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[A study of E-cadherin and beta-catenin expression and their correlation with prognosis of nonsmall cell lung carcinoma].

OBJECTIVE: To investigate the protein and mRNA expression of E-cadherin and beta-catenin in nonsmall cell lung carcinoma (NSCLC) and to find their correlation with histological type, differentiation, metastasis and prognosis. METHODS: High sensitive S-P immunohistochemical method and in situ hibridization were used to detect the protein and mRNA expression of E-cadherin and beta-catenin. RESULTS: Immunohistochemistry revealed that among the 101 cases, the positive rates of E-cadherin and beta-catenin were 68.3% and 81.2% respectively. The abnormal expression rates of these two proteins were 61.4% and 64.4% respectively. There was no significant relationship between E-cadherin and beta-catenin staining and histological type of the tumor (P > 0.05). However, there was a statistically significant difference between well and moderately differentiated cells and poorly differentiated cells (P < 0.05). In cases with lymphatic metastasis, the abnormal expression rates of E-cadherin and beta-catenin were significantly higher than those in nonmetastatic cases (P < 0.05). The mean survival time in cases with abnormal E-cadherin and beta-catenin expression were significantly shorter than that in cases with the expression grading (+ +) approximately (+ + +). In situ hybridization showed that in NSCLC, the positive rate of E-cadherin and beta-catenin mRNA was 38.9% and 47.2% respectively. Their concordant rates with (+ +) approximately (+ + +) protein expression were 78.6% and 82.4%, respectively. CONCLUSIONS: The concordant rate of E-cadherin and beta-catenin mRNA and protein expression was relatively high. They can be used as markers of prognosis of NSCLC in clinical practice.

Adult↗

Increased NCAM expression and vascular development in trisomy 16 mouse embryos: relationship with nuchal translucency.

Increased nuchal translucency in the human fetus is associated with chromosomal abnormalities, enlarged jugular lymphatic sacs, cardiac defects and changed flow through the ductus venosus. The developmental background of this nuchal edema in relation to the associated anomalies remains elusive. We studied the morphologic correlation between neurogenesis and vasculogenesis in neck, heart, and ductus venosus region of wild type and trisomy 16 mice embryos (E10- E18), using an antibody against Neural Cell Adhesion Molecule (NCAM). Trisomy 16 mice are a model for the above described human phenotype. From E12 trisomy 16 mice showed an altered arrangement of cranial nerves IX, X and XI, which are positioned between the carotid artery, jugular vein and enlarged lymphatic sac. The vagal nerve was significantly smaller, compared with wild type embryos. NCAM was over expressed in both neuronal and cardiovascular structures in trisomy 16 mice, being particularly prominent in the 4th and 6th pharyngeal arch arteries, and the ductus venosus. In the 4th and 6th pharyngeal arch arteries, NCAM over expression was located to the part of the vessel wall that is closely related to the vagal and recurrent nerve. In case of 4th pharyngeal arch artery abnormalities NCAM expression, on the other hand, was reduced. In conclusion, the interaction between neurogenesis and vasculogenesis is disturbed in the trisomy 16 mouse model, and might be a common denominator in the spectrum of anomalies associated with increased nuchal translucency.

Animals↗

Relationship between the downregulation of HLA class I antigen and clinicopathological significance in gastric cancer.

AIM: To discuss the expression of human leukocyte antigen (HLA) class I antigens in gastric cancer and correlate these with pathologic type and TNM stage. METHODS: The expression of HLA class I antigen was detected by immunohistochemistry in 185 specimens of gastric cancer, 20 gastric cancer specimens with lymphatic metastasis and 22 controls of normal gastric mucosa using four monoclonal antibodies. RESULTS: The expression of HLA class I antigen (B/C locus) was significantly downregulated in gastric cancer and in lymphatic metastasis than that in normal gastric mucosa (chi2=7.712, P<0.05). The expression of other HLA class I antigens was also downregulated, but the change was slight. There was no relationship between the downregulation of HLA class I antigen and that of beta2m and LMP2. The expression of HLA class I (B/C locus) was statistically correlated with pathologic stage in gastric adenocarcinoma (chi2=4.164, P<0.05). CONCLUSION: The expression of HLA class I antigen (B/C locus) was obviously downregulated in gastric cancer and in lymphatic metastasis. This abnormal expression would provide the tumor cells with a way to avoid immunological recognition.

Adult↗

Usefulness of Technetium-99m human serum albumin lymphoscintigraphy in chyluria.

Chyluria is a urologic manifestation of a lymphatic system disease abnormality and leads to nutritional deficiency. The case of a patient with chyluria is presented, and the results of lymphoscintigraphy with those of contrast lymphangiography are compared. Lymphoscintigraphy very clearly showed the site of the fistulae and was as precise as lymphangiography. Follow-up lymphoscintigraphy 2 months after therapy revealed no radionuclide accumulation. Lymphoscintigraphy is a useful, noninvasive, safe, and simple technique for the diagnosis and follow-up of chyluria.

Aged↗

Peritumor lymphatics induced by vascular endothelial growth factor-C exhibit abnormal function.

Vascular endothelial growth factor (VEGF)-C is known to induce hyperplasia in normal murine lymphatics and in peritumor lymphatics. Here, we examine the function of these hyperplastic peritumor lymphatics. Microlymphangiography of B16F10 melanomas growing in the murine dorsal skinfold chamber showed that the number of functional, draining lymphatics in the peritumor tissue of VEGF-C-overexpressing tumors was significantly greater than that in mock-transduced tumors (9.5 +/- 1.0 versus 6.3 +/- 0.4; n = 6; P < 0.05). Forty percent of functional lymphatics associated with VEGF-C-overexpressing tumors contained proliferating lymphatic endothelial cells. Surprisingly, these new, functional lymphatic vessels displayed a retrograde draining pattern, which indicates possible dysfunction of the intraluminal valves of these vessels.

Animals↗

Yellow nail syndrome and bilateral cystic lung disease.

In patients with yellow nail syndrome (YNS), highly characteristic nail changes are often associated with lymphedema and respiratory disorders due to pleural effusions or bronchiectasis. We describe a 4-year-old girl with the YNS who also had cystic lesions of the lung, affecting first the left lower lobe and, after surgical resection of the involved segments, also the right lower lobe. We discuss the etiology of the pulmonary cysts and hypothesize that abnormalities in pulmonary lymphatic flow, characteristic of YNS, may have decreased lung tissue compliance and determined the unusual progression of the cystic lesions in this patient.

Child, Preschool↗

Clavicular overgrowth in association with cystic hygroma.

Cystic hygroma is a rare congenital abnormality of the lymphatic system of the neck which is now considered to form part of a spectrum of lymphangiomatous malformations. Lytic bone lesions are described in systemic lymphangiomatosis and bony overgrowth (hemihypertrophy) in association with angiomatous malformations of the limbs. Two infants with ipsilateral clavicular overgrowth adjacent to cystic hygromas are reported. This association has not been recorded previously; the possible etiology is discussed.

Clavicle↗

Free radicals in chemical carcinogenesis.

During the past decade, remarkable progress has been made in our understanding of cancer-causing agents, mechanisms of cancer formation and the behavior of cancer cells. Cancer is characterized primarily by an increase in the number of abnormal cells derived from a given normal tissue, invasion of adjacent tissues by these abnormal cells, and lymphatic or blood-borne spread of malignant cells to regional lymph nodes and to distant sites (metastasis). It has been estimated that about 75-80% of all human cancers are environmentally induced, 30-40% of them by diet. Only a small minority, possibly no more than 2% of all cases, result purely from inherent genetic changes. Several lines of evidence confirm that the fundamental molecular event or events that cause a cell to become malignant occur at the level of the DNA and a variety of studies indicate that the critical molecular event in chemical carcinogenesis is the interaction of the chemical agent with DNA. The demonstration that DNA isolated from tumor cells can transfect normal cells and render them neoplastic provides direct proof that an alteration of the DNA is responsible for cancer. The transforming genes, or oncogenes, have been identified by restriction endonuclease mapping. One of the characteristics of tumor cells generated by transformation with viruses, chemicals, or radiation is their reduced requirement for serum growth factors. A critical significance of electrophilic metabolites of carcinogenes in chemical carcinogenesis has been demonstrated. A number of "proximate" and "ultimate" metabolites, especially those of aromatic amines, were described. The "ultimate" forms of carcinogens actually interact with cellular constituents to cause neoplastic transformation and are the final metabolic products in most pathways. Recent evidence indicates that free radical derivatives of chemical carcinogens may be produced both metabolically and nonenzymatically during their metabolism. Free radicals carry no charge but do possess a single unpaired electron, making the radical extremely reactive. That such forms may be important in the introduction of neoplastic transformation by chemicals from two lines of evidence. (1) Various molecules that inhibit the formation of free radicals, many of which are termed antioxidants, can inhibit the carcinogenic action of a variety of chemical carcinogens. (2) There are relatively specific metabolic reactions of certain chemical carcinogens, particularly of polycyclic hydrocarbons, for which it has been shown to proceed through free radical intermediates. In conclusion, free radical processes with direct effects on DNA can be proposed for a variety of human and animal carcinogens.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Mediastinal lymphangiomyoma in a child: report of a case.

Lymphangiomas and lymphangiomyomas are benign abnormal collections of lymphatic vessels which form a cystic mass. The mediastinum is an uncommon location for these hamartomas in children, but may be life-threatening. We report herein the case of a 23-month-old boy who presented with stridor and a history of recurrent respiratory tract infections. Soon after his admission he suddenly developed respiratory failure and was found to have a multiloculated, cystic mediastinal mass which was initially thought to be a lymphangioma. The mass was extensively infiltrative, and histological examination showed prominent smooth muscle proliferation in the walls of the cysts, confirming a diagnosis of lymphangiomyoma. The terminology and relevant literature on the topic are reviewed following the presentation of this case.

Humans↗

Comparative, immunological studies on lymphangiectasia of the small intestine revealed in protein losing gastroenteropathy and Behçet's disease.

Lymphangiectasia of the small intestine was demonstrated in 9 to 18 cases with protein losing gastroenteropathy and in 10 of 26 cases with Behçhet's disease. Protein losing gastroenteropathy was compared to Behçet's disease in view of immunological aspects. Immunoglobulin containing cells in the jejunal mucosa of protein losing gastroenteropathy were decreased, whereas Behçet's disease had normal or increased distribution. This suggested that suggested that immunoglobulin may be lost into the intestinal lumen or that production of those cells may be inhibited in protein losing gastroenteropathy. Decreased DNCB skin reaction and impaired blastoid transformation of peripheral lymphocytes in both of two diseases suggested that there should be immunological defect in those diseases. However, in Behçet's disease, investigation of the thymus disclosed hyperplasia and the presence of lymphoid follicle which does not appear in normal state. In conclusion, protein losing gastroenteropathy is in immunological deficiency state due to the congenital or acquired disorders of lymphatics which implies abnormal protein loss, decreased immunoglobulin containing cells in the jejunal mucosa and decreased sensitivity. On the contrary, in Behçet's disease hyperimmune state is present based on thymic hyperplasia.

Adult↗

Syk and Slp-76 mutant mice reveal a cell-autonomous hematopoietic cell contribution to vascular development.

Developmental studies support a common origin for blood and endothelial cells, while studies of adult angiogenic responses suggest that the hematopoietic system can be a source of endothelial cells later in life. Whether hematopoietic tissue is a source of endothelial cells during normal vascular development is unknown. Mouse embryos lacking the signaling proteins Syk and Slp-76 develop abnormal blood-lymphatic endothelial connections. Here we demonstrate that expression of GFPSlp-76 in a subset of hematopoietic cells rescues this phenotype, and that deficient cells confer focal vascular phenotypes in chimeric embryos consistent with a cell-autonomous mechanism. Endogenous Syk and Slp-76, as well as transgenic GFPSlp-76, are expressed in circulating cells previously proposed to be endothelial precursors, supporting a causal role for these cells. These studies provide genetic evidence for hematopoietic contribution to vascular development and suggest that hematopoietic tissue can provide a source of vascular endothelial progenitor cells throughout life.

Adaptor Proteins, Signal Transducing↗

Solitary pulmonary lymphangioma.

Lymphangioma is an abnormal collection of lymphatics that are developmentally isolated from the normal lymphatic system. Lymphangioma rarely presents as a solitary pulmonary lesion. We present a case of solitary pulmonary lymphangioma and review the literature on its pathogenesis, clinical features, and radiographic findings.

Accidental Falls↗

Abdominal lymphography in thalassaemia major.

The appearances are described of abdominal lymphography in seven patients with thalassaemia major. All were severely and chronically anaemic. An abnormal course of lymphatic channels was seen in only one case. Nodal filling defects were found in all patients, lying centrally and peripherally, in para-aortic and iliac glands. The findings correlate well with the microscopic features of lymph nodes removed at therapeutic splenectomy. These show haemosiderin deposition and foci of extramedullary erythropoeisis.

Adolescent↗

[Yellow nail syndrome. Apropos of 2 cases. Review of the literature].

The yellow nail syndrome is a clinical syndrome without specific biological parameters. It is characterized by the following threesome of symptoms: nail abnormalities, primary lymphedema, and pleuropulmonary manifestations. In most cases lymphography shows abnormalities of the lymphatic vessels and spirometry shows a restrictive defect and rarely obstructive disorders. Pathogenesis of this syndrome is still unknown. It is, however, remarkable that the yellow nail syndrome may occur in association with other diseases, the most frequent of which are cancer affections and immune disorders. We report two cases of the yellow nail syndrome which were associated with cancer (neoplasm of the larynx and breast).

Aged↗

[Yellow nail syndrome with chylous effusions].

Yellow nail syndrome is characterized by a yellow discolouration of the nails associated with idiopathic lymphoedema and pleuropulmonary manifestations. Pleural effusions are usually of the exudate type with a normal lipid content. The case reported here of a 74-year old man who had yellow nails together with chylothorax and chylous ascites provides an opportunity to discuss the origin of these rare effusions which, like the syndrome itself, were most probably due to primary abnormalities of the lymphatic system.

Aged↗

Postthrombotic syndrome: incidence, prevention, and management.

Mild to severe postthrombotic sequelae, including chronic pain, edema, and ulceration, arise in one third of patients short after deep vein thrombosis (DVT). Recurrent DVT is closely associated with the development of postthrombotic syndrome (PTS), whereas if the extent and location of DVT might be relevant remains unclear. Chronic venous hypertension and abnormal microvessel or lymphatic function also correlates with PTS. The diagnosis of PTS is based on clinical grounds only if patients report a history of documented DVT; otherwise, objective testing is required. To abate the prevalence of PTS, the best policy is represented by prevention of recurrent thrombosis and use of stockings. Despite a plenty of surgical options, conservative treatment is preferable because half of the patients improve or remain stable during follow-up, provided they wear elastic stockings. Clinical presentation has a prognostic value, as patients with initially severe symptoms enjoy a more favorable outcome than those who progressively deteriorate over time.

Anticoagulants↗

[Magnetic resonance tomography and magnetic resonance angiography in lymphangiomatosis].

Generalised lymphangiomatosis is a rare benign congenital abnormality of the lymphatic vessels with a complex pattern. 3 patients with different types of lymphangiomatosis were studied by MRT and MRA and histopathologically. All patients had multiple organ involvement in the abdomen, the skeleton and the skull. The basis in each case was lymphangiomatosis of capillary-cavernous, cystic or cavernous type. The results of MRT and MRA in diagnosing splenic, vascular and skeletal changes correlated accurately with operative findings and with the histopathological classification. In summary, MRT combined with MRA and using paramagnetic contrast media are the diagnostic methods of choice for the investigation of generalised lymphangiomatosis with multiple organ involvement.

Abdomen↗