In vitro-cultured 3D structures called organoids have become important tools for biological research, but there is little information concerning simple and efficient methods to evaluate organoid morphology. To address this issue, we attempted to establish a simple method by applying conventional histopathology that enables observation of multiple organoids on a single cross section, maintains good morphology, and is applicable to various histopathological stains. By centrifugation in unsolidified agarose solution, we were able to accumulate the organoids onto a single plane. The morphology was well preserved, and the various morphological types and sizes of organoid structures were identified. This method was also applicable for special staining, immunohistochemistry, and immunofluorescence staining. This method makes it possible to utilize the advantages of conventional pathological methods when studying organoids.

Previously, we demonstrated the antitumor efficacy of the antiglypican-3 (GPC3) antibody GC33 in several human liver cancer xenograft models and the important role of antibody-dependent cellular cytotoxicity (ADCC) in the antitumor mechanism of GC33. Involvement of other mechanisms such as modulation of the functions of GPC3 in antitumor activity remains to be elucidated. In this study, we investigated histopathologically time-course changes in xenografts in mice following a single administration of GC33 to clarify the morphological changes contributing to the tumor growth inhibition of GC33, including the changes in GPC3-related factors/components [proliferation, extracelluar matrices (ECMs) and macrophage]. Histopathological changes peaked 3-5 d after GC33 administration and included increased tumor cell death, tumor cells with round morphology, multinucleated tumor cells and small spindle/round-like cells (mostly F4/80-positive macrophages). No direct effects of GC33 on proliferation activity of tumor cells were observed. Meanwhile, alteration of ECM structures and a remarkable increase in macrophages was noted in the GC33-treated group. Increase in macrophages was observed mainly in the outer layer of tumor nodules; the area of the increase approximately included the area where the change in tumor cells and ECMs were observed. Interestingly, depletion of macrophages in the xenograft models resulted in a marked reduction of the antitumor activity of GC33. In the in vitro ADCC assay, ADCC was only slightly induced by mouse peritoneal macrophages. These data suggest that macrophages play an important role in the antitumor activity of GC33, which is not likely to be direct ADCC by macrophages themselves.

TS-1 is a novel oral anticancer agent comprised of tegafur, a prodrug of 5- flurouracil, and two modulators. A phase i study of tS-1 plus carboplatin combination therapy was conducted to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose limiting toxicities (DLT) in advanced non-small-cell lung cancer (NSClC). TS-1 was given orally at a dose of 80 mg/m(2)/day for 2 weeks, followed by a 2-week rest. Carboplatin was given intravenously on day 8 at a dose of 4.0, 5.0, 6.0 area under the curve (AUC) values. Fifteen patients with advanced NSClC were analyzed. the grade 3-4 toxicities observed during the first cycle were febrile neutropenia (6%), anemia (6%), anorexia (6%), and diarrhea (6%). these toxicities were reversible and manageable. The MTD for carboplatin was evaluated to be more than 6.0 AUC values, as one of six patients developed Dlt at this dose. the RD for carboplatin was estimated as 6.0 AUC values. Objective responses were seen in five patients (response rate 33%).

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SUMMARYA 61-year-old Japanese female was referred to our hospital for surgical treatment of a localized heavily calcified abdominal aorta. Preoperative angiograms and computed tomograms revealed severe stenosis of the aorta, resembling a slit. Bypass grafting between the thoracic and abdominal aorta was successfully performed together with the reconstruction of the celiac artery, superior mesenteric artery, and bilateral renal arteries without extracorporeal circulation. Postoperative angiograms showed patency of the graft and branches. A localized heavily calcified abdominal aorta is relatively rare, and the cause of this entity might be Takayasu's aortitis. (Jpn Heart J 2001; 42: 651-655)