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)

To better understand the mechanisms of esophageal carcinogenesis, abnormalities in DNA content of esophageal squamous cell carcinomas were studied. Cellular DNA content was determined by flow cytometric study of 70 endoscopic biopsy specimens obtained from 26 patients with esophageal squamous carcinoma. High-quality histograms were obtained for 23 patients. Twenty-one patients had at least one aneuploid population in their tumor. In 7 patients, multiple aneuploid peaks were detected. Specimens from 2 patients were diploid. The interpretation of the DNA histograms was difficult in 3 patients; an aneuploid population of cells was probable in 2 of them. A statistically significant relationship was found between the degree of differentiation and DNA content abnormalities in the regions of the tumors that could be evaluated by endoscopic biopsies: well-differentiated carcinomas had diploid or small aneuploid populations containing less than 15% of the cells, whereas DNA histograms of moderately or poorly differentiated carcinomas were characterized by large aneuploid peaks representing 25%-90% of the cells and a higher proliferative fraction. No relationship was found between the size or the stage of the tumor and the DNA content detected in endoscopic biopsy samples. The frequency and the multiplicity of abnormal clones in esophageal squamous carcinomas indicates that this cancer, like esophageal adenocarcinoma, develops an association with an acquired genomic instability that produces abnormal clones of cells, according to the multistep model of neoplastic progression.
 ...
PMID:Flow-cytometric DNA content analysis of esophageal squamous cell carcinomas. 195 24

Seventy-four patients from January 1975 through December 1982, with clinical Stage III Mo non-small cell carcinoma of the lung were treated at our Medical Center with a course of pre-operative radiation therapy to be followed by surgical resection. Radiation therapy consisted of delivering a total dose of 40 Gy with 200 cGy per fraction over a period of 4 weeks to the primary tumor in the lung and the regional lymph nodal areas. Surgical resection was attempted 4 weeks later. Fifty-eight percent of the patients had squamous cell carcinoma whereas the remaining had other histologies like adenocarcinoma, large cell carcinoma, or a combination thereof. All the patients except two were followed up to a minimum of 5 years or until death. Sixty-four patients (82%) had T3 tumors whereas mediastinal nodal involvement was found in 41 patients (55%). Fifteen patients (20%) did not have the operation because of tumor progression, patient's refusal or death. All but two surgically treated patients had tumor resection. Of these 19% had histologically negative specimens, 9 patients (16%) had microscopic disease only, and 37 patients had gross residual disease at the time of surgery. The actuarial 5-year survival and recurrence-free survival rates for the entire group were 20% and 24%, respectively. Patients with a pathologic response had an actuarial recurrence-free survival rate of 53% at 5 years whereas only 17% of those with gross residual disease at surgery had remained recurrence-free at 5 years. One-half of the patients with clinically uninvolved nodes were living recurrence-free at 5 years whereas only 20% of the patients with N2 disease did so. The patterns of failure according to the histology and stage of the disease will be presented.
 ...
PMID:Preoperative radiation therapy in regionally localized stage III non-small cell lung carcinoma: long-term results and patterns of failure. 216 53

Forty-seven patients with advanced non-small cell lung cancer (NSCLC) were treated in a multicentre phase II study with pirarubicin (THP), 4'-O-tetrahydropyranyl-doxorubicin using a dosage of 70 mg/m2 every 3 weeks. The median age of the patients was 59 years (range 45-70) and the performance status grade 0-2 (WHO). Thirty-eight patients had stage IV and 9 stage III (UICC). Twenty-six patients had an adenocarcinoma. 19 a squamous cell carcinoma, and 2 a polymorphocellular carcinoma. Six out of 45 evaluable patients achieved a partial remission leading to an overall response rate of 13%. Eighteen patients showed no change (NC), 12 were progressive (PD), 2 patients had early progression (EP), and 7 patients died during the first course with clinical signs of tumor progression (early death). The median survival time was 4.6 months. Leukocytopenia and thrombocytopenia (WHO grade 4) was experienced in 8.5% and 2.1%, nausea and vomiting (grade 2 and 3) by 32% of the patients. There was no cardiotoxicity or other severe side effects. Pirarubicin has only a moderate antineoplastic activity in patients with advanced NSCLC. Observed response rates are similar to those reported for doxorubicin, but the toxic side effects are milder.
 ...
PMID:Pirarubicin in advanced non-small cell lung cancer. A trial of the Phase I/II Study Group of the Association for Medical Oncology of the German Cancer Society. 216 33

During the years 1975-1988, twenty lung cancer patients with symptomatic pericardial effusion were treated conservatively at our center. Echocardiography demonstrated small pericardial effusion in 2 patients, medium size effusion in 3 patients and large amount of fluid in 15 patients. Fifteen patients developed cardiac tamponade; in three of these patients, this was the presenting manifestation of lung cancer. Pericardiocentesis resulted in prompt, though temporary, symptomatic relief in all patients. Fluid cytology demonstrated suspected malignant cells in 2 patients and malignant cells in 13 patients. Based on cytology, the diagnosis of adenocarcinoma was established in six patients, small cell carcinoma in three patients, and epidermoid carcinoma in one patient. All patients were dead within 9 months from the time of diagnosis of pericardial effusion; 17 died within less than 3 months. It is concluded that pericardial effusion in lung cancer is indicative of rapid tumor progression and short survival. Fluid cytology provides an immediate and accurate means of diagnosis.
 ...
PMID:Symptomatic pericardial effusion in lung cancer patients: the role of fluid cytology. 221 90

A recently established model for local breast cancer recurrence using the 13762NF rat mammary adenocarcinoma was used to evaluate biologic and biochemical properties related to clinical outcome for this class of tumors. Sublines isolated from local tumor regrowths following surgical resection differed from each other and from the 'parental' cell lines for multiple phenotypes, including metastatic propensity. Local recurrence- and primary tumor-derived sublines were examined by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), lectin binding to electrophoretically separated proteins, and lactoperoxidase-catalyzed cell surface iodination; and differential protein patterns were compared to tumor progression and metastatic potential. 2D-PAGE revealed several quantitatively different spots which correlated with lung colonization potential. In particular, quantities of an apparently unique, non-cell-surface protein, P50.9 (Mr approximately 50,900, pI approximately 7.3) correlated inversely with metastatic propensity, suggesting that it may be associated with, among other possibilities, the negative regulation of the metastatic phenotype. P50.9 was unrelated to four similarly sized metastasis-associated proteins--tumor autocrine motility factor; the rat analog of tumor suppressor, p53; rat cytokeratin 14 or procathepsin D--as determined by amino acid analysis. A major wheat germ agglutinin binding sialoglycoprotein, gp93 (Mr approximately 93,000), was present in smaller amounts as cells were passaged in vivo and re-established as in vitro cultures [MTF7 greater than 'primary' tumor-derived lines (sc1, sc3) much greater than local recurrence-derived lines (LR1, LR1a, LR3, LR4, LR5, LR6)]. Besides cell surface glycoprotein losses, two of six local recurrence-derived sublines expressed a wheat germ agglutinin-binding sialoglycoprotein, gp110 (Mr approximately 110,000), previously undetected on any of the other cell lines including the parental populations. gp110 was found in LR3 and LR6 which were relatively highly metastatic; however, correlation with metastatic potential failed because gp110 was not present on the metastatic parental cell line, MTF7. These results demonstrate specific quantitative and qualitative protein differences associated with the selection of locally recurrent mammary tumors.
 ...
PMID:Tumor progression- and metastasis-associated proteins identified using a model of locally recurrent rat mammary adenocarcinomas. 222 68

In order to evaluate the relevance of protooncogene alterations in gastric cancer and to specifically relate these alterations to types and stages of the neoplasia, we studied oncogenes of possible interest in gastric tumors with different clinical parameters. Fifty DNAs from primary gastric adenocarcinoma were analyzed, by the Southern blotting technique, for the presence of amplification or rearrangements of seven different protooncogenes: c-myc, c-erbB2, c-Ki-ras, c-Ha-ras, c-N-ras, hst, and c-mos. All the tumors analyzed were histologically classified and staged. Amplification of the following genes was found: c-myc (2 of 50), hst (3 of 50), c-erbB2 (3 of 50), and c-Ki-ras (5 of 50). The simultaneous amplification of hst (3 cases), c-myc (1 of 3), or c-Ki-ras (2 of 3) was observed. Analysis of DNAs from atrophic and metaplastic gastric mucosa (which can be regarded as preneoplastic lesions) of the 10 patients showing gene amplification demonstrated that this was limited to neoplastic cells. Considering protooncogene amplification in general (i.e., involving different genes and occurring to different degrees) and clinical parameters of tumors, we found a statistically significant association between amplification and both tumor progression and presence of metastases. Therefore, at least for the genes analyzed, amplification is a relatively infrequent phenomenon and represents a late event in the temporal development of gastric cancer.
 ...
PMID:Heterogeneous protooncogene amplification correlates with tumor progression and presence of metastases in gastric cancer patients. 225 24

Adenocarcinomas induced in canine bronchial segments placed subcutaneously have bronchiolo-alveolar regions. Immunocytochemistry and routine staining of adjacent sections strongly suggests that the lining of these regions consists of type II cells. These regions may thus represent true prospective alveolar regions, as also seen in embryonic lungs. This first observation of bronchoalveolar cancer arising from a major bronchus indicates that the carcinogen-induced neoplastic progression in bronchial epithelium may lead to type II cell differentiation and type II cell tumor development. The preservation of cell properties in serial nude mouse transplants suggests that it is a stable type II cell population.
 ...
PMID:Bronchiolo-alveolar regions in adenocarcinoma arising from canine segmental bronchus. 225 36

The epidermal growth factor and the homologous alpha-tumor growth factor are mitogenic polypeptides that act by binding to the epidermal growth factor receptor. The present study investigated whether increased production of epidermal growth factor/alpha-tumor growth factor or increased density of epidermal growth factor receptors may occur in gastric carcinomas as compared with normal mucosa from the same individuals. Epidermal growth factor receptors were measurable by (125I)EGF-binding assays in 13 of 15 normal mucosas and in 15 of 15 carcinomas. The epidermal growth factor-binding capacity was significantly higher in carcinomas than in mucosa. A comparison of pairs of mucosa and carcinomas showed an increase of epidermal growth factor receptors in 9 of 15 carcinomas, no change in 3, and a decrease in 2 carcinomas. One mucinous adenocarcinoma contained extreme numbers of epidermal growth factor receptors (2445 fmol/mg protein) corresponding to a 320-fold increase over normal mucosa. Epidermal growth factor-like activity was increased in 2 of 22 carcinomas compared with mucosa. We conclude that relative overexpression of epidermal growth factor receptors occurs in a fraction of gastric carcinomas. Whether increased expression of epidermal growth factor receptors is associated with particular patterns of tumor progression needs to be investigated.
 ...
PMID:Increased epidermal growth factor receptors in gastric carcinomas. 200 30

The Dunning R-3327 rat prostatic adenocarcinoma and its sublines have been developed as a model system to study prostate tumor progression. We have used this system to study the changes in androgen receptor (AR) and AR mRNA expression which occur during tumor progression from androgen dependent to androgen independent growth. Dorsal prostate and all tumor sublines contained a 10-kilobase AR mRNA on Northern blot analysis. The levels of AR mRNA in each subline compared to dorsal prostate (100%) were: H (75%) greater than G (48%) greater than HI (25%) greater than HI-F = AT-1 = AT-3 = MAT-Lu = MAT-Ly-Lu = less than 5%. Immunocytochemistry showed AR predominantly in acinar epithelial cells of dorsal prostate and the androgen sensitive H subline. In the H subline, both acinar epithelial cells and locally invasive adenocarcinoma cells within the stroma showed positive immunostaining. The androgen responsive, anaplastic G subline also showed strong positive immunostaining. The androgen resistant AT-1 and MAT-Lu sublines lacked immunostaining for the AR. Steroid autoradiography revealed a similar cellular distribution of AR. These data suggest that in the Dunning system the loss of androgen binding and responsiveness is primarily due to selective changes in gene expression and not to gene rearrangements or posttranscriptional or translational modification of the AR mRNA or protein.
 ...
PMID:Expression and localization of androgen receptor in the R-3327 Dunning rat prostatic adenocarcinoma. 240 76

A study was undertaken to determine the ability of the DNA hypomethylating drug 5-aza-2'-deoxycytidine (5-azadCyd) to induce antigen expression in a high proportion of treated tumor cells and to evaluate if this effect could be mimicked by the drug hydroxyurea (HU) which is a genomic DNA hypermethylating agent. Induction of heritable changes in gene expression by 5-azacytidine or the 2'-deoxy analogue (5-azadCyd), at least in some cases, may not be necessarily due to their hypomethylating properties, but to some other induced high frequency genetic change which occurs when DNA synthesis or repair is perturbed. A comparison of 5-azadCyd and HU effects on human and murine tumors was chosen for this study. The phenotypic properties examined with the above treatments were (a) induction of a Mr 110,000 antigen, detected with M111 antibody, in a variant subpopulation (SMeLus7) of human melanoma cells which fail to maximally express this antigen (M111). The parent cell line, MeWo, and other MeWo-derived variant cell cell lines do not demonstrate a similarly inducible phenotype; and (b) induction of class I major histocompatibility complex antigens in a population of mouse mammary adenocarcinoma cells which normally fail to express these antigens. The results showed that 5-azadCyd was effective in inducing antigen expression in both systems whereas HU was effective (and equally so) only in the human melanoma cell line system. In these treatments 5-azadCyd was demonstrated to transiently hypomethylate the same human melanoma cell line whereas HU hypermethylated genomic cytosines. The results suggest that some of the reported effects of 5-azacytidine or 5-azadCyd in inducing very high frequency heritable phenotypic alterations may not necessarily be related to the drugs' ability to cause DNA hypomethylation. The implications of these results are discussed in terms of the use of 5-azacytidine or 5-azadCyd and the effects of chemotherapy on tumor progression and metastasis.
 ...
PMID:Heritable high frequency modulation of antigen expression in neoplastic cells exposed to 5-aza-2'-deoxycytidine or hydroxyurea: analysis and implications. 245 61


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