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)

Although impaired expression of E-cadherin (E-cad) is frequently observed in tumors with aggressive histopathologic characteristics, the correlation between alpha-catenin (alpha-cat) expression and the clinicopathologic features of early gastric cancer have not been fully examined. In this study, we evaluated the expression of E-cad and alpha-cat by early gastric carcinomas, and examined the relationships between this expression and various clinicopathologic characteristics. A total of 69 specimens obtained from surgery were studied by immunohistochemistry. Reduced expression of E-cad and alpha-cat were found in 53.6% and 65.2% of the tumors, respectively, and a significant correlation was observed between the decreased expression of E-cad or alpha-cat and tumor histology, the quantity of stroma, and the infiltration pattern of the tumor. The reduced expression of alpha-cat correlated more strongly with these features than E-cadherin expression. Furthermore, alpha-cat expression was also related to the lymph node metastasis of tumors. The expression of E-cad or alpha-cat in the primary tumor was consistent with the expression of tumor cells that invaded the lymphatic vessels, but discordant with staining in the metastasized lymph nodes. In some cases, as the tumor invaded deeper, the expression of E-cad or alpha-cat changed from preserved to reduced. Our observations suggest that the reduced expression of E-cad or alpha-cat may be involved in the initial steps leading to the invasion and metastasis of early gastric cancer.
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PMID:The expression of cadherin-catenin complex in association with the clinicopathologic features of early gastric cancer. 968 6

Locoregional recurrences and distant metastases are the determinants of the long-term prognosis following curative resection of rectal carcinoma. While distant metastases cannot be affected by the surgical treatment of the primary tumor, avoidance of local recurrence by the surgeon is of special significance as the predominant prognostic factor. Analysis of the long-term results achieved by various surgeons led to the concept of mesorectal excision - the removal of the rectum together with all additional tissue invested by the adjacent visceral fascia, that is, fatty tissue, lymph nodes, and lymphatic vessels, by sharp dissection of the appropriate anatomical plane. In our own patient material the 5-year survival rate following R0 resection was 85% for all stages, provided no local recurrence developed. This contrasts with a figure of only 23% in those who did develop local recurrence. The local recurrence rate decreased from 39.4%, with a 50% 5-year survival rate in 1974, to 9.8% and a 71% survival rate in 1991, although the rate of distant metastases remained constant. Among the patients treated between 1988 and 1994 the local recurrence rate was determined by depth of infiltration (1987 UICC classification: pT1 0%, pT2 10%, pT3 14%, pT4 28%), extent of lymph node infiltration (pN0 6%, pN1 15%, pN2 26%, pN3 25%), grading (G1 9%, G2 12%, G3 21%), and location within the rectum (upper third 13%, middle third 8%, lower third 17%), with combinations of unfavorable initial factors leading to higher local recurrence rates. The elevated local recurrence rates seen in the 1970s, in particular in the case of tumors of the lower third, were traced retrospectively to incomplete mesorectal excision, the implementation of which reduced the local recurrence rate initially to less than 10%, and then to the current 4.1%. From the oncological point of view, mesorectal excision must be considered to confer considerable benefit. In the case of carcinomas of the upper third of the rectum, mesorectal resection carried out to just 5 cm below the lower tumor edge is sufficient, however, without coning, while deeper carcinomas mandate total mesorectal excision.
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PMID:Mesorectal lymph node dissection: is it beneficial? 992 39

Several studies have been published describing the techniques of identification of the "sentinel lymph node" (SN). There are marked differences in the techniques used by different investigators. Although agreement exists about the tracer particle size and the volume of injection, it is unknown what is the best site where to inject the tracer or the vital dye. The aim of the present study was to define the influence of different sites of injection on imaging of the lymphatic ducts and their SNs. We performed a pilot study in 30 consecutive patients with breast cancer who underwent SN biopsy by means of radioguided surgery and vital blue dye mapping. The patients were divided into six groups of five patients each; each patient was given a subdermal (ID) or peritumoral (IP) injection of radiotracer (300 microCi in 150 mL of 99mTc-HSA microcolloids; Albures, Amersham Sorin) above the tumor site in order to localize the SN. After the identification of the SN, a second injection of radiotracer was performed, which was different in each patient subset. In some cases more than one lymph node appeared on the lymphoscintigraphic scans after the second injection of radiotracer. When the peritumoral route was used it took longer to visualize the lymphatic pathways. For the ID route, injection at the exact skin projection over the tumor is optimal. Internal mammary lymph nodes were identified by both IP (2) and ID (1) injection, irrespective of the quadrant in which the tracer was injected. Our findings support the hypothesis of a precise topographic correspondence between the primary tumor and its specific SN. The subdermal route is more accurate than the intraparenchymal route, as it allows faster identification of the lymphatic vessels and SN. We believe these observations should be taken into account for the proper selection of the injection site of either vital dye or radiopharmaceuticals.
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PMID:Different sites and modes of tracer injection for mapping the sentinel lymph node in patients with breast cancer. 1101 10

Head and neck squamous cell carcinomas (HNSCCs) frequently disseminate to regional lymph nodes. To investigate the possible mechanisms involved, we studied the expression of cancer cell adhesion molecules together with lymphatic vascular and blood vascular markers in a panel of 97 primary HNSCC tumors and correlated expression levels with conventional clinicopathological parameters and with long-term prognosis. In particular, we measured the density of intratumoral and peritumoral lymph vessels as assessed with the marker lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) and the density of tumor CD44, a receptor up-regulated in many metastatic cancers. Intratumoral LYVE-1(+) lymphatic vessels were clearly associated with a higher risk for local relapse as well as with poor disease-specific prognosis (P = 0.02 and 0.0009, respectively). In contrast, a high density of peritumoral LYVE-1(+) vessels was a sign of favorable survival (P = 0.05). Strong primary tumor CD44 expression was associated with a poor prognosis, an increased risk of local recurrence (P = 0.03 and 0.02, respectively), and an increase in resistance to radiation therapy (P = 0.03). CD44 was the only factor with an independent prognostic value for the disease-specific overall survival (P = 0.04). Our results suggest that intratumoral lymphatics play a greater role than peritumoral lymphatics in nodal metastasis of HNSCC and that tumor CD44 levels can predict sensitivity to radiation therapy. These parameters may be useful predictive and prognostic tools in the clinical management of HNSCC.
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PMID:Intratumoral lymphatics are essential for the metastatic spread and prognosis in squamous cell carcinomas of the head and neck region. 1467 26

Nearly four centuries after the discovery of lymphatic vessels, the molecular mechanisms underlying their development are beginning to be elucidated. Vascular endothelial growth factor C (VEGF-C) and VEGF-D, via signaling through VEGFR-3, appear to be essential for lymphatic vessel growth. Observations from clinicopathological studies have suggested that lymphatic vessels serve as the primary route for the metastatic spread of tumor cells to regional lymph nodes. Recent studies in animal models have provided convincing evidence that tumor lymphangiogenesis facilitates lymphatic metastasis. However, it is not clear how tumor-associated lymphangiogenesis is regulated, and little is known about how tumor cells escape from the primary tumor and gain entry into the lymphatics. This review examines some of these issues and provides a brief summary of the recent developments in this field of research.
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PMID:Role of lymphangiogenic factors in tumor metastasis. 1498 63

Micrometastasis is a microscopic (less than 2 mm) deposit of malignant cells separated from the primary tumor. The incidence and importance of occult perigastric lymph node involvement were analyzed in 26 pN0 patients using the prospective method. The occult lymph node involvement was detected by immunohistochemical method using the anticytokeratin 8/18 antibody. Prevalence of clinically significant occult lymph node involvement (Mi+) was statistically significant, and found in 38.5% of pN0 patients. Out of tumor characteristics analyzed as possible predictors of occult lymph node involvement, the histological grade (GH) and the involvement of lymphatic vessels within gastric wall (pL1) had significant effect on the respective evaluation. The patients with histological grade 3 and 4 had occult lymph node involvement more often than those with grade 1 and 2 (p<0.05). More than 60% of pL1 patients had occult lymph node involvement LN (Mi+). Due to high prevalence of micrometastatic lymph node involvement, detection with specific immunohistochemical or molecular biology techniques should be a part of routine specimen examination in patients with pN0 gastric cancer.
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PMID:[Prevalence and importance of nodal micrometastasis in patients with gastric adenocarcinoma]. 1561 79

The spread of tumor cells of solid tumors to the regional lymph nodes is an important step in the progression of the disease and also an important prognostic factor. While the significance of the prognostic value of the lymphatic progression had been detected long ago, only increased knowledge of the molecular anatomy and mechanisms involved in the lymphatic spread of tumor cells provided a beginning insight into the understanding of lymphatic metastasis. One group of important molecular factors consists of proteins produced by the tumor cells inducing a proliferation of lymphatic vessels into the primary tumor. The vascular endothelial growth factors have been identified as key factors in this process. In addition there are hints for the fact that chemokines, which are cytokine-like proteins taking part in the regulation of processes of inflammation, and their chemokine receptors control cellular key steps of lymphatic metastasis of tumor cells such as migration, proliferation, and invasion. In conclusion new data point to the possible inhibition of lymphatic spread by selective blockade of growth factor receptors or chemokine receptors. The growing insight into cellular understanding of the mechanisms involved in the metastasis of tumor cells into the lymphatics and lymph nodes will hopefully facilitate the development of new diagnostic and therapeutic tools in the treatment of cancer patients.
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PMID:[Molecular biology approach to explain lymphatic metastasis]. 1591 24

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.
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PMID: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. 1617 Jun 71

An essential prerequisite for a successful sentinel node biopsy (SNB) procedure is an accurate map of the pattern of lymphatic drainage from the primary tumor site. The role of lymphoscintigraphy (LS) in SNB is to provide such a map in each patient. This map should indicate not only the location of all sentinel nodes but also the number of SNs at each location. Such mapping can be achieved using 99mTc-labeled small particle radiocolloids, high-resolution collimators with minimal septal penetration, and imaging protocols that detect all SNs in every patient regardless of their location. This is especially important in melanoma patients, since high-quality LS can identify the actual lymphatic collecting vessels as they drain into each SN. The SN is not always found in the nearest node field and is best defined as "any lymph node receiving direct lymphatic drainage from a primary tumor site." Reliable clinical prediction of lymphatic drainage from the skin or breast is not possible. Patterns of lymphatic drainage from the skin are highly variable from patient to patient, even from the same area of the skin. Unexpected lymphatic drainage has been found from the skin of the back to SNs in the triangular intermuscular space and in some patients through the posterior body wall to SNs in the para-aortic, paravertebral, and retroperitoneal areas. Lymphatic drainage from the head and neck frequently involves SNs in multiple node fields, and can occur from the base of the neck up to nodes in the occipital or upper cervical areas or from the scalp down to nodes at the neck base, bypassing many other node groups. Lymphatic drainage from the upper limb can be directly to SNs above the axilla. Drainage to the epitrochlear region from the hand and arm is more common than was previously thought as is drainage to the popliteal region from the foot and leg. Interval nodes, which lie along the course of a lymphatic vessel between a melanoma site and a recognised node field, are not uncommon especially on the trunk. Drainage across the midline of the body is quite frequent on the trunk and in the head and neck region. In breast cancer, although dynamic imaging is usually not possible, an early postmassage image will also often visualize the lymphatic vessels leading to the SN allowing them to be differentiated from any second tier nodes. Small radiocolloid particles are also needed to achieve migration from peritumoral injections sites and LS allows accurately detection of SNs outside the axilla, which occur in about 50% of patients. These nodes may lie in the internal mammary chain, the supraclavicular region, or the interpectoral region. Intramammary interval nodes can also be SNs in some patients. The location of the cancer in the breast is not a reliable guide to lymphatic drainage, since lymph flow often crosses the center line of the breast. Micrometastatic disease can be present in any SN regardless of its location, and for the SNB technique to be accurate all true SNs must be identified and removed in every patient. LS is an important first step in ensuring that this goal is achieved.
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PMID:Role of lymphoscintigraphy for selective sentinel lymphadenectomy. 1620 76

Preclinical and clinical studies positively correlate the expression of vascular endothelial growth factor (VEGF)-C in tumors and the incidence of lymph node metastases. However, how VEGF-C regulates individual steps in the transport of tumor cells from the primary tumor to the draining lymph nodes is poorly understood. Here, we image and quantify these steps in tumors growing in the tip of the mouse ear using intravital microscopy of the draining lymphatic vessels and lymph node, which receives spontaneously shed tumor cells. We show that VEGF-C overexpression in cancer cells induces hyperplasia in peritumor lymphatic vessels and increases the volumetric flow rate in lymphatics at the base of the ear by 40%. The increases in lymph flow rate and peritumor lymphatic surface area enhance the rate of tumor cell delivery to lymph nodes, leading to a 200-fold increase in cancer cell accumulation in the lymph node and a 4-fold increase in lymph node metastasis. In our model, VEGF-C overexpression does not confer any survival or growth advantage on cancer cells. We also show that an anti-VEGF receptor (VEGFR)-3 antibody reduces both lymphatic hyperplasia and the delivery of tumor cells to the draining lymph node, leading to a reduction in lymph node metastasis. However, this treatment is unable to prevent the growth of tumor cells already seeded in lymph nodes. Collectively, our results indicate that VEGF-C facilitates lymphatic metastasis by increasing the delivery of cancer cells to lymph nodes and therapies directed against VEGF-C/VEGFR-3 signaling target the initial steps of lymphatic metastasis.
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PMID:Imaging steps of lymphatic metastasis reveals that vascular endothelial growth factor-C increases metastasis by increasing delivery of cancer cells to lymph nodes: therapeutic implications. 1691 83


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