Cancer Research and Treatment最新文献

Purpose: Transmembrane channel-like 5 (TMC5) plays a tumor-promoting role in the progression of various tumors. However, its effect on regulating breast cancer cell function remains scarce. The current study aimed to evaluate the effect of TMC5 silence on the proliferation, apoptosis, migration, and invasion of breast cancer cell lines.

Materials and methods: TMC5-specific small interfering RNA (siTMC5) and siNC were transfected into MDA-MB-231 and MCF-7 cell lines; subsequently, the 740Y-P was co-cultured. Then, the proliferation, apoptosis, migration, invasion, and p-AKT expression were determined.

Results: In MDA-MB-231 and MCF-7 cell lines, silence of TMC5 could reduce the proliferation rate at 48 hours (h) and 72 h, migration rate, and invasion rate, while elevate the apoptosis rate. Besides, silence of TMC5 could decrease the p-AKT/AKT expression. The combination of 740Y-P with the silence of TMC5 could reversely increase the proliferation rate at 48h and 72h, migration rate, and invasion rate compared with the silence of TMC5 only. The apoptosis rate showed the opposite trend.

Conclusion: The silence of TMC5 could inhibit the proliferation, migration, and invasion while promoting the apoptosis of breast cancer, while more in vivo validation is needed to explore its potential to be a treatment target for patients with breast cancer.

Purpose: The phase 3 SPOTLIGHT and GLOW trials, in patients with claudin 18 isoform 2-positive, human epidermal growth factor receptor 2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS) and overall survival (OS) with first-line zolbetuximab plus chemotherapy versus placebo plus chemotherapy. This analysis evaluated efficacy and safety in the Korean subgroup from SPOTLIGHT and GLOW.

Materials and methods: Patients were randomized 1:1 to receive zolbetuximab plus chemotherapy or placebo plus chemotherapy (mFOLFOX6 [modified folinic acid, 5-fluorouracil, and oxaliplatin] or CAPOX [capecitabine and oxaliplatin]). Primary endpoint was PFS, assessed per RECIST v1.1 by independent review committee. Other efficacy and safety parameters were assessed.

Results: The Korean subgroup consisted of 49 patients in the zolbetuximab group and 47 in the placebo group. Median PFS (95% confidence interval [CI]) was 12.3 months (7.3-15.3), and median OS was 30.5 months (16.1-45.5) with zolbetuximab versus 8.1 months (4.2-10.4) and 15.8 months (11.8-19.7) with placebo, respectively. Most common TEAEs in patients who received zolbetuximab versus placebo were nausea (79.6% vs. 53.2%), vomiting (55.1% vs. 21.3%), and decreased appetite (53.1% vs. 23.4%). Treatment-related TEAEs led to discontinuation of zolbetuximab and placebo in 4.1% and 2.1% of patients, respectively.

Conclusion: Zolbetuximab plus chemotherapy demonstrated favorable PFS and OS versus placebo plus chemotherapy in the Korean subgroup, with numerically greater efficacy compared with the overall pooled population. This may be potentially attributable to low rates of zolbetuximab discontinuation and toxicity management.

Purpose: Early recurrence reflects aggressive disease and poor prognosis, with patterns varying across breast cancer subtypes. Early recurrence is a major challenge in luminal HER2-negative high proliferative breast cancer, yet reliable biomarkers remain limited. Identifying biomarkers associated with early recurrence is therefore of significant interest.

Materials and methods: Forty-two patients with stage I-III luminal HER2-negative, high-proliferative breast cancer were enrolled in the VGHTPE cohort and underwent targeted next-generation sequencing using the ACTOnco Comprehensive Cancer Panel. Findings were validated in The Cancer Genome Atlas (TCGA) and METABRIC datasets, and in vitro experiments were conducted to assess cell aggressiveness.

Results: We examined 42 patients, including 15 who experienced recurrence within five years and 27 who did not. Next-generation sequencing revealed that the most prevalent alterations in this luminal HER2-negative, high-proliferative breast cancer cohort were mutations in PIK3CA and TP53, and amplifications/gains in MCL1, MYC, and KLF6. Patients with recurrence within five years exhibited a higher frequency of ITGB2 gain compared with non-recurrent patients. Validation in the TCGA and METABRIC cohorts confirmed the prognostic significance of ITGB2 gain in ER+/HER2- breast cancers. Gene Set Enrichment Analysis indicated that high ITGB2 expression was enriched in KRAS and EMT pathways. In vitro experiments further demonstrated that ITGB2 knockdown led to inactivation of Akt and ERK signaling and suppression of cell aggressiveness in ER+/HER2- breast cancer cells.

Conclusion: ITGB2 gain represents an unfavorable prognostic marker for early recurrence in luminal HER2-negative high proliferative breast cancer, with potential therapeutic implications.

Purpose: This multicenter, phase II study examined the efficacy and safety of bendamustine plus rituximab in patients with relapsed or progressive marginal zone lymphoma (MZL).

Materials and methods: Patients received six cycles of bendamustine 90 mg/m2 intravenously on days 2 and 3, rituximab 375 mg/m2 intravenously in cycle 1, and 1,400 mg subcutaneously in cycles 2-8 on day 1 every 4 weeks. Bendamustine dose reduction to 60 mg/m2 (level -1) and 40 mg/m2 (level -2) was allowed based on prespecified toxicity criteria. The primary endpoint was overall response rate (ORR) and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.

Results: Among the 26 evaluable patients, 81.8% achieved an ORR, while 40.7% had a complete response. The median PFS was 46.06 months, and the estimated 3-year OS rate was 92.3%. Hematological toxicities, primarily neutropenia (grade 3/4, 48.1%), were the most common adverse events, resulting in both reduction and interruption of bendamustine doses, accounting for 18 (75%) of 24 dose-reduced cycles and 7 (41%) of 17 missed cycles, respectively. Nonhematologic toxicities were generally mild, with nausea and fatigue identified as the most frequently reported toxicities. The mean relative dose intensities were 76.9% (range, 31.5-100) for bendamustine and 91.3% (range, 72.7-100) for rituximab.

Conclusion: Bendamustine plus rituximab is a highly effective and tolerable treatment for patients with relapsed or progressive MZL, providing durable disease control.

Purpose: Kidney failure is associated with an increased risk of death. However, since the impact of kidney failure on overall and cancer-related mortality among individuals with cancer remains unclear, we investigated kidney failure-related mortality in patients with cancer, stratified by various cancer types.

Materials and methods: A total of 1,307,680 participants newly diagnosed with cancer were identified from the Cancer Public Library Database. We analyzed data from patients with preexisting kidney failure before cancer diagnosis and compared their mortality risk with patients without kidney failure using multivariable Cox proportional hazard models.

Results: All-cause and cancer-related mortality was significantly higher in the kidney failure group. Preexisting kidney failure was associated with an increased risk of mortality in all cancer types after adjusting for comorbidities and treatment modalities (adjusted hazard ratio [aHR] of all-cause death 1.75, 95% CI 1.70-1.81; aHR of cancer-related death 1.27, 95% CI 1.22-1.32). Among specific cancer types, thyroid and breast cancers showed the highest mortality risks of kidney failure, with thyroid cancer presenting the greatest risk. However, the risk of death was attenuated in liver, gallbladder, and lung cancers. Furthermore, aHRs were lower for mortality in metastatic cancer compared to localized and regional stages.

Conclusion: Preexisting kidney failure significantly increases the risk of all-cause and cancer-related death among cancer patients, particularly in localized cancer and specific cancer types.

Purpose: Fibroblast growth factor receptor 2b (FGFR2b) is a promising therapeutic target in gastric cancer; however, its clinical relevance in immune checkpoint inhibitor (ICI)-based chemotherapy remains unclear. Therefore, this study aims to evaluate the expression pattern and predictive value of FGFR2b in patients undergoing first-line nivolumab plus chemotherapy.

Materials and methods: This single-center study included 503 patients diagnosed with gastric cancer. Among them, 296 underwent nivolumab-chemotherapy, while 207 underwent chemotherapy alone. FGFR2b expression was assessed via immunohistochemistry using samples collected after mid-2022. FGFR2b positivity was defined as membranous staining intensity of 2+/3+ in ≥ 1% of tumor cells, with ≥ 10% as overexpression, and 1-9% as low expression.

Results: FGFR2b overexpression and positivity were identified in 9.3% and 18.7% of cases, respectively. Discordance between paired biopsy and surgical samples was observed (20.0% and 40.0% for overexpression and positivity, respectively), indicating marked intratumoral heterogeneity. Among patients who underwent nivolumab-chemotherapy, FGFR2b overexpression and low expression were associated with favorable survival trends compared to those of FGFR2b-negative cases. These associations were not observed in patients treated with chemotherapy alone. Compared to chemotherapy alone, nivolumab-chemotherapy was associated with a greater survival benefit in patients with FGFR2b positivity. Multivariate interaction analyses revealed a significant interaction between FGFR2b expression and nivolumab-based chemotherapy.

Conclusion: FGFR2b expression exhibits substantial intratumoral heterogeneity in gastric cancer and may be linked to favorable outcomes in patients undergoing first-line ICI plus chemotherapy. Therefore, future studies should validate this finding, along with mechanistic investigations.

Purpose: To assess the clinical efficacy of contrast-enhanced ultrasound (CEUS) combined with indocyanine green (ICG) lymphography for the treatment of breast cancer-related lymphedema (BCRL).

Materials and methods: Fifty-two patients with BCRL who underwent lymphaticovenous anastomosis between March 2022 and March 2024 were enrolled, of whom 22 underwent preoperative functional lymphatic vessel localization using ICG lymphography alone and 30 received CEUS combined with ICG lymphography. Treatment efficacy was evaluated using bioimpedance spectroscopy for segmental water content analysis, calculation of the upper extremity lymphedema (UEL) index, and administration of the Lymphedema Quality of Life Questionnaire (LYMQOL). Surgical parameters were also analyzed.

Results: Baseline characteristics were comparable between the groups. However, at both 6 and 12 months postoperatively, patients in the CEUS+ICG group demonstrated significantly improved outcomes compared to those in the ICG-only group, including: Reduced segmental water differences (6 months: 344.3 vs. 474.6 mL, p=0.0221; 12 months: 284.3 vs. 403.6 mL, p=0.0156); Lower UEL index (6 months: 124.2 vs. 134.1, p=0.0010; 12 months: 123.8 vs. 131.9, p=0.0105); Improved LYMQOL scores (6 months: 48.7 vs. 56.6, p=0.0029; 12 months: 47.6 vs. 54.2, p=0.0065). Additionally, the CEUS+ICG group achieved a significantly higher anastomosis success rate (83.2% vs. 63.3%, p<0.001) and reduced procedural time per anastomosis (48.9 vs. 61.6 minutes, p=0.0021).

Conclusion: The combination of CEUS and ICG-L is associated with precise preoperative lymphatic mapping, a reduction in unnecessary incisions, as well as better anastomosis success rates and postoperative decongestion outcomes.

Purpose: This study aimed to develop a novel theranostic nanoplatform that integrates ultrasound imaging and controlled drug delivery for the treatment of breast cancer.

Methods: PTX@Fe₃O₄ nanobubbles (NBs) were synthesised via microfluidics. Characterisation included transmission electron microscopy, dynamic light scattering, drug release kinetics, phantom imaging and biocompatibility assays in vitro and in mice.

Results: The NBs exhibited uniform size (178 ± 12 nm), high drug loading (8.3%) and pH/ultrasound-responsive release (68.2% at pH 5.5+US). Ultrasound signal enhancement correlated linearly with concentration (R² = 0.988), with imaging duration three times longer than SonoVue. The system exhibited minimal haemolysis (<2%) and low cytotoxicity and induced S-phase arrest (68.2%) in MCF-7 cells. No significant toxicity was observed in mice at 10 mg Fe/kg.

Conclusion: PTX@Fe₃O₄ NBs represent a promising, biocompatible theranostic platform for image-guided breast cancer therapy.

Purpose: Herein, a novel prognostic marker based on the skeletal muscle index (SMI) and red cell distribution width (RDW) for patients with colorectal cancer (CRC) was developed.

Materials and methods: 585 Patients with stage I-III CRC who underwent surgery between January 2004 and April 2011 were included. The ratio of SMI to RDW (SRR) was calculated, and patients were grouped into sex-specific quartiles (G1 to G4) based on SRR. The Kaplan-Meier method was employed to estimate survival differences, and the Cox proportional hazards model was applied to evaluate the association between SRR and overall survival (OS). The Concordance Index (C-index) was calculated to assess the individual and combined effects of SMI and RDW on survival.

Results: There was a significant difference in OS across SRR quartiles (G1: 65.0%, G2: 82.9%, G3: 84.1%, G4: 89.8%, p<0.001). G1 had worse OS compared to the other groups, and SRR was confirmed as an independent prognostic factor for OS (G1 vs. G2, HR=0.531, 95% CI=0.320-0.882, p=0.014; G1 vs. G3, HR=0.534, 95% CI=0.302-0.942, p=0.030; G1 vs. G4, HR=0.419, 95% CI=0.212-0.827, p=0.012). SRR demonstrated greater prognostic power for OS than SMI or RDW alone.

Conclusion: SRR is a novel and significant predictor of overall survival in patients with stages I-III CRC demonstrating greater prognostic power than either SMI or RDW alone.

Purpose: Relapsed or refractory (R/R) primary central nervous system lymphoma (PCNSL) is an aggressive malignancy for which salvage chemotherapy has limited efficacy. We conducted an investigator-initiated, single-arm, multicenter phase II trial to evaluate the efficacy and safety of a chemotherapy-free salvage regimen comprising rituximab, lenalidomide, and poseltinib (R2P) in patients with R/R PCNSL.

Materials and methods: The R2P regimen consisted of two phases: six cycles of induction with rituximab, lenalidomide, and poseltinib, followed by three cycles of consolidation with lenalidomide and poseltinib. The primary endpoints were complete response rate (CRR) and overall response rate (ORR). Secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS).

Results: A total of 10 patients were enrolled (one withdrew before cycle 1; nine were evaluable for efficacy). The median age was 70 years (range, 53-75), and all had received methotrexate-based first-line chemotherapy. The ORR was 55.6%, and the CRR was 33.3%. The median PFS was 5.6 months, and the median OS was not reached. Next-generation sequencing was performed in four patients (three responders and one non-responder). CD79B missense mutations were identified in all three responders. A total of 11 adverse events (AEs) were observed in six patients. The most common AE was neutropenia (30.0%). The only grade ≥3 AE was a single case of grade 3 neutropenia. No dose modifications were required due to toxicity.

Conclusion: Poseltinib in combination with lenalidomide and rituximab showed activity in patients with R/R PCNSL, warranting further investigation in larger studies.