[A Case of Pathologic Complete Response Achieved with Preoperative Pembrolizumab Therapy for Transverse Colon Cancer].

A 77-year-old female patient presented with a medical history of 4 cancerous lesions, each with a surgical history. She was referred to our hospital due to anemia. Upon examination, she was diagnosed with transverse colon cancer. Duodenal invasion was suspected, which made performing R0 surgery difficult; therefore, the NAC approach was chosen. Three courses of CAPOX were administered, resulting in tumor obstruction, leading to the formation of an ileum stoma. MSI testing revealed MSI-H, and pembrolizumab treatment was initiated. CT scans showed tumor shrinkage, and PET scans indicated no accumulation, resulting in a cCR. Colon resection including the lesion suspected of stenosis was performed with a strong desire for stoma closure and the determination of potential curative resection. Additionally, a partial resection of the duodenum was performed. Pathological examination did not reveal any evident tumor cells, leading to the determination for a pCR. The patient has been under postoperative surveillance for 1 year without any recurrence.

Air microbubbles as MR susceptibility contrast agent at 1.5 Tesla.

Air microbubbles have been investigated recently at high magnetic field strength (2 Tesla or greater) as potential MR susceptibility contrast agents. We used a phantom to measure their susceptibility at 1.5 T to clarify their usefulness for this purpose. The phantom, filled with fresh Levovist suspension at 4 different doses (67 to 125 mg/mL), was continuously scanned with a gradient-echo technique at a temporal resolution of 10 s. The transverse relaxation increase (R2*) by microbubbles demonstrated a time course of exponential decay at each dose (time-constant, 39 to 57 s). The dependency of R2* on microbubble volume fraction was linear, with a slope of 89 s-1 per percentage microbubble volume fraction. Our study represents the first step towards applying microbubbles as susceptibility contrast agents at 1.5 T.

Core 3 synthase is down-regulated in colon carcinoma and profoundly suppresses the metastatic potential of carcinoma cells.

The core 3 structure of the O-glycan, GlcNAcbeta1-3GalNAcalpha1-Ser/Thr, an important precursor in the biosynthesis of mucin-type glycoproteins, is synthesized by beta1,3-N-acetylglucosaminyltransferase 6 (beta3Gn-T6; core 3 synthase). We generated an anti-beta3Gn-T6 mAb (G8-144 mAb) and performed immunohistochemical analyses. In normal stomach and colon, beta3Gn-T6 was strongly expressed in the Golgi region of epithelia. In contrast, its expression was markedly down-regulated in gastric and colorectal carcinomas. Tissue specimens from a familial adenomatous polyposis patient showed a clear correlation between the down-regulation of beta3Gn-T6 expression and the degree of dysplasia/neoplasia. In vitro, the level of beta3Gn-T6 transcript was increased according to the differentiation of Caco-2 cells. These results suggested that the expression of beta3Gn-T6 is closely regulated during differentiation and dedifferentiation. beta3Gn-T6 would be a useful marker for distinguishing between benign adenomas and premalignant lesions. HT1080 FP-10 cells stably transfected with the beta3Gn-T6 gene showed a decrease in the core 1 structure, Galbeta1,3GalNAcalpha1-Ser/Thr, probably due to competition between the core 1 synthase and core 3 synthase. The migration activity of the transfectants was markedly lower than that of mock transfectants in vitro, and lung metastasis after i.v. injection of the transfectants into nude mice was significantly suppressed. These findings indicated that the core structures of O-glycans are profoundly involved in the metastatic capacity of cancer cells.

Role of complex cadherins in cell-cell adhesion evaluated by spheroid formation in renal cell carcinoma cell lines.

We have previously shown that renal cell carcinoma (RCC) cell lines expressed a complex set of cadherins, e.g. E-cadherin, N-cadherin and cadherin-6. It is also reported that E-cadherin and cadherin-6 have a predictive value for estimating a patient's prognosis in RCC. However, E-cadherin is infrequently expressed in RCC as compared with N-cadherin and cadherin-6. In the present study, therefore, we performed a functional analysis of these cadherins as a cell adhesion molecule using spheroid culturing and spheroid-blocking assay. In E-cadherin expressers, compact spheroid formation was observed, and it was inhibited by anti-E-cadherin antibody. In contrast, in E-cadherin-absent lines, cadherin-6 apparently played a role to form relatively loose spheroids and this spheroid formation was inhibited by anti-cadherin-6 antibody. In both spheroids, the anti-N-cadherin antibody could not inhibit their formation, suggesting that N-cadherin was not an essential molecule for spheroid formation in the cell lines expressing complex cadherins. The anti-N-cadherin antibody inhibited spheroid formation only in the cell line that expressed N-cadherin alone. Using western blot analysis, immunohistochemistry and immunoprecipitation, these cadherins were linked to catenins to make a functional adhesion molecule. In conclusion, E-cadherin and cadherin-6 are shown to act in cell-cell adhesion whereas N-cadherin might play a somewhat different role from cell-cell adhesion in RCC cell lines.

Detection of cadherin-6 mRNA by nested RT-PCR as a potential marker for circulating cancer cells in renal cell carcinoma.

To detect circulating RCC cells, we established a nested RT-PCR system for cadherin-6 mRNA, which is specifically expressed in RCC. A total of 121 samples of peripheral blood (34 healthy volunteers and 87 patients with RCC) were analyzed in this study. Total RNA of the monocyte fraction of the blood was extracted, then nested RT-PCR using specific primers was performed to detect mRNA of N-cadherin or cadherin-6. Nested RT-PCR revealed that expression of cadherin-6 mRNA was not present in the blood of most healthy volunteers (absent in 32/34), but positive expression was observed in the blood at concentrations of 10 cells/ml or greater of the SKRC-33 RCC cell line, which is a strong expresser of cadherin-6. In peripheral blood from patients with metastatic disease, cadherin-6 mRNA was detected in 70.4% (19/27). Messenger RNA of cadherin-6 was detectable in 45.0% (27/60) of patients with localized tumors. The PCR-based detection system for peripheral blood samples from patients with metastatic disease could reveal the presence of circulating RCC cells in the blood. Detection of cadherin-6 mRNA in non-metastatic presurgical RCC patients suggests that careful follow-up study is necessary in these patients.