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Background: Treatment via a peripherally inserted central venous catheter is important for anticancer treatment, perioperative management, and nutrition management. In this study, we aimed to investigate the usefulness of cyanoacrylate glue (CG) in managing peripherally inserted central venous catheters in adults. Methods: This retrospective cohort study enrolled 411 adults requiring a central venous catheter for treatment in the Chiba University Esophageal‐Gastro‐Intestinal Surgery department between January 2021 and October 2022. The preventive effect of CG in reducing adverse events, including infection, tip migration, and thrombus formation, was evaluated by reviewing electronic medical records, chest radiographs, and contrast‐enhanced computed tomography scans. Results: CG and other dressings were used in 158 (CG group) and 253 (control group) patients, respectively. The incidence of catheter infection based on the clinical course was lower in the CG group (3.2%) than in the control group (9.1%; P = 0.03). However, cases of infection confirmed by blood or catheter cultures did not differ between the CG (1.3%) and control (1.9%) groups (P = 1.0). Chest radiographs revealed that catheter tip migration (mean ± SD) was lesser in the CG group (8.2 ± 6.7 mm) than in the control group (15.0 ± 15.8 mm; P < 0.01). There were two cases of venous thrombus formation in the control group. Conclusion: In a population dominated by esophago‐gastroenterological malignancy, peripherally inserted central catheter securement via CG was associated with decreased catheter removal because of suspected catheter infection. Further research on larger cohorts is needed to determine if other adverse events decrease following peripherally inserted central catheter securement via CG. [ABSTRACT FROM AUTHOR]

Bone metastasis is a frequent occurrence in prostate cancer patients and often is lethal. Zoledronic acid (ZOL) is often used for bone metastasis with limited efficacy. More effective models and treatment methods are required to improve the outcome of prostate cancer patients. In the present study, the effects of tumor-targeting Salmonella typhimurium A1-R were analyzed in vitro and in vivo on prostate cancer cells and experimental bone metastasis. Both ZOL and S. typhimurium A1-R inhibited the growth of PC-3 cells expressing red fluorescent protien in vitro. To investigate the efficacy of S. typhimurium A1-R on prostate cancer experimental bone metastasis, we established models of both early and advanced stage bone metastasis. The mice were treated with ZOL, S. typhimurium A1-R, and combination therapy of both ZOL and S. typhimurium A1-R. ZOL and S. typhimurium A1-R inhibited the growth of solitary bone metastases. S. typhimurium A1-R treatment significantly decreased bone metastasis and delayed the appearance of PC-3 bone metastases of multiple mouse models. Additionally, S. typhimurium A1-R treatment significantly improved the overall survival of the mice with multiple bone metastases. The results of the present study indicate that S. typhimurium A1-R is useful to prevent and inhibit prostate cancer bone metastasis and has potential for future clinical use in the adjuvant setting.

UnlabelledPeritoneal disseminated cancer is highly treatment resistant. We here report the efficacy of intraperitoneal (i.p.) administration of tumor-targeting Salmonella typhimurium A1-R in a nude mouse model of disseminated human ovarian cancer. The mouse model was established by intraperitoneal injection of the human ovarian cancer cell line SKOV3-GFP. Seven days after implantation, mice were treated with S. typhimurium A1-R via intravenous (i.v.) or i.p. administration at the same dose, 5 × 10(7) CFU, once per week. Both i.v. and i.p. treatments effected prolonged survival compared with the untreated control group (P=0.025 and P

Essentially every population of cancer cells within a tumor is heterogeneous, especially with regard to chemosensitivity and resistance. In the present study, we utilized the fluorescence ubiquitination-based cell cycle indicator (FUCCI) imaging system to investigate the correlation between cell-cycle behavior and apoptosis after treatment of cancer cells with chemotherapeutic drugs. HeLa cells expressing FUCCI were treated with doxorubicin (DOX) (5 μM) or cisplatinum (CDDP) (5 μM) for 3 h. Cell-cycle progression and apoptosis were monitored by time-lapse FUCCI imaging for 72 h. Time-lapse FUCCI imaging demonstrated that both DOX and CDDP could induce cell cycle arrest in S/G2/M in almost all the cells, but a subpopulation of the cells could escape the block and undergo mitosis. The subpopulation which went through mitosis subsequently underwent apoptosis, while the cells arrested in S/G2/M survived. The present results demonstrate that chemoresistant cells can be readily identified in a heterogeneous population of cancer cells by S/G2/M arrest, which can serve in future studies as a visible target for novel agents that kill cell-cycle-arrested cells.

The aim of this study is to determine if fluorescence-guided surgery (FGS) can eradicate human fibrosarcoma growing in the retroperitoneum of nude mice. One week after retroperitoneal implantation of human HT1080 fibrosarcoma cells, expressing green fluorescent protein (GFP) (HT-1080-GFP), in nude mice, bright-light surgery (BLS) was performed on all tumor-bearing mice (n = 22). After BLS, mice were randomized into 2 treatment groups; BLS-only (n = 11) or the combination of BLS + FGS (n = 11). The residual tumors remaining after BLS were resected with FGS using a hand-held portable imaging system under fluorescence navigation. The average residual tumor area after BLS + FGS was significantly smaller than after BLS-only (0.4 ± 0.4 mm(2) and 10.5 ± 2.4 mm(2), respectively; p = 0.006). Five weeks after surgery, the fluorescent-tumor areas of BLS- and BLS + FGS-treated mice were 379 ± 147 mm(2) and 11.7 ± 6.9 mm(2), respectively, indicating that FGS greatly inhibited tumor recurrence compared to BLS. The combination of BLS + FGS significantly decreased fibrosarcoma recurrence compared to BLS-only treated mice (p < 0.001). Mice treated with BLS+FGS had a significantly higher disease-free survival rate than mice treated with BLS-only at five weeks after surgery. These results suggest that combination of BLS + FGS significantly reduced the residual fibrosarcoma volume after BLS and improved disease-free survival.

Prognosis of patients with lung metastases of soft-tissue sarcoma is still poor. Therefore, novel systemic therapy is needed to improve the survival of soft-tissue sarcoma. In the present study, tumor-targeting therapy with a genetically-modified auxotrophic strain of Salmonella typhimurium, termed A1-R, was evaluated. Mouse models of primary soft tissue sarcoma and spontaneous lung metastasis were obtained by orthotopic intra-muscular injection of HT1080-RFP human fibrosarcoma cells. S. typhimurium A1-R was administered from day 14, once a week for two weeks. On day 28, lung samples were excised and observed with a fluorescence imaging system. The number of lung metastasis was 8.8 ± 3.4 in the untreated group and 0.8 ± 0.8 in the treated group (P = 0.024). A mouse model of experimental lung metastasis was obtained by tail vein injection of HT1080-RFP cells. The mice were treated with S. typhimurium A1-R (i.v.) on day 7, once a week for three weeks. S. typhimurium A1-R significantly reduced lung metastases and improved overall survival (P = 0.004). S. typhimurium A1-R bacterial therapy has future potential for treating advanced soft tissue sarcoma and improving prognosis of patients with lung metastasis.

In order to develop a model for fluorescence-guided surgery (FGS), 143B human osteosarcoma cells expressing red fluorescent protein (RFP) were injected into the intramedullary cavity of the tibia in nude mice. The fluorescent areas of residual tumors after bright-light surgery (BLS) and FGS were 10.2 ± 2.4 mm(2) and 0.1 ± 0.1 mm(2) , respectively (p

Bone metastasis is a lethal and morbid late stage of breast cancer that is currently treatment resistant. More effective mouse models and treatment are necessary. High bone-metastatic variants of human breast cancer cells were selected in nude mice by cardiac injection. After cardiac injection of a high bone-metastatic variant of breast cancer, all untreated mice had bone metastases compared to only 20% with parental cells. Treatment with tumor-targeting Salmonella typhimurium A1-R completely prevented the appearance of bone metastasis of the high metastatic variant in nude mice (P < 0.001). After injection of the highly bone-metastatic breast cancer variant to the tibia of nude mice, S. typhimurium A1-R treatment significantly reduced tumor growth in the bone (P < 0.001). These data indicated that S. typhimurium A1-R is useful to prevent and inhibit breast cancer bone metastasis and should be of future clinical use for breast cancer in the adjuvant setting.

Introduction: Immune checkpoint inhibitors (ICIs) are expected to improve the prognosis of gastric cancer (GC). Also, hepatic steatosis has been reported to be associated with cancer cachexia and is expected to be a cancer biomarker. The purpose of this study was to evaluate prognostic impact of hepatic steatosis in ICI therapy for GC. Methods: Unresectable or recurrent GC treated with ICIs was investigated. Using unenhanced CT, the liver-to-spleen CT attenuation ratio (LSR) was calculated as a parameter of hepatic steatosis. LSR was compared with the presence of sarcopenia and inflammatory markers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). These parameters were also compared with disease-specific survival (DSS) and progression-free survival (PFS). Associations of LSR with insulin-like growth factor 1 (IGF-1) and growth hormone were also evaluated. Results: A total of 70 patients were investigated. LSR of sarcopenia patients was significantly lower than that of non-sarcopenic ones (p = 0.02). LSR showed significant negative correlations with NLR, PLR, and MLR (p = 0.003, 0.03, 0.01, respectively). Lower LSR was significantly associated with a higher level of serum IGF-1 (p = 0.03). In univariate analysis, LSR was significantly correlated with DSS and PFS (both p < 0.0001), and multivariate analysis demonstrated that LSR was the independent prognostic factor for both DSS and PFS (both p = 0.01). ROC analysis demonstrated that LSR >1.263 was a good predictive marker for favorable DSS (>5.3 months) with an AUC of 0.80. Conclusion: Hepatic steatosis can be a promising prognostic biomarker for ICI therapy of GC, associated with sarcopenia and the elevation of inflammatory markers. Our data suggested that GC with steatohepatitis might be less responsive to ICI therapy. [ABSTRACT FROM AUTHOR]

Introduction: We determined the soluble programmed cell death-1 ligand-1 (sPD-L1) concentration in patients with esophageal squamous cell carcinoma (ESCC), and confirmed the PD-L1 expression in resected specimens. Methods: Blood samples were collected from 73 patients with histologically proven ESCC. The serum levels of sPD-L1 were measured using an enzyme-linked immunosorbent assay. The correlations between the sPD-L1 concentration and the expression of PD-L1 in tumor specimens and tumor depth, lymph node metastasis, disease stage, and various laboratory data were assessed. Results: sPD-L1 levels in patients with high PD-L1 expression levels in tumor tissue were significantly higher than in patients with low PD-L1 expression levels (p = 0.042). The OS of the sPD-L1-high group was significantly worse than that of the low group (p = 0.028). Similarly, patients in whom a tissue specimen was PD-L1-positive group showed significantly poorer OS. Conclusion: The sPD-L1 concentration was correlated with the PD-L1 expression in tissues. Patients with PD-L1-positive tissue specimens showed significantly higher sPD-L1 levels in comparison to PD-L1-negative cases. Furthermore, patients with high sPD-L1 expression levels had a significantly worse prognosis than those with low sPD-L1 expression levels, and patients with a PD-L1-positive tissue specimen had a significantly worse prognosis than patients in whom the tissue specimen showed a low PD-L1 expression level. [ABSTRACT FROM AUTHOR]