Issei Kodama

HLA class-I-restricted and tumor-specific CTL in tumor-infiltrating lymphocytes of patients with gastric cancer

Immune recognition of human cancers except melanoma is not well understood at either the cellular or the molecular level. We demonstrate in this study the existence of HLA class‐I‐restricted and tumor‐specific CTL in IL‐2‐activated TIL (tumor‐infiltrating lymphocytes) of all 4 gastric cancer patients tested. We established HLA A2‐restricted and adenocarcinoma‐specific CTL in 2 HLA A0201+ patients, and HLA A2402‐restricted CTL recognizing both adenocarcinoma and squamous‐cell carcinomas (SCC) in the 2 remaining HLA A2402+ patients. Further, HLA A3101‐restricted and adenocarcinoma‐specific CTL were established in 1 of the 2 HLA A2402+ patients who had HLA A3101 allele. HLA A2‐, A2402‐ and A3101‐restricted CD8+ CTL clones were established from these parental CTL lines. The 2 HLA A2‐restricted CTL lines lysed 8 of 13 HLA A2+ adenocarcinoma cell lines established from different organs (stomach, colon, lung and breast) with different subtypes (HLA A0201, A0206 and A0207). The HLA A2‐restricted CTL line recognized 9 and 6 different HPLC fractions of peptides eluted from the HLA A0201+ breast and HLA A0201+ colon adenocarcinoma cell lines, respectively. Allele‐specific deletion of HLA A2 or A24 molecules was observed in some tumor lines that were not susceptible to lysis by the CTL lines. These results suggest that TIL of gastric cancer possess CTL recognizing different peptide antigens binding to different HLA‐A alleles that are widely expressed on adenocarcinomas and also, to some extent, on SCC from different organs. Int. J. Cancer 70:631–638, 1997.

Effect of perfusion and blood content on ultrasonic backscattering of liver tissue

The purpose of this study was to determine the effect of blood flow perfusion and red cell content on ultrasonic scattering by liver tissue. Data acquisition for ultrasonic tissue characterization (UTC) employing analysis of the backscattered echoes from the power spectrum was obtained from the same region of pig liver tissue under four conditions: 1) normal perfusion in situ, 2) ischemia in situ in the living pig, 3) ischemia in situ immediately postmortem, and 4) immediately after excision of the liver. Discriminant function analysis was used to evaluate differences in the two basic parameters from the normalized power spectrum: slope and intercept. Normal perfused liver had significantly higher intercept values and lower slope values than liver under the other three conditions. Excised liver showed the lowest intercept and highest slope values (p < 0.01). These experiments indicate that differences in perfusion produce significant differences in ultrasonic scattering by liver tissue (ischemia caused a 3 dB drop in intercept amplitude). Normal or ischemic in vivo and in vitro liver tissue is associated with different patterns of ultrasonic scattering, and scattering data under these various circumstances are not equivalent.

Evaluation of the cell kinetics of MNNG-treated rat gastric mucosa based on AgNOR and ODC activity

To investigate the process of carcinogenesis in gastric cancer, we studied the histological features and cell kinetics in the gastric mucosa of N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)-treated rats. Samples of gastric mucosa from both MNNG-treated and control rats were histologically examined by staining with nucleolar argylophilic nonhistone (AgNOR) proteins, and their ornithine decarboxylase (ODC) activity was determined every 2 months for 10 months. In 40% of the MNNG-treated rats, atrophy of the gastric mucosa was observed after 2 months, followed by adenomatous proliferation. More AgNOR-positive granules were found in the pyloric glands than in the fundic glands, and the total number of positive granules increased over time. Cancerous and hyperplastic lesions preferentially developed in the pyloric glands and showed significantly more AgNOR-positive granules than the normal mucosa. After 6 months the ODC activity in the MNNG-treated rats was significantly higher than that in the control rats. These results thus suggest that the pyloric glands have a high growth activity, while in addition, adenomatous proliferation is a characteristic pathological feature of precancerous lesions in the stomach in MNNG-treated rats.

Expression of CD44 Molecule in Gastric Cancer

The expression of the CD44 molecule was investigated in 111 cases of a resected gastric cancer, and also in 5 gastric cancer cell lines. An immunohistochemical study using frozen sections revealed that the mucosal lymphocytes and the pyloric glands deep in the normal mucosa reacted to the anti-CD44 monoclonal antibody. 54 cases (48.6%) were stained on the cell surface involving the intercellular aspect. Well-differentiated cancer showed the highest frequency of CD44 expression, among the various histological types. Moreover, cases with extensive vascular invasion frequently expressed CD44 (75%) and CD44-positive cases had a significantly higher rate of metastasis to the liver than did negative cases. Flowcytometric analysis revealed expression of CD44 on the cell surface in one of 5 examined cell lines.

A study of the lymphatics in the stomach wall with hydrogen peroxide technique.

胃癌症例38例を対象に新鮮切除胃標本を過酸化水素法にて膨脹させ, 胃壁内リンパ管, とくに粘膜固有層表層毛細リンパ管を肉眼的, 組織学的に検討し, 以下の結果を得た.粘膜面からの肉眼的観察で白色の小斑が十二指腸輪状ヒダ部, 幽門腺および中間帯領域小弯部 (幽門腺萎縮と腸上皮化生が高度な部), 胃底腺領域皺襞部に多数観察され, 組織学的にこの小斑は過酸化水素法により膨脹された粘膜固有層の毛細リンパ管が密に分布する部位と一致した. 活性炭に切除標本を浸漬させた後過酸化水素法で処理した例では, 小斑部毛細リンパ管を含めリンパ管内に活性炭の流入が認められ, 小斑部毛細リンパ管が物質の吸収に関与しているものと思われた.