Hisakazu Yamagishi

Specific and non-specific immunologic mechanisms of tumor growth facilitation.

Specific and non‐specific mechanisms of tumor growth facilitation were studied using methylcholanthrene (MCA)‐induced fibrosarcomas in C3H/HeJ mice. In early and late stages of tumor growth, mice possessed non‐specific, tumor‐facilitating cells detected by local adoptive transfer assay (LATA). These cells appeared to be macrophages; they were radioresistant (700 rads), phagocytic, and adherent to plastic. Specific tumor facilitation was induced by treatment either with crude 3M KCl extracts, or with an acidic pIEF fraction (pI 3.5). After treatment with this material, animals displayed facilitated outgrowth of only MCA‐F, but not the antigenically distinct MCA‐D or MCA‐C tumors. Thus in addition to non‐specific stimuli, which accelerate neoplastic growth, tumors bear tumor‐specific transplantation antigens (TSTA), which induce specific facilitation.

Changes in spleen morphology and lymphoid cell activity during tumor progression

Abstract Morphologic alterations in the spleen and dynamic changes in the biologic activity of its cellular components occur concomitant with the neoplastic progression of a murine methylcholanthrene induced fibrosarcoma. Spleen size, weight and cell number increased with tumor growth. Using the local adoptive transfer assay (LATA), spleens from tumor bearing mice in the early and late stages of neoplastic growth were shown to possess non-specific, tumor-facilitating cells which were radioresistant, phagocytic and adherent, presumably macrophages. On the other hand, spleens from mice in the intermediate and late stages of tumorigenesis displayed specific, tumor-neutralizing cells, which were radiosensitive and Thy 1.2 positive, presumably T-cells. Thus, a balance of tumor-facilitating and neutralizing cells may determine neoplastic progression in susceptible, syngeneic hosts.

Streptococcal immunotherapy of a chemically induced murine fibrosarcoma: Effect of dose, route, sham surgery, and splenectomy on adjuvant action

SummaryAdjuvant immunotherapy with hemolytic streptococci abates the growth of a syngeneic methylcholanthrene (MCA)-induced fibrosarcoma propagated in C3H/HeJ mice. Interperitoneal (IP) administration of streptococci either prior to or after tumor inoculation reduced neoplastic outgrowth. While subcutaneous (SC) administration of streptococci prior to tumor inoculation did not influence tumor outgrowth, SC treatment afterwards was effective. Thus, therapeutic effects of streptococcal vaccine depend upon the route and/or timing of administration.Surgery performed shortly before tumor inoculation abrogated host response to streptococci. On the other hand, surgery performed 3 days after tumor inoculation did not alter the adjuvant action of streptococcal vaccines. The failure of attempts to achieve an immunotherapeutic effect in splenectomized hosts suggests that the spleen was essential for the action of the streptococcal vaccine.

Production of a tumor-specific xenoantiserum from partially purified immunoprotective tumor antigen

SummaryRabbits imunized with the immunoprotective TSTA fraction partially purified by preparative isoelectric focusing of 3 M KCl extracts from a chemically induced murine sarcoma, MCA-F, produced specific xenoantisera as assessed by an indirect membrane immunofluorescence assay. Only the immunizing tumor, MCA-F, and not the antigenically distinct MCA-D or MCA-T target cells were stained by the xenoantiserum. Absorption of anti-MCA-F antiserum with the antigenically distinct MCA-D or MCA-T cells did not reduce its capacity to bind to MCA-F cells. The immunofluorescence reaction was competitively inhibited by MCA-F fractions that induced specific immunoprotection: crude 3 M KCl extract, isoelectrically focused TSTA (fraction 15), and intact irradiated MCA-F cells. The TSTA specificity of these xenoantisera suggests that they may provide useful reagents for rapid isolation and characterization of the immunoprotective moiety.

A Case of Primary Peritoneal Cystadenocarcinoma: Diagnosis, Treatment, and Clinical Course

症例は80歳の女性で, 平成16年5月に軽度の下痢・腹痛・右下腹部腫瘤のために近医を受診した. 腹部CT, X線検査にて右下腹部に手拳大の腹壁浸潤を疑う嚢胞性腫瘤を認めた. 腫瘤は充実性成分を持ち, CT・MRI・FDG-PET・腫瘍マーカーなどより「虫垂癌・腹膜播種」と考えた. 手術時診断も同様であったが, 病理組織学的診断は乳頭状腺癌がclear cell carcinoma成分を持つ非常にまれな原発性腹膜嚢胞性腺癌であり, 中腎傍管 (paramesonephric duct/mullerian) 由来であると考えられた. 文献的には非常に予後の悪い癌であるが, 本症例においては外科的切除に加えてCDDP+TS-1の術後化学療法にて再発腫瘍の縮小を認め, 手術後17か月で外来通院治療中である.

Clinicopathological Studies of Central Type of Cholangiocarcinoma Compared with Hilar Bile Duct Cancer.

胆管細胞癌中枢型肝切除例10例と肝門部胆管癌肝切除例13例を比較検討した.腫瘍の肉眼型は, 胆管細胞癌10例中9例では肝内に明らかな腫瘤を形成し周囲の肝実質に浸潤性に発育していたのに対し, 肝門部胆管癌では腫瘤形成よりも胆管壁に沿う浸潤が主体であった.腫瘍の体積は, 胆管細胞癌では肝門部胆管癌に比較して有意に大きかった.胆管細胞癌では, 肝門部胆管癌に比較して大血管浸潤のほかに肝胆道の周囲臓器への浸潤を高率に認めた.胆管細胞癌でも12, 13, 8番へのリンパ節転移, ly, v, pn (+) を肝門部胆管癌と同じく高率に認めた.ew (+) は両者とも80%以上の高率であり, 主にly, v, pnの存在によった.hw (+) は肝門部胆管癌で有意に高率であった.肝門部胆管癌の5年生存率は62.5%と良好であったが, 胆管細胞癌では3年生存率17.9%と不良であった.両者は同一の規約で検討されるべき多くの類似点を有しているが, 進展様式, 予後などに違いが認められた.

Investigation on the Surgical Treatment for Multifocal Early Gastric Cancers. Based on the Cell Proliferation Analysis by DNA-cytofluorometry.

私たちの教室で治療した胃癌症例中で多発胃癌は5.6%あるが, 早期胃癌の中では多発のものは8.6%を占めて近年増加傾向にある. この多発早期胃癌は単発早期胃癌と比較して高齢者に多く, 隆起型, 分化型 (高分化腺癌) の頻度が高く, 占居部位は大半が胃体部, 幽門部で幽門側切除が可能であった. 私たちは多発早期胃癌の悪性度評価法として, 各病巣の癌細胞増殖動態を顕微測光法で解析してきた. 予後良, 好例では各病巣のDNAプロイディ・パターンはdiploidで増殖動態は類似し, 病巣間で著差を認めなかった. 一方, 予後不良例ではS-G2期細胞の増加, 多倍体化などの進行胃癌で見られる増殖動態を示し, これらの所見は病巣間でばらつきを示した. したがって, DNAプロイディ・パターンは多発早期胃癌の悪性度の指標になりうると考えられた. また, リンパ節転移の頻度は単発例と差がなく, 単発早期胃癌と同様な進行度評価を適用しうると考えられた.

An Experimental Study of the Sequential Determination of Molecular and Conventional Parameters for the Evaluation of the Coagulation and Fibrinolytic Status during the Anhepatic Phase.

Veno-venous (V-V) バイパスの凝固能にあたえる影響をみるため, ブタ (n=6) を用いて凝固線溶系分子マーカーについて検討した.凝固系分子マーカーであるthrombin-antithrombin (TAT) 複合体は無肝期直前に10.2±4.6μg/l (n=6) と低値であったのが無肝期の早期 (30分) に58.6±5.1μg/l (p<0.01) へと著明な増加を示し, その後も時間経過とともに軽度増加した.一方, フィブリンモノマー (FM) テストは無肝期60分から120分を境に (-) から (+) へと変化を示した.一方, 線溶系ではDダイマ-は無肝期直前に65±5ng/mlであったのが, 無肝期30分, 60分, でそれぞれ70.0±10.1ng/ml, 76.0±8.7ng/ml, と軽度上昇を示したにとどまった.しかし, 120分, 150分では100±11.3ng/mlおよび121±10.8ng/ml (p<0.05) と明らかな増加傾向を示した.プラスミン-α2プラスミンインヒビター (PIC) は有意な変化を示さなかった.無肝期における凝固系分子マーカーの指標としてTAT複合体が, また線溶系分子マーカーではDダイマーがよい指標と考えられ, 従来の凝血学的諸指標より鋭敏であった.

Influence of pre-operative irradiation and surgical interviention for immunity of esophageal cancer patients. A study of lymphocytes and T cell subsets.

食道癌に対する術前照射が宿主の免疫能, とくに外科手術後の免疫能に与える影響を解析し, 術前照射を併用する場合の問題点を明らかにした. 1期的に切除しえた食道癌15例を対象とし, 照射前後, 手術前後にin vitroで細胞性免疫能の検査を行った. 術前照射群は, 照射によって総リンパ球数は1,000/mm3以下となり, この低下は手術後30日を経過しても改善されなかった. T cellサブセットでは, OKT4の低下が著明で, この低下はhelper T cellに起因しており, 手術後30日を経過しても改善されておらず, 手術単独群と比べて有意に低下していた (p<0. 001).宿主免疫能の立場からは, 食道癌に対する術前照射はマイナスの因子と考えられた.