Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Radio-labelled antimyosin-monoclonal antibodies (AMA) have been introduced to demonstrate myocardial necrosis after cardiac infarction or in cardiac allograft transplants. As rhabdomyosarcoma (RMS) and leiomyosarcoma (LMS) are tumors of myogenic origin, thus often containing myosin, we decided to use the 111In-labelled Fab fragment of AMA (Centocor) in scintigraphic tumor detection. We examined 13 children with histologically-confirmed RMS and LMS, and five other children with other types of soft tissue sarcomas. Conventional techniques were used to determine the extent of the tumor. An uptake of the tracer was observed in all known tumor sites in seven RMS patients. As the scans were negative in three RMS patients who were in complete remission (CR) and in two other patients (fibrosarcoma and haemangiopericytoma) with a measurable tumor mass, we considered them to be "true negative". In the three remaining CR patients (1 RMS, 2 LMS) the scans were positive but weak in the primary tumor site in two cases and in a distant site (bone) in the third respectively. We considered them to be "false positive" as no tumor cells were evident in the biopsy specimen. In one case, the antimyosin uptake was presumably the result of damage to the muscles after radiation. Interestingly, in three patients with other malignancies such as rhabdoid and peripheral neuroectodermal tumors there was a noticeably strong uptake of the tracer in the primary tumors and the scans turned negative after complete remission was achieved. The diagnostic AMA scanning showed no side-effects. The reason why antimyosin antibodies permeate the membrane of the tumor cells is yet undetermined.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Radio-immunodetection of myosarcoma using 111indium antimyosin. 216

Several human rhabdomyosarcoma cell lines, cultured primary tumor explants, and biopsies of tumor and normal skeletal muscle tissue expressed a 2.0-kilobase transcript that hybridized to the mouse muscle determination gene MyoD1. This transcript was found in tumor cell lines and primary explants that developed multinucleated myotubes but was absent in Wilms' tumors or cell lines and primary explants that developed multinucleated myotubes but was absent in Wilms' tumors or cell lines derived from other mesenchymal tumor cell types. Expression of the human homolog of MyoD1 therefore can define a tumor as a rhabdomyosarcoma. Transfection of the mouse MyoD1 gene into the human rhabdomyosarcoma cell line RD increased the ability of the tumor cells to differentiate into multinucleated myotubes and enhanced myosin heavy-chain gene expression but did not decrease tumorigenicity in nude mice.
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PMID:Expression of the MyoD1 muscle determination gene defines differentiation capability but not tumorigenicity of human rhabdomyosarcomas. 260 95

A rare case of oral leiomyosarcoma diagnosed with the aid of immunohistochemical and electron microscopic examinations together with a review of the literature are reported. The patient was a 70-year-old Japanese man. The primary tumor involved the maxillary gingiva and bone and metastasized to the cervical lymph nodes. On histologic examination the tumor showed invasive growth into the maxillary bone. It was composed of interlacing fascicles of spindle-shaped cells with eosinophilic cytoplasm and elongated, blunt-ended nuclei. The tumor formed extensive metastatic foci in the cervical lymph nodes. On immunohistochemical examination most of the tumor cells were positive for desmin, smooth muscle-specific actin, and myosin. The ultrastructural characteristics of the tumor cells were abundant microfilaments, pinocytotic vesicles, and basement membrane formation. The findings were indicative of a tumor demonstrating myogenic differentiation. A review of the literature during the past 50 years disclosed a total of 60 oral leiomyosarcomas, including our case.
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PMID:Primary leiomyosarcoma of the maxilla with regional lymph node metastasis. Report of a case and review of the literature. 748 75

In rhabdomyosarcoma (RMS) of childhood and adolescence very little is known about interactions of cytotoxic drugs and tumor cells. In recurrent RMS the tumor cells are often more mature than in the primary tumor. The biological properties of these cells are still a subject of controversy. We investigated two human (RD2 and TE 671) cell lines by cultivating them with doxorubicin, cisplatinum, and etoposide. Degree of differentiation and proliferation rate were estimated morphologically and by means of immunohistochemistry and a monolayer proliferation assay. Both morphological and immunohistochemical maturation was measurable in most resistant cell lines. An increase in myosin expression was most marked in the etoposide- and doxorubicin-resistant RD cell lines. The proliferation rate was decreased in almost all resistant cell lines. Nevertheless, the resistant cell lines tolerated high-dose levels of cytotoxic drugs at a higher proliferation rate than parental cell lines cultivated under similar conditions. The maturation seen in some recurrent tumors of RMS can be simulated in vitro by cultivating cell lines with cytotoxic drugs at sublethal doses. Interestingly, the resistance-associated induced maturation was not accompanied by p170 expression. After comparing these in vitro results with the maturation seen in RMS specimens after chemotherapy, we conclude that chemotherapy-induced differentiation in vivo might be a morphological sign of chemoresistance.
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PMID:Induction of drug resistance in human rhabdomyosarcoma cell lines is associated with increased maturation: possible explanation for differentiation in recurrences? 1200 20

S100A4 is known to be involved in cancer cell motility by virtue of its ability to activate non-muscle myosin. In the current study, we investigated the interrelationship of clinico-pathological findings and S100A4 expression in oral squamous cell carcinoma (SCC). The expression of S100A4 was examined immunohistochemically in 41 clinical specimens of oral SCC. S100A4 expression was detected in 11 (26.8%) of 41 cases. Although the expression of S100A4 was not associated with the primary tumor site and degree of differentiation, there was a significant correlation between the increased S100A4-expression and the mode of invasion (p < 0.0001). In addition, the S100A4 status showed a clear correlation with lymph node metastasis (P < 0.01). These results lead us to conclude that S100A4 expression status may be a useful prognostic factor in patients with invasive and metastatic oral SCCs.
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PMID:Correlation of S100A4 expression with invasion and metastasis in oral squamous cell carcinoma. 1500 21

Dissemination of neoplastic cells from the primary tumor (invasion and metastasis) is a fundamentally dangerous step in multistage carcinogenesis. Recent evidence suggests that Rho GTPase-mediated signaling is linked to dissemination of cells from several different types of human tumors. The Rho family of proteins is typically associated with the regulation of cytoskeletal activity, including actin assembly, microtubule dynamics, and myosin II-dependent contractility of the actin-rich cortex. We examined the effect of overexpression of constitutively active RhoA on islands and monolayers of epithelial cells. Although newly plated cells initially formed small spread islands, there was also a significant population of cells that detached from the substrate, floated in the medium, and then could reattach to the substrate to form new colonies. Detachment of cells from transfected epithelial islands or monolayers occurred in correlation to the plane of cytokinesis after misorientation of the mitotic spindle axis. We suggest that these alterations result from Rho-induced increase of contractility of the cortex of dividing cells, which, during cytokinesis, produces a cell that has budded out of an existing layer of cells. Cell division-mediated detachment of cells from tissue structures may be an important mechanism of tumor dissemination and metastasis.
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PMID:Rho overexpression leads to mitosis-associated detachment of cells from epithelial sheets: a link to the mechanism of cancer dissemination. 1530 43

Long-term clinical outcomes are dependent on whether carcinoma cells leave the primary tumor site and invade through adjacent tissue. Recent evidence links tissue rigidity to alterations in cancer cell phenotype and tumor progression. We found that rigid extracellular matrix (ECM) substrates promote invasiveness of tumor cells via increased activity of invadopodia, subcellular protrusions with associated ECM-degrading proteinases. Although the subcellular mechanism by which substrate rigidity promotes invadopodia function remains to be determined, force sensing does appear to occur through myosin-based contractility and the mechanosensing proteins FAK and p130(Cas). In addition to rigidity, a number of ECM characteristics may regulate the ability of cells to invade through tissues, including matrix density and crosslinking. 3-D biological hydrogels based on type I collagen and reconstituted basement membrane are commonly used to study invasive behavior; however, these models lack some of the tissue-specific properties found in vivo. Thus, new in vitro organotypic and synthetic polymer ECM substrate models will be useful to either mimic the properties of specific ECM microenvironments encountered by invading cancer cells or to manipulate ECM substrate properties and independently test the role of rigidity, integrin ligands, pore size and proteolytic activity in cancer invasion of various tissues.
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PMID:Regulation of cancer invasiveness by the physical extracellular matrix environment. 1945 99

Breast cancer is the leading cause of cancer in women and the third leading cause of cancer mortality in the United States. We report a case of a patient who underwent bilateral simple mastectomies and right sentinel node biopsy for invasive lobular carcinoma in the right breast. An ipsilateral sentinel lymph node showed a microscopic focus of ductal elements. Although residual lobular carcinoma was identified in the right breast, no ductal carcinoma was identified in either breast. The ducts were discrete distributed in a 3-mm focus in the lymph node parenchyma as well as the subcapsular sinus. By immunohistochemistry, the ducts were positive for cytokeratin, estrogen receptor/progesterone receptor and did not show a myoepithelial layer by P63 or smooth-muscle myosin heavy-chain staining. The differential diagnosis includes heterotopic epithelial inclusions and benign mechanical transport. Mechanical transport of the breast tissue was ruled out because primary tumor type in the breast and the ductal structures in the lymph nodes were of different types. The diagnosis of occult metastatic tumor was based on the lack of the myoepithelial layers associated with the ductal structures. The diagnostic dilemma of the differential diagnoses is discussed, and pertinent literature is reviewed.
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PMID:Heterotopic breast tissue versus occult metastatic carcinoma in lymph node, a diagnostic dilemma. 2063 31

Mammary tumors are a major health threat to women and female dogs. In both, metastasis of the primary tumor to distant organs is the most common cause of tumor-related death. Nevertheless, the molecular mechanisms of tumor metastasis are far from being understood, and it is still unknown why some human and canine carcinomas metastasize and others do not. Using 2D-DIGE and MALDI-TOF-MS we identified 21 proteins with significant changes (fold change >1.5; p < 0.05) in protein expression between metastasizing (n = 6) and nonmetastasizing (n = 6) canine mammary carcinomas. Quantitative RT-PCR was used to identify transcriptional or post-transcriptional regulation of protein expression. Up-regulated proteins in metastatic carcinomas included proliferating cell nuclear antigen, ferritin light chain, bomapin, tropomyosin 3, thioredoxin-containing domain C5, adenosin, ornithine aminotransferase, coronin 1A, RAN-binding protein 1,3-phosphoglycerate dehydrogenase, and eukaryotic translation elongation factor 1. Down-regulated proteins in metastatic carcinomas included calretinin, myosin, light chain 2, peroxiredoxin 6, maspin, ibrinogen beta chain, vinculin, isocitrate dehydrogenase 1, tropomyosin 1, annexin A5, and Rho GTPase activating protein 1. Interestingly, 19 of these 21 proteins have been described with a malignancy-associated expression in human breast cancer and other human cancer types before. Further investigations are now necessary to test whether these markers are of prognostic value for canine mammary carcinomas and whether their expression is directly involved in canine mammary carcinogenesis or represent solely a secondary reactive phenotype.
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PMID:Proteome of metastatic canine mammary carcinomas: similarities to and differences from human breast cancer. 2093 60

Ovarian cancer is the fifth leading cause of cancer related deaths in the United States(1). Despite a positive initial response to therapies, 70 to 90 percent of women with ovarian cancer develop new metastases, and the recurrence is often fatal(2). It is, therefore, necessary to understand how secondary metastases arise in order to develop better treatments for intermediate and late stage ovarian cancer. Ovarian cancer metastasis occurs when malignant cells detach from the primary tumor site and disseminate throughout the peritoneal cavity. The disseminated cells can form multicellular clusters, or spheroids, that will either remain unattached, or implant onto organs within the peritoneal cavity(3) (Figure 1, Movie 1). All of the organs within the peritoneal cavity are lined with a single, continuous, layer of mesothelial cells(4-6) (Figure 2). However, mesothelial cells are absent from underneath peritoneal tumor masses, as revealed by electron micrograph studies of excised human tumor tissue sections(3,5-7) (Figure 2). This suggests that mesothelial cells are excluded from underneath the tumor mass by an unknown process. Previous in vitro experiments demonstrated that primary ovarian cancer cells attach more efficiently to extracellular matrix than to mesothelial cells(8), and more recent studies showed that primary peritoneal mesothelial cells actually provide a barrier to ovarian cancer cell adhesion and invasion (as compared to adhesion and invasion on substrates that were not covered with mesothelial cells)(9,10). This would suggest that mesothelial cells act as a barrier against ovarian cancer metastasis. The cellular and molecular mechanisms by which ovarian cancer cells breach this barrier, and exclude the mesothelium have, until recently, remained unknown. Here we describe the methodology for an in vitro assay that models the interaction between ovarian cancer cell spheroids and mesothelial cells in vivo (Figure 3, Movie 2). Our protocol was adapted from previously described methods for analyzing ovarian tumor cell interactions with mesothelial monolayers(8-16), and was first described in a report showing that ovarian tumor cells utilize an integrin -dependent activation of myosin and traction force to promote the exclusion of the mesothelial cells from under a tumor spheroid(17). This model takes advantage of time-lapse fluorescence microscopy to monitor the two cell populations in real time, providing spatial and temporal information on the interaction. The ovarian cancer cells express red fluorescent protein (RFP) while the mesothelial cells express green fluorescent protein (GFP). RFP-expressing ovarian cancer cell spheroids attach to the GFP-expressing mesothelial monolayer. The spheroids spread, invade, and force the mesothelial cells aside creating a hole in the monolayer. This hole is visualized as the negative space (black) in the GFP image. The area of the hole can then be measured to quantitatively analyze differences in clearance activity between control and experimental populations of ovarian cancer and/ or mesothelial cells. This assay requires only a small number of ovarian cancer cells (100 cells per spheroid X 20-30 spheroids per condition), so it is feasible to perform this assay using precious primary tumor cell samples. Furthermore, this assay can be easily adapted for high throughput screening.
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PMID:In vitro mesothelial clearance assay that models the early steps of ovarian cancer metastasis. 2237 Nov 43


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