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One of the major factors for successful DCs immunotherapy is thought to be the maintenance of the migratory activity of matured DCs. We evaluated the effectiveness of PSK on OK432-activated DCs, in terms of maturation, migration and induction of CTLs. When DCs were treated with both OK432 and PSK, migration ability of the DCs were significantly high as compared to OK432 alone preserving the beneficial effect of OK432 treatment. BRM cocktail treatment with OK432 and PSK induced high level of migration activity in activated DCs, suggesting a potential protocol for more effective DCs immunotherapy for cancer.

Background. To determine the significance of bone marrow disseminated tumor cells in gastric cancer, we investigated the mRNA expression levels of carcinoembryonic antigen (CEA), cytokeratin 19 (CK19), and cytokeratin 20 (CK20) using the real-time quantitative reverse-transcription polymerase chain reaction (RQ-PCR). Methods. Bone marrow samples were aspirated from the sternum at the time of surgery in 65 patients with resectable gastric cancer. Total RNA was extracted from bone marrow; and the expression levels of CEA, CK19, and CK20 mRNA were determined by RQ-PCR using an ABI PRISM 7000 and quantified against the GAPDH mRNA level. Results. The detection limits of these genes were determined in the gastric cancer cell line MKN-45 and the colon cancer cell line C-1, which had been serially diluted in peripheral blood mononuclear cells (PBMCs). A rate of 1 cancer cell/ million PBMCs was obtained by detecting CEA and CK19 mRNA in MKN-45 and by detecting CK20 mRNA in C-1. In the clinical samples, only 1 of the 65 gastric cancer patients (1.5%) who had stage IV disease was positive for CEA, CK19, and CK20 mRNA; none of CEA, CK19, or CK20 mRNA was positive in the remaining 64 patients. No significant correlation was observed between disseminated cancer cells in bone marrow and clinicopathological features, including simultaneous or metachronous hepatic metastasis and patient survival. Conclusion. The incidence of disseminated cancer cells in bone marrow in our study appears low, unlike that in previous reports. The significance of disseminated cancer cells in bone marrow may also be quite low in gastric cancer.

症例は59歳の女性で, 健康診断の上部消化管内視鏡検査にて胃体中部大彎に約10mmの隆起性病変を指摘され, 生検にて胃カルチノイドと診断された. 血液検査では血清ガストリン値が2,069pg/mlと高値であった. 超音波内視鏡検査では粘膜下層までの浸潤が認められた. 胃カルチノイドの診断で手術を施行. 術中色素法によるセンチネルリンパ節 (sentinel node; 以下, SNと略記) 生検にて, SNがNo4dに2個同定され, 1個に転移が認められた. 幽門側胃切除術およびD2リンパ節郭清を施行した. 病理組織検査にて腫瘍は長径9mmで深達度がSM2であり, SNとして同定されたリンパ節以外にリンパ節転移は認めなかった. 胃粘膜に慢性萎縮像は認めなかった. 術後血清ガストリン値は正常化した. sm胃カルチノイドではsm胃癌と同等のリンパ節転移が認められることから, SN生検は術中の正確なリンパ節転移診断法として有用であると思われる.

症例は49歳,女性.下腹部痛を主訴に来院.虫垂炎,胆石症にて2度の開腹歴を有した.入院の上鎮痛剤にて経過観察するも腹痛は次第に増強し, 6時間後には右側腹部の膨隆と右下腹部の筋性防御を認めた.腹部CT検査では右側の後腹膜腔に集積したイレウス腸管と腹水を認めた.絞扼性イレウスの診断にて緊急手術を施行した. Treitz靱帯をヘルニア門として小腸のほとんどが右側の後腹膜腔に嵌入し絞扼されていた.輸出脚の回腸には強い鬱血と色調変化を認めたが,還納後に温生食に浸すと色調が回復した.腸切除をせずにヘルニア門を縫合閉鎖し手術を終了した.術後経過は良好であった. 傍十二指腸ヘルニアは検索しえた範囲では自験例を含め87例と稀な疾患で術前の確定診断は困難と思われた.本症例では画像上特徴的な所見も呈していたと考えられたが,手術既往歴もあり癒着によるイレウスとの鑑別は困難であった.

症例は19歳の女性, 学校検診にて胸部X線写真上, 左中肺野の径約9mmの腫瘤影を指摘された.経過観察にて腫瘤影の増大を認めたため胸腔鏡にて肺部分切除施行.術後の組織診にて胞巣状軟部肉腫との診断を得た.転移と考え全身検索を行ったが, 明らかな原発巣を指摘できなかった.現時点では原発か転移かは明らかでないが, 再発, 転移の兆候なく外来経過観察中である.

Thoracoscopic microwave coagulonecrotic therapy (TMCT) has been reported to be one of the useful approaches in the management of hepatocellular carcinoma (HCC) that is located in the subphrenic area of the liver.In the present study, TMCT was performed on a 75-year-old woman with HCCs and liver cirrhosis. On admission, computed tomography revealed low density areas [exceeding 3 cm in Couinaud's segment 8 (S8) and 1 cm in segment 2 (S2)]. TMCT was selected for the HCC in S8 because percutaneous ethanol injection therapy (PEIT) and transcatheter arterial embolization (TAE) were not effective and surgical resection was not possible due to hepatic dysfunction and multicentric carcinogenesis. A thoracoscope was introduced into the thoracic cavity through the 5 th intercostal space on the midaxillary line, and two other trocars were placed in the appropriate intercostal spaces along the anterior and posterior axillary lines. We treated the HCC in S8 with TMCT across the diaphragma using laparoscopic ultrasonography and in S2 with intraoperative PEIT to avoid complications due to its location near Glisson's sheath. The efficiency of the coagulation and ethanol injection was proven by employing postoperative enhanced computed tomography.It was suggested that multimodal minimally invasive treatment such as TMCT is effective when combined with interstinal therapy for multiple HCCs with liver cirrhosis.

Dendritic cells (DCs) are potent antigen-presenting cells that are central to the regulation, maturation, and maintenance of the cellular immune response against cancer. In contrast, CD4(+)CD25(+) regulatory T cells (Tregs) play a central role in self-tolerance and suppress antitumor immunity. In this study, we investigated the clinical significance of mature CD83(+) DCs and Foxp3(+) Tregs in the primary tumor and regional lymph nodes from the viewpoint of the two opposing players in the immune responses.We investigated, immunohistochemically, the density of CD83(+) DCs and Foxp3(+) Tregs in primary lesions of gastric cancer (n = 123), as well as in regional lymph nodes with (n = 40) or without metastasis (n = 40).Decreased density of CD83(+) DCs and increased density of Foxp3(+) Tregs were observed in the primary tumor and metastatic lymph nodes. Density was significantly correlated with certain clinicopathological features. Poor prognosis was observed in patients with a low density of CD83(+) DCs and a high density of Foxp3(+) Tregs in primary lesions. For patients with metastatic lymph nodes, the density of CD83(+) DCs in negative lymph nodes was found to be an independent prognostic factor by multivariate analysis.The density of CD83(+) DCs and Foxp3(+) Tregs was inversely correlated with tumor progression and reflected the prognosis of gastric cancer.

Claudin, occludin, and zonula occludens (ZO)-1 are known as tight-junction-associated proteins. The aim of this study was to examine the expression of these proteins in gastric carcinoma. Gastric cancer tissues (n = 124) were obtained from 124 patients who underwent gastrectomy at our hospital between January 2000 and December 2004. The expression of the above tight-junction-associated proteins in carcinoma, normal mucosa, and metaplastic epithelium was examined using immunohistochemistry. In addition, the expression of claudin-4 mRNA was examined in fresh frozen tissue obtained from 34 patients. Significant correlations were seen between the expression of claudin-4, occludin, and ZO-1. In regard to claudin-4, significant correlations were seen between the expression of claudin-4 evaluated by immunohistochemistry and the expression of claudin-4 mRNA. Claudin-4 expression was significantly decreased in tumors with undifferentiated-type adenocarcinoma, advanced T stage, lymph node metastasis, and peritoneal metastasis. Occludin and ZO-1 expression was significantly decreased in tumors with undifferentiated-type adenocarcinoma. Overall survival was significantly shorter in patients with low claudin-4 expression. Cox multivariate analysis revealed that low claudin-4 expression was independently associated with significantly decreased overall survival. Tight-junction-associated proteins, particularly claudin-4, may play important roles in determining invasiveness, metastatic potential, and survival in gastric cancer.

The streptococcal preparation OK-432 induces maturation of T cells and dendritic cells (DCs). However, the mechanisms by which OK-432 induces DC maturation are not well understood.The effects of OK-432 and TNF-alpha on peripheral blood mononuclear cells (PBMCs) were compared. Antibody-based approaches were used to detect proteins characteristic of antigen-presenting cells and cytokines. Cytotoxicity was evaluated by measuring the release of LDH after incubation of effector and target cells. The TLR-4 levels were measured by real-time quantitative PCR.Changes in cell surface marker levels were detected in both treatment groups but OK-432 had a greater effect on induction of Th-1-type cytokines. Furthermore, TLR-4 mRNA was up-regulated in cells from two out of five patients in response to OK-432, but not in response to TNF-alpha.OK-432 has a more profound effect on human DCs than TNF-alpha and may act through multiple signaling pathways.