Anticancer research最新文献

Background/aim: This study investigated the synergistic effects of combining cisplatin and SH003 treatment on the viability, apoptosis, cytotoxicity, migration and epithelial-mesenchymal transition (EMT) in cisplatin-resistant cancer cell lines YD-8/CIS, YD-9/CIS and YD-38/CIS.

Materials and methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess cell viability, while trypan blue exclusion assay was used to evaluate cytotoxicity. Flow cytometry and western blot analysis measured apoptotic cell death. Wound-healing assays evaluated cell migration and EMT markers. Combination index (CI) plots were used to evaluate the combinatory effects of the treatment.

Results: Combination therapy significantly reduced cell viability more effectively than each agent alone, as demonstrated by the MTT assay, with CI plots confirming notable synergism. Trypan blue exclusion assays indicated increased cell death and cytotoxicity in combination treatment than in both monotherapies, although the increase was not significant. Flow cytometry and western blot analysis revealed no significant synergistic effect on apoptotic cell death. However, wound-healing assays revealed that the combination of cisplatin and SH003 significantly inhibited cell migration and regulated EMT markers, indicating the potential reversal of EMT.

Conclusion: Combining cisplatin and SH003 therapy may potentially be a more effective strategy for treating cisplatin-resistant cancer by increasing cytotoxicity and inhibiting metastasis. Further research is required to elucidate the underlying mechanisms and evaluate the in vivo efficacy of this combination therapy.

Background/aim: The emergence of novel DNA damage repair (DDR) pathways in molecular-target therapy drugs (MTTD) has shown promising outcomes in treating patients with metastatic castration-resistant prostate cancer (mCRPC). About 25% of mCRPC patients have actionable deleterious aberrations in DDR genes, primarily in the homologous recombination (HR) pathway. However, the response rate in patients with BRCA1/2 or mutations in HRR-related genes is only 45%-55%, when exposed to poly ADP ribose polymerase (PARP) inhibitor-based therapy (PARPi). A frequent characteristic feature of prostate cancer (PC) is the occurrence of genomic rearrangement that affects the transmembrane protease serine 2 (TMPRSS2) and E26 transformation-specific (ETS)- transcription factor-related gene (ERG).

Materials and methods: In this study, a total of 114 patients with mCRPC had their RNA and DNA sequenced using next-generation sequencing.

Results: Based on their genetic profile of deleterious gene alterations of BRCA1/2 or ATM, six patients were selected for PARPi. Patients with TMPRSS2:ERG gene fusion and homozygous alteration in ATM or BRCA2 (n=2) or heterozygous alterations (BRCA1 or BRCA2) and lack of TMPRSS2:ERG gene fusion (n=2) did not show clinical benefit from PARPi (treatment duration <16 weeks). In contrast, patients (n=2) without TMPRSS2:ERG gene fusion and homozygous deleterious alterations in ATM or BRCA2 all had clinical benefit from PARPi (treatment duration ≥16 weeks).

Conclusion: The TMPRSS2:ERG transcript product might be used as a PARPi resistance biomarker.

Background/aim: To investigate the factors related to non-reversal of ostomy after cytoreductive surgery in ovarian cancer. In many women with ovarian cancer, transitory ostomies are performed to limit the consequences of anastomotic leak. Although intended to be temporary, a proportion of these ostomies might never be reversed.

Patients and methods: This was a retrospective study of patients with 2014 International Federation of Obstetrics and Gynecology stage IIB-IVB ovarian cancer requiring a transitory ostomy during primary or secondary cytoreductive surgery at the Bergonie Institute, France, and the University Hospital of Las Palmas, Spain, between January 2012 and December 2022. Rate of ostomy reversal, its timing (weeks) and postoperative complications were assessed. Multivariate logistic regression analysis was performed to identify limiting factors for ostomy reversal.

Results: During the study period, we reviewed data on 181 consecutive patients with ovarian cancer with transitory ostomy creation; 89 (49.2%) patients were not candidates for an ostomy reversal surgery because of disease progression (n=65), death (n=16), and patient's refusal of surgery (n=8). A total of 92 patients were candidates for reversal surgery and were therefore included in the final analysis. In total, 57 (62%) patients had their ostomy reversed. The mean time from ostomy creation to ostomy closure was 47.7 (standard deviation=33.1) weeks. Hartmann's procedure (leaving a rectal stump of 5-6 cm) was identified as an independent predictive factor for non-reversal of ostomy (odds ratio=6.42, 95% confidence interval=1.61-25.53; p=0.008). Complications after ostomy reversal occurred in 32 patients (34.8%).

Conclusion: Hartmann's procedure is a limiting factor for ostomy reversal in patients with ovarian cancer. We recommend avoiding Hartmann's procedure during cytoreductive surgery, even after colorectal anastomotic leak.

Background/aim: Comparing gene expression profiles according to recurrence risk using spatially resolved transcriptomic analysis has not been reported. This study aimed to identify distinct genetic features of breast carcinoma associated with a high Oncotype DX Recurrence Score (ORS).

Patients and methods: Patients were categorized into two groups, ORS-high (ORS-H; two patients) and ORS-non-high (ORS-NH; five patients). We performed digital spatial profiling and bioinformatic analyses to investigate the spatial transcriptomic profiles.

Results: Lysozyme (LYZ), complement C1q C chain (C1QC), and complement C1q B chain (C1QB) exhibited the highest fold changes in the stromal compartment of the ORS-H group. Gene ontology enrichment analysis of the ORS-H group revealed significant up-regulation of genes associated with immune response in the stromal compartment, including lymphocyte-mediated immunity, adaptive immune response related to the immunoglobulin superfamily, and leukocyte-mediated immunity. Gene set enrichment analysis showed significant positive enrichment of gene sets associated with interferon (IFN) response and complement pathways in the stromal compartment.

Conclusion: This study highlights significant differences in gene expression profiles and spatially resolved transcriptional activities between ORS-H and ORS-NH breast carcinomas. The significant up-regulation of genes and pathways associated with cell-mediated immunity, IFN response, and complement C1q in the stromal compartment of the ORS-H group warrants further evaluation with larger population cohorts.

Background/aim: The function of the S-100 protein family member hornerin (HRNR) in gastric cancer (GC) tissues is largely unknown. We researched the clinical significance of HRNR expression in GC tissues of patients with pathological (p)Stage II/III GC after curative resection.

Patients and methods: We included patients with pStage II/III GC who underwent curative gastrectomy (n=253). Expression levels of HRNR in GC tissue and in the adjacent normal mucosa were determined using quantitative real-time polymerase chain reaction. Clinicopathological features and overall survival (OS) were compared in patients with different HRNR expression levels in GC tissue.

Results: HRNR expression levels were significantly higher in GC tissues than in the adjacent normal mucosa. HRNR expression level in GC tissue showed sex differences. The 5-year OS rate in the high-HRNR expression group was significantly worse than that in the low-expression group (5-year survival 53.6% vs. 74.9%; p=0.004). Furthermore, on multivariate analysis, high-HRNR expression was an independent predictor of poor OS (hazard ratio=1.534; 95% confidence interval=1.130-2.618; p=0.011).

Conclusion: In patients with pStage II/III GC after curative gastrectomy, HRNR expression in GC tissue may be a useful prognostic marker.

Background/aim: The study aim was to analyze the feasibility and efficacy of palliative radiotherapy in patients receiving advanced/interventional pain therapy, such as epidural or spinal anesthesia or subcutaneous pump delivery of opioids. Endpoints such as pain relief, treatment in the last month of life and survival were evaluated.

Patients and methods: Different baseline parameters including but not limited to age and Eastern Cooperative Oncology Group performance status (ECOG PS) were assessed. Outcomes were abstracted from electronic health records. The Edmonton Symptom Assessment System (ESAS) was utilized to score pain intensity.

Results: The study included 48 patients, 44 of whom completed radiotherapy as prescribed. Device malfunction was not observed. Overall, 31 patients (65%) had journal notes available allowing for evaluation of pain relief. Twenty-six of 31 experienced pain relief (54% in the intention-to-treat population of 48 study patients). Twelve patients (25%) stopped interventional pain therapy and were converted to transdermal or oral drugs. Median survival was 1.6 months. Forty-four percent had received radiotherapy during the last month of life. Sixty-four percent of patients with ECOG PS 3-4 had received radiotherapy during the last month of life, compared to 22% of those with ECOG PS <3, p=0.004.

Conclusion: Palliative radiotherapy was feasible in this setting, but given the short median survival and high likelihood of treatment during the last month of life, patient selection and choice of fractionation regimen should be optimized. The record review identified several patients who experienced worthwhile pain relief, sometimes leading to conversion of pain therapy back to non-invasive oral or transdermal application.

Background/aim: No studies have investigated the advantage of laparoscopic hepatectomy (LH) compared with open hepatectomy (OH) from a nutritional perspective. This study aimed to compare the postoperative nutritional status between LH and OH.

Patients and methods: A total of 186 patients who underwent partial hepatic resection for liver tumors were analyzed retrospectively. We compared perioperative variables between LH and OH. The nutritional status was assessed using serum albumin (Alb) and rapid turnover protein concentrations. We investigated risk factors for postoperative malnutrition using univariate and multivariate analyses.

Results: The LH group, compared with the OH group, had a significantly shorter operative time (239 vs. 344 min, p<0.03), less intraoperative blood loss (100 vs. 343 g, p<0.01), and a shorter length of postoperative stay (8 vs. 11 days, p<0.01). Postoperative serum Alb and prealbumin concentrations in the LH group were significantly higher than those in the OH group (3.4 vs. 3.2 g/dl, p<0.01; 15.0 vs. 12.0 mg/dl, p=0.02, respectively). The multivariate analysis showed that OH (p=0.02) and hepatocellular carcinoma (p<0.01) were significant and independent risk factors for postoperative malnutrition.

Conclusion: LH may be superior to OH in terms of the postoperative nutritional status, intraoperative blood loss, and length of postoperative stay.

Background/aim: The study aimed to investigate the efficacy of radiotherapy or chemoradiotherapy for isolated locoregional recurrence after pancreatectomy for pancreatic cancer.

Patients and methods: Twenty-eight patients who had isolated locoregional recurrence after pancreatectomy for pancreatic cancer between 2007 and 2021 were retrospectively analyzed. We investigated the effect of the treatment method [radiotherapy or chemoradiotherapy (radiotherapy with concurrent chemotherapy)] on progression-free survival (PFS) and post-recurrence survival (PRS).

Results: The median disease-free survival was 16.1 months (range=4.7-47.1 months). Five patients received radiotherapy and 21 patients received chemoradiotherapy [radiotherapy concurrent with gemcitabine (GEM) or S-1] for locoregional recurrence. All patients except one patient with interstitial pneumonia were treated with salvage chemotherapy after irradiation. The median PFS rates of the radiotherapy group and the chemoradiotherapy group were 2.8 months (range=1.5-5.4 months) and 16.8 months (range=2.7-42.8 months), respectively. The median PRS rates were 23.7 months (range=8.1-26.4 months) for the radiotherapy group and 26.2 months (range=6.0-64.7 months) for the chemoradiotherapy group. Multivariate analysis identified radiotherapy [hazard ratio (HR)=12.2, 95% confidence interval (CI)=3.29-45.6, p<0.001] and serum DUPAN-2 >150 U/ml (HR=2.90, 95%CI=1.22-6.93, p=0.02) as independent predictors of PFS, and UICC TNM Stage ≥III (HR=3.23, 95%CI=1.17-8.96, p=0.02) and modified Glasgow prognostic score before the treatment for the recurrence 1 or 2 (HR=3.05, 95%CI=1.15-8.08, p=0.03) as independent predictors of PRS.

Conclusion: Chemoradiotherapy for isolated locoregional recurrence after pancreatectomy for pancreatic cancer could suppress re-recurrence more effectively than radiotherapy.

Background/aim: We herein examined T cell immunity in esophageal cancer patients with and without Helicobacter pylori infection to establish a foundation for immunotherapeutic strategies targeting esophageal cancer in the presence of H. pylori infection.

Materials and methods: Twenty-six patients with esophageal squamous cell carcinoma between 2015 and 2017 were enrolled in the present study. Serum antibodies against H. pylori were measured. Fresh tumor tissues were obtained by endoscopic biopsy or from surgical resection. A cell suspension of these tissues was subjected to a flow cytometric analysis.

Results: Among the 26 patients analyzed, 10 (38.5%) were seropositive for H. pylori. The flow cytometric analysis of tumor-infiltrating lymphocytes revealed that the percentage of CD103⁺CD4⁺ T cells in esophageal tumors was significantly lower in H. pylori-positive patients than in H. pylori-negative patients (p=0.0105). Conversely, the percentage of CD45RA-CD25hi effector Treg cells in esophageal tumors was significantly higher in H. pylori-positive patients than in H. pylori-negative patients (p=0.0022), indicating an immunosuppressive tumor microenvironment in the former. Following neoadjuvant chemotherapy, the number of CD45RA-CD25hi effector Treg cells decreased (p=0.0248).

Conclusion: The tumor immune microenvironment of esophageal cancer patients with H. pylori infection exhibited an immunosuppressive phenotype. The targeting of Treg cells has potential in immunotherapy for this patient population.