Anticancer research最新文献

Background/aim: Although hormone receptor-positive (HR+) invasive ductal carcinoma (IDC) is the most common breast cancer subtype, there is limited evidence describing how demographic and clinical features vary across U.S. regions. Understanding geographic disparities is essential for improving screening and treatment planning. To examine regional variations in demographic, socioeconomic status (SES), and stage-at-diagnosis characteristics among U.S. patients with HR+ IDC.

Patients and methods: This cross-sectional study used data from the National Cancer Database (NCDB) for patients diagnosed with HR+ IDC between 2004 and 2020. Patients were categorized into 6 U.S. geographic regions: Northeast, Southeast, Midwest, Southwest, Mountain, and Pacific, based on the Commission on Cancer facility location. Descriptive and comparative analyses evaluated age, sex, race and ethnicity, insurance type, income, urban-rural residence, and American Joint Committee on Cancer stage.

Results: Among 136,280 patients (mean age, 64.4 years; 98.8% female), racial and SES composition differed significantly across regions. Black patients comprised 19.5% of the Southeast cohort and 18.1% of the Southwest cohort, compared with 2.9% in the Mountain region. The Asian population was highest in the Pacific (13.1%). Low-income households (<$63,000) were most prevalent in the Southwest (74.7%) and Southeast (69.5%), while the Pacific region had the highest proportion of higher-income households (46.4%) and metropolitan residents (94.3%). Stage III-IV disease at diagnosis occurred most often in the Southwest (17.6%) and least in the Northeast (14.0%).

Conclusion: Significant variation exists in the demographic and SES profile of patients with HR+ IDC, corresponding to differences in stage at diagnosis, and BC-related overall outcomes. These disparities likely reflect inequities in screening access, SES, and healthcare infrastructure, underscoring the need for region-specific public health strategies. Targeted regional interventions and equitable screening expansion are warranted to reduce geographic disparities and improve overall BC-related outcomes.

Background/aim: Prostate cancer (PCa) is a leading malignancy in men, with biochemical recurrence (BCR) indicating potential disease progression in up to 50% of patient's post-curative therapy. The liprin-α family gene PPFIA2 has emerged as a potential biomarker in PCa, yet its prognostic role in localized disease remains underexplored.

Materials and methods: PPFIA2 expression was analyzed using high throughput data from TCGA-PRAD, CPC, Stockholm, and GSE54460 cohorts, with validation in an in-house cohort via immunohistochemistry (IHC). Kaplan-Meier and Cox regression analyses assessed its prognostic value for BCR and overall survival. In vitro, PPFIA2 knockdown effects were evaluated in LNCaP and C4-2 cell lines using CCK-8 and Transwell assays. Gene Set Enrichment Analysis (GSEA) explored biological pathways, and mutation profiles were analyzed using maftools.

Results: High PPFIA2 expression was associated with earlier BCR across multiple cohorts. IHC confirmed elevated PPFIA2 protein levels in PCa tissues, correlating with poorer prognosis. PPFIA2 knockdown reduced proliferation and migration in PCa cell lines. GSEA revealed PPFIA2's activation of proliferation-related pathways and suppression of protein synthesis. High PPFIA2 expression was linked to a lower SPOP mutation frequency.

Conclusion: PPFIA2 is an unfavorable prognostic biomarker for localized PCa. Its oncogene effect highlights its potential for risk stratification and targeted therapy.

Background/aim: Few studies have examined how the response to neoadjuvant chemotherapy (NAC) for locally advanced colorectal cancer affects prognosis.

Patients and methods: A total of 162 patients who received NAC followed by radical resection with curative intent between April 2016 and December 2024 were included. Patients were classified into two groups: good response (n=43) and poor response (n=119). Clinicopathological characteristics and prognosis were compared between the groups.

Results: The good response group had a lower rate of combined resection of adjacent organs (11.6% vs. 25.2%, p=0.046), higher clinical N status before NAC (93.0% vs. 71.4%, p=0.002), lower pathological T4 rate (2.3% vs. 23.5%, p<0.001), and less lymphovascular invasion (30.2% vs. 68.9%, p<0.001). Median follow-up duration was 41 months (range=1-66 months). Good responders tended to have better relapse-free survival (RFS; 83.7% vs. 70.5%; p=0.092). Overall survival was similar between the groups (88.6% vs. 78.6% p=0.629). In the poor response group, patients who received adjuvant chemotherapy had significantly better RFS than those who did not (67.3% vs. 70.1%, p<0.05).

Conclusion: Patients with a good response to NAC tended to have a better prognosis. Adjuvant chemotherapy might improve outcomes in patients with poor response to NAC.

Background/aim: The Oncotype DX Recurrence Score (RS) is widely implemented to guide adjuvant chemotherapy in early hormone receptor-positive (HR+)/HER2- breast cancer. However, discordance between RS and conventional clinicopathological risk assessment (clinical risk, CR) remains a significant clinical challenge, particularly in real-world practice.

Patients and methods: We retrospectively analyzed 216 consecutive patients with early HR+/HER2- breast cancer who underwent Oncotype DX testing at Osaka Metropolitan University Hospital. CR was defined according to the St. Gallen criteria, and patients were categorized into four groups: RS-low/CR-low, RS-high/CR-high, RS-low/CR-high, and RS-high/CR-low. The concordance/discordance between RS and CR, their associations with clinicopathological features, and the impact on adjuvant chemotherapy decisions were evaluated.

Results: Concordance was observed in 122 patients (56.5%), consisting of 93 (43.1%) with RS-low/CR-low and 29 (13.4%) with RS-high/CR-high. Discordance was found in 94 patients (43.5%), including 90 (41.7%) with RS-low/CR-high and 4 (1.8%) with RS-high/CR-low. Compared with RS-low, RS-high patients more often had tumors >2 cm (57.1% vs. 30.4%, p=0.002), nodal metastasis (34.3% vs. 21.5%, p<0.001), and Ki67 >20% (60.0% vs. 15.5%, p<0.001). Histological grade >2 was more frequent but not significant (34.3% vs. 5.0%, p=0.104). Regarding therapy, 73.2% received endocrine therapy alone, 19.4% combination endocrine therapy, and 7.4% intravenous chemotherapy. Chemotherapy was strongly associated with concordance: 93.7% of treated cases were concordant, versus 6.3% discordant (p<0.001).

Conclusion: Clinical-genomic discordance was common. RS reflected tumor biology rather than nodal status, and chemotherapy use depended more on genomic-clinical concordance than CR alone. Integration of clinical and genomic risk is essential for optimizing adjuvant strategies in early HR+/HER2- breast cancer.

Background/aim: Thoracoscopic esophagectomy for esophageal cancer remains highly invasive, with venous thromboembolism (VTE) representing a serious postoperative complication. The early post-operative incidence and clinical significance of asymptomatic pulmonary embolism (PE) remain poorly defined.

Patients and methods: This single-center prospective study enrolled 57 patients who underwent thoracoscopic esophagectomies for esophageal or esophagogastric junction cancer between May 2020 and October 2024. Contrast-enhanced computed tomography (CT) was routinely performed on postoperative day (POD) 3 to detect PE and deep vein thrombosis. Clinical, surgical, and laboratory parameters, including coagulation markers and inflammatory indices, were analyzed to identify the potential risk factors.

Results: Postoperative thrombotic events were observed in 70% (n=40) of the patients. Asymptomatic PE was detected in 24.6% (n=14) of patients and azygos arch stump thrombosis in 43.9% (n=25). A higher preoperative platelet-to-lymphocyte ratio and elevated soluble fibrin levels on POD 1 were associated with VTE, although multivariate analysis did not identify any independent predictors of PE. Most thrombi resolved with anticoagulant therapy without severe complications.

Conclusion: Routine POD 3 CT revealed a high incidence of asymptomatic PE following thoracoscopic esophagectomy. Given the limited predictive utility of conventional markers, early postoperative imaging or tailored prophylactic anticoagulation should be considered to mitigate the thromboembolic risk.

Background/aim: Gastric cancer prognosis remains poor, and neoadjuvant chemotherapy (NAC) is not widely used in Japan. While docetaxel-based regimens have shown promise internationally, the biological basis of their efficacy is not fully understood.

Materials and methods: We performed a transcriptomic analysis of tumor sections from 24 patients with gastric cancer who received docetaxel plus S-1 (DS) or docetaxel with cisplatin plus S-1 (DCS) as NAC between 2011 and 2015. Our goal was to identify key biological differences between pathologically responsive and non-responsive groups.

Results: The non-responding group had a significantly worse prognosis (p=0.017) despite similar baseline patient characteristics. Their tumors were marked by enrichment of proliferation-related gene sets, and a low infiltration of CD8+ and CD4+ effector memory cells and dendritic cells. We found no difference in key immune pathways, such as interferon-γ and interferon-α response. A final key finding was the significantly lower expression of five genes, namely zinc finger protein 296 (ZNF296), RAS association domain family member 10 (RASSF10), exocyst complex component 3-like 1 (EXOC3L1), microtubule-associated tyrosine carboxypeptidase 2 (KIAA0895), and polypeptide N-acetylgalactosaminyltransferase 1 (GALNTL1), in the non-response group.

Conclusion: Our study suggests that the lack of NAC response to DS/DCS therapy is associated with increased tumor proliferation, a poor antitumor immune response, and the reduced expression of these five genes (ZNF296, RASSF10, EXOC3L1, KIAA0895 and GALNTL1). These genes represent promising candidates for further investigation as biomarkers for predicting treatment efficacy and as novel therapeutic targets.

Background/aim: Subcutaneous fixed-dose combination of pertuzumab and trastuzumab (Phesgo) has been recently introduced as an alternative to intravenous administration in the treatment of HER2-positive breast cancer. Although pivotal trials demonstrated its non-inferior efficacy and safety, real-world evidence in Japanese clinical practice remains limited.

Patients and methods: We retrospectively analyzed patients with HER2-positive breast cancer who received neoadjuvant chemotherapy at Osaka Metropolitan University between April 2019 and March 2025. A total of 102 patients were included: 71 treated with intravenous pertuzumab plus trastuzumab (IV group) and 31 with Phesgo (SC group). Pathological complete response (pCR) rate, adverse events, and treatment efficiency (measured by treatment room occupancy time) were compared.

Results: The pCR rate was significantly higher in the SC group than in the IV group (77.4% vs. 49.3%, p=0.008). Subgroup analysis showed a pCR rate of 57.1% vs. 38.6% in hormone receptor (HR)-positive patients (p=0.427) and 83.3% vs. 66.7% in HR-negative patients (p=0.211), respectively. Treatment-related AEs were observed in 41.9% of SC group patients, including injection site reactions (16.1%), arthralgia (16.1%), diarrhea (9.7%), fatigue (3.2%), pruritus (3.2%), and infusion reaction with fever (3.2%). Importantly, no grade ≥3 AEs were observed. The mean treatment room occupancy time was significantly shorter in the SC group compared with the IV group (32 min vs. 108 min, p<0.001).

Conclusion: Phesgo demonstrated comparable or superior efficacy and favorable safety with markedly improved treatment efficiency in real-world Japanese practice. Phesgo represents a promising alternative to intravenous administration, reducing patient burden and optimizing healthcare resource utilization.

Background/aim: Standard chemotherapy is limited by severe side effects and drug resistance, driving the need for novel, low-toxicity agents like the flavonoid quercetin. This study aimed to evaluate the anticancer effects of quercetin and isoquercetin from Streptomyces griseoaurantiacus HNF214 against HepG2 cells, focusing on inhibition of the PI3K/Akt/mTOR signaling pathway.

Materials and methods: Quercetin and isoquercetin were purified from microbial culture. Cytotoxicity (MTT assay on HepG2/Vero) and apoptosis markers (MMP, Annexin V, caspase) were assessed. The inhibitory mechanism was studied via ELISA quantification of key proteins (PI3K p85, pAkt, pmTOR), supplemented by molecular docking against the PI3K/AKT/mTOR complex.

Results: Both compounds showed concentration-dependent HepG2 inhibition (IC₅₀'s ≈ 380 μg/ml) with minimal Vero cell cytotoxicity. Apoptosis was confirmed by MMP depolarization and a dose-dependent increase in activated caspase-3/9 levels. Mechanistic analysis showed a significant reduction in PI3K p85, leading to decreased pAkt/total Akt and pmTOR/total mTOR ratios. Molecular docking predicted that quercetin binds directly to the active sites of PI3K and AKT.

Conclusion: The microbial-derived quercetins effectively induce apoptosis and inhibit HepG2 proliferation by inactivating the PI3K/Akt/mTOR signaling pathway. Quercetin is specifically predicted to directly inhibit PI3K and AKT proteins, underscoring the potential of these compounds as targeted anticancer candidates.

Background/aim: This multicenter retrospective study aimed to compare the oncological outcomes of laparoscopic colorectal cancer (CRC) resection as a bridge to surgery after self-expanding metal stent (SEMS) insertion for patients with obstructive CRC (OCRC) with those of elective laparoscopic CRC resection for patients with non-OCRC.

Patients and methods: One hundred patients with stage II or III OCRC who underwent SEMS placement as bridge to surgery (SEMS group) and 657 patients with non-OCRC who underwent elective surgery (control group) were included in this study. A propensity score-matching analysis was performed to eliminate confounding factors for prognosis.

Results: One hundred patients in the control and SEMS groups were identified using propensity score matching. The incidence of postoperative complications did not differ between the groups. There was no significant difference in 5-year overall survival (control group: 74.1% vs. SEMS group: 82.8%, p=0.365) or cancer-specific survival rates (control group: 82.1% vs. SEMS group: 88.2%, p=0.375). Subgroup analyses stratified by pathological stage or tumor location demonstrated no difference in prognosis between the two groups.

Conclusion: SEMS placement followed by laparoscopic surgery is a feasible treatment modality for patients with OCRC.

Background/aim: Pancreaticoduodenectomy (PD) is the standard curative option for pancreatic head carcinoma, but R1 resections remain frequent. The superior mesenteric artery (SMA) "artery-first" approach (AFA) may improve oncologic clearance and operative safety. We conducted a systematic review and meta-analysis comparing AFA versus standard PD.

Materials and methods: Following the PRISMA 2020 guidelines, PubMed and Scopus were searched to January 27, 2025. Comparative studies reporting R0 resection or survival outcomes were eligible. Data were extracted independently, and random-effects meta-analyses were performed for dichotomous (risk ratios, RR) and continuous outcomes (mean differences, MD). Sensitivity analyses included fixed-effect models, alternative continuity corrections, and exclusion of zero-event studies. Publication bias was assessed with funnel plots and Egger's test.

Results: Twenty-two studies (2 randomized trials, 20 retrospective; 945 AFA, 1,173 standard PD patients) were included. R0 resection was reported in 15 studies. Pooled analysis favored AFA (RR: 1.13, 95% CI=1.08-1.19; I²=9.1%), robust across sensitivity analyses, with no evidence of publication bias (Egger p=0.47). Estimated blood loss was significantly reduced with AFA (MD -86.7 ml, 95% CI=-164.8 to -8.7; I²=63.8%), though results were moderately sensitive to individual studies. Other perioperative outcomes - including operative time, complications, and hospital stay - showed no consistent differences. Long-term survival outcomes were inconsistently reported but suggested at least equivalence. Subgroup analysis indicated that randomized trials did not consistently replicate the R0 advantage seen in retrospective series.

Conclusion: AFA for PD is associated with higher R0 resection rates and lower blood loss compared to standard PD, without added morbidity. Observational data strongly support AFA, but confirmatory evidence from well-powered randomized trials remains essential.