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

The medullary thyroid carcinoma was characterized as clinicopathological entity by Hazard, Hawk and Crile as early as 1959. As reported in literature the incidence of these tumors ranges from 3.5 to 11.9% of the thyroid carcinomas. In the study presented the morphological, histochemical and electron microscopical investigations in 8 cases of medullary thyroid carcinoma are reported. Different methods are used to demonstrate polysaccharides, proteins, especially polypeptide hormones, and amyloid. Furthermore several silver impregnation techniques for differentiation of argentaffin and argyrophilic cells were performed. The age of the 8 patients ranged from 30 to 65 years, 5 patients were females, the sex ratio of females to males runs to 1.7:1. In 4 cases metastases in regional lymph nodes were found. The tumor tissue preponderately showed a solid-travecular pattern. The tumor cells were seen in cord-like and nest-like arrangement. In places also a typical endocrine structure was present revealing an orientation of cells around capillaries here and there. A differentiation of light and dark cells was possible. Electron microscopically these light microscopical observations could be confirmed: dark cells possessed more organeles than light cells. Infiltrations of blood vessels did not occur, but infiltrations of lymph vessels were the rule. The tumors contained variable amounts of amyloid which could be seen by fluorescence and polarization microscopical methods in fine fiber-like structures or in coarse deposits. At the ultrastructural level typical secretory granules varying in electron density and having a diameter of 220-560 nm were visible. Some light tumor cells exhibited 50-120 A thick fibrils which could not be distinguished from extracellular amyloid fibrils. The histochemical findings evidenced moderately abundant proteins in the cytoplasm of tumor cells. Histochemically the amyloid corresponds to the so-called apudamyloid. A great deal of the proteins is orderly arranged in amyloid whereas this is not the case in the tumor cell cytoplasm as proved by the coupled tetrazonium reaction which was evaluated polarization microscopically. In amyloid tryptophan was absent. The medullary thyroid carcinoma has a low-grade malignancy and, in accordance to other authors, it is to be stated that this tumor is histogenetically related to the parafollicular cells (C-cells). Its distinction from other thyroid tumors is warranted basing on morphological and pathophysiological features. Structural patterns common with those of other endocrine tumors are demonstrable. The findings point to a relationship of medullary thyroid carcinoma with the APUD series or Feyrter's Helle-Zellen-System. Considering the possible simultaneous occurrence of pheochromocytomas and adenomas of the parathyroid gland it must be assumed that the medullary thyroid carcinoma is one of the dysplasias of the neural ectoderm.
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PMID:[Morphology and histochemistry of medullary thyroid carcinomas (author's transl)]. 446 14

The concentration of adenosine 3':5'-cyclic monophosphate in the spinal fluid of ten patients with liver dysfunction was analyzed. Ages of the patients ranged from 31 to 75 years. The state of consciousness varied between normality and stupor. After a liver biopsy the diagnoses were as follows: cirrhosis in six cases, porphyria cutanea tarda in one case, hepatic metastases in two cases and Wilson's disease in one case. Mean values in these patients (22.91 +/- 4.18 pM/ml) have been significantly greater (p less than 0.0005) than those in ten control individuals (15.55n control individuals (15.44 +/- 3.66 pM/ml). Values corresponding to two patients in coma were still higher (52.62 and 36.50 pM/ml respectively). A previous lumbar puncture carried out in one of these patients when he was conscious showed a figure of 23 pM/ml. These results suggest a progressive rise of cyclic adenosine monophosphate in the spinal fluid in relation to clinical impairment, and may indicate a similar behaviour for this nucleotide to that of tryptophan, as reported by other authors. These findings point toward the role of the alteration of neurotransmitters in the pathogenesis of hepatic coma.
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PMID:[Cyclic adenosine monophosphate in the cerebrospinal fluid of patients with liver disease (author's transl)]. 737 36

Positron emission tomography (PET) makes it possible to study effects of medical treatment in vivo. Carcinoid tumors with liver metastases, especially those of midgut origin, produce serotonin via the precursors tryptophan and 5-hydroxytryptophan (5-HTP) and this overproduction contributes to the clinical symptoms of the carcinoid syndrome. Seven patients with histopathologically verified neuroendocrine tumors and liver metastases, five of whom with ileal carcinoids, one a lung carcinoid and one an endocrine pancreatic tumor, were included in the study. All patients had elevation of urinary 5-HIAA with the exception of one patient with a solitary liver metastasis of midgut origin. After an intravenous injection of 11C-5-HTP, PET was performed and the uptake of radioactivity in tumor tissue, normal liver and plasma were compared. All patients with elevated urinary 5-HIAA and also the patient with a solitary liver metastasis and normal urinary 5-HIAA had high accumulation and signs of a high rate of binding of 5-HTP in the liver metastases. The uptake was relatively homogeneous in midgut carcinoid liver metastases but in large necrotic metastases the radioactivity was localized to the periphery. In three patients PET examination was repeated after 3 months of interferon treatment and in agreement with circulating tumor markers and ultrasonography the uptake of 5-HTP was unchanged. Another patient who received the somatostatin analog somatuline progressed on treatment and accordingly the uptake of 5-HTP also increased. The experience with PET in neuroendocrine gastrointestinal tumors is very limited. Our results so far indicate that 5-HTP can be used to visualize serotonin-producing neuroendocrine tumors and furthermore it might prove to be of value to monitor the effects of treatment, possibly also as an early predictive test of the outcome of treatment.
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PMID:Positron emission tomography (PET) in neuroendocrine gastrointestinal tumors. 768 63

Steady state and time-resolved fluorescence spectroscopy were employed to study the fluorescence from non-metastatic, metastatic and non-tumorigenic cell lines from different species. Excitations at 310 nm and 350 nm were used to monitor tryptophan and reduced nicotinamide adenine dinucleotide (NADH) fluorescence respectively. Subtle and consistent differences were observed between different categories of cell lines. It was found that the tryptophan to NADH fluorescence intensity ratio is higher in metastatic cell lines than in non-metastatic and normal cell lines. The fluorescence decay of the tryptophan residue in different cell lines was best described by triple exponential kinetics, whereas the NADH fluorescence decay was best described by mainly double and, in some cases, triple exponential kinetics. The average fluorescence lifetimes for tryptophan were in the range 2.5-3.7 ns. The average lifetime of NADH was lower (by a factor of approximately three) in metastatic cells than in non-metastatic cells and this finding is consistent for cell lines from different origins (rat or human). Correcting the fluorescence intensity for the average fluorescence lifetime of each species and for the volume of each cell line, it was shown that the concentrations of tryptophan and NADH are consistently higher in malignant metastatic cancer cells than in non-metastatic cells.
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PMID:Steady state and time-resolved fluorescence properties of metastatic and non-metastatic malignant cells from different species. 858 78

Recently, major advances have been made in the identification of antigens from human melanoma which are recognized by T cells. In spite of this, little is known about the optimal ways to use these antigens to treat patients with cancer. Progress in this area is likely to require accurate preclinical animal models, but the availability of such models has lagged behind developments in human tumor immunology. Whereas many of the identified human melanoma antigens are normal tissue differentiation proteins, analogous murine tumor antigens have not yet been identified. In this paper we identify a normal tissue differentiation antigen, tyrosinase-related protein 2 (TRP-2), expressed by the murine B16 melanoma which was found by screening a cDNA library from B16 with tumor-reactive cytotoxic T lymphocytes (CTL). A peptide conforming to the predicted MHC class I H2-Kb binding motif, TRP-2181-188, was identified as the major reactive epitope within TRP-2 recognized by these anti-B16 CTLs. By site-directed mutagenesis, it was shown that alteration of this epitope eliminated recognition of TRP-2. It was further demonstrated that a CTL line raised from splenocytes by repeated stimulation in vitro with this peptide could recognize B16 tumor and was therapeutic against 3-d-old established pulmonary metastases. The use of TRP-2 in a preclinical model of tumor immunotherapy may be helpful in suggesting optimal vaccination strategies for cancer therapy in patients.
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PMID:Identification of tyrosinase-related protein 2 as a tumor rejection antigen for the B16 melanoma. 905 45

Direct gene transfer to solid tissues or metastatic cancer cells requires vectors capable of in vivo transduction to specific cells. The predominant retroviral vectors of murine origin are inactivated by human complement, which precludes their use in vivo. Such inactivation does not take place with vectors based on human retroviruses. Murine retroviral vectors are also limited to proliferating cells, which human retroviruses are not. In this study we examined whether or not a vector using components from the human retroviruses HIV-1 and HTLV-1 could infect small-cell lung cancer cells and resting CD34+ hematopoietic stem cells. While HIV-1 itself was unable to infect cells lacking the CD4-membrane molecule, chimeric viral particles (pseudotype virus) with HIV-1 genome and HTLV-1 envelope components were able to infect both CD4-containing lymphocytic cells, CD4-negative tumour cells and hematopoietic stem cells. After infection with the pseudotype vector, the RNA genome was reverse transcribed and integrated. Transduction efficiency and gene expression under the HIV-1 LTR promoter in both tumour and stem cells were found to be of a similar or greater magnitude than in lymphocytic cells. These results suggest that gene transfer targeting proliferating as well as resting cells in vivo may be realized using components from human retroviruses.
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PMID:Transduction potential of human retroviruses in highly proliferating small-cell lung cancer cells as well as non-proliferating hematopoietic stem cells. 935 Feb 17

Wnt-1 was first identified as a protooncogene activated by viral insertion in mouse mammary tumors. Transgenic expression of this gene using a mouse mammary tumor virus LTR enhancer causes extensive ductal hyperplasia early in life and mammary adenocarcinomas in approximately 50% of the female transgenic (TG) mice by 6 months of age. Metastasis to the lung and proximal lymph nodes is rare at the time tumors are detected but frequent after the removal of the primary neoplasm. The potent mitogenic effect mediated by Wnt-1 expression does not require estrogen stimulation; tumors form after an increased latency in estrogen receptor alpha-null mice. Several genetic lesions, including inactivation of p53 and over-expression of Fgf-3, collaborate with Wnt-1 in leading to mammary tumors, but loss of Sky and inactivation of one allele of Rb do not affect the rate of tumor formation in Wnt-1 TG mice.
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PMID:Use of MMTV-Wnt-1 transgenic mice for studying the genetic basis of breast cancer. 1071 83

We have previously documented the cell-type-specific and hormone-dependent expression of the EphB4 receptor in the mouse mammary gland. To investigate its role in the biology of the mammary gland, we have established transgenic mice bearing the EphB4 receptor under the control of the MMTV-LTR promoter, which represents the first transgenic mouse model to investigate the effect(s) of unscheduled expression of EphB4 in adult organisms. Transgene expression in the mammary epithelium was induced at puberty, increased during pregnancy, culminated at early lactation and persisted until day three of post-lactational involution. In contrast, expression of the endogenous EphB4 gene is downregulated during pregnancy, is essentially absent during lactation and is re-induced after day three of post-lactational involution. The unscheduled expression of EphB4 led to a delayed development of the mammary epithelium at puberty and during pregnancy. During pregnancy, less lobules were formed, these however exhibited more numerous but smaller alveolar units. Transgenic mammary glands were characterized by a fragile, irregular morphology at lactation; however, sufficient functionality was maintained to nourish the young. Transgenic mammary glands exhibited untimely epithelial apoptotic cell death during pregnancy and abnormal epithelial DNA synthesis at early post-lactational involution, indicating a disturbed response to proliferative/apoptotic signals. Mammary tumours were not observed in the EphB4 transgenic animals; however, in double transgenic animals expressing both EphB4 and the neuT genes, tumour appearance was significantly accelerated and, in contrast to neuT-only animals, metastases were observed in the lung. These results implicate EphB4 in the regulation of tissue architecture, cellular growth response and establishment of the invasive phenotype in the adult mammary gland.
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PMID:Altered mammary epithelial development, pattern formation and involution in transgenic mice expressing the EphB4 receptor tyrosine kinase. 1180 21

We hypothesize that elevation of nm23-HI metastasis suppressor gene expression in micrometastatic tumor cells may reduce their subsequent colonization and invasion, and induce differentiation, with a clinical benefit. This report presents the first analysis of the nm23-HI promoter to identify sites which can increase its transcription. Deletion mapping of a 2.1 kb nm23-H1 promoter fragment tethered to a reporter gene identified three regions involved in its differential expression levels among a panel of human breast carcinoma cell lines: a 195 bp NheI-XbaI fragment responsible for basal expression levels, a 248 bp AvrII-Nhel fragment which contributed to the elevated nm23-H1 expression observed in the high expressing cell lines, and a 544 bp AvrII fragment containing an inhibitory element. Examination of the 248 bp AvrII-NheI fragment revealed the unexpected presence of three transcription factor binding sites (MAF/Ets, CTF/NF1 half site and ACAAAG enhancer) previously identified in the MMTV-LTR, and in WAP and milk gene promoters, proposed to mediate mammary-specific gene expression. Mutation of the three sites, individually or together, resulted in two-fold reductions in reporter gene expression. As controls, the same panel of mutations caused a different pattern of reporter gene expression in a non-mammary cell line, and mutation of another nearby site was without effect on nm23-HI. Our data identify a complex regulatory pattern for nm23-H1 transcription, and suggest that a mammary-specific cassette of transcription factors contribute to its elevated expression
Clin Exp Metastasis 2002
PMID:MMTV-associated transcription factor binding sites increase nm23-H1 metastasis suppressor gene expression in human breast carcinoma cell lines. 1191 81

TGF-betas play diverse and complex roles in many biological processes. In tumorigenesis, they can function either as tumor suppressors or as pro-oncogenic factors, depending on the stage of the disease. We have developed transgenic mice expressing a TGF-beta antagonist of the soluble type II TGF-beta receptor:Fc fusion protein class, under the regulation of the mammary-selective MMTV-LTR promoter/enhancer. Biologically significant levels of antagonist were detectable in the serum and most tissues of this mouse line. The mice were resistant to the development of metastases at multiple organ sites when compared with wild-type controls, both in a tail vein metastasis assay using isogenic melanoma cells and in crosses with the MMTV-neu transgenic mouse model of metastatic breast cancer. Importantly, metastasis from endogenous mammary tumors was suppressed without any enhancement of primary tumorigenesis. Furthermore, aged transgenic mice did not exhibit the severe pathology characteristic of TGF-beta null mice, despite lifetime exposure to the antagonist. The data suggest that in vivo the antagonist may selectively neutralize the undesirable TGF-beta associated with metastasis, while sparing the regulatory roles of TGF-betas in normal tissues. Thus this soluble TGF-beta antagonist has potential for long-term clinical use in the prevention of metastasis.
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PMID:Lifetime exposure to a soluble TGF-beta antagonist protects mice against metastasis without adverse side effects. 1207 Feb 99


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