BMC Cancer最新文献

Objective: The aim of this study was to investigate the mechanism by which quercetin (Que) affects apoptosis and autophagy in pediatric acute myeloid leukaemia (AML) cells by inhibiting the activation of the PI3K/AKT signaling pathway through the regulation of the miR-224-3p/PTEN axis.

Methods: Blood samples were collected from AML children and healthy volunteers. miR-224-3p and PTEN expression levels were measured. AML cells were pre-treated with Que. MiR-224-3p and PTEN expression levels in AML cells were altered via plasmid transfection. After intervention, PI3K/AKT phosphorylation, AML cell proliferation and apoptosis, concentrations of interleukin-1 β (IL-1β) and tumor necrosis factor-α (TNF-α) in AML cell culture supernatant, apoptosis-related genes Bax and Bcl-2, and autophagy markers LC3-I and LC3-II were tested. The targeting relationship between miR-224-3p and PTEN was identified.

Results: MiR-224-3p expression was elevated in AML children, while PTEN was decreased. Que was available to accelerate AML cell apoptosis and restrain its autophagy. Que inhibited miR-224-3p expression and promoted PTEN expression. Upregulating miR-224-3p or downregulating PTEN weakened the effect of Que on AML cell apoptosis and autophagy. MiR-224-3p negatively modulated PTEN expression. Up-regulation of PTEN reversed the effects of up-regulation of miR-224-3p on apoptosis and autophagy in AML cells. In addition, Que inhibited PI3K/AKT signaling pathway activation, while up-regulation of miR-224-3p or down-regulation of PTEN could attenuate the inhibitory effect of Que on PI3K/AKT signaling pathway. Moreover, up-regulation of PTEN reversed the effect of up-regulation of miR-224-3p on the PI3K/AKT signaling pathway.

Conclusion: Que affects apoptosis and autophagy in pediatric AML cells by inhibiting PI3K/AKT signaling pathway activation through regulation of miR-224-3p/PTEN axis.

Objectives: This study aimed to assess the effectiveness and safety of conventional transarterial chemoembolization (c-TACE) followed by irreversible electroporation (IRE) for the treatment of hepatocellular carcinoma (HCC).

Methods: From January 2019 to September 2019, 12 patients with HCC who received c-TACE followed by IRE comprised the study group. The control group comprised 15 patients who received c-TACE followed by radiofrequency ablation (RFA). The 1-month, 3-month, 6-month, and 12-month local control rates and median progression-free survival (PFS) were compared between the two groups. Additionally, postoperative complications were assessed.

Results: The study group comprised 12 patients (median age: 57.5 years; range: 46-68 years), while the control group consisted of 15 patients (median age: 56 years; range: 31-69 years). Local control rates at 1, 3, 6, and 12 months were 91.7%, 91.7%, 83.3%, and 33.3%, respectively, for the study group, and 73.3%, 66.7%, 66.7%, and 20.0% for the control group. Statistical analysis revealed no significant differences between the two groups. In terms of survival, 9 patients (75%) in the study group and 11 patients (73.3%) in the control group were still alive at the last follow-up. The median PFS was 8 months in the study group and 7 months in the control group, with no significant difference between the two groups (p = 0.96). Notably, no severe surgery-related side effects were observed in either group, and also no significant differences were found in postoperative complications between the two groups (p = 0.64).

Conclusions: The long-term therapeutic outcomes of c-TACE followed by IRE were found to be similar to those of c-TACE followed by RFA in the study. The research suggests that c-TACE followed by IRE offered an effective and safe treatment option for HCC.

Background: Triglyceride-Glucose (TyG) index, a novel surrogate marker for insulin resistance, has been linked to the risk of various cancers, such as breast and colorectal cancers. However, the relationship between the TyG index and its related indices with the risk of pancreatic cancer(PC) remains unclear.

Methods: This large-scale, prospective cohort study utilized data from the UK Biobank, involving 428,152 participants who were free of PC at baseline. The primary outcome was incident PC. To evaluate the relationships between TyG-related indices and PC onset, covariate-adjusted Cox proportional hazards regression models and restricted cubic spline (RCS) analyses were employed. Additionally, we explored the relationships between TyG-related indices and incident PC within subgroups defined by age, gender, diabetes, hypertension, pancreatitis history, smoking status, and drinking status. Sensitivity analyses were conducted to confirm the robustness of our findings.

Results: Over an average follow-up period of 13.8 years, a total of 1,759 PC cases occurred. The risk of developing PC increased with higher levels of TyG-related indices. RCS curves illustrated a linear positive relationship between TyG-related indices and incident PC. Subgroup analyses indicated that the relationships between the TyG index, TyG-waist circumference, and TyG-waist-to-hip ratio and PC risk were more pronounced in participants without hypertension, without pancreatitis history, and those with drinking history (P for interaction < 0.05). Sensitivity analyses further validated the robustness of these findings.

Conclusions: TyG-related indices were independently related with a higher risk of incident PC, highlighting the importance of incorporating these indices into PC risk assessment tools and provides strong support for constructing a more comprehensive PC risk assessment framework.

Background: Colorectal cancer with liver metastasis affects both men and women. However, therapeutic strategies and long-term outcomes could be influenced by patients' sex, due to variations in tumour biology, lifestyle, and dietary habits. By conducting a comprehensive comparative analysis, this study aims to detail differences in tumour characteristics, postoperative complications, recurrence rates, and survival outcomes between sexes.

Methods: Single-centre retrospective analysis between 2010 and 2022 of all patients undergoing liver surgery for colorectal liver metastases (CRLM) at the Department of Surgery, Charité- Universitätsmedizin Berlin. Patients were stratified by sex. Statistical analysis was performed using RV4.2.

Results: We analysed 642 patients who underwent hepatic resections for CRLM. Baseline patient characteristics were comparable between sexes: However, significant differences (p < 0.001) were noted in body mass index (BMI), with females exhibiting lower BMIs (median BMI in females: 23.7 kg/m² vs. males: 26.5 kg/m²). Primary tumour locations varied significantly (p = 0.008), with females presenting more sigmoid colon tumours (37%), while males predominantly had rectal tumours (35%). RAS mutation rates were higher in females (54%) than males (34%, p = 0.005). A higher prevalence of bilobar metastases were evident in men (62%, p = 0.011), yet surgical techniques and complications showed comparable distributions. The time for resection was longer in males (median 304 min vs. 290 min in females); however, conversion to open surgery took place more often in females (5.2% vs. 2.3% in males). Postoperative complications and survival rates showed no significant differences by patients' sex.

Conclusion: Distinct sex-related patterns in tumour characteristics and postoperative outcomes in patients with CRLM were observed, emphasizing the need for further investigations to understand and address gender-based disparities for more personalized clinical management in the future.

Trial registration: This research was conducted with ethical approval from the relevant institutional review board Ethikkommission der Charité- Universitätsmedizin Berlin' (reference numbers EA2/006/16 and EA4/084/17). No other registration applied.

Background: There is no consensus regarding whether primary tumour resection (PTR) should be performed in non-small cell lung cancer (NSCLC) patients with unexpected pleural dissemination (PD) discovered at thoracotomy.

Materials and methods: Consecutive NSCLC patients with surgically confirmed PD were retrospectively enrolled from two high-volume centres between January 2016 and December 2023. Patients were divided into the primary tumour resection (PTR) and exploratory thoracotomy (ET) group. PTR included wedge resection, segmentectomy and lobectomy. Patients in the ET group received biopsy only. Propensity score matching (PSM) was used to reduce selection bias from confounding factors. Disease-specific survival (DSS) and progression-free survival (PFS) were analysed using the Kaplan‒Meier method, and comparisons were made using the log-rank test. Multivariate Cox regression analyses were performed to identify the independent prognostic factors.

Results: A total of 223 patients were identified: 167 (74.9%) in the PTR group and 56 (25.1%) in the ET group. The median follow-up time and median survival time (MST) were 39.0 months and 49.0 months, respectively. The MST for the ET and PTR groups were 44.0 and 60.0 months, respectively (HR 0.80, 95% CI 0.51-1.24; p = 0.3097). After PSM, there were no significant differences in terms of median disease-specific survival (DSS: 60.0 vs. 61.0 months, p = 0.3419) or progression-free survival (PFS: 30.0 vs. 47.0 months, p = 0.5471) between the two groups. Multivariate analysis revealed that smoking history and a tumour size ≥ 3 cm were independent risk factors for DSS and PFS, whereas targeted therapy was an independent protective factor.

Conclusion: Our results suggest that primary tumour resection does not improve long-term survival in NSCLC patients with unexpected PD discovered at thoracotomy. It is high time to re-evaluate the value of surgery for NSCLC patients with PD and avoid overtreatment, especially in the era of targeted therapy and immunotherapy.

Trial registration: ClinicalTrials.gov NCT06232967 (approval date: January 31, 2024).

Background: For patients with spine metastases, stereotactic radiosurgery (SRS) provides excellent local control and pain response. Despite increasing use of this treatment modality, there is no consensus on the optimal dose and fractionation of spine SRS for efficacy and toxicity. We have initiated a single-center phase III randomized trial that compares two dose regimens with similar biological equivalent dose (BED) to determine the isolated effect of SRS fractionation on local control.

Methods: Patients with one to three cervical, thoracic, or lumbar spine metastases spanning no more than two contiguous vertebral levels in need of radiation will be eligible for enrollment. Patients will be assigned 1:1 to receive either 22 Gy in 1 fraction or 28 Gy in 2 fractions. Biased coin randomization will be used to randomly assign patients while balancing the following stratifying variables between the two treatment arms at baseline: gastrointestinal histology (yes/no), paraspinal tissue extension (yes/no), epidural compression (low-/high-grade), and number of sites treated (one to three). The primary endpoint is one-year local control, defined per Spine Response Assessment in Neuro-Oncology (SPINO) criteria. The secondary endpoints include patient-reported health-related quality of life (HRQOL), pain associated with the treated site, vertebral compression fracture (VCF), and two-year local control. Patients will be followed for these outcomes at one to two weeks, one month, three months, and six months after treatment, and every six months thereafter until 24 months after treatment. While on the study, patients will receive routine co-interventions as clinically indicated.

Discussion: The studies published thus far comparing the single- and multi-fraction SRS are lacking long-term local control outcomes and are limited by selection bias as well as single-fraction arms with higher BED, which is correlated with improved local control. Our study will isolate the effect of fractionation by comparing one-year local control in patients treated with single- and multi-fraction SRS with equivalent BED. We anticipate that the results of this, as well as secondary endpoints such as pain response, adverse effects, and quality of life will provide much-needed guidance regarding optimal dose and fractionation for both maximizing local control and minimizing toxicity.

Clinical trial information: NCT#06173401. Approved by Stanford Scientific Review Committee (study ID: BRN0060) on 9/12/2023 and Stanford Institutional Review Board (study ID: IRB-72248) on 11/14/2023.

Purpose: Bladder volume variations during radiotherapy can significantly influence dose distribution to both target volumes and surrounding organs-at-risk (OARs). This study aims to assess the dosimetric impact of variable bladder volume on the clinical target volume (CTV) and OARs in cervical cancer patients undergoing MR-guided radiotherapy.

Method: A total of 27 cervical cancer patients were included in this study: 12 received radical radiotherapy, and 15 underwent postoperative radiotherapy. All patients were treated with the Elekta Unity MR-linac system. The dose requirement was 95-100% of the prescribed dose to the PTV(45 Gy/25 sessions/5 weeks). Daily images were acquired at the time of treatment using the MR-linac. For this study, MR images from the first three treatments of each patient were selected to contour the CTV and OAR (bladder, small bowel, rectum, right and left lateral femoral heads), and the treatment plan was recalculated using the Monaco TPS. The dosimetric effects of bladder volume changes on the CTV and OAR were analyzed by SPSS.

Result: Regarding the dosimetric effects on the CTV, in the postoperative radiotherapy group, D₉₈ and D₉₅ of the CTV decreased as the bladder filled. In contrast, for patients undergoing radical radiotherapy, the mean dose of the CTV increased from 5223.55 cGy to 5273.93 cGy as the bladder filled. For the dosimetric effects on the bladder, in the postoperative radiotherapy group, V₃₀ and V₂₀ of the bladder decreased as the bladder filled. In the radical radiotherapy group, the minimum dose of the bladder decreased with increasing bladder volume, but the maximum dose increased from 5347.68 cGy to 5581.63 cGy. For the rectum and small bowel, in the postoperative radiotherapy group, changes in bladder volume did not significantly affect the dose of the small bowel and rectum. However, in the radical radiotherapy group, the minimum and mean doses to the rectum and the D₂ of the small bowel decreased with bladder filling.

Conclusion: This study evaluated the dosimetric and volumetric impact of bladder filling on the Clinical Target Volume (CTV) and Organs at Risk (OAR) using daily magnetic resonance (MR) images from the MR-linac. The findings indicate that variations in bladder filling significantly affect dose distribution to both the CTV and OAR.

Background: To differentiate inoperable non-small cell lung cancer (NSCLC) subtypes by mono-exponential (MEM), bi-exponential (BEM), and stretched- exponential models (SEM) intravoxel incoherent motion (IVIM), and ¹⁸F-FDG PET parameters.

Materials and methods: A total of 106 cases of NSCLC were included in this analysis, of which 68 cases were adenocarcinoma (AC) and 38 cases were squamous cell carcinoma (SCC). MEM derived parameter ADC; BEM derived parameters D, D*, and f, SEM derived parameters α, DDC; and ¹⁸F-FDG PET derived parameters MTV, SUV_max, and TLG were recorded and compared. Area under the receiver operating characteristic curve (AUC) was performed for diagnostic efficacy.

Results: SUV_max, MTV and TLG were lower and ADC, f, D and DDC were higher in AC than in SCC (p all < 0.001), whereas D* and α were not significantly different (p = 0.824, 0.152). Logistic regression analysis showed that the stage, ADC, and TLG were independent predictors for identification of SCC and AC, and when combined they showed best diagnostic result (AUC, 0.906; sensitivity, 79.41%; specificity, 94.74%), which was higher than any single clinical factor (maximum diameter, sex smoking, stage, and CT readout; AUC = 0.725, 0.686, 0.707, 0.721, and 0.666, respectively), IVIM (ADC, f, and D; AUC = 0.772, 0.686, and 0.696, respectively) or ¹⁸F-FDG PET-derived variable (SUV_max, MTV, and TLG; AUC = 0.693, 0.712, and 0.774, respectively).

Conclusion: The stage, ADC, and TLG were independent predictors for differentiating subtypes of inoperable NSCLC, and when combined they showed optimal diagnostic performance and could be a superior imaging marker.