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)

Bone scans, serum tissue-specific polypeptide antigen (TPS), prostate specific antigen (PSA), and neuron-specific enolase (NSE) were assessed in a total of 80 hormonally treated prostate cancer patients. Thirty-nine patients were free of osseous lesions; in 8 subjects, 3 or fewer scintigraphic hot spots were found; in 29 patients, more than 3 bone lesions were recorded. In 3 patients, a partial contribution of endocrine cell cancer structures was found, while in one patient, a homogeneous small cell carcinoma was detected at autopsy. Measurement of the serum PSA test showed a clear-cut rise from stage D0 subjects to stage D2 patients, with a small number of bone lesions (> or = 3). However, a relative decrease in the mean PSA level was measured with further progression in a number of hot spots in bone (> 3). Androgen threshold that is critical for the induction of the PSA (and PAP) expression seems to differ markedly in various cell subpopulations that arise during adenocarcinoma dedifferentiation. This fact explains not only the rise in serum PSA in the majority of progressive and previously castrated subjects after an initial period of hormonal responsiveness, but also a relative decline of androgen-dependent PSA expression with further tumor progression. Localized disease was accompanied with normal or just slightly elevated TPS concentration. In metastatic tumors, serum TPS values revealed a steady increase with the progression in bone. These data seem to reflect not only an increase in tumor proliferation rate with progressively transformed genome, but also the rise in the number of proliferating cells. The presence of nonepithelial transformed tumor structures, such as small cell cancer within a bulk of adenocarcinoma, reduces or normalizes numerical serotests values of both TPS and PSA even during tumor progression. The extent of such decline depends upon the bulk of the endocrine component. The assessment of the above parameters, especially when associated with elevated plasma NSE concentrations, may help in distinguishing an advanced adenocarcinoma with and without elements of malignant neuroendocrine structures. The proposed approach, modified by applying corresponding organ-specific markers, may be checked for its possible general use in staging protocols of various heterogeneous tumors.
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PMID:A more objective staging of advanced prostate cancer--routine recognition of malignant endocrine structures: the assessment of serum TPS, PSA, and NSE values. 750 85

A hormone-dependent, clonal carcinoma cell line, designated RM22-F5, was derived from a malignant mammary mixed tumor spontaneously arising in an outbred old female Wistar rat. These cells expressed keratin and desmosomal protein and formed epithelial monolayers in a growth factor and hormone-supplemented medium (LHC-8) containing 10% fetal bovine serum (E-type cells). Cells subcultured for 6 to 8 passages in RPMI 1640 medium containing 10% fetal bovine serum without supplements appeared to be fibroblastic and expressed vimentin (F-type cells). The shift to a fibroblast-like morphology was associated with a more malignant phenotype which included rapid, hormone-independent growth and invasive sarcoma-like character in nude mice. F-type cells were no longer able to express their original epithelial phenotype in LHC-8 medium. Cytogenetic analysis revealed that both E- and F-type cells had essentially the same karyotype. Analysis of PCR-amplified DNA further demonstrated a point mutation of the H-ras-1 gene at codon 12 and loss of the normal H-ras-1 allele in both cell types. Genetic tagging of E-type cells with the neomycin-resistance gene resulted in the generation of F-type cells with neomycin resistance in RPMI 1640 medium, suggesting that F-type cells are a malignant variant of E-type cells arising during in vitro culture. Somatic cell fusion between E- and F-type cells revealed that with most hybrid clones tested, the fibroblast-like phenotype was greatly suppressed. These results suggest that an irreversible phenotypic transition, representative of tumor progression from hormone-dependent adenocarcinoma to more malignant hormone-independent spindle carcinoma cells, is a recessive event and may involve loss of a suppressor function.
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PMID:Progression of hormone-dependent adenocarcinoma cells to hormone-independent spindle carcinoma cells in vitro in a clonal spontaneous rat mammary tumor cell line. 752 36

Laboratory studies have suggested that rapidly alternating chemotherapy and radiation therapy might act synergistically. We undertook this study to evaluate the toxicity and effectiveness of this approach in patients with carcinoma involving the hypopharynx or esophagus. Between 1987 and 1991, we treated 47 patients (23 with carcinoma involving the hypopharynx and 24 with carcinoma involving the esophagus) by three cycles of chemotherapy (during weeks 1, 4, and 7) rapidly alternating with twice-a-day radiation therapy (during weeks 2, 5, and 8). Chemotherapy consisted of cisplatin 100 mg/m2 and 5-fluorouracil 3-4 g/m2 given over 4 days. Radiation therapy consisted of 180-200 cGy twice each day to 2000 cGy/cycle, total 6000 cGy over 7 weeks. The histology was squamous cell carcinoma in 44 patients and adenocarcinoma in 3 patients with esophagus cancer. Median follow-up is 2 years (range 1-5 years). The observed survival rate for all 47 patients was 54% at 1 year and 38% at 2 years. Acute toxicity was considerable. Twelve patients (25%) died during therapy from toxicity, without tumor progression, leaving 35 patients (18 hypopharynx, 17 esophagus) evaluable for response. Among the hypopharyngeal patients, 83% had a complete response, 11% had a partial response, and 6% had no response. Among the esophageal patients, 94% had a complete response, and 6% had a partial response. Local control was better for the esophageal patients than the hypopharyngeal patients (98% vs. 52% at 2 years, p = 0.038). The incidence of distant metastases was 25% at 2 years and not significantly different between the two groups. A high rate of local control was achieved, particularly in esophageal cancer, by delivering chemotherapy and radiation therapy in a rapidly alternating fashion. This was achieved at a considerable cost in terms of toxicity, however. Although our response rates and local control compare favorably with those of other recently published studies of combined modality therapy in esophagus or head and neck cancer, much additional work is required to reduce the toxicity and, in hypopharyngeal cancer, to further improve the local control.
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PMID:Chemotherapy rapidly alternating with twice-a-day accelerated radiation therapy in carcinomas involving the hypopharynx or esophagus: an update. 758 5

Oncostatin M (OSM) and leukemia inhibitory factor (LIF) are involved in stimulation of acute-phase protein during inflammatory processes. We recently suggested that these two cytokines may play a role in human immune surveillance during tumor progression. The present study was designed to determine the capacity of OSM in modulating LIF production by human tumor cells and to provide a better definition of the interactions between these two molecules during inflammatory reaction due to neoplasia. LIF content in culture supernatants was assayed by a specific ELISA (sensitivity: 25 pg/ml). In vitro exposure to recombinant OSM increased LIF production 2 to 6-fold in all human melanoma cell lines tested. This effect was not limited to melanoma cell types since LIF production was also enhanced by an MDA breast undifferentiated adenocarcinoma line. Moreover, a synergistic effect was observed for OSM and TNF-alpha. LIF increase was apparently due to up-modulation through LIF synthesis since LIF transcript expression was also enhanced in these tumor cell lines. It is concluded that OSM can induce inflammatory reaction not only directly but also via LIF production by tumor cells.
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PMID:Modulation of LIF expression in human melanoma cells by oncostatin M. 759 Sep 43

Accumulating evidence suggests that integrins, which participate in many complex cellular processes, are important for tumor progression and metastasis. In order to understand the role of these cell-surface receptors and of their ligands in the biological behavior of ovarian tumor cells, we have examined the expression of integrins in the human ovarian-adenocarcinoma cell line IGROV1. These cells expressed the alpha v sub-unit and used it to attach on vitronectin (Vn). A monoclonal antibody (MAb) (69-6-5) specific to alpha v blocked the attachment of IGROV1 cells on Vn and fibrinogen (Fg), but not on fibronectin (FN) and other adhesive ligands. Immunoprecipitation of surface biotinylated cells followed by Western blotting showed that the alpha v sub-unit was associated with beta 3, but not with beta 1, beta 5 or beta 6. When cells were cultivated on glass coverslips or on Vn sub-stratum in serum-free medium, immunofluorescence staining with MAb 69-6-5 revealed the presence of alpha v at cell-cell contacts and at focal contacts, supporting its active participation in adhesion as part of a functional heterodimer. Furthermore, immunofluorescence data showed the presence of Vn as a fibrillar network in IGROV1 cells cultivated on FN-coated slides. These results suggest that alpha v beta 3 and its Vn ligand may play a important role in the behavior of ovarian epithelial tumors.
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PMID:Implication of the alpha v beta 3 integrin in the adhesion of the ovarian-adenocarcinoma cell line IGROV1. 759 Dec 63

Mutations in the p53 tumor suppressor gene have been found to be the most frequent genetic alterations in human malignancies. To further examine the idea that neoplastic progression is associated with mutations in the p53 gene, we analyzed matched primary and metastatic tumor samples. The samples included 15 pairs of breast cancer and metastases to lymph nodes, four pairs of gastrointestinal adenocarcinomas and metastases to liver, one colon adenocarcinoma and metastasis to a lymph node, and one lung carcinoma and metastasis in the pleura. Genomic DNA or cDNA from each tumor sample was amplified by the polymerase chain reaction and labeled by using one biotinylated primer. The DNA strands were separated with magnetic streptavidin beads and sequenced directly. p53 mutations were detected in 11 of 21 patients (52%) in either primary tumors, metastases, or both. In six of these patients the primary tumor and matched metastasis shared the same single mutation. In the other patients an additional mutation in the primary tumor only or a mutation in the metastasis only was observed. Our data suggest that tumor development and progression toward metastasis involves structural alterations in the p53 gene that occur early in carcinogenesis. In some cases, genetic changes in metastatic spreading may also include the appearance of a mutation in a metastasis derived from a primary tumor expressing wild-type p53, a selection of metastatic cells with a single mutation from a primary tumor expressing two different mutations, or loss of heterozygosity.
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PMID:p53 mutations in matched primary and metastatic human tumors. 761 19

"Incidental" cancer refers to predominantly well differentiated cancer that arises in the transition zone and is found by chance in TURP chips. These tumours are frequently small and may be completely resected by TURP, although a significant number have an additional tumour that is unreachable with a resectoscope. These tumours often co-exist with benign prostatic hyperplasia. Putative precursors of incidental carcinoma include high grade PIN and AAH, and these lesions are frequently found in the transition zone in prostatectomies for cancer. The single most significant question in treating incidental adenocarcinoma is how to separate tumours that will progress from those that will not progress during the expected lifetime of the patient. The 1992 revision of the TNM staging system separated non-aggressive (T1a) and aggressive (T1b) incidental cancer according to the number of foci of cancer, using more than three foci as the cutpoint to identify more aggressive cancer. However, 8-37% of patients with T1 a cancer will develop cancer progression within 10 years if untreated, with the risk of progression increasing with additional years of follow-up. Important prognostic factors include the patient's age, tumour location (peripheral zone v. transition zone), tumour grade, tumour volume, serum PSA concentrations and morphometric factors such as nuclear roundness. Studies directed at early detection allow discovery of increasingly smaller cancers.
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PMID:The pathology of incidental carcinoma. 762 75

Nerve growth factor-beta (NGF beta) and a NGF beta-immunoreactive protein derived from human prostatic stromal cell secretory protein (hPS) have been shown to stimulate the growth of prostate epithelial cells. An NGF beta-immunoreactive protein has been localized to the stroma of human prostate tissues, and a low affinity NGF receptor (gp75NGFR) has been localized to the adjacent epithelia, consistent with the paracrine regulation of prostate growth. Interestingly, gp75NGFR is progressively lost during neoplastic progression of the human prostate. In this report we have characterized the expression of the signal-transducing component of the NGF receptor, the Trk tyrosine receptor kinase, in prostate epithelial cells that bind exogenous NGF beta and an endogenous NGF beta-immunoreactive protein in hPS. In this context, a pan-Trk antibody that recognizes all of the members of the Trk receptor family (TrkA, TrkB, and TrkC) specifically localized expression of the Trk receptor to the epithelial component of normal prostate tissue, benign prostatic hyperplasia, and adenocarcinoma tissue. The binding of [125I]NGF beta to the surface of primary cultures of human prostate epithelia and the TSU-pr1 human metastatic prostate tumor cell line was displaced with either excess cold NGF beta or hPS, whereas binding was not displaced by epidermal growth factor or platelet-derived growth factor. Scatchard plot analysis of [125I]NGF beta binding to these cells identified a low affinity binding site (Kd = 1.9 x 10(-9) M) and a high affinity binding site (Kd = 1.8 x 10(-11) M) on the primary prostate epithelia, whereas only a high affinity binding site (Kd = 1.3 x 10(-11) M) was observed on the TSU-pr1 tumor cells. Stimulation of TSU-pr1 cells with either NGF beta or hPS induced tyrosine phosphorylation of Trk proteins, whereas no phosphorylation was evident in untreated cells, cells treated with hPS immunoprecipitated with anti-NGF beta antibody, or brain-derived neurotrophic factor- and neurotrophin-3-treated cells. The Trk protein was also observed in these cells by immunoblot analysis with pan-Trk antibody. These results demonstrate a functional Trk receptor in the epithelia of the human prostate that is responsive to exogenous NGF beta and an endogenous NGF beta-immunoreactive protein in hPS, thereby supporting the concept of the paracrine regulation of growth in the human prostate via a stromal neurotrophin-epithelial Trk receptor interaction.
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PMID:Expression of a Trk high affinity nerve growth factor receptor in the human prostate. 782 39

We report overexpression of the proto-oncogene bcl-2 in gastrointestinal adenocarcinoma and its precursor lesions. The bcl-2 proto-oncogene is centrally involved in the oncogenesis of human follicular lymphoma via a chromosomal translocation t(14;18)(q32;q21) and is also expressed in the epithelial regenerative compartment or the basal crypts of the normal colon and small intestine. We describe an immunohistochemical analysis of fixed, paraffin-embedded tissue using both a polyclonal rabbit and a monoclonal mouse antibody to the Bcl-2 protein. In addition to confirming bcl-2 expression in normal colonic and small intestinal crypts, we also observed expression in the gastric epithelial regenerative compartment, the mucous neck region. No increased expression was found in nonneoplastic or inflammatory gastrointestinal conditions, including ulcerative colitis, Crohn's disease, or inflammatory or hamartomatous polyps. Increased bcl-2 expression, however, was present in hyperplastic colonic polyps and in the majority of dysplastic lesions, from the earliest precursors through large adenomas, high grade flat dysplasia, and adenocarcinoma, all in comparison with adjacent internal control normal epithelium. Increased expression was present in dysplastic glandular lesions from all gastrointestinal sites, including colon, small bowel, and stomach. Furthermore, bcl-2 expression was frequently abnormal in nondysplastic epithelium surrounding dysplastic lesions, suggesting that altered expression occurred before the development of morphological dysplasia. Specifically, directly contiguous morphologically nondysplastic epithelium often showed abnormal bcl-2 expression throughout the full length of the crypt-villus axis. This expression pattern gradually diminished to involve only the crypt base (the normal pattern of expression), proceeding away from malignant or dysplastic lesions. Abnormal bcl-2 immunoreactivity in 1), the earliest precursor dysplastic lesions and its persistence throughout neoplastic progression and 2), contiguous morphologically unaltered nondysplastic epithelium suggests that bcl-2 alterations occur early during the morphological and molecular sequence of events leading to gastrointestinal epithelial neoplasia.
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PMID:The bcl-2 proto-oncogene and the gastrointestinal epithelial tumor progression model. 785 28

The purpose of this study was to determine if proton irradiation can increase the localization of radiolabeled monoclonal antibodies (MAb) in subcutaneous (s.c.) or intracranial (i.c.) human lung tumors xenotransplanted in athymic rats. Rats with carcinoembryonic antigen (CEA)-expressing (NCI-H441) tumors were irradiated using 3 different proton time-dose regimens, followed by 111In-ZCE025, an anti-CEA MAb, which was injected 2 hr after the last dose of irradiation, and the animals were euthanized 3 days later for biodistribution and other assays. Proton irradiation at 10 gray (Gy) as a single dose or in 2 Gy fractions given on 5 consecutive days increased the uptake of 111In-ZCE025 into s.c. tumors by 292% and 182%, respectively, compared to nonirradiated controls. No enhancement in radiolabeled MAb delivery was seen after hemibrain irradiation in animals with i.c. tumors. Histopathological examination of both implantation sites showed a viable poorly differentiated adenocarcinoma with a decrease in blood vessel density, a decrease in mitotic activity, and an increase in areas of necrosis following irradiation as compared with adjacent nonirradiated tissue. CEA expression was generally maintained in vivo in that the marker was detectable in the tumor, plasma, and cerebrospinal fluid. Oxygen radical production by peripheral blood cells from s.c. and i.c. tumor-bearing rats exhibited strikingly different patterns of responsiveness. I.c. injected animals were 24% lighter than their s.c. injected counterparts, but no neurological signs of tumor progression were noted. The results indicate that proton irradiation can be used effectively to increase the delivery of radiolabeled MAb to s.c. implanted human lung tumor xenografts. However, in order to accomplish this in the brain, other radiation time-dose schedules and treatments may be needed.
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PMID:Pilot study of monoclonal antibody localization in subcutaneous and intracranial lung tumor xenografts after proton irradiation. 787 72


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