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

Cytopathic effects and local immune responses in repeated neoadjuvant HSV-tk + ganciclovir gene therapy for prostate cancer

ObjectiveCytopathic effects and local immune response were analyzed histologically in prostatic carcinoma (PCa) with in situ herpes simplex virus-thymidine kinase (HSV-tk)/ganciclovir (GCV) gene therapy (GT). MethodsFour high-risk PCa patients who received HSV-tk/GCV GT were investigated. After two cycles of intraprostatic injection of HSV-tk and administration of GCV, radical prostatectomy was performed. Formalin-fixed, paraffin-embedded sections were evaluated using immunohistochemistry. PCa with hormone therapy (HT, n = 3) or without neoadjuvant therapy (NT, n = 4) that were equivalent in terms of risk were also examined as reference. Immunoreactively-positive cells were counted in at least three areas in cancer tissue. Labeling indices (LI) were calculated as percentage values. ResultsssDNA LI in GT increased, indicating apoptosis, as well as tumor-infiltrating lymphocytes and CD68-positive macrophages, compared with their biopsies. GT cases showed significantly higher numbers of ssDNA LI, CD4/CD8-positive T cells and CD68-positive macrophages including M1/M2 macrophages than HT or NT cases. However, there was no significant difference in CD20-positive B cells among the types of case. There were strong correlations between CD8+ T cells and CD68+ macrophages (ρ = 0.656, p < 0.0001) as well as CD4+ T cells and CD20+ B cells (ρ = 0.644, p < 0.0001) in PCa with GT. ConclusionsEnhanced cytopathic effect and local immune response were might be indicated in PCa patients with HSV-tk/GCV gene therapy.Cytopathic effects and local immune response were analyzed histologically in prostatic carcinoma (PCa) with in situ herpes simplex virus-thymidine kinase (HSV-tk)/ganciclovir (GCV) gene therapy (GT..

Invasive behavior of ulcerative colitis-associated carcinoma is related to reduced expression of CD44 extracellular domain: comparison with sporadic colon carcinoma

<p>Abstract</p> <p>Background</p> <p>To elucidate relations of invasion of ulcerative colitis (UC)-associated carcinoma with its prognosis, the characteristics of invasive fronts were analyzed in comparison with sporadic colonic carcinomas.</p> <p>Methods</p> <p>Prognoses of 15 cases of UC-associated colonic carcinoma were compared with those of sporadic colon carcinoma cases, after which 75 cases of sporadic invasive adenocarcinoma were collected. Tumor budding was examined histologically at invasive fronts using immunohistochemistry (IHC) of pancytokeratin. Expressions of beta-catenin with mutation analysis, CD44 extracellular domain, Zo-1, occludin, matrix matalloproteinase-7, laminin-5γ2, and sialyl Lewis X (Le^X) were immunohistochemically evaluated.</p> <p>Results</p> <p>UC-associated carcinoma showed worse prognosis than sporadic colon carcinoma in all the cases, and exhibited a tendency to become more poorly differentiated when carcinoma invaded the submucosa or deeper layers than sporadic carcinoma. When the lesions were compared with sporadic carcinomas considering differentiation grade, reduced expression of CD44 extracellular domain in UC-associated carcinoma was apparent. Laminin-5γ2 and sialyl-Le^Xexpression showed a lower tendency in UC-associated carcinomas than in their sporadic counterparts. There were no differences in the numbers of tumor budding foci between the two lesion types, with no apparent relation to nuclear beta-catenin levels in IHC.</p> <p>Conclusions</p> <p>UC-associated carcinoma showed poorer differentiation when the carcinoma invaded submucosa or deeper parts, which may influence the poorer prognosis. The invasive behavior of UC-associated carcinoma is more associated with CD44 cleavage than with basement membrane disruption or sialyl-Lewis-antigen alteration.</p

A PATHOLOGICAL STUDY OF 32 AUTOPSY CASES OF THE SO-CALLED SPLENIC AGENESIS SYNDROME

A total of thirty-two autopsy cases of the so called splenic agenesis syndrome (or Ivemark’s syndrome) were collected and studied pathomorphologically. The splenic agenesis syndrome is composed of three main elements; namely, congenital splenic agenesis, characteristic anomalies of the cardiovascular system, and abdominal heterotaxy with right sidedness of the visceral organs. The cases were classified into three types according to severity of these anomalies; complete (having all these three components), incomplete (asplenia and one of the other two), and simple (only congenital absence of the spleen). Anomalous pulmonary venous return and abnormality of the efferent hepatic veins, both of which were occasionally seen associated in this syndrome, seem to give some influence on the survival period of patients. As for the secondary changes caused by these cardiovascular anomalies, mild hypoplasia of the media, fibrous thickening of the intima, and thrombus formation in the lumen due to stenosis or arteria of the pulmonary trunk were frequently found in the small pulmonary arteries. Various changes of the so-called morbus caeruleus were observed in the liver, kidney, etc. As a possible, compensatory reaction to congenital absence of the spleen, the lymph follicles were found appearing in the bone marrow about one year after birth. Infectious changes were observed, as the direct cause of death, in five cases, all of which were below one year of age

DNA ANALYSIS OF PERIAMPULLARY CANCERS

The nuclear DNA content in 71 cases of periampullary cancer (27, cancer of the head of the pancreas (Ph); 24, cancer of the ampulla of Vater (A) ; and 20, cancer of the inferior common bile duct (Bi)) was measured cytofluorometrically using the archival paraffin-embedded specimens of the primary lesions. They were analyzed in relation to prognosis, tumor size, histological differentiation, lymph node metastasis, lymphatic invasion, venous invasion, perineural invasion, and growth pattern. The results show that “Ph” has more unfavorable prognosis compared with the other two and it has more DNA content under the same conditions such as tumor from 2.1 to 4 cm in its greatest dimension, well differentiated adenocarcinoma, with or without lymph node metastasis, with or without venous invasion, with lymphatic invasion, with perineural invasion, and in the intermediate growth pattern between expansive and infiltrative. In conclusion, this study demonstrates a close correlation between the DNA content and prognosis and the significant clinical value of DNA analysis for predicting the prognosis in patients of periampullary cancer