Nihon Kikan Shokudoka Gakkai Kaiho

Toll signaling activates two major targets, NF-κB and IRF-3, leading to production of inflammatory cytokines and interferon α/β, respectively. Toll-like receptor (TLR) adapters are involved in the selection of TLR signaling in antigen-presenting dendritic cells: TLR2 and TLR4 link MyD88 to activate NF-κB while TLR3 and 4 link TICAM-1 (TRIF) to activate mainly IRF-3. BCG-cell-wall skeleton (CWS) activates the MyD88-dependent pathway via TLR2/4 and polyI:C activates the TICAM-1 pathway via TLR3. We previously showed that BCG-CWS activates the MyD88-dependent pathway in bone marrow-derived dendritic cells (mDCs), leading to eliciting of antitumor CTL against an exogenously added tumor antigen (Ag). Here we investigated the mechanism whereby the other adjuvant polyI:C participates in induction of antitumor immunity using syngeneic mouse tumor models (B16 melanoma in C57BL/6, EL4 in C57BL/6). Mice, when intraperitoneally injected with polyI:C, induced NK as an early phase effecter leading to partial regression of an implanted tumor. NK activation was induced in parallel with IFN-β induction due to TLR3 and other receptors. TLR3-TICAM-1-mediated mDC maturation was a prerequisite for activation of antitumor NK. In addition, CTL response was observed when the mice were preimmunized with tumor Ag and polyI:C, which led to complete remission of the tumor. PolyI:C-mediated retardation of implanted tumor growth was abrogated in TICAM-1-/-and IFNAR-/-mice, while other KO mice with IFN-β-/-, PKR-/- or MyD88-/-suppressed tumor growth in response to polyI:C similar to wild-type mice. These results infer that TICAM-1 is unique in mDC-mediated NK activation and that MyD88 and TICAM-1 pathways are individually involved in cross-priming required for MHC class I Ag presentation. Thus, efficient tumor suppression by polyI:C is attributable to the TICAM-1 pathway in mDCs.

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Viral pathological analyses on autopsy cases with viral infections were reviewed. Particularly, the pathogenesis of esophageal ulcer caused by herpes simplex virus or varicella-zoster virus, and the pathogenesis of lung lesions infected with SARS-associated cornavirus and influenza viruses including highly pathogenic avian influenza were summarized.

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FDG-PET is a useful modality for cancer diagnosis. It, however, often needs assistance from morphological imaging modalities such as CT or MRI for accurate diagnosis. PET-CT is a combination of a functional imaging tool, PET, and a morphological imaging tool, CT. The areas around the esophagus and bronchi contain complicated anatomical structures and display many variations of physiological uptake of FDG, which makes PET interpretation difficult. PET-CT solves this problem and allows easier and more confident interpretations. Though MRI may be superior to FDG-PET in diagnosis of primary cancer, FDG-PET is very useful in detecting unknown primary cancers which are negative on CT or MRI. In staging, it is possible to accurately localize nodal or other metastases, which has a bearing on surgical or radiation treatment planning. There are some issues in determining therapeutic efficacy, such as optimal timing of evaluation and avoiding false positive findings due to postradiation inflammation. Nonetheless, there is a report recommending evaluation using the change of SUV of FDG uptake in the tumor. Radiation therapy planning using PET-CT has been tried in several institutes and new challenges using PET-CT are to be expected.

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1. Screening by iodine staining: Because not all lesions unstained with iodine are cancers, it is necessary to distinguish between benign and malignant tumors on the basis of morphological features. Irregular-shaped lesions unstained with iodine, 5 mm or more in diameter, with a sharply protruding, irregular border and periglandular stromal condensation are likely to be cancers. Unstained lesions of more than 10 mm in diameter have an extremely high risk of cancer.
2. Screening with a narrow band imaging (NBI) system: An NBI system facilitates the discovery of small, fine mucosal abnormalities by providing images that enhance blood vessels and delicate patterns on the mucosal surface. Cancers appear as sharply demarcated, blackish-brown lesions with hyperplasia of intraepithelial papillary capillary loops. Cancers can be easily detected, irrespective of site and size.
3. Endoscopic diagnosis of the depth of tumor invasion: In esophageal cancer, the depth of invasion is intimately related to vascular invasion and the frequency of lymph-node metastasis. Preoperative assessment of the depth of invasion plays an important role in determining treatment policy. Esophageal cancers can be classified into 3 groups according to the depth of invasion: (1) cancer confined to the lamina propria mucosae (m1 or m2), with no evidence of lymph-node metastasis; (2) cancer reaching or invading the muscularis mucosae (m3) or confined to the surface layer of the submucosa (sm1), associated with lymph-node metastasis in about 10% of cases; and (3) cancer invading the middle layer of the submucosa (sm2) or the deep layer of the submucosa (sm3), associated with lymph-node metastasis in about 40% of cases and a high incidence of vascular invasion. In m1 or m2 cancers, the rate of correctly diagnosing the depth of invasion was 95%, indicating good results. In m3 or sm1 cancers, the rate of correct diagnosis was only 74%. Even with the use of both magnifying endoscopy and an NBI system, invasion depth was correctly diagnosed in only 79% of m3 or sm1 cancers.

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