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

Bone marrow biopsy specimens were evaluated retrospectively in 63 of 88 (72%) patients with small cell lung cancer (SCLC). Significant differences were not found between extensive disease (ED) patients with or without bone marrow metastases in survival nor in nadirs of leucocytes or platelets subsequent to chemotherapy. A panel of antibodies was used to investigate whether immunohistochemical analysis on routinely processed bone marrow biopsy specimens could detect marrow metastases more effectively than conventional microscopy. In histologically proven marrow metastases and in control SCLC sections a combination of an antibody against cytokeratin 8, 18 and 19 (NCL5D3) and an antibody against neurone specific enolase was validated for detection of metastases. In histologically negative marrow biopsy samples, however, this combination did not yield any additional tumour positive cases. Therefore, histological evaluation of a bone marrow biopsy specimen, even when analysed by immunohistochemistry, does not contribute information relevant for staging, therapy evaluation or prognosis in SCLC.
 ...
PMID:Examination of bone marrow biopsy specimens and staging of small cell lung cancer. 196 46

Keratin 8 (K8) and keratin 18 (K18) are the most common and characteristic members of the large intermediate filament gene family expressed in 'simple' or single layer epithelial tissues of the body. Their persistent expression in tumor cells derived from these epithelia has led to the wide spread use of keratin monoclonal antibodies as aids in the detection and identification of carcinomas. Oncogenes which activate ras signal transduction pathways stimulate expression of the K18 gene through transcription factors including members of the AP-1 (jun and fos) and ETS families. The persistent expression of K8 and K18 may reflect the integrated transcriptional activation of such transcription factors and, in the cases of ectopic expression, an escape from the suppressive epigenetic mechanisms of DNA methylation and chromatin condensation. Comparison of the mechanisms of transcriptional control of K18 expression with expression patterns documented in both normal and pathological conditions leads to the proposal that persistent K8 and K18 expression is a reflection of the action of multiple different oncogenes converging on the nucleus through a limited number of transcription factors to then influence the expression of a large number of genes including these keratins. Furthermore, correlation of various tumor cell characteristics including invasive behavior and drug sensitivity with K8 and K18 expression has stimulated consideration of the possible functions of these proteins in both normal development and in tumorigenesis. Recent developments in the analysis of the functions of these intermediate filament proteins provide new insights into diverse functions influenced by K8 and K18.
Cancer Metastasis Rev 1996 Dec
PMID:Oncogenic regulation and function of keratins 8 and 18. 903 3

One major obstacle to the successful treatment of epithelial derived tumors, such as breast and prostate carcinoma, is the presence of a multiple drug resistance phenotype. The drug resistance which is observed in growing epithelial derived cancer cells could either be an intrinsic, selected and/or an acquired characteristic. A survey of the survival data from several laboratories suggests that epithelial derived tumor cells, which have never been challenged with damaging agents, are in some cases 10 to 2,000 times more resistant to various chemotherapeutic agents as compared to hematopoietic cell lines. An intrinsic characteristic of epithelial cells is their resistance to the lethal effects of multiple types of damaging agents. A major feature of epithelial derived tumors is the expression of the intermediate filament type proteins known as cytokeratin. The simplest cytokeratin combination, cytokeratin 8 and 18, is a major cytoplasmic element within the cells of epithelial derived tumors. Earlier work showed that cytokeratin could be modified by mitoxantrone, a chemotherapeutic agent used in the treatment of breast cancer. Increasing data indicates that the intrinsic drug resistance phenotype is due in part to the presence of continued expression of the cytokeratin 8 and 18. The cytokeratin dependent drug resistance (C-MDR) has been observed in two different cell types that were engineered to contain cytokeratin 8 and 18 expression. The cytokeratin monomers are known to self assemble into intermediate filament networks as shown by numerous basic studies. Experiments using transfected cell lines which are unable to assemble networks indicated that C-MDR does not depend upon the formation of an intermediate filament network. Selection of cytokeratin network defective tumor cells did not increase their sensitivity to chemotherapeutic agents. These data are interesting since it suggests that the C-MDR phenotype is not dependent upon the structural nature (i.e. network forming ability) of the cytokeratin. Our current working hypothesis is that the interaction of the damaging agent with cytokeratin may initiate signaling response(s) for cell survival.
Cancer Metastasis Rev 1996 Dec
PMID:Multiple drug resistance and intermediate filaments. 903 6

A 57-year-old female patient presented with painless obstructive jaundice and mild mesogastric pain; she was in good general condition on admission. Abdominal ultrasonography revealed diffuse tumoral invasion of the liver, suggesting diffuse metastases. A liver biopsy showed a tumour with a trabecular growth pattern, composed of uniform relatively small cells, very suggestive of an endocrine carcinoma. Additional immunohistochemical stains, however, did not show any endocrine differentiation, but showed positivity for both hepatocyte-type cytokeratins (cytokeratin 8 and 18) and bile duct-type cytokeratins (cytokeratin 7 and 19). In addition, parathyroid hormone-related peptide, shown to be a good marker for cholangiocarcinoma, was immunoreactive. Electron microscopy revealed tumour cells with an intermediate phenotype: the cells clearly showed hepatocyte features on one hand and bile duct cell features on the other hand. Nine days after admission, the patient died due to liver failure and hepatic encephalopathy. Autopsy excluded another primary tumour site. Overall, this tumour was a primary liver tumour with an intermediate phenotype and with a very rapid clinical course. The intermediate (between hepatocyte and bile duct cell) phenotype suggests an immature progenitor cell origin, which is concordant with a rapid clinical course. This type of tumour has not been described previously and provides additional evidence for the existence of progenitor cells in human liver.
 ...
PMID:Primary liver tumour of intermediate (hepatocyte-bile duct cell) phenotype: a progenitor cell tumour? 976 16

Much remains to be learned about drug resistance in the biology of RCC and its metastases. We measured MDR-1/P-glycoprotein expression in 19 tumor samples from patients with metastatic RCC by RNase protection and quantitative PCR assays. The median level of the 16 tumor metastases was 4.9 (range: 0.10 to 156.2) relative to the level of 10 assigned to a reference cell line, SW620, which has been characterized as expressing a minimum level of MDR-1. Since these levels were lower than expected for RCC, we asked whether the metastases possessed a phenotype different from primary RCC and examined MDR-1 expression in 5 paired cell lines derived from primary and metastatic RCC. In 8/10 lines, MDR-1 expression was >10. Relative to the level in the primary line, MDR-1 expression was decreased (3 to 50-fold) in 3 metastatic lines, was increased in 1, and unchanged in 1. MRP mRNA expression was lower in the metastatic lines while EGFR expression was variable. IC50 values for 6 compounds (including 4 standard agents and one new Phase 1 agent) were determined for the paired lines. Rhodamine and calcein efflux assays were performed as measures of P-glycoprotein and MRP function. Rhodamine efflux correlated with MDR-1 mRNA expression (r = 0.87) and with the IC50s (r = 0.60) for paclitaxel in the paired cell lines. In contrast, calcein efflux did not correlate with MRP expression. Lastly, MDR-1 expression correlated with cytokeratin 8 (CK8) protein levels, a measure of cellular differentiation. In sum, these data suggest renal cell carcinoma (RCC) metastases have altered MDR-1 expression potentially due to altered differentiation relative to the primary tumor. Thus, the drug resistance phenotype of primary RCC tumors may not reflect that of their metastases.
 ...
PMID:Intrinsic drug resistance in primary and metastatic renal cell carcinoma. 1037 90

Flow cytometric DNA content measurements have demonstrated extensive DNA ploidy heterogeneity in primary breast carcinomas. However, little is known at the molecular level about the clonal relationship between these tumor cell subpopulations, or about the molecular genetic changes associated with aneuploidization. We have used flow cytometric cell sorting to dissect some of this complexity by isolating clonal subpopulations in breast carcinomas for comparative molecular genetic analysis. Clonal subpopulations were isolated from 12 primary breast carcinomas and 5 lymph node metastases from 4 cases based on DNA content and cytokeratin 8/18 labeling. DNA from these clones was screened for allelic imbalances with 92 polymorphic microsatellite markers mapped to 39 different chromosome arms. Diploid and aneuploid populations were concurrently present in 11 out of 12 primary tumors. The DNA ploidy status of primary tumors was identical to that of the related lymph node metastases. Allelic imbalance was present in 10 out of 11 diploid clones (mean, 3.4 +/- 4.2). All allelic imbalances observed in the diploid clones recurred in the cognate aneuploid clones, but were, in the latter, accompanied by additional allelic imbalances at other loci and/or chromosome arms (mean, 10.9 +/- 5.8). In only two of the four metastatic cases did the allelotypes of metastatic clones show small differences relative to their cognate primary tumors. The primary diploid tumor clone recurred in all lymph node metastases. This study indicates that the majority of allelic imbalances in breast carcinomas are established during generation of DNA ploidy diversity. Recurrence of the allelic imbalances in diploid clones in the aneuploid clones suggests linear tumor progression, whereas the simultaneous presence of early diploid and advanced aneuploid clones in both primary and metastatic tumor sites suggests that acquisition of metastatic propensity can be an early event in the genetic progression of breast cancer.
 ...
PMID:Allelotype analysis of flow-sorted breast cancer cells demonstrates genetically related diploid and aneuploid subpopulations in primary tumors and lymph node metastases. 1082 2

In the period 1993-1998, digital carcinomas in 64 cats were examined. In all animals primary complaints were painful digit(s). Eight cats had a primary squamous cell carcinoma which involved one digit or two adjacent digits of one leg. Fifty-six cats had metastases of a pulmonary carcinoma in the digits, and in general multiple digits of different legs were involved. In many of these cats metastases also occurred in other organs, including the skin and muscles. No primary sweat gland carcinomas of the digits were seen. Primary squamous cell carcinomas of the digits were characterized by cornification and the absence of PAS-positive cells, PAS-positive secretory material. Immunohistochemically, these neoplasms stained negative with the monoclonal antibody CAM 5.2 directed against Keratin 8 (K 8). The metastases of pulmonary carcinomas to the digits showed one or more of the following histological features: goblet cells, ciliated epithelial cells, PAS-positive cells or lakes, and/or a PAS-positive lining of luminal membranes and no cornification. Immunohistochemically, they showed positive staining for CAM 5.2 (K8). Thoracic radiographs from three cats with a primary squamous cell carcinoma showed no abnormalities, whereas all cases of metastases from a pulmonary carcinoma to the digits available for follow-up showed evidence of a primary pulmonary carcinoma on radiography and/or postmortem examination (25 out of 56). The conclusion of this study was that most carcinomas in the digits of cats were metastases of a primary pulmonary carcinoma (87.5%). Primary squamous cell carcinomas occurred infrequently. The prognosis of metastases of a pulmonary carcinoma in the digits is poor with an average survival time of 4.9 weeks, in contrast to 29.5 weeks in cats with a squamous cell carcinoma. These data stress the importance of taking thoracic radiographs of cats with digital tumours before surgical intervention.
 ...
PMID:Primary and metastatic carcinomas in the digits of cats. 1095 43

A 21-year-old thoroughbred mare had a 35 x 14 x 10 cm mass involving the mammary gland. Metastases were found in the kidneys, lungs, skeletal muscles, and regional lymph nodes. Histopathologic examination of the tumor revealed a ductal solid carcinoma with extensive intraductal and intralobular involvement and focal infiltration of the adjacent stroma. The intralobular neoplasms were divided into irregularly shaped islands and sheets of polygonal and spindle-shaped epithelial cells by thick or thin fibrous connective tissue bundles. The neoplastic cells had a small or moderate amount of cytoplasm that stained faintly with eosin and round or oval hyperchromatic nuclei. Immunohistochemically, the neoplastic cells were strongly positive for Lu-5, weakly positive for AE1/AE3, vimentin, and glial fibrillary acidic protein, and negative for cytokeratin 8, cytokeratin 14, alpha-smooth muscle actin, calponin, and S100. The neoplasm was diagnosed as an invasive ductal carcinoma of the mammary gland with multiple metastases.
 ...
PMID:Invasive ductal carcinoma of the mammary gland in a mare. 1262 17

The lymph nodes status is one of the most important prognostic factors in breast cancer. The routine hematoxilin-eosin staining is efficient for the metastases detection only when there is a large number of tumor cells, while a small number of metastatic cells can easily remain undetectable. For those situations, the immunohistochemistry for cytokeratins, markers of the epithelial cells, is a very sensitive method. We have investigated the cytokeratin 8 expression in 10 primary breast carcinomas and in the corresponding axillary lymph nodes, comparing with hematoxilin-eosin. The routine examination has detected axillary lymph nodes metastases in six cases, confirmed by the immunohistochemistry for cytokeratin 8. Four cases were diagnosed as negative for the axillary lymph nodes metastases by the hematoxilin-eosin staining. In all those four cases, immunohistochemistry for cytokeratin 8 has detected a small number of tumor cells, either spread in the lymph nodes tissues, either confluent as small islets.
 ...
PMID:[Detection of lymph nodes micrometastases in breast carcinoma using immunohistochemistry for cytokeratin 8]. 1497 17

In the present study, we examined the expression of the mammaglobin genes, MGB1 and MGB2, in the sentinel lymph nodes (SLNs) of patients with breast cancer and compared our results with the histologic status of the same SLNs. Compared with immunohistochemical staining for cytokeratin 8, which detected metastases in 17 of 42 patients, reverse transcription-polymerase chain reaction (RT-PCR) for MGB1 or MGB2 genes was positive in 22 patients. The concordance between the expression of any mammaglobin and histologic status was 79% (33/42), with a sensitivity of 88% and specificity of 72%. The detection of patients with metastases was more sensitive when testing for both MGB1 and MGB2 (P < .0001) rather than MGB2 (P < .0005) or MGB1 (P < .05) alone. The increased detection rate relative to histologic examination suggests that using RT-PCR for the mammaglobin genes might identify patients at higher risk compared with patients with negative RT-PCR results.
 ...
PMID:RT-PCR for mammaglobin genes, MGB1 and MGB2, identifies breast cancer micrometastases in sentinel lymph nodes. 1515 Dec 3


1 2 3 Next >>