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At least 73 records · Page 4Linked to original sources
PubMed2005

Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity.

Metastasis via the lymphatics is a major risk factor in squamous cell carcinoma of the oral cavity (OSCC). We sought to determine whether the presence of metastasis in the regional lymph node could be predicted by a gene expression signature of the primary tumor. A total of 18 OSCCs were characterized for gene expression by hybridizing RNA to Affymetrix U133A gene chips. Genes with differential expression were identified using a permutation technique and verified by quantitative RT-PCR and immunohistochemistry. A predictive rule was built using a support vector machine, and the accuracy of the rule was evaluated using crossvalidation on the original data set and prediction of an independent set of four patients. Metastatic primary tumors could be differentiated from nonmetastatic primary tumors by a signature gene set of 116 genes. This signature gene set correctly predicted the four independent patients as well as associating five lymph node metastases from the original patient set with the metastatic primary tumor group. We concluded that lymph node metastasis could be predicted by gene expression profiles of primary oral cavity squamous cell carcinomas. The presence of a gene expression signature for lymph node metastasis indicates that clinical testing to assess risk for lymph node metastasis should be possible.

Adult↗
PubMed2005

Vascular endothelial growth factor-D induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer.

The presence of lymphatic metastases is a strong indicator for poor prognosis in patients with ductal pancreatic cancer. In order to better understand the mechanisms controlling lymphatic growth and lymph node metastasis in human ductal pancreatic cancer, we analyzed the expression pattern of the vascular endothelial growth factor-D (VEGF-D), its receptor VEGF-receptor-3 (VEGFR-3) and the lymphatic endothelium-specific hyaluronan receptor LYVE-1 in a panel of 19 primary human ductal pancreatic tumors and 10 normal pancreas specimens. We further addressed the biological function of VEGF-D for induction of lymphatic metastasis in a nude mouse xenograft model using two human ductal pancreatic cancer cell lines with overexpression of VEGF-D. Compared to normal human pancreas, pancreatic cancer tissue showed overexpression of VEGF-D and VEGFR-3 in conjunction with a high lymphatic vascularization as determined by immunohistochemistry and in situ hybridization. Tumors derived from VEGF-D-overexpressing cells had a higher microvessel density compared to their mock-controls, as determined based on CD31 immunohistochemistry. Importantly, these tumors also revealed a significant induction of intra- and peritumoral lymphatics, as judged from immunohistochemical detection of LYVE-1 expression. This was associated with a significant increase in lymphatic vessel invasion by tumor cells and an increased rate of lymphatic metastases, as indicated by pan-cytokeratin reactive cells in lymph nodes. Our results suggest that VEGF-D plays a pivotal role in stimulating lymphangiogenesis and lymphatic metastasis in human ductal pancreatic cancer, and therefore represents a novel therapeutic target for this devastating disease.

Animals↗
PubMed2004

[Expression of matrix metalloproteinase-2,9 in hypopharyngeal carcinoma and its relationship with lymphatic metastasis].

OBJECTIVE: To study the relationship between matrix metalloproteinase-2,9 (MMP-2,9) and the biology behavior, lymphatic metastasis of hypopharyngeal carcinoma by investigating the expression of MMP-2,9. METHOD: Two-step immunohistochemical method was used to examine the expression of monoclona antibody in hypopharyngeal carcinoma tissues. RESULT: It was found that the positive rate of MMP-2 in 32 hypopharyngeal carcinoma tissues was 53.12% (17/32),and the positive rate of MMP-9 was 59.38% (19/32). The difference of the expression in tumor tissue and normal mucosa beside the tumor was significant. The positive rate in those carcinoma with cervical lymph node metastasis was much higher than that in cases without cervical lymph node metastasis. And there was no significant difference found in the expression of MMP-2 and MMP-9. CONCLUSION: MMP-2 and MMP-9 may relate with the lymph node metastasis in hypopharyngeal carcinoma.

Adult↗
PubMed2000

[Effects of ultrasonography on evaluating the status of cervical lymphatic metastasis in patients with oral squamous cell carcinoma].

OBJECTIVE: To investigate effects of ultrasonography on evaluating the status of cervical lymphatic metastasis in patients with oral squamous cell carcinoma (OSCC). METHODS: Nineteen OSCC patients with the diagnosis confirmed by biopsy of primary focus were included in this study. All the patients were hospitalized in the department of stomatology, Beijing Medical University during June, 1995 and June, 1996, among them there were 13 men and 6 women. The ages were ranged from 31 to 71 years old, with the average of 54.4 years old. The primary focus of 13 cases were in tongue, 3 cases in cheek, 2 cases in gum, and 1 case in the conjunction of gum, mouth floor and tongue respectively. All the patients were examined by ultrasonography prior to operation, and operated with the procedures of excision of primary focus and radical neck dissection. The length, width, Vmax and Vmin and Resistance Index (RI = (Vmax-Vmin)/Vmax) of blood flow of cervical lymphatic nodes were measured with acuson 128 xp/10 color Doppler flow imaging scanner with a 7.5 MHz probe. The total of 34 cervical lymphatic nodes were examined by the scanner. L/W ratios in all nodes, RI and Vmax in 16 nodes were obtained respectively. All results were divided into two groups, metastases and non-metastases groups based on the pathological findings for further statistic analysis. Student t test was employed in the study. RESULTS: The average L/W ratios, the average Vmax and the average RI were 1.95 and 2.17, 0.24 and 0.14, and 0.80 and 0.56 in metastases and non-metastases groups respectively. There was a significant difference between RI in two groups, but no statistical differences were revealed in L/W ratios and Vmax, despite the great difference in the average Vmax in the two groups. When RI > or = 0.65 and Vmax > or = 0.20 m/s were regarded as the criterion for positive diagnosis, the accuracy rate, the sensibility and the specificity was 91.2%, 90%, and 91.7% respectively in making diagnosis of OSCC. CONCLUSION: The status of cervical lymphatic metastases in OSCC patients could be evaluated accurately by the color Doppler flow imaging scanner, which might be helpful in making accurately diagnosis of OSCC, selecting the appropriate operation procedure of neck dissection leading to increased survival ratio and improved quality of life for the patients.

Adult↗
PubMed2001

[Detection of telomerase activity in laryngeal carcinoma and the association between telomerase activity and lymphatic metastasis].

OBJECTIVE: To investigate the telomerase activity in human laryngeal squamous cell carcinomas (LSCC) and the association between telomerase activity and lymphatic metastasis. METHOD: Telomerase activity was determined in 47 specimens of LSCC and 10 specimens of laryngeal inflammatory polyps using PCR-ELISA. RESULT: Telomerase activity was detected in 39 of 47 (83%) LSCC, but was not detected in all 10 laryngeal inflammatory polyps. There were significant differences between them (P < 0.01). Telomerase activation in LSCC with positive cervical lymph node involvement appeared to be higher (13 out of 13 cases, 100%) than in LSCC with negative cervical lymph node involvement (26 out of 34, 76.47%), (P < 0.05). CONCLUSION: Telomerase is activated frequently in LSCC and may become a biomarker of LSCC. The detection of telomerase activity in LSCC may have some value for predicting metastasis potential and prognosis and can guide the clinical practices applying selective neck dissection.

Adult↗
PubMed2002

Thrombospondin-1 selectively inhibits early-stage carcinogenesis and angiogenesis but not tumor lymphangiogenesis and lymphatic metastasis in transgenic mice.

The roles played by the endogenous angiogenesis inhibitor thrombospondin-1 (TSP-1) in the early stages of multi-step carcinogenesis and in the control of hematogenous versus lymphatic metastasis are unknown. To investigate these issues we compared tumor development in normal mice and in transgenic mice with targeted overexpression of TSP-1 in the epidermis following a standard two-step chemical skin carcinogenesis regimen. Overexpression of TSP-1 resulted in delayed and reduced development of premalignant epithelial hyperplasias, but did not inhibit the malignant conversion to squamous cell carcinomas. TSP-1 overexpression also suppressed tumor angiogenesis and distant organ metastasis, but failed to inhibit tumor-associated lymphangiogenesis or lymphatic tumor spread to regional lymph nodes. Concomitant with these results, we found that the endothelial TSP-1 receptor CD36 was mostly absent from cutaneous lymphatic vessels. Our findings indicate the potential use of TSP-1 for the prevention of premalignant stages of tumorigenesis and are likely to have implications for the further development of anti-angiogenic cancer therapies.

Animals↗
PubMed1985

Repression of lymphatic metastasis by a second implant of the same tumor.

Previous work in the rat D-12 fibrosarcoma model has shown that the incidence of macroscopic metastasis, located primarily in regional lymph nodes, is markedly increased after surgical removal of a primary subcutaneous tumor implant, in all probability by facilitating the outgrowth of already established micrometastases. The present work shows that a second implant of live D-12 tumor cells into a remote site effectively represses the outgrowth of macroscopic metastases. For the manifestation of the repressive effect, both the time interval elapsing between surgery and reimplantation of tumor cells and the size of the inoculum appear critical. Implantation of heavily irradiated D-12 cells or the prolonged delivery of ascites fluid by osmotic mini-pumps had no such repressive effect on metastatic tumor growth. Corynebacterium parvum administered into the tumor-bearing limb a few days before its amputation, but not into a remote subcutaneous site, suppressed the outgrowth of macroscopic metastases. The occurrence and efficient operation of concomitant tumor resistance in the D-12 tumor model, in which metastasis is primarily via lymphatics and resistance appears to involve a substantial portion nonspecific reactivity, is further evidence for a basic role of tumor/tumor interrelations in determining the final outcome of the host/tumor interaction.

Animals↗
PubMed1993

Establishment and characterization of a rat yolk sac tumor cell line, NMT-1, producing alpha-fetoprotein, with potential for lymphatic metastasis.

A new cell line producing alpha-fetoprotein, designated NMT-1, was established from rat yolk sac tumor with the potential for lymphatic metastasis in inbred Wistar rats. In this paper, we investigated the characteristics of NMT-1 cells. The cell line grew in a monolayer and had a polygonal epithelioid appearance in phase-contrast microscopy. The doubling time of NMT-1 cells during exponential growth was approximately 16 h in RPMI-1640 with 10% fetal calf serum. The D0 value for radiation sensitivity was 97 +/- 3 cGy. The extrapolation number, n, for NMT-1 was 1.08 +/- 0.15. In the log phase, the G0/G1, S and G2/M fractions were 23.2%, 62.1% and 14.3%, respectively. Tumor take was observed in all of the rats inoculated with NMT-1 cells. In the case of flank tumor, the mean survival time was 104 days after inoculation with 10(6) tumor cells. Inguinal, axillary, paraaortic, mesenteric and mediastinal lymphnode metastases were observed in all rats inoculated with NMT-1 cells. Rats which survived for a long time developed metastases in a lymphatic vessels of the liver, lung and/or kidney microscopically. The biological behavior and the histopathological features of the tumor induced by inoculation with NMT-1 cells were the same as those of the original tumor induced by fetectomy.

Animals↗
PubMed2004

Preexisting lymphatic endothelium but not endothelial progenitor cells are essential for tumor lymphangiogenesis and lymphatic metastasis.

Endothelial progenitor cells have been shown to contribute to angiogenesis in various tumor models. Here, we have studied the relative contributions of bone marrow (BM)-derived endothelial progenitors and pre-existing lymphatic vessels to tumor lymphangiogenesis. We did not find significant incorporation of genetically marked BM-derived cells in lymphatic vessels during tumor- or vascular endothelial growth factor C-induced lymphangiogenesis. The degree of tumor lymphangiogenesis correlated with lymphatic vessel density in the peritumoral area, and despite tumor lymphangiogenesis, lymphatic metastasis failed to occur in gene-targeted vascular endothelial growth factor C(+/-) mice that have hypoplasia of the lymphatic network. Our data demonstrate that during tumor lymphangiogenesis and cancer cell dissemination via the lymphatics, the newly formed lymphatic vessels sprout from the pre-existing local lymphatic network with little if any incorporation of BM-derived endothelial progenitor cells.

Animals↗
PubMed2006

Analysis of risk factors for skip lymphatic metastasis and their prognostic value in operated N2 non-small-cell lung carcinoma.

BACKGROUND: The aim of this study is to report a series and to analyze risk factors for skip lymphatic metastasis an their prognostic value in operated N2 non-small-cell lung carcinoma. METHODS: From 1997 to 2002, 142 patients classified pN2 were included in the study. Tumours were classified according to the TNM classification. Skips metastases were defined by the cases of N2 disease without lobar and interlobar and hilar lymph node involvement. A skip (+) and a skip (-) group were defined. Characteristics of tumours, ganglionar involvement and survival were analysed in both groups. RESULTS: Forty-two patients fulfilled the criteria for skip metastasis. The average number of mediastinal lymph nodes resected by patient was similar in both groups, whereas more intrapulmonary nodes were dissected in the skip (-) group (4.7 +/- 3 vs 3 +/- 3; p < 0.002). The ratio of involved to resected lymph nodes was 0.47 +/- 0.27 in the skip (-) group vs 0.23 +/- 0.20 in the skip (+) group (p < 0.0001). In the skip (+) group, 85% of the patients presenting with a right upper lobe tumour had involvement of the superior mediastinal lymph nodes against 40% in the skip (-) group. The 5-year survival rate was 48% in the skip (-) group vs 37% in the skip (+) group (p = 0.49). In multivariate analysis, incomplete resection, tumour size, extended resection and pT were significant prognostic factors. CONCLUSIONS: Skip metastasis are frequent in non-small-cell lung cancer and complete dissection of hilar and mediastinal lymph nodes should remain the surgical standard procedure for this disease. However, skip metastasis are not an independent prognostic factor in survival.

Adult↗
PubMed2003

Expression of vascular endothelial growth factor C and D (VEGF-C and -D) is an important risk factor for lymphatic metastasis in undifferentiated early gastric carcinoma.

BACKGROUND: Vascular endothelial growth factor C (VEGF-C) and D (VEGF-D) are considered to be potentially lymphangiogenic and can selectively induce hyperplasia of the lymphatic vasculature. In this study, we aimed to clarify the relation between expression of VEGF-C and -D and lymphatic metastasis in early gastric cancers. METHODS: Using the specific antibodies, we classified 105 cases which were treated as gastrectomy with standard lymphadenectomy at the First Department of Surgery, Tokyo University Hospital, between 1994 and 2001, into three groups (diffuse type, focal type and negative type) for VEGF-C and two groups (positive and negative) for VEGF-D. RESULTS: There was a significant correlation between the expression of VEGF-C and -D and lymphatic invasion but not with venous invasion. All of the 22 cases that were negative for VEGF-C and -D were histologically classified as adenocarcinoma of undifferentiated type and showed negative lymph node metastasis and also negative lymphatic invasion. VEGF-C was positive in all tumors of differentiated type, while its expression varied in tumors of undifferentiated type. The VEGF-D positive rate is much lower than that of VEGF-C. In undifferentiated tumors in particular, VEGF-D was positive only in 4/64 (6%) and three of these four had nodal metastasis. Therefore, in tumors of differentiated type, expression of VEGF-C and -D had no clinical relevance. In tumors of undifferentiated type, the negative expression of VEGF-C suggests lack of nodal metastasis, while the positive expression of VEGF-D suggests nodal metastasis. The lymph node metastasis was significantly related to the expression of VEGF-C and -D in adenocarcinomas of undifferentiated type but not in those of differentiated tumors. CONCLUSIONS: In early gastric cancers of histologically undifferentiated type with negative expression of VEGF-C and -D, limited surgery might be safely applied because the possibility of nodal metastasis is very low. These observations are based only on retrospective analysis of a small case series and further evaluation with a larger number of cases is necessary.

Aged↗
PubMedDate not supplied

Pathology of malignant tumors of the nose and throat and their relationship to lymphatic metastasis.

One hundred cases of malignant tumors of the larynx, pharynx, oral cavity, nose and paranasal sinuses were studied. The hypopharynx was the most frequent site and the most common type of tumor was squamous cell carcinoma. Lymph nodes were palpable in 59% of cases, of which 72.8% showed histological evidence of metastasis. The highest incidence of metastasis was found in nasopharyngeal growths and the lowest in the nose and the sinuses. In laryngeal tumors the site of the tumor was the most important factor influencing regional lymphatic metastasis. The grade of the tumor influenced the lymph node metastasis in the regions of the hypopharynx, tonsil and base of tongue. At other sites the differentiation of the tumor did not seem to have any correlation with the incidence of metastasis.

Adult↗
PubMed2004

Mode of spread in the early phase of lymphatic metastasis in pancreatic ductal adenocarcinoma: prognostic significance of nodal microinvolvement.

BACKGROUND: The aim of this study was to assess the prognostic significance of nodal microinvolvement as well as the mode of spread in the early phase of lymphatic metastasis in patients with node-negative pancreatic ductal adenocarcinoma. METHODS: Lymph nodes from 48 node-negative patients with R0 resected pancreatic ductal adenocarcinoma were sampled from 3 different compartments: 1) distal hepatoduodenal ligament, 2) superior-anterior compartment, and 3) posterior-inferior. Tissue sections of 148 lymph nodes classified as tumor free by routine histopathology were examined, using a sensitive immunohistochemical assay with the antiepithelial monoclonal antibody Ber-EP4 for tumor cell detection. With regard to histopathologic tumor staging and grading, 26 (54.2%) of the patients were staged as pT1/pT2, 22 (45.8%) as pT3/pT4, while 31 (64.6%) as G1/G2 and 17 (35.4%) patients as G3. Of the 148 "tumor free" lymph nodes, 56 contained Ber-EP4-positive tumor cells. These 56 lymph nodes were from 28 of the 48 patients. The multivariate Cox regression analysis revealed the independent prognostic impact of nodal microinvolvement on relapse-free and overall survival. Analysis by compartment, from which the lymph nodes were collected, revealed that overall survival time (P = 0.006) and time to local recurrence (P = 0.015) depend on the presence of nodal microinvolvement in the superior-anterior compartment. CONCLUSIONS: The influence of occult tumor cell dissemination in lymph nodes of patients with histologically proven pancreatic ductal adenocarcinoma supports the need for further tumor staging through immunohistochemistry. This could be a helpful tool in proper selection of patients for adjuvant chemotherapy.

Biomarkers, Tumor↗
PubMed2005

A new model for lymphatic metastasis: development of a variant of the MDA-MB-468 human breast cancer cell line that aggressively metastasizes to lymph nodes.

Breast cancer often spreads from the primary tumor to regional lymph nodes. Lymph node status provides clinically important information for making treatment decisions. Spread via lymphatics is also important for the biology of breast cancer, as tumor cells in lymph nodes may provide a reservoir of cells leading to distant, lethal metastases. Improved understanding of the biology of lymphatic spread thus is important for improved breast cancer survival. Advances towards understanding the interactions between tumors cells and lymphatic vessels have in part been limited by the lack of suitable cell lines and experimental models. We have addressed this need by developing a new model of lymphatic metastasis. Here we describe the establishment of 468LN cells, a variant of the MDA-MB-468 human breast adenocarcinoma cell line, which produces extensive lymph node metastasis following orthotopic injection of nude mice. 468LN cells are also more aggressive in vitro, produce more osteopontin and express different surface integrins compared to the parent line. The dramatic in vitro and in vivo phenotypic and molecular differences of 468LN and parental 468GFP cells make this pair of cell lines a unique model for the specific study of lymph node metastasis of breast cancer.

Adenocarcinoma↗
PubMed2005

VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis.

The mechanisms of tumor metastasis to the sentinel lymph nodes are poorly understood. Vascular endothelial growth factor (VEGF)-A plays a principle role in tumor progression and angiogenesis; however, its role in tumor-associated lymphangiogenesis and lymphatic metastasis has remained unclear. We created transgenic mice that overexpress VEGF-A and green fluorescent protein specifically in the skin, and subjected them to a standard chemically-induced skin carcinogenesis regimen. We found that VEGF-A not only strongly promotes multistep skin carcinogenesis, but also induces active proliferation of VEGF receptor-2-expressing tumor-associated lymphatic vessels as well as tumor metastasis to the sentinel and distant lymph nodes. The lymphangiogenic activity of VEGF-A-expressing tumor cells was maintained within metastasis-containing lymph nodes. The most surprising finding of our study was that even before metastasizing, VEGF-A-overexpressing primary tumors induced sentinel lymph node lymphangiogenesis. This suggests that primary tumors might begin preparing their future metastatic site by producing lymphangiogenic factors that mediate their efficient transport to sentinel lymph nodes. This newly identified mechanism of inducing lymph node lymphangiogenesis likely contributes to tumor metastasis, and therefore, represents a new therapeutic target for advanced cancer and/or for the prevention of metastasis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Small primary de novo adenocarcinoma of the colon with mesenteric lymphatic metastasis.

It is felt that the majority of colorectal carcinomas develop by malignant degeneration of previously benign adenomatous polyps. A small primary colon carcinoma, thought to have developed de novo directly from the colonic mucosa without the usual polyp-cancer sequence, is reported. This small nonulcerated lesion did not have the gross endoscopic appearance of a carcinoma and was associated with lymphatic metastasis. The need to include fiber-optic colonoscopy as part of the routine preoperative work-up and postoperative follow-up to rule out synchronous and metachronous lesions not detected by barium contrast x-ray studies is stressed.

Adenocarcinoma↗
PubMed2005

Direct role of PDGF-BB in lymphangiogenesis and lymphatic metastasis.

Genetic instability of tumor cells often leads to amplified expression of multiple growth factors that contribute to angiogenesis and tumor growth. Members of the platelet-derived growth factor (PDGF) family are frequently utilized growth factors by many tumors to support their growth. PDGFs have previously been found to induce tumor growth by directly stimulating cell growth of certain types of tumors. We have recently demonstrated that PDGFs are potent angiogenic factors. Particularly, the angiogenic activity of PDGFs can be potentiated in the presence of other angiogenic factors. In addition to stimulation of blood angiogenesis, we have recently found that PDGFs can directly stimulate lymphangiogenesis and lymphatic metastasis. In this review, multiple roles of PDGFs in control of tumor growth and metastasis are discussed.

Animals↗