The Role of Vitamin A-Storing Cells (Stellate Cells) in Inflammation and Tumorigenesis

Characteristic localization and distribution of vitamin A-storing cells (stellate cells) were demonstrated as hepatic stellate cells in the hepatic lobule and as subepithelial myofibroblasts in the colonic crypt. The stem cell-stem cell niche is maintained by stellate cells in the periportal area and crypt base. Periportal vitamin A-rich stellate cells decrease in patients with chronic hepatitis C who are habitual smokers. Mice fed a vitamin A-supplemented diet show reduced severity of dextran sulfate sodium (DSS)-induced colitis and development of subsequent colonic neoplasia in a model of the ulcerative colitis-dysplasia-carcinoma sequence, compared with mice fed a vitamin A-deficient diet. Decreased colonic subepithelial myofibroblasts and IgA/IgG-positive cells, and increased CD11c-positive dendritic cells in the colonic mucosa, in the vitamin A-deficient state suggest dysfunction of the stem cell niche at the colonic crypt base and colonic immunity. Accordingly, vitamin A deficiency may worsen inflammation and subsequent tumor development, indicating the possibility that vitamin A supplementation might be effective against chronic inflammation and cancer development

Prediction of outcome of patients with oral squamous cell carcinoma using vascular invasion and the strongly positive expression of vascular endothelial growth factors.

Vascular invasion and lymph node metastasis have been used as histopathological prognosticators of cancers including oral squamous cell carcinoma (OSCC). In addition to metastatic potential via blood vessels, tumor-induced angiogenesis might also be associated with prognosis. However, the efficacy of combined evaluation of vascular invasion and angiogenesis-associated molecules for the prognosis of OSCC remains obscure. This is also the case in lymph node metastasis and lymphovasculogenesis-associated molecules. The aim of this study was to examine factors related to prognosis to improve the accuracy of prognostic prediction of OSCC using vasculogenesis-associated markers. Ninety specimens of patients from 1991 to 2002 with previously untreated OSCC, who underwent either biopsy or surgery, were histopathologically and immunohistochemically analyzed using antibodies for vascular endothelial growth factor (VEGF)-A, VEGF-C, cyclooxygenase (COX)-2 and Midkine. The ninety cases were composed of 72 well-differentiated, 12 moderately differentiated and 6 poorly differentiated OSCC. Efficient models of prognostic prediction were evaluated by extensive statistical analyses. The presence of vascular invasion or lymph node metastasis was confirmed to be significantly associated with poor prognosis in the univariate analysis. Multivariate logic regression analysis suggested that patients with the strongly positive expression of either VEGF-A or VEGF-C had a significant association with poor prognosis even in patients without vascular invasion and in early-stage patients. Neither COX-2 nor Midkine contributed to predict the prognosis of the patients. The strongly positive expression of VEGF-A or VEGF-C was suggested to reinforce the histopathological diagnosis of vascular invasion and improve the accuracy and efficacy of prognostic prediction of OSCC

Midkine expression correlating with growth activity and tooth morphogenesis in odontogenic tumors

Midkine (MK; a low molecular weight heparin-binding growth factor) is a multifunctional cytokine. MK plays a role in morphogenesis of many organs including teeth through epithelial-mesenchymal interactions. We immunohistochemically examined MK expression in various human odontogenic tumors. There was no difference in positive rate and intensity of MK between benign odontogenic tumors and their malignant counterparts. Ameloblastoma showed MK localization in the peripheral columnar cells in budding processes from the parenchyma, which frequently expressed proliferating cell nuclear antigen. MK was also preferentially expressed in keratinized cells in acanthomatous ameloblastoma and keratocystic odontogenic tumor. In odontogenic mixed tumors except for odontoma, intense immunoreactivity to MK was found in epithelial follicles, the surrounding odontogenic ectomesenchymal tissue, and the basement membrane between them. Intensity in the odontogenic ectomesenchyme decreased in relation to distance from the epithelial follicles. No expression was found in tumor cells associated with production of dental hard tissues in odontogenic mixed tumors including odontoma. These findings suggested that MK is involved in the reciprocal interaction between odontogenic epithelium and odontogenic ectomesenchymal tissue in areas without dental hard tissue formation in odontogenic mixed tumors. Coexpression of MK and proliferating cell nuclear antigen was also observed in epithelial follicles and highly cellular nodules in the ectomesenchyme of odontogenic mixed tumors. MK is considered to mediate growth activity of odontogenic tumors and cell differentiation of odontogenic mixed tumors through molecular mechanisms similar to those involved in morphogenesis of the tooth

Prognostic Value of Podoplanin Expression in Oral Squamous Cell Carcinoma―A Regression Model Auxiliary to UICC Classification

Podoplanin, a type I transmembrane glycoprotein with an effect of platelet aggregation, has been reported to be one of the possible prognostic factors of oral squamous cell carcinoma (OSCC). However, the biological significance of podoplanin is largely unclear. The aim of this study was to develop a practical model for the prediction of prognosis using the grade of podoplanin expression, and also to evaluate the biological function of podoplanin. Eighty-two specimens of patients with previously untreated OSCC, who underwent either biopsy or surgery, were histopathologically and immunohistochemically analyzed. These 82 cases were composed of 66 well-differentiated, 10 moderately differentiated and 6 poorly differentiated OSCC. Podoplanin was successfully immunostained in 78 specimens, and was detected in most cases, but the frequency of positive cells varied. The prognosis of patients with more than 50 % podoplanin-positive tumor cells was significantly poorer than that of the other patients. Multivariate hazards regression analysis suggested that a linear combination of covariates, OSCC patients with more or less than 50 % podoplanin expression, age of more or less than 70 years old, mode of invasion and T3, T4 or T2 versus T1 of the UICC T-stage classification was the most effective model for evaluating the prognosis of OSCC patients. Additionally, podoplanin expression had a significant relationship to UICC clinical stage and the expression of Ki-67. An effective regression model using podoplanin expression was developed for evaluating the prognosis of OSCC and the biological significance of podoplanin was suggested to be associated with the growth and/or progression of OSCC

Cytoglobin expression of rectal subepithelial myofibroblasts: Significant alterations of cytoglobin+ stromal cells in long-standing ulcerative colitis

Cytoglobin/stellate cell activation-associated protein (Cygb/STAP), a hemoprotein, functions as part of an O2 reservoir with protective effects against oxidative stress in hepatic stellate cells. Heterogeneous expression of the neural cell adhesion molecule (NCAM)+ and/or α-smooth muscle actin (αSMA)+ has been noted in subepithelial myofibroblasts and interstitial cells of the same lineage in the colorectum. We have demonstrated that early genomic instability of both epithelial and stromal cells in ulcerative colitis (UC) is important for colorectal tumorigenesis, as well as for mucosal remodeling. To further clarify possible roles of stromal cells in mucosal remodeling and tumor development in UC, we here focused on Cygb expression of subepithelial myofibroblasts and interstitial cells, as well as αSMA and HSP47. Noncancerous mucosa of resected rectae from UC patients with or without colorectal neoplasia (14 and 20 cases, respectively) and of sporadic rectal cancer cases (16) was analyzed immunohistochemically, as well as by immuno-fluorescence and electron microscopy. The results, heterogeneous phenotypes of Cygb+, αSMA+ and HSP47+ subepithelial myofibroblasts and interstitial cells, corresponding to rectal stellate cells, were demonstrated. A decrease of Cygb+ subepithelial myofibroblasts and an increase of αSMA+ interstitial cells were significant in UC, as compared to normal rectal mucosa. Furthermore, a decrease of Cygb+ subepithelial myofibroblasts, correlating with αSMA+ and HSP47+ cells, was significant in long-standing UC with neoplasia. In conclusion, there are heterogeneous phenotypes of Cygb+, αSMA+ and HSP47+ subepithelial myofibroblasts and interstitial cells in the rectal mucosa. Mucosal remodeling with alterations of Cygb+ and/or αSMA+/HSP47+ stromal cells might have some relation to UC-associated tumorigenesis

Evaluation of chromID strepto B as a screening media for Streptococcus agalactiae

BACKGROUND: Streptococcus agalactiae (Group B Streptococcus, GBS), a leading cause of sepsis and meningitis in infants, can be transmitted vertically from mother to infant during passage through the birth canal. Detection of GBS colonization in perinatal women is a major strategy for the prevention of postpartum neonatal disease. The U.S. Centers for Disease Control and Prevention recommends that all women undergo vaginal-rectal screening for GBS colonization at 35-37 weeks of gestation. ChromID Strepto B (STRB) is a chromogenic GBS screening media on which GBS colonies appear pink or red, while other bacteria are either inhibited or form colonies in other colors. In this study, we compared STRB with a conventional GBS detection method using 5% sheep blood agar (BA) followed by a selective enrichment broth. METHODS: Anovaginal swabs were collected from 1425 women during weeks 35 to 37 of their pregnancies. The swabs were used to inoculate both STRB and BA plates after enrichment with selective Todd Hewitt Broth (THB). A GBS latex agglutination test was used to confirm the identity of isolates from each plate. RESULTS: GBS was recovered from 319 (22.4%) samples with one or both media: 318 on STRB compared to 299 using BA. One false negative was observed on STRB, and 20 false negatives were observed on BA. In addition, non-hemolytic GBS was recovered from 19 (6.0%) samples using STRB. CONCLUSIONS: STRB offers effectiveness and convenience over BA for GBS screening in clinical laboratories. STRB produces fewer false negatives, has a higher detection rate and uses a simple color screen that is ideal for technician-level applications. We recommend STRB as the media of choice for GBS screening