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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From September 1979 to February 1983, 268 patients with unresectable, locally advanced (RTOG Stage III), non-small cell lung cancer were randomized to receive radiation therapy alone (RT) (50 Gy large field and 10 Gy boost), or combined with misonidazole (400 mg/m2 2-4 hr prior to RT daily for 5-6 weeks to a maximum dose of 12 g/m2 or until tumor progression). One hundred twenty-three patients who received irradiation alone and 116 given RT + misonidazole were evaluable for toxicity, time to tumor progression, and survival as of April 1987. The distribution of patient characteristics was similar in both treatment groups; 59% of the patients had a Karnofsky score of 90 or better, 53% had adenocarcinoma or large cell tumors, and 47% had Stage T3 tumors. Complete tumor regression was reported for 33 (27%) patients treated with radiation therapy alone and 24 (21%) who received misonidazole + RT. Median survival was 8 months with RT alone and 7.4 months with misonidazole + RT. Ninety-five percent of the patients have died. Seventy percent of the patients treated with radiation alone and 77% of those treated with misonidazole + RT died of progressive disease. Three patients treated with radiation alone and two with RT + misonidazole died subsequent to radiotherapy-related pneumonitis or pulmonary fibrosis. There was no significant improvement in response rates, local control, or survival for patients who received daily misonidazole along with irradiation compared with patients treated by irradiation alone.
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PMID:Radiation therapy alone or combined with misonidazole in the treatment of locally advanced non-oat cell lung cancer: report of an RTOG prospective randomized trial. 254 97

To augment the antitumor effect of high-dose melphalan and determine pharmacokinetics we conducted a phase I trial of escalating doses of high-dose IV melphalan with the chemosensitizer misonidazole for patients with advanced colorectal carcinoma. Fourteen patients with modified Dukes D adenocarcinoma of the colorectum were treated with a single course of melphalan (40-60 mg/m2 i.v. bolus q.d. X 3 days) and misonidazole (1-3 g/m2 p.o. q.d. X 3 days) followed by autologous bone marrow transplantation. Toxicity consisted of severe myelosuppression, moderate nausea and vomiting, and mild mucositis and diarrhea. One patient developed unexplained renal tubular acidosis, and a diffuse encephalopathy occurred in another patient. Three patients died within the first 30 days after the start of treatment, two due to tumor progression and one due to sepsis and disseminated intravascular coagulation-induced intracerebral hemorrhage. Six of 14 patients achieved a partial response, and the median response duration was 4 months (range 3-10 months). Analysis of misonidazole serum concentrations showed similar pharmacokinetics to those previously reported, suggesting no significant drug interaction with intravenous melphalan. Mean peak serum concentrations ranged from 81.8 micrograms/ml to 115.2 micrograms/ml at the second and third misonidazole dose levels, which approximate those known to provide effective chemosensitization with melphalan in animal models. In this phase I study, we showed that maximally tolerated doses of intravenous melphalan can safely be combined with oral misonidazole. In view of the large volumes of oral misonidazole required at the highest dose level, subsequent studies to determine the maximally tolerated dose of misonidazole should employ the intravenous form.
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PMID:High-dose melphalan, misonidazole, and autologous bone marrow transplantation for the treatment of metastatic colorectal carcinoma. A phase I study. 265 May 27

Early diagnosis and accurate, biologically meaningful classification of prostate neoplasia remain important goals. The relation of evolving clinicopathologic concepts of histologic appearances to potential tumor progression is a major advance in classification of prostatic neoplasia. The criteria for recognizing incidental or "occult" stage A-l adenocarcinomas remain problematic in diagnosis, and focal neoplasms with little or no propensity to progression must be differentiated from cancers with a high likelihood of aggressive behavior. Current histologic grading systems in classifying prostate adenocarcinoma accurately identify two cancer subsets: 1) focal well differentiated tumors which rarely progress, and 2) diffuse poorly differentiated tumors which invariably develop metastatic disease. Unfortunately, the majority of prostatic cancers are classified in the intermediate group in which the prognosis is variable and difficult to differentiate purely by histology. Our laboratory recently adapted image analysis of cellular DNA quantitation--a major improvement in accurately predicting tumor behavior, especially in the intermediate histologic grades. We and others have found that tumors with abnormal (aneuploid) DNA content are more likely to progress than neoplasms with normal (diploid) DNA content.
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PMID:Histopathologic diagnosis and classification of prostate adenocarcinoma: biologic significance. 267 Aug 42

We studied the progressive factors for incidental carcinoma of the prostate of 38 patients. Effects of anti-androgen drugs for the development of incidental carcinoma were examined. There were no statistical differences with age, tumor size, histopathological grade, or invasion of BPH capsule. However, the tumor progression rate was high for a tumor size of more than 10 mm or poorly differentiated adenocarcinoma. Therefore, tumor progression was related with tumor size and histopathological grade. Of 15 patients with stage A1 disease, two patients had tumor progression. Patients with stage A1 disease are being followed with no treatment, but radical treatment may be necessary for young men. Patients with stage A2 disease must be treated with radical prostatectomy, radiation therapy or hormone therapy case by case. None of the patients who were treated with anti-androgen drugs had stage A1 disease. Patients not treated had stage A1 and A2 diseases. Anti-androgen drugs may have inhibited the development of stage A1 disease.
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PMID:[Studies of progressive factors of stage A prostatic cancer]. 273 37

Clinically applicable markers for tumor progression may be uncovered by selective analysis of biochemical parameters, supposedly participating in this complex process. Owing to the importance of specific protein-carbohydrate interactions in diverse biological processes, the pattern of the receptor part in this glycobiochemical recognition system, the sugar receptors (lectins), conceivably reflects biological properties of tumor cells in glycobiochemical terms. Therefore, we established and characterized xenografts from surgically removed specimens of a human primary colon adenocarcinoma and its metastatic lesions to liver of the same patient and of a histomorphologically similar primary colon adenocarcinoma of another patient in nude mice. Xenotransplantation and subsequent glycobiochemical analysis of material from early passages with a standardized procedure had been preferred to cell culture in monolayer on account of maintenance of a higher degree of organized histotypic assembly. Despite histomorphological similarities, the sugar receptor profile revealed significant differences in tumor-tumor and tumor-metastasis comparison, especially for alpha- and beta-galactoside-binding proteins. Tumor-metastasis differences were substantiated by a second successfully xenotransplanted pair of specimens. Comprehensive expansion of these initial data may eventually lead to desirable functional correlations with the different biological properties of histomorphologically similar primary colon adenocarcinomas and of the metastatic phenotype and to a rational development of therapeutic modalities to restrict tumor growth and spread.
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PMID:Detection of metastasis-associated differences for receptors of glycoconjugates (lectins) in histomorphologically unchanged xenotransplants from primary and metastatic lesions of human colon adenocarcinomas. 275 8

The effect of tumor on somatomedin level in blood was investigated. This index, which is generally high in patients with primary tumors of the breast, cervix uteri, colon rectum and prostate, was found to decrease in step with tumor progression (stages II-IV). In well--differentiated adenocarcinoma of the endometrium and large bowel, it was higher than in moderately- and poorly-differentiated forms. In breast cancer patients, a relatively high blood--somatomedin level was mostly observed in solid forms, this being matched by relatively high somatomedin levels in tumor tissue. The tissue of 60% of large bowel tumors was shown to produce an inhibitor of somatomedin activity. It is suggested that there is a relationship between blood-somatomedin level in cancer patients and tumor mediated by somatomedin-like and -inhibiting factors produced by it.
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PMID:[Somatomedin activity in patients with malignant neoplasms]. 283 69

A total of 285 patients with medically inoperable (RTOG Stage T1-2, N0-1) or unresectable (RTOG Stage T3, N0-1) non-small cell carcinoma of the lung were randomized by the Radiation Therapy Oncology Group (RTOG) to receive radiation therapy (6000 cGy total dose/6 weeks) plus levamisole (2.5 mg/kg twice weekly for 2 years or until tumor progression) or a placebo. One hundred twenty-nine evaluable patients were assigned to placebo and 131 to levamisole. This report is based on 260 (91%) eligible patients who started treatment and have adequate follow-up. Fifty percent of the patients in both treatment groups had Karnofsky scores of 90-100; 72% had squamous cell carcinoma, 12% adenocarcinoma, and 16% large cell undifferentiated carcinoma; 60% had RTOG Stage I or II primary tumors and 40% had Stage III (T3, N0-1) tumors. Complete regression of tumor was reported in 20% of the patients treated with levamisole and 36% of those receiving placebo. An additional 33% and 19%, respectively, had a partial response (trend test p = 0.08). Median survival was 9 months for patients treated with levamisole and 12 months for those on placebo (two-sided p less than 0.01); at 2 years, patients treated with levamisole had a 15% survival rate as compared to 24% in those receiving placebo. The cumulative proportion failing within the irradiated field with or without other sites of progression at 2 years was 30% in the levamisole group and 34% in the placebo patients. Median progression-free survival was 6 months for patients on levamisole and 7 months for those on placebo (overall two-sided p = 0.014); the estimated proportions progression-free at 2 years were 11% and 18%, respectively. The study showed no significant prolongation of survival, progression-free survival, or differences in patterns of failure in irradiated patients treated with levamisole compared with a placebo. Toxicity related to this immunoadjuvant was, in general, of moderate clinical importance. This study confirms a report by the Southeastern Cancer Study Group concluding that levamisole combined with definitive irradiation has no benefit in the treatment of unresectable non-small cell carcinoma of the lung.
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PMID:Thoracic irradiation with or without levamisole (NSC #177023) in unresectable non-small cell carcinoma of the lung: a phase III randomized trial of the RTOG. 284 86

Barrett's esophagus develops as a complication of chronic gastroesophageal reflux and predisposes patients to the development of dysplasia and adenocarcinoma of the esophagus. Because light microscopy of dysplasia in Barrett's esophagus shows diminished or absent mucus, we used transmission electron microscopy to compare cytoplasmic organelles required for mucus production in dysplastic and nondysplastic esophageal columnar epithelium. These observations of the rough endoplasmic reticulum, Golgi apparatus, and secretory granules were correlated with histologic interpretations and flow cytometric measurements of abnormalities of DNA content. Ultrastructural abnormalities included depletion and alteration of organelles required for mucus biosynthesis. These abnormalities often were accompanied by cells with markedly distended rough endoplasmic reticulum and massive accumulation of cytoplasmic glycogen aggregates. All 9 patients who had Barrett's dysplasia with or without early adenocarcinoma had ultrastructural abnormalities, as did 3 of 8 patients whose biopsy histology was indefinite for dysplasia. Abnormalities measured by flow cytometry correlated well with the presence of these ultrastructural aberrations. All 9 patients with Barrett's dysplasia with or without early adenocarcinoma had abnormalities observed by electron microscopy and aneuploidy or increased G2/tetraploid fractions measured by flow cytometry. Two of the 3 patients whose biopsies were indefinite for dysplasia and who had ultrastructural abnormalities also had aneuploidy or increased G2/tetraploid fractions. Neither ultrastructural nor flow cytometric abnormalities were found in the remaining 5 patients whose biopsies were indefinite for dysplasia, in 19 of 22 patients with Barrett's specialized metaplasia, or in any of the 7 patients with gastroesophageal reflux disease without Barrett's specialized metaplasia. Two of the 22 patients with Barrett's specialized metaplasia had distended rough endoplasmic reticulum in rare cells, and one other had an aneuploid cell population. We conclude that neoplastic progression in Barrett's esophagus is associated with abnormalities of cytoplasmic organelles required for mucus production. With few exceptions, these ultrastructural aberrations correspond to the presence of dysplasia or of aneuploidy or increased G2/tetraploid fractions. Electron microscopy and flow cytometery detect abnormalities associated with the development of dysplasia and cancer in Barrett's esophagus that may be biologically significant.
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PMID:Correlation of ultrastructural aberrations with dysplasia and flow cytometric abnormalities in Barrett's epithelium. 291 Jul 57

Barrett's esophagus is a condition in which metaplastic columnar epithelium replaces squamous esophageal epithelium as a consequence of chronic gastroesophageal reflux. Patients with this condition are at increased risk for the development of adenocarcinoma. To better understand the progression to adenocarcinoma in this disease, we studied abnormalities in DNA content of epithelial cells in Barrett's esophagus. Using flow cytometry, we examined the spatial distribution of abnormal nuclear DNA contents (aneuploidy) in the esophagi of 14 patients with Barrett's adenocarcinoma. Multiple (2 to 14) populations of aneuploid cells were seen in 12 of the 14 cases. Some early carcinomas appeared to be associated with a single aneuploid population of cells. Surrounding dysplastic epithelium often contained multiple, different overlapping aneuploid populations. These data suggest that neoplastic progression in Barret's esophagus is associated with a process of genomic instability which leads to evolution of multiple aneuploid populations, with the ultimate development of a clone of cells capable of malignant invasion. Thus, detection of multiple aneuploid populations of cells in Barrett's esophagus may indicate a high risk of cancer. Barrett's esophagus provides a unique and readily accessible model for the study of neoplastic progression in human epithelial malignancy.
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PMID:Progression to cancer in Barrett's esophagus is associated with genomic instability. 291 Nov 84

Barrett's esophagus develops as a complication of regurgitant esophagitis and predisposes patients to the development of dysplasia and esophageal adenocarcinoma. Prior ultrastructural studies have suggested that Barrett's epithelium is a mucous secretory epithelium that shares some morphologic features with the intestine. The origin and development of Barrett's epithelium and the cellular abnormalities accompanying its neoplastic progression are poorly understood. In an attempt to better understand the histogenesis of the mucus-producing cells that predominate in Barrett's epithelium, these cells were studied by transmission electron microscopy and compared with other upper gastrointestinal epithelia: esophageal glands, normal gastric surface, pit, and cardiac gland regions, gastric intestinal metaplasia, and normal jejunal villous tip and crypt regions. A total of 134 mucosal biopsies from the stomach and esophagus of 28 patients with Barrett's esophagus and 37 biopsies from 14 other control patients were studied. Barrett's specialized metaplastic surface cells display a spectrum of ultrastructural features among three main surface columnar epithelial cell types: mucous cells resembling those seen in the normal gastric surface epithelium or resembling mucous neck cells normally seen in the gastric pits; goblet cells similar to those seen in the jejunum; and "pseudoabsorptive" cells with features of both gastric mucous secretory cells and jejunal absorptive cells. Cytoplasmic organelles of Barrett's specialized metaplastic, normal gastric mucous neck, and normal gastric surface mucous epithelial cells, including rough endoplasmic reticulum, glycogen aggregates, Golgi apparatus, and mucous secretory granules, have common ultrastructural features associated with mucus synthesis. The morphologic heterogeneity of Barrett's specialized metaplastic cells and common ultrastructural features associated with normal mucus biosynthesis suggest that they develop from a gastrointestinal stem cell that retains the capacity for a wide range of normal and abnormal differentiation in the esophagus. The identity of this undifferentiated cell, which may reside in normal proximal gastric or esophageal mucosa, remains unknown. However, the gastric mucous neck cell has properties that suggest it could be the progenitor cell for Barrett's esophagus because it is a stem cell that has ultrastructural similarities to Barrett's specialized metaplastic epithelial cells and it is located in intact gastric mucosa adjacent to where Barrett's esophagus forms.
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PMID:Specialized metaplastic columnar epithelium in Barrett's esophagus. A comparative transmission electron microscopic study. 292 81


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