMID:Clinical study of intracranial nongerminomatous germ cell tumors producing alpha-fetoprotein. 170 Mar 27

The concept of a combination of radiotherapy and hormonal therapy for the treatment of locally advanced carcinoma of the prostate was evaluated in view of an improved success rate compared to radiotherapy alone. At present, however, radiotherapy still remains the central mode of therapy in the treatment of the local tumor. The time sequence in a combination with hormonal therapy is of importance. Antecedent hormonal treatment can reduce tumor size, thus improving local conditions for percutaneous--and especially interstitial--radiotherapy; it is indicated in patients with voiding problems. An improvement in survival rates has so far not been achieved, however, local tumor remission rates are better. With concomitant hormonal therapy, compared to radiotherapy alone, tumor progression rates are lower. It remains to be seen, whether these results can be improved by using newer pharmacological ways of androgen blockade. The application of androgen withdrawal as a secondary measure with local tumor persistence or progression after radiotherapy remains a palliative treatment of limited efficacy. Due to the heterogeneity of the available study reports and the concurrent lack of controlled, randomized trials, a conclusive evaluation of the concept of combined radio- and hormonal therapy of prostatic cancer is as yet not possible.
Strahlenther Onkol 1991 Sep
PMID:[The combined radiation and hormonal therapy of prostatic carcinoma: a conceptual analysis]. 171 45


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