Anticancer research最新文献

Background/aim: Hypo-fractionated radiotherapy (HF-RT) is gaining popularity in prostate cancer treatment. HF-RT can lead to cystitis, particularly in cases with small bladder volumes. This study evaluated the bladder volume during a course of moderate HF-RT. This knowledge is required for the protocol of a prospective trial.

Patients and methods: Seventy-six patients receiving HF-RT (20×3.0 Gy) for prostate cancer were retrospectively evaluated. The number of HF-RT sessions with a bladder volume <200 ml and corresponding risk factors were investigated.

Results: Mean and median numbers of sessions with a bladder volume <200 ml were 13.4 (±6.7) and 16.0 (interquartile range=8.0-19.0), respectively. Higher numbers of radiotherapy sessions with a bladder volume <200 ml were associated with a pre-radiotherapy volume <200 ml (p<0.001). Mean numbers of sessions with a bladder volume <200 ml were 16.0 (±5.5) in patients with a pre-radiotherapy bladder volume <200 ml and 7.9 (±5.9) in patients with a bladder volume ≥200 ml, respectively.

Conclusion: Bladder volume was <200 ml during many HF-RT sessions. Patients with a pre-radiotherapy bladder volume <200 ml may benefit from an app reminding them to drink water before their HF-RT sessions.

Background/aim: Over-expression of matrix metalloproteinase-1 (MMP-1) has been suggested as a biomarker for endometriosis. However, the genetic influence of MMP-1 in the pathogenesis of endometriosis remains unclear, with its role yet to be fully elucidated. This study aimed to investigate the association between MMP-1 rs1799750 promoter polymorphisms and the risk of developing endometriosis.

Patients and methods: This hospital-based case-control study included 203 women diagnosed with endometriosis and 636 age-matched controls. Genotyping of the MMP-1 rs1799750 polymorphism was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.

Results: Among the patients with endometriosis, the distribution of genotypes 2G/2G, 2G/1G, and 1G/1G at MMP-1 rs1799750 was 52.7%, 41.4%, and 5.9%, respectively. This distribution significantly differed from that of the control group, which exhibited frequencies of 41.3%, 48.3%, and 10.4%, respectively (p for trend=0.0092). In the dominant model, carriers of the 2G/1G and 1G/1G genotypes had a reduced prevalence in the endometriosis group compared to 2G/2G carriers [odds ratio (OR)=0.63, 95% confidence interval (95%CI)=0.46-0.87, p=0.0058]. Additionally, the 1G allele frequency in the endometriosis group was 26.6%, significantly lower than the 34.5% observed in controls (OR=0.69, 95%CI=0.54-0.88, p=0.0037).

Conclusion: The 1G allele of MMP-1 rs1799750 is associated with reduced susceptibility to endometriosis in the Taiwanese population. These results highlight the potential of MMP-1 rs1799750 polymorphism as a protective genetic marker, warranting further investigations to explore its genotype-phenotype correlation and underlying biological mechanisms.

Background/aim: Ivermectin is a widely-used anti-parasitic agent and has shown early promise as an anticancer agent. Recombinant methioninase (rMETase) is a methionine-depleting enzyme targeting the methionine addiction of cancer and has broad efficacy against all tested cancer types. However, the combination efficacy of ivermectin and rMETase on breast cancer cells remains unexplored. The present study aimed to determine the synergistic efficacy of ivermectin and rMETase on MCF-7 human breast cancer cells in vitro.

Materials and methods: The IC₁₀ of ivermectin and IC₅₀ of rMETase were determined on MCF-7 cells using the WST-8 reagent to measure cell viability in vitro. MCF-7 cells were treated with four groups: untreated control; ivermectin alone (4.89 μM, IC₁₀); rMETase alone (2.75 U/ml, IC₅₀); and a combination of ivermectin (4.89 μM) and rMETase (2.75 U/ml). Cell viability was assessed 72 hours after treatment with the WST-8 reagent.

Results: Treatment with ivermectin (4.89 μM) did not significantly reduce the viability of MCF-7 cells. rMETase (2.75 U/ml) alone significantly reduced MCF-7 cell viability compared to the control group. The combination of ivermectin and rMETase resulted in a significantly greater reduction in cell viability than either agent alone, including a 9.9-fold greater efficacy than ivermectin alone, demonstrating synergistic efficacy (p<0.05).

Conclusion: The combination of ivermectin and rMETase had synergistic efficacy against MCF-7 breast cancer cells in vitro. The present findings suggest that the combination of ivermectin and rMETase is a promising strategy for breast cancer requiring further preclinical and clinical evaluation.

Background/aim: The development of immune checkpoint blockade (ICB) agents targeting programmed death protein 1(PD-1), PD-1 ligand (PD-L1), cytotoxic T-lymphocyte- associated protein 4 (CTLA-4), and CD40 has gained increasing interest in clinical cancer treatment. Among these targets, blocking of PD-1 binding to its ligand PD-L1 managed to induce immune responses and inhibit tumor growth. In this work, we aimed to screen a specific PD-L1 nanobody against human PD-L1, derived through phage display assay, and further study its biological characteristics and antitumor ability.

Materials and methods: Specific PD-L1 nanobody was screened through phage display and its biological characteristics were explored by surface plasmon resonance (SPR) analysis. In addition, its cytotoxicity and antitumor ability was confirmed in vitro and in vivo.

Results: After all, an anti-PD-L1 nanobody with high specificity and affinity was generated. This PD-L1 nanobody was highly specific for human PD-L1 and had strong penetration ability due to its size. PD-L1 nanobody enhanced immune cell-killing ability by inhibiting the immune checkpoint and further activating innate response. Furthermore, this new PD-L1 nanobody also had high binding affinity, as shown by its use in western blotting, flow cytometry staining and immunofluorescence staining methods.

Conclusion: The new PD-L1 nanobody substantially improved upon the FDA-approved PD-L1 monoclonal antibody by surpassing the disadvantage of having large molecular weight (MW) and low tissue penetration. The cytotoxicity and antitumor ability of PD-L1 nanobody, in vitro and in vivo, also support its potential as a therapeutic agent for lung cancer immunotherapy.

Background/aim: Previous studies have demonstrated that breast cancer cells secrete exosomes into the tumor microenvironment, promoting tumor progression. However, the paracrine influence of noncancerous breast epithelial cells on the growth of triple-negative breast cancer (TNBC) cells has largely been overlooked. We hypothesize that exosomes from noncancerous breast epithelial cells are secreted into the tumor microenvironment, stimulating TNBC growth.

Materials and methods: Exosome-containing media were prepared using exosomes isolated from triple-negative patient-derived xenografts (PDX) or noncancerous MCF-10A breast epithelial cells and used to treat MCF-7 or TNBC cells. Exosome-containing media from MCF-10A cells were characterized using ELISA. Subsequently, MDA-MB-231 and MDA-MB-468 cells treated with the MCF-10A exosome-containing media, and their impact on proliferation, migration, protein expression and gene expression were analyzed using Alamar blue assays, wound healing assays, western blotting, immunofluorescence, and gene expression arrays, respectively.

Results: Exosomes extracted from the PDX and MCF-10A cells stimulated the growth of all examined cell lines. The MCF-10A exosome-containing media expressed CD9 and CD63; however, the MDA-MB-231 and MDA-MB-468 cells treated with these media exhibited differential expression of these proteins. Exposure of MDA-MB-231 and MDA-MB-468 cells to the MCF-10A exosome-containing media stimulated their growth and migration. Exposure of MDA-MB-231 cells to MCF-10A exosome-containing media caused down-regulation of genes involved in cell-cell adhesion, DNA damage response, epithelial-mesenchymal transition drivers, tumor suppression, and up-regulation of the MYC oncogene.

Conclusion: Secreted factors from noncancerous cells, identified as exosomes, induce cancer cell proliferation and prime the tumor microenvironment by enhancing disease progression-associated pathways.

Background/aim: Urothelial carcinoma, common in older adults, is rare in younger populations and even less common in the prostatic urethra. Advanced disease is typically managed with platinum-based chemotherapy, immune checkpoint inhibitors, and targeted therapies. However, rare presentations in young patients with aggressive disease highlight the need for innovative and personalized treatment strategies.

Case report: This case report presents a rare instance of metastatic urothelial carcinoma originating in the prostatic urethra of a 37-year-old male. Initial symptoms led to diagnosis through imaging, biopsy, and genetic profiling, revealing mutations in TP53 and RB1. The patient underwent multiple treatments, including dose-dense chemotherapy, pembrolizumab immunotherapy, and targeted antibody-drug conjugates (Enfortumab Vedotin and Sacituzumab Govitecan). Despite aggressive therapies, disease management remained challenging, leading to experimental treatments, including a personalized vaccine.

Conclusion: This case underscores the importance of precision medicine and the need for innovative treatment options for rare and aggressive cancers.

Background/aim: The prognostic significance of prostate-specific antigen (PSA) kinetics in metastatic castration-sensitive prostate cancer (mCSPC) patients treated with upfront therapy remains unclear. This study investigated the correlation between early PSA response and clinical outcomes in patients with mCSPC who received upfront therapy.

Patients and methods: We analyzed 106 patients with mCSPC who received upfront therapies [abiraterone acetate (ABI), enzalutamide (ENZ), apalutamide (APA), and docetaxel (DOC)] at Kurume University Hospital and its affiliated hospitals.

Results: Thirty-nine, 15, 38, and 14 patients were treated with ABI, DOC, ENZ, and APA, respectively. Among the total number of patients, 67 met the criteria for high-volume disease. Additionally, 83 patients were categorized as high risk. Patients with a PSA decline rate of ≥90% at 4 and 12 weeks post-upfront therapies had a significantly longer time to develop CRPC than those with a PSA decline of <90%. PSA cutoff values >26 ng/ml at 4 weeks post-upfront therapies and a PSA decline rate of ≥90% at 12 weeks post-upfront therapies were independent predictors of poor prognosis. Furthermore, patients were stratified into three groups based on PSA levels at 4 weeks and PSA decline rate at 12 weeks.

Conclusion: A larger PSA decline within three months of initiating upfront therapy is significantly associated with a longer time to CRPC in patients with mCSPC treated with upfront therapy. A combination of early PSA kinetics can be used to stratify the risk of CRPC progression in patients with mCSPC treated with upfront therapies.

Background/aim: To evaluate the safety and survival benefits of adjuvant chemotherapy (AC) in elderly patients who underwent radical resection for stage II/III colon cancer.

Patients and methods: This retrospective study included patients aged >70 years treated at a tertiary hospital between January 2012 and December 2017. We evaluated the clinical and pathological characteristics and adverse events of chemotherapy. The 5-year overall survival (OS) and disease-free survival (DFS) of the surgery-only (SO) and AC groups were compared by stage using the Kaplan-Meier method and Cox-regression analysis.

Results: Of the 163 patients included in the study, 75 were diagnosed with stage II cancer, with 43 patients in the SO group and 32 in the AC group. A total of 88 patients were diagnosed with stage III cancer, including 20 in the SO group and 68 in the AC group. Patients with stage II disease in the SO group were older, with less frequent venous invasion than the AC group. Comorbidities, tumor location, and surgical methods did not differ. In stage III, age, comorbidities, tumor location, surgical methods, and pathological outcomes did not differ. The 5-year OS and DFS did not differ significantly in those with stage II disease but were significantly better in the AC than the SO group in stage III cases (48.2% vs. 71.6%, p=0.012; and 42.6% vs. 60.0%, p=0.029).

Conclusion: AC may provide a survival advantage in elderly patients with stage III colon cancer.

Background/aim: The prognosis of biliary tract cancer is extremely poor, with a 5-year survival rate of 20%. Surgery is the only treatment that can be expected to cure biliary tract cancer, but because many cases are unresectable or recurrent, chemotherapy has become the standard treatment. The effects of first-line administration of durvalumab have not been explored. This study examined whether durvalumab has an additive effect in the first line.

Patients and methods: Twenty-three patients who were diagnosed with recurrent or non-resected biliary tract cancer requiring anticancer chemotherapy were recruited. Three of these cases were excluded because they had only received one course of durvalumab. We retrospectively collected clinical and laboratory data. Progression-free survival (PFS) and overall survival (OS) were compared between patients who received durvalumab as first-line therapy (first group, FG) and those who received it as second-line or later therapy (second group, SG). PFS and OS were also compared in durvalumab-treated patients aged 75 years and older (older group) and in younger patients. Immune-related adverse events (irAEs) were graded using the Common Terminology Criteria for Adverse Events (CTCAE v5) based on the clinical notation available in the patient charts.

Results: Kaplan-Meier curves showed that SG was significantly associated with worse PFS (p=0.018), and the FG group also showed significantly prolonged OS (p=0.030). In addition, PFS from the start of durvalumab treatment was significantly longer in the older group compared to the younger group. However, no significant difference in OS was observed between the two groups.

Conclusion: Durvalumab appears to contribute to prolonged PFS and OS when administered as an initial treatment. It may also contribute to improved outcomes in older patients with biliary tract cancer.

Background/aim: Glioblastoma multiforme (GBM) is the most aggressive brain tumor. Temozolomide (TMZ) is the first-line treatment for GBM. However, most patients with GBM develop drug resistance. Our previous study showed the effects of camptothecin (CPT) and CRLX101, a nanoparticle of CPT, in suppressing GBM growth by targeting drug-sensitive glioblastoma cells. This study evaluated the effects of CPT on drug-resistant glioblastoma cells and explored the underlying molecular mechanisms.

Materials and methods: Expression of type I topoisomerase (Topo-1) gene in GBM was analyzed using the UALCAN database. Human U87MG-R and mouse GL261-R TMZ-resistant glioblastoma cells were developed. After CPT treatment, apoptotic events were successively determined. The role of the p53-p21-cyclin D1 (CD1)/cyclin-dependent kinase 6 (CDK6)-E2F1-Bcl-xL signaling axis was subsequently investigated.

Results: The expression of Topo-1 gene was up-regulated in human GBM compared to normal human brains. Treatment of human U87MG-R cells with CPT decreased cell viability. Sequentially, exposure to CPT led to activation of caspase-3, fragmentation of chromosomal DNA, and cell apoptosis. Furthermore, intracellular reactive oxygen species (iROS) were augmented following CPT treatment. Suppression of iROS production concurrently alleviated CPT-triggered apoptotic insults. CPT enhanced the levels of p53, phosphorylated p53, and p21. In contrast, levels of CDK6, CD1, E2F1, and Bcl-xL were decreased by CPT. Attenuating p53 transactivation activity using pifithrin-α also mitigated the CPT-induced apoptosis. The effects of CPT on killing drug-resistant glioblastoma cells were further confirmed in mouse GL261-R cells.

Conclusion: CPT could effectively induce apoptosis in drug-resistant glioblastoma cells via iROS-mediated activation of the p53-p21-CD1/CDK6-E2F1-Bcl-xL axis.