KLK10 derived from tumor endothelial cells accelerates colon cancer cell proliferation and hematogenous liver metastasis formation

Kato K., Noda T., Kobayashi S., et al. KLK10 derived from tumor endothelial cells accelerates colon cancer cell proliferation and hematogenous liver metastasis formation. Cancer Science , (2024); https://doi.org/10.1111/cas.16144.Tumor endothelial cells (TECs), which are thought to be structurally and functionally different from normal endothelial cells (NECs), are increasingly attracting attention as a therapeutic target in hypervascular malignancies. Although colorectal liver metastasis (CRLM) tumors are hypovascular, inhibitors of angiogenesis are a key drug in multidisciplinary therapy, and TECs might be involved in the development and progression of cancer. Here, we analyzed the function of TEC in the CRLM tumor microenvironment. We used a murine colon cancer cell line (CT26) and isolated TECs from CRLM tumors. TECs showed higher proliferation and migration than NECs. Coinjection of CT26 and TECs yielded rapid tumor formation in vivo. Immunofluorescence analysis showed that coinjection of CT26 and TECs increased vessel formation and Ki-67+ cells. Transcriptome analysis identified kallikrein-related peptide 10 (KLK10) as a candidate target. Coinjection of CT26 and TECs after KLK10 downregulation with siRNA suppressed tumor formation in vivo. TEC secretion of KLK10 decreased after KLK10 downregulation, and conditioned medium after KLK10 knockdown in TECs suppressed CT26 proliferative activity. Double immunofluorescence staining of KLK10 and CD31 in CRLM tissues revealed a significant correlation between poor prognosis and positive KLK10 expression in TECs and tumor cells. On multivariate analysis, KLK10 expression was an independent prognostic factor in disease-free survival. In conclusion, KLK10 derived from TECs accelerates colon cancer cell proliferation and hematogenous liver metastasis formation. KLK10 in TECs might offer a promising therapeutic target in CRLM

Results of a Randomized Clinical Study of Gemcitabine Plus Nab-Paclitaxel Versus Gemcitabine Plus S-1 as Neoadjuvant Chemotherapy for Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma (RCT, CSGO-HBP-015)

The version of record of this article, first published in Annals of Surgical Oncology, is available online at Publisher’s website: https://doi.org/10.1245/s10434-024-15199-8.Background: The optimal neoadjuvant chemotherapy (NAC) regimen for patients with localized pancreatic ductal adenocarcinoma (PDAC) remains uncertain. This trial aimed to evaluate the efficacy and safety of two neoadjuvant chemotherapy (NAC) regimens, gemcitabine plus nab-paclitaxel (GA) and gemcitabine plus S-1 (GS), in patients with resectable/borderline-resectable (R/BR) PDAC. Patients and Methods: Treatment-naïve patients with R/BR-PDAC were enrolled and randomly allocated. They received two cycles (2 months) of each standard protocol, followed by radical surgery for those without tumor progression in general hospitals belonging to our intergroup. The primary endpoint was to determine the superior regimen on the basis of achieving a 10% increase in the rate of patients with progression-free survival (PFS) at 2 years from allocation. Results: A total of 100 patients were enrolled, with 94 patients randomly assigned to the GS arm (N = 46) or GA arm (N = 48). The 2-year PFS rates did not show the stipulated difference [GA, 31% (24–38%)/GS, 26% (18–33%)], but the Kaplan–Myer analysis showed significance (median PFS, GA/GS 14 months/9 months, P = 0.048; HR 0.71). Secondary endpoint comparisons yielded the following results (GA/GS arm, P-value): rates of severe adverse events during NAC, 73%/78%, P = 0.55; completion rates of the stipulated NAC, 92%/83%, P = 0.71; resection rates, 85%/72%, P = 0.10; average tumor marker (CA19-9) reduction rates, −50%/−21%, P = 0.01; average numbers of lymph node metastasis, 1.7/3.2, P = 0.04; and median overall survival times, 42/22 months, P = 0.26. Conclusions: This study found that GA and GS are viable neoadjuvant treatment regimens in R/BR-PDAC. Although the GA group exhibited a favorable PFS outcome, the primary endpoint was not achieved

Clinical significance of intragraft miR‐122 and ‐155 expression after liver transplantation

Aim Recurrent hepatitis C (RHC) and acute cellular rejection (AR) remain critical problems following liver transplantation (LT) in hepatitis C virus (HCV) positive recipients because of the similar clinical features. Discrimination between these conditions can be problematic, and adjunctive biomarkers would be useful to discriminate these processes. The aim of our study was to investigate the possibility of the intragraft miR‐122 and ‐155 expression as new biomarkers after LT. Methods A total of 29 HCV positive recipients were enrolled in this study. Intragraft expressions of miR‐122 and ‐155 were studied between RHC predominant (n = 17) and AR predominant cases (n = 12) using quantitative reverse transcription polymerase chain reaction. Furthermore, we investigated the correlations between these expression levels and clinical serum parameters. Results Intragraft miR‐122 expression had a good correlation with serum alkaline phosphatase (P = 0.02), but it was not correlated with the serum HCV viral load. The expression levels of miR‐122 in the AR group were significantly higher than those in the RHC group (P = 0.0006) and, inversely, the expression levels of miR‐155 in the AR group were significantly lower than those in the RHC group (P = 0.01). Conclusion Our study emphasizes a useful pattern of miR‐122 and ‐155 as ancillary markers to discriminate AR predominant cases from RHC in HCV positive patients after LT

Agenesis of the left hepatic lobe undergoing laparoscopic hepatectomy for hepatocellular carcinoma: a case report

Abstract Background Agenesis of the left hepatic lobe is a rare anomaly. It is defined as the absence of liver tissue to the left of the gallbladder fossa. Additionally, agenesis of the left hepatic lobe accompanied by hepatocellular carcinoma is quite rare. We experienced the case of a patient with agenesis of the left hepatic lobe, undergoing laparoscopic hepatectomy for HCC. Case presentation A 79-year-old man was referred to our department with epigastralgia. Abdominal computed tomography revealed agenesis of the left hepatic lobe, accompanied by hepatocellular carcinoma in segments 7 and 8. He underwent laparoscopic partial hepatectomy of segments 7 and 8. The operative findings revealed complete agenesis of the liver to the left of the falciform ligament. The patient had a favorable clinical course without liver dysfunction or any complications. Conclusions We experienced a case with agenesis of the left hepatic lobe undergoing laparoscopic hepatectomy for HCC. Awareness of such anomaly is important for surgeons to avoid postoperative complications