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Tissue Invasion (tissue + invasion)
Selected AbstractsPlectin deposition at podosome rings requires myosin contractilityCYTOSKELETON, Issue 8 2008Annica Gad Abstract Metalloproteinase-dependent tissue invasion requires the formation of podosomes and invadopodia for localized matrix degradation. Actin cytoskeleton remodeling via Arp2/3-mediated actin polymerization is essential for podosome formation, and dynamic microtubules have an important role in maintaining podosome turnover in macrophages and osteoclasts. Little is known, however, about the involvement of the intermediate filament cytoskeleton in formation, stabilization, and turnover of podosomes. Here we show that vimentin intermediate filaments colocalize with the early sites of podosome formation at the stress fiber - focal adhesion interface in cultured vascular smooth muscle cells, but do not directly contribute to podosome formation, or stabilization. In unstimulated A7r5 cells the cytolinker protein plectin poorly colocalized with vimentin and the microdomains, but following induction by phorbol ester accumulated in the rings that surround the podosomes. In plectin-deficient A7r5 cells actin stress fiber remodelling is reduced in response to PDBu, and small podosomes remain localized at stable actin stress fibres. Pharmacological inhibition of actomyosin contractility by blebbistatin leads to an aberrant localization of podosomes away from the cell periphery and induces failure of plectin to surround the outer perimeter of these invasive adhesions. Taken together, we conclude that plectin is involved in growth and maturation of podosomes by reducing focal adhesion and stress fiber turnover, and that actomyosin-dependent contractility is required for the peripheral localization and specific deposition of plectin at the podosome rings. Cell Motil. Cytoskeleton 2008. © 2008 Wiley-Liss, Inc. [source] Strain persistence of invasive Candida albicans in chronic hyperplastic candidosis that underwent malignant changeGERODONTOLOGY, Issue 2 2001DW Williams Abstract Objectives: The aim of this study was to assess persistence and tissue invasion of Candida albicans strains isolated from a 65 year-old patient with chronic hyperplastic candidosis (CHC), that subsequently developed into squamous cell carcinoma (SCC). Materials and Methods: C. albicans (n=7) were recovered from the oral cavity of the patient over seven years. Confirmation of CHC and SCC in this patient was achieved by histopathological examination of incisional biopsy tissue. DNA fingerprinting was performed on the seven isolates from the CHC patient together with a further eight isolates from patients with normal oral mucosa (n=2), chronic atrophic candidosis (n=1), SCC (n=1) and CHC (n=4). Genotyping involved the use of inter-repeat PCR using the eukaryotic repeat primer 1251. Characterisation of the tissue invasive abilities of the isolates was achieved by infecting a commercially available reconstituted human oral epithelium (RHE; SkinEthic, Nice, France). After 24 h. C. albicans tissue invasion was assessed by histopathological examination. Results: DNA fingerprinting demonstrated strain persistence of C. albicans in the CHC patient over a seven year period despite provision of systemic antifungal therapy. The strain of C. albicans isolated from this patient was categorised as a high invader within the RHE compared to other isolates. Conclusions: Candidal strain persistence was evident in a patient with CHC over seven years. This persistence may be due to incomplete eradication from the oral cavity following antifungal therapy or subsequent recolonisation from other body sites or separate exogenous sources. The demonstration of enhanced in vitro tissue invasion by this particular strain may, in part, explain the progression to carcinoma. [source] Escape from microenvironmental control and progression of intraepithelial neoplasiaINTERNATIONAL JOURNAL OF CANCER, Issue 6 2005Weitian Zhang Abstract We previously reported that normal human keratinocytes controlled neoplastic progression of tumor cells at an early stage of transformation in stratified squamous epithelium. We now studied if cells at a more advanced stage of transformation were also subject to such microenvironmental control. To accomplish this, 3D human tissues that mimic intraepithelial neoplasia were fabricated by mixing genetically marked (,-gal), early-stage (II-4 cells) or advanced-stage (SCC13) transformed keratinocytes with normal keratinocytes, and tumor cell fate and phenotype were monitored in organotypic culture and after surface transplantation to nude mice. In vivo, SCC13 cells evaded local growth suppression to undergo connective tissue invasion at significantly lower tumor cell volumes (12:1, 50:1 normal:tumor cells) than II-4 cells. This behavior was explained by the growth suppression of II-4 cells, while advanced-stage tumor cells escaped this control and continued to undergo clonal expansion in mixed cultures to form large, intraepithelial tumor clusters. These communities of tumor cells underwent autonomous growth that was associated with altered expression of markers of differentiation (keratin 1) and cell,cell communication (connexin-43). Furthermore, significantly greater numbers of SCC13 cells expanded into a basal position after low-calcium stripping of suprabasal cells of mixed cultures compared to II-4 cells, suggesting that expansion of these cells enabled tumor cell invasion after transplantation. These findings demonstrated that early tumor development in human stratified squamous epithelium required escape from microenvironmental growth control that was dependent on the transformation stage of intraepithelial tumor cells during the premalignant stage of cancer progression. © 2005 Wiley-Liss, Inc. [source] Solitary floating vena caval thrombus as a late recurrence of renal cell carcinomaINTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2004ANDREA MINERVINI Abstract We report an unusual case of solitary thrombus floating in the inferior vena cava (IVC) in a patient who underwent radical nephrectomy for a renal cell carcinoma (RCC) of the right kidney extended into the renal vein with no capsular and perinephric tissue invasion (pT3b). Twenty months after surgery, a routine computed tomography scan identified an intraluminal mass floating in the IVC. Cavotomy and thrombectomy with no caval resection were successfully performed. A review of the literature showed only three previous published cases of RCC recurring in the IVC only, with no local recurrence or distant metastases. We outline the possible etiology of these unusual and solitary recurrences in the IVC and we emphasize the need for a strict surveillance for all patients with RCC and especially for those with pT1b, pT2 and pT3 disease. An early diagnosis of this rare recurrence can permit an easy removal of the thrombus with no caval resection and graft replacement, making this disease potentially curable by surgery. [source] Invasive intraductal papillary-mucinous neoplasm of the pancreas: Comparison with pancreatic ductal adenocarcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 1 2009Yoshiaki Murakami MD Abstract Background and Objectives The aim of this study was to clarify the clinicopathological differences between patients with invasive intraductal papillary-mucinous neoplasm (IPMN) of the pancreas and pancreatic ductal adenocarcinoma. Methods The medical records of 16 patients with invasive IPMN and 106 patients with pancreatic ductal adenocarcinoma, who underwent surgical resection, were retrospectively reviewed, and the clinicopathological factors and survival were compared between the two groups. Results The presence of retroperitoneal tissue invasion, portal or splenic vein invasion, nodal involvement, and positive surgical margins were significantly lower in patients with invasive IPMN than in those with ductal adenocarcinoma (P,<,0.05). The actuarial 5-year overall survival rates in patients with invasive IPMN and ductal carcinoma were 40% and 18%, respectively (P,=,0.008). However, the actuarial 5-year survival rate of patients with invasive IPMN was only 27% for UICC stage II disease, although this was significantly higher than that of patients with UICC stage II ductal adenocarcinoma (P,=,0.049). Conclusions Invasive IPMN has a favorable prognosis compared with pancreatic ductal adenocarcinoma that is likely due to the less aggressive nature of the disease. However, the prognosis for cases of advanced invasive IPMN is not always favorable despite complete tumor resection. J. Surg. Oncol. 2009;100:13,18. © 2009 Wiley-Liss, Inc. [source] The changing faces of Streptococcus antigen I/II polypeptide family adhesinsMOLECULAR MICROBIOLOGY, Issue 2 2010L. Jeannine Brady Summary Streptococcus mutans antigen I/II (AgI/II) protein was one of the first cell wall-anchored adhesins identified in Gram-positive bacteria. It mediates attachment of S. mutans to tooth surfaces and has been a focus for immunization studies against dental caries. The AgI/II family polypeptides recognize salivary glycoproteins, and are also involved in biofilm formation, platelet aggregation, tissue invasion and immune modulation. The genes encoding AgI/II family polypeptides are found among Streptococcus species indigenous to the human mouth, as well as in Streptococcus pyogenes, S. agalactiae and S. suis. Evidence of functionalities for different regions of the AgI/II proteins has emerged. A sequence motif within the C-terminal portion of Streptococcus gordonii SspB (AgI/II) is bound by Porphyromonas gingivalis, thus promoting oral colonization by this anaerobic pathogen. The significance of other epitopes is now clearer following resolution of regional crystal structures. A new picture emerges of the central V (variable) region, predicted to contain a carbohydrate-binding trench, being projected from the cell surface by a stalk formed by an unusual association between an N-terminal ,-helix and a C-terminal polyproline helix. This presentation mode might be important in determining functional conformations of other Gram-positive surface proteins that have adhesin domains flanked by ,-helical and proline-rich regions. [source] Carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-binding recombinant polypeptide confers protection against infection by respiratory and urogenital pathogensMOLECULAR MICROBIOLOGY, Issue 5 2005Darryl J. Hill Summary The human-specific pathogens Neisseria meningitidis, N. gonorrhoea, Haemophilus influenzae and Moraxella catarrhalis share the property of targeting the carcinoembryonic antigen (CEA)-related cell adhesion molecules (CEACAMs) expressed on human epithelia. CEACAMs are signalling receptors implicated in cell adhesion and regulation of several physiological functions. Their targeting by pathogens can lead to tissue invasion. Although the CEACAM-binding ligands of the bacteria are structurally diverse, they target a common site on the receptor. We have generated a recombinant polypeptide that blocks the interactions of the mucosal pathogens with human epithelial cells and antibodies against it inhibit M. catarrhalis interactions with the receptor. As such, it is a potential antimicrobial agent to prevent infection via a strategy unlikely to promote bacterial resistance and a vaccine candidate against M. catarrhalis. In addition, it could serve more widely as a novel research tool and as a potential therapeutic agent in CEACAM-based physiological disorders. [source] Production of hybrid phage displaying secreted aspartyl proteinase epitope of Candida albicans and its application for the diagnosis of disseminated candidiasisMYCOSES, Issue 3 2007Qiong Yang Summary The secreted aspartyl proteinases (Saps) of Candida albicans have been implicated as immunodominant antigens and virulence factors associated with adherence and tissue invasion. A hybrid phage displaying the Sap epitope VKYTS was constructed by cloning the corresponding DNA fragments into the pfd88 vector. Similar to native Sap, the phage-displayed epitope showed reactivity to sera from mice and patients with systemic C. albicans infection but not from those with oropharyngeal candidiasis and healthy individuals on Western blot. Furthermore, a new enzyme-linked immunosorbent assay was developed to detect the anti-Sap antibody with hybrid phage displaying Sap epitope VKYTS that can be recognised by anti-Sap antibodies. Sequential sera were tested from patients and mice with systemic candidiasis and oropharyngeal candidiasis, and serum samples from healthy individuals were also included. The sensitivity and specificity were 77% and 88.3% for experimental mice, respectively. These values reached 60% and 85%, respectively, for human patients. These data indicate this phage-displayed epitope as an effective and less expensive reagent would be a valuable probe for the detection of specific Sap antibody in the sera of patients and mice with systemic C. albicans infection. [source] Hydrolytic enzymes as virulence factors of Candida albicansMYCOSES, Issue 6 2005Martin Schaller Summary Candida albicans is a facultative pathogenic micro-organism that has developed several virulence traits enabling invasion of host tissues and avoidance of host defence mechanisms. Virulence factors that contribute to this process are the hydrolytic enzymes. Most of them are extracellularly secreted by the fungus. The most discussed hydrolytic enzymes produced by C. albicans are secreted aspartic proteinases (Saps). The role of these Saps for C. albicans infections was carefully evaluated in numerous studies, whereas only little is known about the physiological role of the secreted phospholipases (PL) and almost nothing about the involvement of lipases (Lip) in virulence. They may play an important role in the pathogenicity of candidosis and their hydrolytic activity probably has a number of possible functions in addition to the simple role of digesting molecules for nutrition. Saps as the best-studied member of this group of hydrolytic enzymes contribute to host tissue invasion by digesting or destroying cell membranes and by degrading host surface molecules. There is also some evidence that hydrolytic enzymes are able to attack cells and molecules of the host immune system to avoid or resist antimicrobial activity. High hydrolytic activity with broad substrate specificity has been found in several Candida species, most notably in C. albicans. This activity is attributed to multigene families with at least 10 members for Saps and Lips and several members for PL B. Distinct members of these gene families are differentially regulated in various Candida infections. In future, prevention and control of Candida infections might be achieved by pharmacological or immunological tools specifically modulated to inhibit virulence factors, e.g. the family of Saps. [source] Relationship between boron and calcium in the N2 -fixing legume,rhizobia symbiosisPLANT CELL & ENVIRONMENT, Issue 11 2003M. REDONDO-NIETO ABSTRACT Because boron (B) and calcium (Ca2+) seem to have a strong effect on legume nodulation and nitrogen fixation, rhizobial symbiosis with leguminous plants, grown under varying concentrations of both nutrients, was investigated. The study of early pre-infection events included the capacity of root exudates to induce nod genes, and the degree of adsorption of bacteria to the root surface. Both phenomena were inhibited by B deficiency, and increased by addition of Ca2+, resulting in an increase of the number of nodules. The infection and invasion steps were investigated by fluorescence microscopy in pea nodules harbouring a Rhizobium leguminosarum strain that constitutively expresses green fluorescent protein. High Ca2+ enhanced cell and tissue invasion by Rhizobium, which was highly inhibited after B deficiency. This was combined with an increased B concentration in nodules of plants grown on B-free medium and supplemented with high Ca2+ concentrations, and that can be attributed to an increased B import to the nodules. Histological examination of indeterminate (pea) and determinate (bean) nodules showed an altered nodule anatomy at low B content of the tissue. The moderate increase in nodular B due to additional Ca2+ was not sufficient to prevent the abnormal cell wall structure and the aberrant distribution of pectin polysaccharides in B-deficient treatments. Overall results indicate that the development of the symbiosis depends of the concentration of B and Ca2+, and that both nutrients are essential for nodule structure and function. [source] A Biochemical Comparison of Proteases from Pathogenic Naegleria fowleri and Non-Pathogenic Naegleria gruberiTHE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 5 2007JESÚS SERRANO-LUNA ABSTRACT. Naegleria fowleri is the etiologic agent of primary amoebic meningoencephalitis (PAM). Proteases have been suggested to be involved in tissue invasion and destruction during infection. We analyzed and compared the complete protease profiles of total crude extract and conditioned medium of both pathogenic N. fowleri and non-pathogenic Naegleria gruberi trophozoites. Using SDS-PAGE, we found differences in the number and molecular weight of proteolytic bands between the two strains. The proteases showed optimal activity at pH 7.0 and 35 °C for both strains. Inhibition assays showed that the main proteolytic activity in both strains is due to cysteine proteases although serine proteases were also detected. Both N. fowleri and N. gruberi have a variety of different protease activities at different pH levels and temperatures. These proteases may allow the amoebae to acquire nutrients from different sources, including those from the host. Although, the role of the amoebic proteases in the pathogenesis of PAM is not clearly defined, it seems that proteases and other molecules of the parasite as well as those from the host, could be participating in the damage to the human central nervous system. [source] LIM kinase-2 targeting as a possible anti-metastasis therapyTHE JOURNAL OF GENE MEDICINE, Issue 3 2004Eigo Suyama Abstract Background Metastatic properties of tumors involve movement of cancerous cells from one place to another and tissue invasion. Metastatic cells have altered cell adhesion and movement that can be examined by in vitro chemotaxis assays. The Rho/ROCK/LIM kinase pathway is one of the major signaling pathways involved in tumor metastasis. It is involved in the regulation of the actin cytoskeleton. Using the randomized ribozyme library, we initially found that metastatic human fibrosarcoma cells harboring ribozyme specific for ROCK lose their metastatic properties. In this study, we have determined the effect of ribozymes specific for LIM kinase-2 on metastatic and proliferative phenotypes of human fibrosarcoma cells. Methods We attempted to target LIM kinase-2 (LIMK-2) expression by hammerhead ribozymes (Rz) in human metastatic fibrosarcoma cells. An effective ribozyme was selected based on the expression analysis. Cells were stably transfected with Rz specifically effective for LIMK-2 and were examined for metastatic and proliferative properties. Results Analyses of cellular phenotypes such as cell proliferation, cell migration and colony-forming efficiency revealed that the suppression of LIMK-2 expression in human fibrosarcoma cells limits their migration and dense colony-forming efficiency without affecting cell proliferation rate or viability. Conclusions Specific targeting of metastatic and malignant properties of tumor cells by LIMK-2 ribozyme may serve as an effective therapy for invasive tumors with minimum effect on the surrounding normal cells. Copyright © 2004 John Wiley & Sons, Ltd. [source] Pregnancy as a Model of Controlled Invasion Might Be Attributed to the Ratio of CD3/CD8 to CD56AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2000P.C. ARCK PROBLEM: Pregnancy can be considered as a model of successfully controlled tissue invasion. Cellular mediated immunity appears to regulate the controlled invasion of fetal trophoblast cells. In endometrium cancer, a dysregulation of invasive malignant cells can be observed. Since immuncompetent cells are known to be involved in recognition and rejection of ,non-self' antigens, we investigated the presence and distribution pattern of CD3, CD8, CD56, and CD68 positive cells in decidua from normal and failing pregancies, compared with malignant and benign endometrium. METHOD OF STUDY: Decidual tissue from first trimester normal pregancies (NP; n=15) and abortion (AB; n=12), endometrial samples from premenopausal women (NE; n=8), and endometrioid adenocarcinoma (EA; n=8) were examined by immunohistochemistry using monoclonal antibody against large spectrum cytokeratin, and against the receptors CD3, CD8, CD56 and CD68, respectively. RESULTS: In NP, we observed 32.5% CD3, 44.7% CD56, and 22.9% CD68+ cells. In AB, we found 36.9% CD3, 45.3% CD56, and 17.8% CD68+ cells. The differences in ratio between normal pregnancy and abortion were not statistically significant. In NE, we counted 39.5% CD3, 30.2% CD56 and 30.2% CD68+ cells. In EA, we observed 47.9% CD3, 12.4% CD56 and 39.7% CD68+ cells. The decrease of CD56 positive cells in endometrioid adenocarcinoma was statistically significant. Interestingly, we found 4.1% of cells positive for CD8 in NP, 4.9% in AB, 22.7% in NE, and 48.2% in EA. CONCLUSIONS: The increase of CD8 cells in NE, and particularely in EA, and decrease of CD56 cells, compared with NP or AB, suggests an interaction between CD8 cells and CD56 cells. Studying different pathological situations in the uterus, such as malignancies or ectopic pregnancies, might help us to understand the mechanisms involved in the maintenance of pregnancy. [source] Giant basal cell carcinoma masquerading as an osteogenic sarcomaAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 1 2009Paul Cherian SUMMARY An 88-year-old man presented to the dermatology outpatient clinic with an 11-month history of a rapidly growing mass overlying a clavicular fracture site. The lesion was 8 × 6 cm, painful, fixed to deeper structures and ulcerated. Superficial and deep biopsies yielded invasive basal cell carcinoma. Imaging demonstrated extensive soft tissue invasion into muscle, bone and potentially into the lung parenchyma. Due to complications arising from subsequent diagnostic procedures, the patient declined further invasive tests. The cutaneous lesion was treated with palliative radiotherapy. We explore the literature regarding the tumorigenic effects of peri-fracture cytokines on the biological behaviour of basal cell neoplasms. [source] Crystallization and preliminary crystallographic analysis of cysteine synthase from Entamoeba histolyticaACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 6 2007Chinthalapudi Krishna Entamoeba histolytica, the causative agent of human amoebiasis, is essentially anaerobic, requiring a small amount of oxygen for growth. It cannot tolerate the higher concentration of oxygen present in human tissues or blood. However, during tissue invasion it is exposed to a higher level of oxygen, leading to oxygen stress. Cysteine, which is a vital thiol in E. histolytica, plays an essential role in its oxygen-defence mechanisms. The major route of cysteine biosynthesis in this parasite is the condensation of O -acetylserine with sulfide by the de novo cysteine-biosynthetic pathway, which involves cysteine synthase (EhCS) as a key enzyme. In this study, EhCS was cloned, expressed in Escherichia coli and purified by affinity and size-exclusion chromatography. The purified protein was crystallized in space group P41 with two molecules per asymmetric unit and a complete data set was collected to a resolution of 1.86,Ĺ. A molecular-replacement solution was obtained using the Salmonella typhimuriumO -acetylserine sulfhydrylase structure as a probe and had a correlation coefficient of 37.7% and an R factor of 48.8%. [source] Intraoperative diagnosis and treatment of parathyroid cancer and atypical parathyroid adenomaBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 5 2007G. Ippolito Background: Distinction of parathyroid cancer from atypical parathyroid adenoma (APA) at operation is difficult. The aim of this study was to determine whether parathyroid cancer and APA have different operative findings and long-term outcomes. Methods: A retrospective review was undertaken of patients with suspicious or malignant parathyroid tumours treated between 1974 and 2005. Parathyroid cancer was defined as a lesion with vascular or tissue invasion, and APA as a neoplasm with broad fibrous bands, trabecular growth, mitosis and nuclear atypia. Results: Twenty-seven patients with suspicious or malignant parathyroid tumours were identified. After histological review, parathyroid cancer was confirmed in 11 patients (group 1) and 16 tumours were classified as APA (group 2). The clinical presentation and operative findings of the two types of tumour were indistinguishable. At initial surgery, seven patients in group 1 underwent en bloc resection, and four had parathyroidectomy. Four of the seven patients who had en bloc resection had recurrences. No recurrences were observed in the other seven patients in group 1 at a median follow-up of 65 months. In group 2, eight patients had en bloc resection and eight had parathyroidectomy; no patient had recurrence at a median follow-up of 91 months. Conclusion: Operative findings cannot distinguish APA from parathyroid cancer reliably. Without evidence of macroscopic local invasion, the value of en bloc resection at initial surgery remains debatable. Copyright © 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||