There has been an increasing interest in reabsorbed or degradable biomaterials with hyaluronan (HA)-based high molecular polymers in tissue engineering techniques, where scaffold biomaterials are used as a career matrix, and materials of culture cells or three-dimensional tissue reconstruction. Clinical application of biopolymers has been described using different molecular engineering strategies involving a variety of biosynthetic and modified natural polymers like ECM molecules including hyaluronan and glucosaminoglycans. The present report attempts to evaluate HA-based biomaterials as reconstructive or augmentation materials for repair tissue loss or great tissue damage. Excellent histocompatibility and biodegradability in HA-based biomaterials as HYAFF^® are achieved in cases of synthetic bioskin and biosynthetic osteo-cartilage tissues for tissue reconstruction. A variety of growth factors and cytokines have also served to promote cell migration, proliferation and new tissue formation onto biomaterials.

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Squamous differentiation/squamous metaplasia is a common feature associated with lung and endometrial adenocarcinomas, but is very rare in the case of colonic and gastric adenocarcinomas. Cases of squamous cell carcinoma and adenosquamous carcinoma (criteria of the Japan Lung Cancer Society) of the lung and endometrial adenocarcinoma with squamous differentiation infected with human papillomavirus (HPV) are frequently seen in Okinawa. A correlation between squamous differentiation and HPV infection was demonstrated (p<0.05) [11, 31], and the squamous cell carcinoma components are HPV-positive by in situ hybridization method. The adenocarcinoma cells adjacent to the squamous cell carcinoma components are enlarged, and are also positive for HPV. The production of high molecular weight keratin (HMK) (Moll's No. 1, 5, 10, and 14) [1, 14] and involucrin is induced in the squamous cell carcinoma component and also in adjacent enlarged cells. Further, in Okinawa, squamous metaplasia of the bronchial epithelium are occasionally positive for HPV by in situ hybridization. We postulated that HPV causes phenotype change/squamous metaplasia. We then transfected human papillomavirus 6, 16 and 18 in plasmid pBR322 into cultured adenocarcinoma cells (DLD-1 [4] and PC-14 cells) [13, 16]. DLD-1 cells were the cultured human intestinal adenocarcinoma (moderately differentiated), and PC-14 cells were cultured human lung adenocarcinoma. In our experiments, we chose these two cultured adenocarcinoma cells for following reasons. Squamous differentiation is frequently observed in the case of lung carcinomas, but rare in colonic carcinomas. We used one each of the cultured adenocarcinoma cell lines from both groups. Further, to investigate the effects of HPV transfection on apoptosis and inhibition of the growth, p53 gene mutated (inactivated) carcinoma cells [20, 34] were used. The phenotype change/squamous metaplasia was observed, and was apparent in the case of HPV 16 transfected DLD-1 cells, although in the case of human intestinal adenocarcinoma, squamous differentiation was very rare. It was considered that squamous differentiation was induced by HPV transfection regardless of the tissue type [13]. For this reason, in this report we consider HPV 16 transfected DLD-1 cells. Immunohistochemically HMK (Moll's No. 1, 5, 10 and 14) [1, 15] and involucrin [35] were strongly demonstrated in the cytoplasm of HPV transfected cells. Further, the transglutaminase I [6] and involucrin mRNA were also detected by use of RT-PCR. The growth of the HPV transfected cells was reduced, and the population of G0-G1 phase cells increased. The expression levels of the cell cycle related molecules, cdk2 and cyclin D3 decreased. On the other hand, the proportion of apoptotic cells increased, and the expression level of DNase γ also increased markedly [13].
Although the HPV E6-p53 and E7-Rb interactions have been well known, transcriptional trans-activity of HPV for other cellular genes, for example, cytokeratin and cell cycle associated genes, might be considered [13, 33].

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For 34 advanced and refractory cases of epithelial ovarian cancer, we immunohistochemically analyzed modification of p53 expression in tissue from both primary and secondary surgeries, focusing on the relationship with chemotherapeutic effects caused by two different regimens: high-dose chemotherapy (HDC) and conventional chemotherapy (CONV). Following the primary surgery, 18 cases were treated with HDC and 16 cases with CONV. The p53 expression was more markedly decreased in the HDC-treated cases (78% for the primary; 39% for the secondary), compared to that in the CONV-treated cases (50% for the primary; 43% for the secondary). Sixty-seven percent (12/18) of the HDC-treated cases showed an obvious decrease in p53 expression, whereas 81% (13/16) of the CONV-treated cases showed no change in expression. In the comparison of these two groups, the survival ratio was higher in the 12 HDC-treated cases than that in the 13 CONV-treated cases (p<0.05). In conclusion, as p53 expression in epithelial ovarian cancers is considerably influenced by chemotherapy regimen, it was suggested that the regimen yielding a distinct decrease in expression could yield a more favorable outcome.

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Anaplastic large cell lymphoma (ALCL) has recently been recognized as a distinct clinicopathologic entity of CD30⁺ large cell lymphomas, restricted to T or null cell lineage. They may or may not express the anaplastic lymphoma kinase (ALK) protein, and most of them express cytotoxic granule-associated protein (e.g. TIA-1). We report three such cases studied by flow cytometry analysis (FCM), immunohistochemistry (IHC) and electron microscopy (EM). According to the new WHO classification, two cases were primary systemic ALCLs of which one case was of small cell variant (case 1) and the other case was a common variant (case 2). The third case (case 3) was primary cutaneous ALCL which showed a giant cell rich pattern. IHC combined with FCM indicated that all cases were T/null cell phenotypes, and all were positive for CD30, TIA-1 and ALK protein (p80). Electron microscopically, three types of cytotoxic granules (dense core, multivesicular and intermediate types) were seen in all cases. In conclusion, the three cases with different morphologic variants of ALCL share the same clinical, phenotypical, cytogenetic and ultrastructural characteristics. These results further support the view that ALK-positive ALCL is a distinct clinicopathologic entity.

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Our previous study indicated that the acinar cells regenerated actively in the rat pancreatic remnant after partial (90%) pancreatectomy. On that occasion, a twofold higher mitotic activity was observed in the cells of paraduodenal than those of the medial and stump regions (regional difference). Since cholecystokinin (CCK) has been known to have various physiological functions in the digestive system, especially in the pancreas, through the CCK-A receptor, we determined the effect of a CCK-A receptor competitive antagonist (CCK-RA) (SR27897B) on pancreatic regeneration after pancreatectomy. A group of Wistar rats was administered 1 mg/kg CCK-RA twice daily for 5 days. On the 2nd day of administration, partial pancreatectomy was performed. Proliferation activity of both exocrine and endocrine cells was found to be enhanced uniformly 5 days after the pancreatectomy, and the effect was inhibited by CCK-RA. Plasma CCK level was increased by 90% pancreatectomy and decreased by CCK-RA. CCK was hypothesized to be an important factor of pancreatic exocrine and endocrine regeneration. Administration with CCK-RA suppressed mitotic activity uniformly in the three regions of paraduodenal, medial and stump. From the evidence, it was presumed that regional difference in regeneration was produced not by paracrine factor from the duodenum but by some other unknown mechanism including anatomical difference in vascular and autonomic nervous system.

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