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At least 109 records · Page 6Linked to original sources
PubMed2006

Prostate cancer metastasis: role of the host microenvironment in promoting epithelial to mesenchymal transition and increased bone and adrenal gland metastasis.

BACKGROUND: The ARCaP cell line was established from the ascites fluid of a patient with metastatic prostate cancer. This study characterized the host microenvironmental role in cancer progression, epithelial to mesenchymal transition (EMT), and bone and adrenal metastasis in parental ARCaP and its derived cell subclones. METHODS: Cytogenetic profiles, growth, migration, invasion, cellular interaction, drug sensitivities, and gene expression of ARCaP cell subclones were compared. In vivo gene expression, behavior, and metastasis of ARCaP subclones were analyzed by serial intracardiac injections into SCID mice. RESULTS: ARCaP(E) cells, with cobblestone morphology, underwent EMT through cellular interaction with host bone and adrenal gland. Lineage-derived ARCaP(M) cells, with spindle-shape fibroblastic morphology, exhibited decreased cell adhesion and increased metastasis to bone and adrenal gland. Cytogenetic analyses of parental and ARCaP subclones confirmed their clonality. CONCLUSIONS: ARCaP uniquely models the molecular basis of prostate cancer bone and adrenal metastases and epithelial to mesenchymal transition.

Adenocarcinoma↗
PubMed1989

Merkel cell carcinoma. Long term survival in a patient with proven brain metastasis and presumed choroid metastasis.

Merkel cell carcinoma (Trabecular carcinoma) is a rare malignant tumor of the skin. Because these tumors tend to spread locally via the lymphatic system, very few papers have dealt with the treatment of distant metastasis. Systemic disease is uncommon and usually fatal. In this paper, we report a case of Merkel cell carcinoma with proven brain metastasis and a solid choroidal tumor. The patient responded well to radiation and chemotherapy and is alive and neurologically intact three years after diagnosis. All previous patients with metastatic Merkel cell carcinoma to the brain died within two months of the diagnosis. We use this case to discuss possible routes of metastatic dissemination and to review the treatment options in patients with distant metastatic disease. To our knowledge, this is the first reported case of presumed choroidal metastasis of Merkel cell carcinoma and the longest documented survival in a patient with brain involvement.

Brain Neoplasms↗
PubMed1992

Metastasis induction by incomplete tumor resection. A new metastasis model using inoculation sarcomas in adult nude mice after long-term cultivation of sarcoma cells.

In searching an animal model to study metastasis formation we used cultured cells of experimental rhabdomyosarcomas and their inoculation tumors in adult nude mice. Supplementing earlier observations (Katenkamp et al. 1987) we found that long-term cultured sarcoma cells induce tumors in adult nude mice which do not metastasize spontaneously but produce lung metastases after repeated incomplete tumor removal. Possible factors and mechanisms responsible for metastasis emergence are discussed. The metastasis model introduced may be apt to study cellular changes at cytogenetic and molecular biological level that occur during tumor progression and metastatic dissemination.

Animals↗
PubMed2006

Metastasis tumor antigen family proteins during breast cancer progression and metastasis in a reliable mouse model for human breast cancer.

PURPOSE: Chromatin remodeling pathways are critical in the regulation of cancer-related genes and are currently being explored as potential targets for therapeutic intervention. The metastasis tumor antigen (MTA) family of proteins, MTA1, MTA2, and MTA3, are components of chromatin remodeling pathways with potential roles in breast cancer. Although all three MTA family proteins have been shown to be associated with metastatic progression of breast cancers, the expression characteristic of MTA1-3 proteins in a multistep breast cancer progression model remains unknown. Structural and functional studies have suggested that they are heterogeneous in the Mi-2/NuRD complex, exhibit tissue-specific patterns of expression, and impart unique properties to estrogen receptor-alpha (ERalpha) action. This led us to hypothesize that each member of the MTA family possesses a unique role and interacts with different pathways in the stepwise process of breast cancer development and progression. EXPERIMENTAL DESIGN: MTA family proteins were examined by immunohistochemistry in breast cancer processes ranging from normal duct, to premalignant lesions, to invasive carcinoma, and to metastasized tumors in PyV-mT transgenic mice, which represents a reliable model for multistage tumorigenesis of human breast cancer. We also determined the association of MTA proteins with the status of cell proliferation, ER, E-cadherin and cytoplasmic beta-catenin, and cancer-related coactivators, AIB1 and PELP1. RESULTS: The expression of all three MTA proteins was altered in primary breast tumors. Each MTA protein had a unique expression pattern during the primary breast tumor progression. Altered expression of MTA1 was observed in both premalignant lesion and malignant carcinoma, but an elevated nuclear expression was observed in ER-negative carcinomas. MTA3 was exclusively expressed in a subset of cells of ER-positive premalignant lesions but not in carcinomas. MTA2 expression seems to be unrelated to ER status. Loss of MTA3 expression and more nuclear localization of MTA1 occurred with loss of E-cadherin and decreased cytoplasmic beta-catenin, two molecules essential for epithelial cell adhesion and important tumor cell invasion. At the late stage of tumor formation, MTA1 is usually expressed in the center of tumors. Coincidentally, the distribution of MTA1-positive cells at this stage was complementary to that of AIB1 and PELP1, which were localized to the tumor periphery with relatively active cell proliferation, scattered ER-positive cells and a limited differentiation. In metastasized lung tumors, the expression pattern of MTA-protein expression was distinct from that in primary counterparts. CONCLUSIONS: The findings presented here support the notion that each member of the MTA family might potentially play a stepwise role in a cell type-specific manner during breast cancer progression to metastasis. On the basis of the noted temporal expression patterns of MTA proteins with ER status, cell adhesion-essential regulators (E-cadherin and cytoplasmic beta-catenin), and coactivators, we propose that MTA protein-related chromatin remodeling pathways interact with steroid receptors, growth factor receptors, and other transcriptional signaling pathways to orchestrate the governing of events in breast cancer progression and metastasis.

Animals↗
PubMed2000

Prevention of metastasis by a polyamine synthesis inhibitor in an animal bone metastasis model.

In order to better understand the development of skeletal metastases, we developed an appropriate animal model, as the natural progression of metastases in humans cannot be studied on the cellular level. In this study, we established a new animal model which developed bone metastasis in a bone grafted subcutaneously. C57BL/6 mice, which had received a bone (femur or tibia) transplanted in the dorsal subcutis, were injected with B16 melanoma cells into the left heart ventricle. Metastasis was found in approximately 70% of the extraskeletal bones. Using this model, the antimetastatic effect of a polyamine synthesis inhibitor was investigated. Inhibitors of the polyamine biosynthetic pathway have received considerable attention for their potential use in the treatment of cancer as they are responsible for the greatly increased production of the polyamines putrescine, spermidine, and spermine. A polyamine synthesis inhibitor, methylglyoxal-bis(cyclopentylamidinohydrazone) MGBCP, was investigated for its inhibitory effects on bone metastases. MGBCP (20 mg/kg) was administered intraperitoneally every day for 4 weeks and demonstrated strong inhibitory effects on bone metastases. MGBCP inhibited angiogenesis in the transplanted bone and the growth of B16 melanoma cells, thus suggesting a preventive mechanism in bone metastasis. No remarkable adverse effects of MGBCP were observed in any animal throughout the experimental period. Our results indicate that MGBCP has a strong potential for use as an anti-metastatic drug.

Animals↗
PubMed2004

Microarray analysis of metastasis-associated gene expression profiling in a murine model of thyroid carcinoma pulmonary metastasis: identification of S100A4 (Mts1) gene overexpression as a poor prognostic marker for thyroid carcinoma.

Tumor cell invasion and metastasis are the hallmark of malignant neoplasm. Despite advances in the management of thyroid carcinoma and other solid tumors, metastasis continues to be the most significant cause in cancer mortality. To gain new insights into this complex process in thyroid carcinoma, we established a thyroid carcinoma cell line (ARO-met2) with high metastatic capacity to the lung by sequential passage of a human anaplastic thyroid cancer cell line (ARO) through the lung of a nude mouse. Global patterns of gene expression were analyzed in cells of the parental ARO and the ARO-met2, using Atlas human cancer 1.2 array with 1176 cancer-related genes. In total, 184 genes were differentially expressed more than 1.5 times, and 64 genes were differentially expressed over two times. Among those 64 genes, 43 were overexpressed, and 21 genes were underexpressed. Many genes whose increased expression was thought to be related to tumor progression were identified, such as c-Met, ezrin, integrin, motility-related protein-1, cadherin, and S100A4. The most highly expressed gene is the S100A4 (8-fold higher than control), which is a member of a small calcium binding protein family and is involved in the cell proliferation and cancer progression. The S100A4 overexpression in the ARO-met2 cells was later confirmed by Northern blot and real-time reverse transcriptase-PCR. Analysis of 49 thyroid tumor specimens by real-time reverse transcriptase-PCR (eight benign goiters, 36 papillary, and five anaplastic carcinomas) revealed that S100A4 overexpression was present in most advanced thyroid carcinomas and lymph node metastases, and was associated with poor prognosis. None of the benign goiters was found to have S100A4 overexpression. These data suggest that S100A4 could be used as a prognostic marker for thyroid carcinoma. Given that S100A4 is involved in tumor progression and metastasis, it may be a potential target for therapeutic intervention.

Animals↗
PubMed2005

Colonic carcinoma metastasis to the thyroid: a case of skip metastasis.

Colonic carcinoma metastasis to the thyroid is rare. Here the authors present the case of an 81-year-old lady who presented with metastatic colonic adenocarcinoma in her thyroid gland. This case is unique as it is the first to demonstrate metastasis from the colon to the thyroid with no other site involvement. The use of cytokeratin immunohistochemical staining is reviewed along with the current perspectives on the concept of skip metastasis.

Adenocarcinoma↗
PubMed2002

Establishment of in vivo metastasis model of human adenoid cystic carcinoma: detection of metastasis by PCR with human beta-globin gene.

Cells from the human adenoid cystic carcinoma (ACC) line, KOA-1, originating from the minor salivary gland and showing histological features of a dominantly solid pattern of ACC, were transplanted into the subcutaneous tissue of nude mice. The occurrence of lung metastasis was then examined both histologically and by PCR with a human-specific base arrangement of the beta-globin gene. Histologic examinations revealed lung metastasis in 5 of 30 mice. On the other hand, PCR showed a higher positive rate: 26 of 67 mice (0/10 at 1 month, 5/15 at 2 months, and 21/42 at 3 months after the transplantation). When some lungs which showed positive results by PCR analysis were transplanted into other mice, KOA-1 tumors developed. The results suggested that this experimental model could be a standard in vivo model of metastasis of human ACC.

Animals↗
PubMed2004

[Study on the inhibitory effect of small tripeptide CMS024 on tumor growth and metastasis in nude mice model of human hepatocellular carcinoma metastasis].

OBJECTIVE: This experiment was designed to study the effect of small molecule tripeptide CMS024 on tumor growth and metastasis in a nude mice model of human hepatocellular carcinoma (HCC) metastasis. METHODS: Highly metastatic human HCC cell strain HCCLM6 was injected into subcutaneous region of nude mice. When the subcutaneous tumor reached 0.8 cm in diameter, the tumor was removed and cut into small pieces about 1 mm in diameter and implanted orthotopically into the liver of 20 BALB/c nude mice, which were randomized into treatment group and control group each with 10 mice. The treatment group received daily CMS024 intraperitoneal injection at the dose of 300 microg/kg beginning from the second postoperative day. The control group received intraperitoneal injection of equal amount of 0.85% sodium chloride solution. The mice were observed for signs of disease development. Thirty-five days later, the mice were sacrificed and abdominal and pulmonary metastases were recorded and peripheral blood hematological and biochemical parameters were determined. RESULTS: After 35 days of intervention, all the 10 mice in the treatment group were alive and well, but there were only 9 living mice in the control group. The mean tumor weights were 1.9 g +/- 0.5 g in the treatment group and 2.3 g +/- 0.8 g in the control group (P > 0.05). The abdominal wall metastases and intraperitoneal metastases were 100% for the control group and only 60% and 50%, respectively, for the treatment group (P < 0.05). Bloody ascites and gross intrahepatic metastatic nodules were found in 70% and 90% of nude mice, respectively, for the control group, and 20% and 40%, respectively, for the treatment group (P > 0.05). The median number of grades I, II, III and IV pulmonary metastases were 92, 24, 15 and 16, respectively, for the control group, and 24, 20, 10 and 8, respectively, for the treatment group. There were statistically significant differences in the number of grade I pulmonary metastases between the treatment group and the control group (24 vs 92, P < 0.05). No statistically significant differences in the body weight, peripheral blood hematological and biochemical parameters were observed between the two groups. No toxic effects were observed during the observation period. CONCLUSIONS: Small molecule tripeptide CMS024 demonstrated positive effects to retard tumor growth and inhibit loco-regional and long distance metastases in a nude mice model of human HCC metastasis, and no obvious toxic or side effects on the tumor bearing nude mice.

Animals↗
PubMed2004

[Successful treatment of liver metastasis and extrahepatic metastasis with hepatic arterial infusion of CDDP, CPT-11, and 5-FU].

A 63-year-old man, who had been operated with right hemicolectomy 1 year and 3 months ago, had giant liver metastasis, lung metastasis, and local dissemination tumor due to ascending colon cancer. He was treated by systemic chemotherapy with 5-FU and the treatment evaluation was PD on CT. After admission to our hospital, he was treated by hepatic arterial infusion chemotherapy with CDDP, CPT-11, and 5-FU. After 3 courses of the treatment, each recurrent lesion decreased on CT and the CEA level decreased. There were no side effects except mild diarrhea. We believe hepatic arterial infusion chemotherapy with CDDP, CPT-11, and 5-FU may be an effective strategy against liver metastasis and extrahepatic metastsis due to colon cancer.

Antimetabolites, Antineoplastic↗
PubMed1997

A molecular epidemiological approach to the study of expression of a metastasis marker in primary melanomas and its correlation with individual patient's risk of recurrence or metastasis.

Tumour cells in malignant melanomas express molecules associated with tumour progression; however, up until now, no marker has been able to identify the tumour cells from which metastases are derived. It has recently been shown that in human melanoma cell lines, populations expressing peanut agglutinin (PNA)-binding glycoproteins are able to generate metastases, and that such cells do exist in primary human melanomas, their presence being associated with the degree of local invasion that governs the metastasis risk. To further investigate the correlation between the expression of PNA-binding glycoconjugates by cells from primary melanomas and the patient's individual risk of recurrence or metastasis, a molecular epidemiological approach employing histochemical techniques within a case-control design was developed. The main objective of this study is to determine whether an histochemical staining with the lectin PNA of cells in the primary lesion is associated with an increased risk of local recurrence of metastasis, and with survival, independently of Breslow's tumour thickness. The study comprises the comparison of the PNA labelling index and of the type and intratumour location of the staining as a function of clinical outcome in two matched series of patients with known clinical outcome: patients who had died at 5 years and patients alive at 5 years (to assess association with survival), and patients who experienced a recurrence within the first 5 years and patients alive without recurrence at 5 years (to assess association with risk of recurrence). A matched case-control design was used with a variable number of controls matched to each case. Apart from age (+/-5 years), sex and centre where diagnosis was made, matching was made on histogenetic type and primary tumour thickness (four categories being considered: <0.75, 0.76-1.5, 1.51-3 and >3 mm).

Biomarkers, Tumor↗
PubMedDate not supplied

[Renal carcinoma revealed by sternal metastasis and posterior contralateral adrenal metastasis].

We report a exceptional case of renal cell carcinoma whose first manifestation was bone metastases located in the sternum. Three years after radical nephrectomy solitary contralateral adrenal metastasis appeared. Exeresis bone metastasis, radical nephrectomy and adrenalectomy were performed. The patient is alive with no evidence of disease with hormonal substitute treatment 5 years and 2 months after esternal metastasis exeresis and 1 year and 3 months after right adrenalectomy.

Adrenal Gland Neoplasms↗
PubMed1995

Suppressive role of the metastasis-related nm23-H1 gene in human ovarian carcinomas: association of high messenger RNA expression with lack of lymph node metastasis.

The nm23-H1 gene has been proposed as a metastasis suppressor gene. It is located on the long arm of chromosome 17, which is frequently deleted in ovarian cancer, and shows altered expression and structure in some advanced neoplasms. To evaluate the role of nm23-H1 in ovarian carcinogenesis, we have analyzed this gene in 66 primary human ovarian carcinomas at both the DNA and RNA levels. Despite the high frequency (76%) of nm23-H1 loss of heterozygosity (LOH), the complete absence of gene mutations in the coding portions of the retained allele clearly indicated that, in ovarian carcinomas, this gene does not function in the same way as do classic oncosuppressor genes. The relationship of clinicopathological parameters with nm23-H1 gene deletions and expression levels was also investigated. LOHs were more common in the serous and endometrioid histotypes (85 and 93%, respectively), and the highest LOH frequency was detected in poorly differentiated tumors (89%). A significant relationship between nm23-H1 mRNA expression and lymph node metastasis was observed in high-grade tumors, which are intrinsically more invasive than are low-grade tumors. In particular, among the poorly differentiated tumors showing areas of undifferentiated solid carcinoma (classified as G3/G4), lymph node-negative tumors displayed expression levels that were significantly higher than those of lymph node-positive tumors (P < 0.001). In conclusion, our data suggest that the nm23-H1 gene product may exert an inhibitory effect on the lymphatic dissemination of human ovarian tumors. However, several other factors, biological or time and patient dependent, influence the complex metastatic progression of ovarian tumors and may cooperate with nm23-H1 in the promotion or inhibition of this process.

Adenocarcinoma↗
PubMed1989

An index for estimating the probability of lymph node metastasis in rectal cancers. Lymph node metastasis and the histopathology of actively invasive regions of cancer.

We examined resected specimens from 40 cases of advanced rectal cancer to determine the extent of microtubular cancer nests and undifferentiated cancer cells (budding). We investigated the relationship between this budding and lymphatic invasion (ly), venous invasion (v), and lymph node metastasis (n), respectively. Moreover, we examined the relationship between ly, budding, and n in the preoperative biopsy specimens of 112 patients, including those of the 40 cases mentioned above. The degree of budding, which was abundant in the actively invasive region, showed a strong correlation with the degree of ly and the existence of n in the resected specimens. Also, budding was recognized in a relatively large portion of the biopsy specimens (52 of 112 [46.4%]) and lymph node metastasis was found in 41 of 52 specimens (78.8%). In 57 specimens, neither ly nor budding was found, and 16 of these specimens (28.1%) had positive lymph nodes. These results implied that the degree of budding in the actively invasive region can be a great help in predicting the presence of n. The presence or absence of budding in preoperative biopsy specimens also can be an important factor (along with the degree of differentiation and ly) in estimating the probability of n.

Adult↗
PubMed2004

High-mobility group protein 1(Y): metastasis-associated or metastasis-inducing?

Metastasis is the major cause of mortality and morbidity for patients with cancer. The high-mobility group protein 1(Y) [HMG-1(Y)] has a role in the transcription of many genes involved at different steps in the metastatic cascade and has been linked with cancer in human and animal models. This may represent a potential therapeutic target for patients. The following review summarizes and critically appraises the evidence for the role of HMG-1(Y) in metastasis.

Animals↗
PubMedDate not supplied

Type-oriented therapy for gastric cancer effective for lymph node metastasis: management of lymph node metastasis using activated carbon particles adsorbing an anticancer agent.

Activated carbon particles are taken selectively up by lymphatics when injected into the tissues and visualize regional lymph nodes colored black. Furthermore, carbon particles adsorb a large amount of the anticancer agent mitomycin C (MMC) on their surface and release the drug reversibly. Using these properties of activated carbon particles, we have applied it for lymph node dissection and chemotherapy of lymph node metastasis. After injection of carbon particles, regional lymph nodes of the stomach were found to be black; blackened lymph nodes extending widely from perigastric to para-aortic nodes were identified from other structures. Four hundred and twenty-four patients with gastric cancer were treated with this method for lymph node metastasis during 1984-1988. Involved nodes were generally colored in high incidence, about 70% of involved ones except for highly positive nodes, which was the same as noninvolved nodes. In highly positive nodes, the colored incidence was decreased to about 48%. The cumulative 5-year survival rate of the patients treated with this series was 74.6%, which was significantly higher than the figures without this method.

Carbon↗
PubMed2005

Umbilical metastasis after laparoscopic retroperitoneal paraaortic lymphadenectomy for cervical cancer: a true port-site metastasis?

BACKGROUND: We present a case of umbilical metastasis after laparoscopic retroperitoneal paraaortic lymphadenectomy for cervical cancer. CASE: A 59-year-old woman with stage IIIB cervical adenocarcinoma underwent laparoscopic paraaortic lymphadenectomy as well as a conventional laparoscopy to assess the presence of peritoneal carcinomatosis. The pathologic examination revealed metastasis in one paraaortic node. Peritoneal cytology proved negative for malignant cells. Seven months after completion of chemoradiotherapy, the patient presented a 2.5-cm umbilical tumor involving the trocar tract together with recurrence of the cervical mass. Histological examination of the excised umbilical mass showed recurrence of the cervical adenocarcinoma, with strong peritumoral CD31 immunocytochemical expression. CONCLUSION: The peritumoral increase in microvessel density and strong CD31 positivity suggests angiogenesis as a potential factor lead to seeding of tumor cells at the umbilical port.

Abdominal Neoplasms↗
PubMed2003

MKK4 and metastasis suppression: a marriage of signal transduction and metastasis research.

MAP kinase kinase 4 (MKK4) is a member of the stress-activated protein kinase (SAPK) signaling cascade and is involved in the regulation of many cellular processes. We have recently demonstrated a functional role for MKK4 in the suppression of metastases. In this review, we discuss the established cellular and biochemical functions of MKK4, as well as a new function for MKK4 as a metastasis suppressor gene. Because of the importance of signaling studies to this translational work, a detailed example of the strategy and tools that can be employed to define the biochemical mechanism of MKK4-mediated metastasis suppression is presented. Finally, the potential therapeutic utility of these findings is discussed.

Animals↗