Journal of cancer research and therapeutics最新文献

Introduction: The current treatment regimens for Hodgkin's lymphoma (HL) are associated with high incidences of adverse events.

Purpose: This study aimed to compare the efficacy and safety of doxorubicin + bleomycin + vincristine + dacarbazine (ABVD) and standard bleomycin + etoposide + doxorubicin + cyclophosphamide + vincristine + procarbazine + prednisone (BEACOPP) chemotherapy in the treatment of advanced stage HL.

Methods: This multicenter, randomized, parallel, open, positive control noninferiority trial was conducted from 2016 to 2019 and comprised 93 subjects who were randomized in a 1:1 ratio between the treatment (BEACOPP; n = 44) and control (ABVD; n = 49) groups.

Results: The primary efficacy endpoint of this trial was the objective response rate (ORR) after eight cycles of chemotherapy, which was 100.00% (36/36) in the treatment group and 95.74% (45/49) in the control group. The incidence of adverse reactions was 100% in both groups. Significant differences (P < 0.05) in the incidences of grade 3 (39/44 [88.64%] vs. 23/49 [46.94%]) and grade 4 (27/44 [61.36%] vs. 8/49 [16.94%]) adverse events were observed between the treatment and control groups, respectively. However, most of these reactions were manageable, with no serious consequences, and were reversible after discontinuation of the treatment.

Conclusion: Both regimens had a similar ORR and were associated with a high number of adverse events. The ABVD regimen was better tolerated and safer than the standard BEACOPP regimen. This study indicates that the standard BEACOPP regimen may be considered as a treatment option for patients with advanced HL.

Objective: This study aimed to explore the role of IGF2BP2 in esophageal squamous cell carcinoma (ESCC) progression.

Materials and methods: The Cancer Genome Atlas (TCGA) dataset, transcriptome sequencing, and the Gene Expression Omnibus (GEO) dataset were used to detect the expression of m6A-associated genes in ESCC. The in vitro and in vivo assays were used to explore the role of IGF2BP2 in ESCC.

Results: IGF2BP2 was significantly overexpressed in human ESCC specimens, which was confirmed by analyzing the GEO dataset. IGF2BP2 overexpression was correlated with poor prognosis in patients with ESCC. Altering the expression of IGF2BP2 influenced the proliferation, migration, and invasion of ESCC cells in vitro and tumorigenicity in vivo. IGF2BP2 could bind to and stabilize hepatoma-derived growth factor (HDGF) transcripts in ESCC in an m6A-dependent manner and promote HDGF expression.

Conclusions: These findings indicate that the novel IGF2BP2-HDGF axis is pivotal for ESCC cancer progression and can serve as a target for developing therapeutics.

Purpose: Metformin (MET), a type 2 diabetes treatment, has attracted increased attention for its potential antitumor properties; however, the precise mechanism underlying this activity remains unclear. Our previous in vivo and in vitro studies revealed MET's inhibitory effect on ovarian cancer, with the synergistic effects of MET and the MDM2 inhibitor RG7388 contributing to ovarian cancer treatment. This study further explores the mechanism underlying MET's inhibition of ovarian cancer.

Materials and methods: Following MET treatment, we analyzed the differentially expressed proteins in ovarian cancer cells using a tandem mass tag (TMT)-based proteomic approach coupled with bioinformatics.

Results: Using A2780 and SKOV3 ovarian cancer cells, we identified six upregulated and two downregulated proteins after MET treatment. Bioinformatics analysis revealed that these proteins predominately affect ovarian cancer cells by regulating iron ion transport, iron ion homeostasis, and mitochondrial and ribosomal functions. Validation via western blot confirmed MET-induced elevation of hydroxybutyrate dehydrogenase type 2 (BDH2) protein expression levels in A2780 and SKOV3 cells.

Conclusions: Overall, our findings suggest that combining MET with other metabolic drugs, such as iron-chelating agents and mitochondrial inhibitors, may result in synergistic antitumor effects, thereby offering novel avenues for ovarian cancer treatment development.

Objective: To explore the differences between clinical features and computed tomography (CT) findings of early-stage glottic cancer (EGC) with or without recurrence after transoral laser microsurgery (TLM) and to establish a preoperative nomogram to predict postoperative recurrence.

Methods: The clinical and CT features of 168 consecutive patients with EGC with or without recurrence were analyzed retrospectively. Multivariate logistic regression analysis was used to determine the independent predictors of recurrence. A nomogram was constructed to preoperatively predict recurrence. To assess the nomogram's performance, the C-index and calibration plot were used.

Results: EGCs with and without recurrence differed significantly in T-stage, depth, and normalized CT values in the arterial phase (NCTAP) and venous phase (NCTVP) (all P < 0.05). T-stage, depth, and NCTVP were independent predictors of recurrence in EGCs (all P < 0.05). The C-index (0.765, 95% confidence interval: 0.703-0.827) and calibration plot showed that the nomogram has good prediction accuracy. Nomograms based on T-stage and CT variables provided numerically predicted recurrence rates and were better than those based on only T-stage (C-index of 0.765 vs. 0.608).

Conclusions: Using clinical and CT variables, we developed a novel nomogram to predict the recurrence of EGC before TLM, which may be a potential noninvasive tool for guiding personalized treatment.

Objective: This study aimed to evaluate the incidence and predict the risk factors of lymph node (LN) metastasis among patients with grossly apparent early-stage epithelial ovarian cancer (EOC).

Methods: We retrospectively reviewed the clinicopathologic data and follow-up information of 266 patients who underwent LN dissection for apparent early-stage EOC between January 2018 and September 2022 at the Obstetrics and Gynecology Hospital of Fudan University.

Results: Among 266 patients, 44 (16.5%) showed LN metastasis, of which 65.9% and 59.1% presented in the pelvic region and para-aortic region, respectively. Univariate analysis revealed higher LN positivity in patients with high-grade serous carcinoma (HGSC), preoperative imaging suggestive of LN metastasis, bilateral adnexal involvement, lymphovascular space invasion (LVSI), positive peritoneal cytology, and clinical stage IIA. LN metastases were identified in 7.9%, 10.2%, and 39.7% of clinical stage IA/B, IC, and IIA disease cases, respectively. Multivariate analysis confirmed significantly higher LN positivity rates in patients with HGSC, LVSI, and clinical stage IIA. In clinical stage IIA EOC, the 3-year progression-free survival (PFS) rates were 65.8% and 77.4% (P = 0.360) for LN-negative and LN-positive groups, respectively. In clinical stage I EOC, the 3-year PFS rates were 93.5% and 59.4% (P < 0.001) for LN-negative and LN-positive groups, respectively.

Conclusions: High-grade serous histology, LVSI, and clinical stage IIA disease are predictive factors for LN involvement in early-stage EOC. In addition, LN metastasis appears to be associated with worse PFS in clinical stage I EOC compared with clinical stage IIA EOC.

Objective: This retrospective study is to explore the risk factors and prognostic factors of brain metastases of triple-negative breast cancer (TNBC) in a single center.

Methods: Clinical data of patients with stages I-III TNBC were collected. The Kaplan-Meier method, log-rank test, and stepwise COX regression were performed.

Results: The 437 patients with stages I-III TNBC were followed up for five years. Among them, 89 cases (20.4%) developed brain metastases, and they were followed up for 2 years after brain metastasis. The cumulative brain metastasis rates of TNBC patients at six months, one year, two years, three years, and five years were 1.38%, 5.75%, 12.94%, 17.63%, and 21.26%, respectively. Multivariate analysis suggested that the first diagnosis age ≤35 years old, advanced pathological stage, lymph node metastasis, and Ki-67 ≥30% represented the risk factors for brain metastasis. In contrast, the surgical method was a protective factor for brain metastasis. The median survival time after brain metastasis was 4.87 months. The survival rates at one, three, six, 12, and 24 months were 84.27%, 60.67%, 34.83%, 15.69%, and 6.64%, respectively. The age >60 years at first diagnosis, Ki-67 ≥30%, local recurrence, and distant metastasis were closely related to the poor prognosis of TNBC patients with brain metastases, while radiotherapy alone, systemic therapy, and combined chemotherapy and radiotherapy represented the prognostic protective factors.

Conclusions: Patient age, Ki-67 level, metastasis, and treatment methods are the risk factors and prognostic factors for brain metastasis of TNBC. Surgical resection of the primary lesion during the first treatment is essential to reduce the incidence of brain metastases. Close postoperative follow-up (such as brain magnetic resonance imaging [MRI]) within 2-3 years after surgery is recommended to improve the prognosis.

Aims: Papillary thyroid cancer (PTC) is a serious threat to human health worldwide, while metastasis in the early phase limits therapeutic success and leads to poor survival outcomes. The CXC chemokine receptor type 4 (CXCR4) plays an important role in many cellular movements such as transcriptional modulation, cell skeleton rearrangement, and cell migration, and the change in CXCR4 levels are crucial in various diseases including cancer. In this study, we explored the role of CXCR4 in the migration and invasion of PTC and investigated the potential mechanisms underlying its effects.

Subjects and methods: We analyzed the expression levels of CXCR4 in PTC tissues and cell lines. Would healing migration, Transwell invasion assay in vitro, and tail-vein lung metastasis assay In vivo were performed to evaluated the migration and invasion abilities of PTC cells with stable CXCR4 knockdown or overexpression. Signal transducers and activators of transcription (STAT3) signaling pathway-related protein expressions were examined by Western blotting assays.

Results: The results showed that CXCR4 was highly expressed in PTC cell lines and PTC tissues. CXCR4 knockdown in PTC cells dampened the migration, invasion, and epithelial-mesenchymal transition (EMT), whereas CXCR4 overexpression enhanced these properties. In vivo, we also found that CXCR4 promoted the metastasis of PTC. Mechanistic studies showed that CXCR4 played these vital roles through the STAT3 signaling pathway. Furthermore, PTC patients with high CXCR4 or p-STAT3 expression correlated with aggressive clinical characteristics such as extrathyroidal extension (ETE), and lymph node metastasis (LNM).

Conclusions: We provided evidence that CXCR4 might activate the STAT3 signaling pathway and further promote PTC development. Thus, CXCR4 might be a novel therapeutic target for PTC.

Introduction: Elevated plasma D-dimer levels are an unfavorable prognostic indicator for various tumors. However, its predictive value for prognosis in pediatric patients with Wilms tumor (WT) remains unknown. We aimed to investigate the clinical and prognostic value of preoperative plasma D-dimer levels and other clinicopathological characteristics in patients with favorable histology WT (FHWT).

Materials and methods: The clinical data of 74 children with FHWT from January 2010 to January 2022 were retrospectively analyzed. The clinicopathologic characteristics, preoperative laboratory parameter results, including D-dimer level, and follow-up data were collected. Based on the postoperative recovery status, the patients were divided into tumor-free survival and disease progression groups. The risk factors affecting disease progression in pediatric patients with WT and the impact of plasma D-dimer levels on overall survival (OS) were evaluated.

Results: Over a median follow-up of 33 months (range: 2-145 months), 56 patients survived without progression. Relapses and metastases occurred in 18 patients, of which four survived and 14 died. Higher preoperative plasma D-dimer levels (>0.865) (Odds ratio [OR] = 7.240, 95% confidence interval (CI) = 1.276-33.272, P = 0.011) and tumor rupture (OR = 19.984, 95% CI = 1.182-338.013, P = 0.038) were independent prognostic factors for disease progression. Additionally, patients with elevated D-dimer levels demonstrated a worse 5-year OS than those with low D-dimer levels (Hazard ratio (HR) =4.278, 95% CI = 1.074-17.035, P = 0.039).

Conclusions: Elevated D-dimer levels are a prognostic factor for a poorer outcome in pediatric patients with WT and are expected to become a clinical biomarker for predicting the prognosis of WT.

Background and purpose: Radiation therapy is a crucial treatment for nonsmall cell lung cancer (NSCLC), but its effectiveness is limited by the resistance of tumor cells to radiation. This study aimed to evaluate the effect of epicatechin (EC) on radiosensitivity in NSCLC and to determine its relationships with matrix metalloproteinase (MMP)-9.

Methods: MMP-9 expression was detected by Western blotting, and the expression of the DNA damage marker protein was detected by immunofluorescence. Cell viability was assessed using the CCK-8 assay, and cell proliferation was evaluated using the clonogenesis assay. Flow cytometry was used to determine the cell apoptosis, whereas cell migration and invasion were detected using the transwell assays. The cells were treated with ionizing radiation (IR) and EC to verify the sensitizing effect of EC on radiation therapy.

Results: MMP-9 expression was elevated in the NSCLC cells and tissues. DNA damage and cell apoptosis were increased, whereas cell vigor, proliferation, migration, and invasion were significantly decreased after IR. MMP-9 knockdown strengthened the impact of IR on the biological behaviors of the cells. EC + IR had the best effect on promoting DNA damage and the biological behaviors of the NSCLC cells; alternatively, the overexpression of MMP-9 weakened the role of EC.

Conclusions: This study shows that EC can downregulate MMP-9 expression, promote DNA damage, reduce cell viability, proliferation, migration, and invasion, and facilitate cell apoptosis, thus, showing potential as a radiosensitizer for NSCLC.

Abstract: Complications of head and neck cancers and their treatment can lead to dysphagia. Two fifty-seven-year-old male cases, one with laryngeal cancer and one with tongue cancer, were included in the study. After 16 weeks of swallowing rehabilitation, positive changes were observed in the physical parameters, quality of life, and nutritional status of the patients. In conclusion, patients with head and neck cancer should be evaluated by physiotherapists for dysphagia. The participation and motivation of the patients in the rehabilitation program are highly effective in the outcome of the treatment.