Journal of Buon最新文献

Purpose: To detect the expression characteristic of circ_0006948 in bladder cancer (BC), and to analyze its relationship with pathological parameters and prognosis in BC patients. In addition, molecular mechanisms of circ_0006948 on driving the malignant progression of BC by activating epithelial-mesenchymal transition (EMT) was explored.

Methods: Circ_0006948 levels in 72 BC and paracancerous tissues were detected, and their relationship with pathological parameters and prognosis in BC patients was analyzed by chi-square test. After establishing circ_0006948 knockdown model in 253j and T24 cells, phenotype changes were assessed by cell counting kit-8 (CCK-8), transwell and wound healing assay. Regulatory effects of circ_0006948 on EMT-associated gene expressions in BC cells were determined by Western blot. Finally, the interaction between circ_0006948 and N-cadherin was evaluated by rescue experiments.

Results: Circ_0006948 was upregulated in BC tissues and cell lines. High level of circ_0006948 indicated advanced tumor stage, high rates of lymph node metastasis and distant metastasis, and poor prognosis in BC. Knockdown of circ_0006948 reduced proliferative and metastatic abilities in BC cells. The key protein in the EMT signaling E-cadherin was upregulated by knockdown of circ_0006948 in BC cells, while N-cadherin, Vimentin, β-catenin and MMP-9 were downregulated. The interaction between circ_0006948 and N-cadherin was identified, and they were co-responsible for the malignant development of BC.

Conclusions: Circ_0006948 is upregulated in BC samples, and it is closely linked to tumor stage, metastasis and prognosis in BC patients. It drives proliferative and metastatic abilities in BC cells by activating EMT.

Purpose: Recently, neoadjuvant treatment approach has gained importance in locally advanced HER-2 positive breast cancer. Adding pertuzumab increases pathological complete response (pCR). In this study, we aimed to examine the clinicopathologic features that predict the pCR in patients receiving neoadjuvant pertuzumab, trastuzumab, and chemotherapy in locally advanced HER2 positive breast cancer.

Methods: Locally advanced HER2 positive breast cancer patients who were followed up in 4 different oncology centers and received 4 cycles of pertuzumab, trastuzumab and taxane were retrospectively evaluated. A total of 58 (92%) patients received anthracycline chemotherapy before combination of dual her-2 blockade and taxanes. Fisher's and chi-square tests were used for nominal variables and numeric data analyses.

Results: A total of 63 female patients were included in the study. Their median age was 46 years (21-75) and 40 (63.5%) patients were premenopausal. Median tumor size was 25 mm (2-70) and there were 22 (34.9%) patients with Stage 3a. pCR was 66% and 75% in the whole group and in the hormone negative group, respectively. Statistically significant increase was found in pCR in patients with grade 3 tumors and cerbB2 with 3+ immunohistochemical staining. No relationship was found between pCR and age at diagnosis, menopausal status, tumor infiltrating lymphocyte, dose-dense anthracycline, Ki67≥40, body mass index (BMI) ≥ 30 kg/m2 and accompanying DCIS.

Conclusion: Four cycles of pertuzumab, trastuzumab and taxane after neoadjuvant anthracycline for locally advanced HER2 breast cancer are associated with increased pCR in patients with grade 3 tumors and high cerbB2 expression.

Purpose: To elucidate the diagnostic and prognostic potentials of lncRNA AK126393 in bladder cancer.

Methods: The expression levels of AK126393 in 60 matched bladder cancer tissues and paracancerous tissues were determined. In addition, AK126393 level in bladder cancer patients with different tumor staging (stage I-II and stage III-IV) was detected as well. Receiver operating characteristic (ROC) was introduced for assessing the diagnostic potential of AK126393 in bladder cancer. Based on the cut-off value of AK126393 in the enrolled 60 bladder cancer patients, they were assigned into high and low expression groups, respectively. Correlation between AK126393 level and pathological indexes of bladder cancer patients was analyzed by chi-square test. By collecting 5-year follow-up data, Kaplan-Meier method was conducted to evaluate survival influenced by AK126393. Moreover, Cox regression model was applied for analyzing potential factors affecting the prognosis of bladder cancer patients.

Results: AK126393 was downregulated in bladder cancer tissues than in paracancerous ones. Its level remained lower in bladder cancer patients with stage III-IV relative to those with stage I-II. ROC illustrated the diagnostic potential of AK126393 in bladder cancer (AUC=0.8647, diagnosis threshold=2.03, sensitivity=76.7%, specificity=96.7%, Youden index=0.734). Besides, lower level of AK126393 was observed in bladder cancer patients with stage III-IV, lymph node metastasis or high-level differentiation. Kaplan-Meier curves demonstrated worse prognosis in bladder cancer patients expressing low level of AK126393. Cox regression analysis showed that AK126393 level, TNM staging, lymph node metastasis and tumor differentiation were independent risk factors influencing the prognosis of bladder cancer.

Conclusions: AK126393 is downregulated in bladder cancer and closely linked to high rate of metastasis, advanced stage and poor prognosis. AK126393 may serve as diagnostic and prognostic hallmark in bladder cancer.

Purpose: To explore the clinical efficacy and safety of neoadjuvant chemotherapy (NACT) combined with minimally invasive laparoscopic cytoreductive surgery in the treatment of patients with advanced ovarian cancer (AOC).

Methods: The clinical data of 116 patients with AOC were divided into NACT group (NACT combined with laparoscopic cytoreductive surgery, n=58) and control group (cytoreductive surgery alone, n=58). The short-term efficacy, surgery-related indexes, incidence of adverse reactions, and changes in levels of serum human epididymis protein 4 (HE4), vascular endothelial growth factor (VEGF) and carbohydrate antigen 125 (CA125) before and after treatment were compared between the two groups. The survival status of patients after treatment was recorded.

Results: The operation time, intraoperative blood loss, ascites volume, postoperative ventilation time, and average postoperative length of hospitalization in NACT group were all significantly shorter and less than those in the control group. The optimal cytoreduction rate in NACT group was far higher than that in the control group. The overall response rate in NACT group was obviously higher than that in the control group. After treatment, the levels of serum HE4, VEGF and CA125 greatly declined in the two groups compared with those before treatment, while they were obviously lower in the NACT group than those in the control group. The follow-up results revealed that the median overall survival (OS) was 31.1 months and 28.9 months, and the 3-year OS rate was 43.1% (25/58) and 31.0% (18/58), respectively, in the NACT group and control group.

Conclusion: NACT can significantly shorten the duration of cytoreductive surgery of AOC, reduce intraoperative blood loss, accelerate postoperative recovery, raise the optimal cytoreduction rate, and enhance the clinical efficacy, without greatly improving the survival of patients.

Purpose: In this study we compared the clinical and dosimetric outcomes of simultaneous integrated boost intensity modulated radiation therapy (SIB-IMRT) and sequential boost (SEQ-IMRT) techniques in preoperative rectal cancer (RC).

Methods: We analyzed 67 preoperative RC patients who received RT with Helical TomoTherapy (HT) device. 27 of patients were irradiated with SEQ-IMRT and 40 were irradiated with SIB-IMRT technique. The primary tumor and involved lymph nodes were simultaneously treated using the SIB-IMRT (50.4Gy/25 fraction). SEQ-IMRT delivered 45Gy/25 fractions to primary tumor (involved lymph nodes) and 5.4Gy/3fractions to boost volume. Dosimetric parameters, acute toxicities and 5year overal survival (OS), disease-free survival (DFS) and local control (LC) between two techniques were compared.

Results: In the SIB-IMRT group planning treatment volume (PTV) homogeneity index (HI) was better than in the SEQ-IMRT group. PTV doses of Dmax for SEQ-IMRT group were higher than the SIB-IMRT group (p<0.05). The bladder doses of Dmax in the SIB-IMRT group were higher than SEQ-IMRT group (p<0.005). There were no significant differences in other dosimetric parameters between groups. Median follow up was 29.06 months (range 4.3-92.07) and 36.46 months (range 8.7-79.6) in the SIB-IMRT and SEQ-IMRT groups, respectively. No significant difference was found between the SIB-IMRT and SEQ-IMRT groups in acute toxicity (p=0,909). Five-year OS, DFS and LC were 73.15%, 66.75% and 75.55% in SIB-IMRT group and 65.19%, 55.53% and 60.22% in the SEQ-IMRT group, respectively. No statically significant differences were found between the two groups regarding 5-year OS, DFS and LC.

Conclusions: SIB-IMRT and SEQ-IMRT tecniques provided similar outcomes for dosimetric and clinical results for RC in HT treatment.

Purpose: To explore the safety and effectiveness of paclitaxel and tegafur, gimeracil and oteracil potassium (S-1) combined with apatinib in the conversion therapy for unresectable advanced gastric cancer.

Methods: A total of 66 patients with advanced gastric cancer received treatment with paclitaxel + S-1 + apatinib. Patients evaluated as resectable advanced gastric cancer by the multiple disciplinary team (MDT) underwent the surgery. The clinical efficacy and adverse reactions of the patients receiving conversion therapy and the related indicators of those undergoing operation were recorded. Later, the survival of the patients was compared between successful conversion therapy (surgery) group and unsuccessful conversion therapy (non-surgery) group.

Results: All the 66 patients completed 3-7 cycles of chemotherapy, with a median of 5 cycles, and the objective response rate (ORR) after conversion therapy was 71.2% (47/66). Among them, 48 patients received operation for (225.2±37.3) min on average, with the intraoperative blood loss of (168.2±40.9) mL and (50.9±12.3) intraoperative dissected lymph nodes, including 34 (70.8%) cases of R0 resection. According to the postoperative pathological tumor regression grading (TRG), there were 2 (4.2%) TRG 0 cases, 10 (20.8%) TRG 1 cases, 28 (58.3%) TRG 2 cases and 8 (16.7%) TRG 3 cases. The follow-up results revealed that the one-year overall survival (OS) of the patients was 93.8% (45/48) in successful conversion therapy (surgery) group and 61.1% (11/18) in unsuccessful conversion therapy (non-surgery) group.

Conclusion: Paclitaxel and S-1 combined with apatinib can achieve a higher R0 resection rate, and improve the survival rate of patients with successful conversion therapy, showing high safety and efficacy.

Purpose: Sorafenib combined with transcatheter arterial chemoembolization (TACE) is one of the common methods in the clinical treatment of advanced hepatocellular carcinoma (HCC), but its efficacy and safety are still controversial. Therefore, we used meta-analysis to evaluate the efficacy and safety of sorafenib combined with TACE in the treatment of advanced HCC.

Methods: Up to March 14, 2021, the databases of PubMed, EMBASE, Cochrane Library, CNKI and Wanfang were searched, and the randomized controlled clinical trials (RCTs) of sorafenib combined with TACE in the treatment of primary HCC were included. Two researchers independently screened the literature, extracted data and evaluated the quality according to the inclusion and exclusion criteria. Revman5.4 software was used for meta-analysis.

Results: A total of 3076 patients were included in 23 studies, including sorafenib combined with TACE group (n=1542) and TACE group (n=1534). The results of meta-analysis showed that sorafenib combined with TACE could increase the objective response rate (ORR) (RR=1.35, 95%CI: 1.24-1.48, p<0.00001), disease control rate (DCR) (RR=1.19, 95%CI: 1.11-1.28, p<0.00001), prolong the time of disease progression (TTP) (HR=0.80, 95%CI: 0.70-0.92, p=0.001), reduce the expression level of alpha-fetoprotein (AFP) (SMD=2.01, 95%CI: 1.27-2.75, p<0.00001) and vascular endothelial growth factor (VEGF) (SMD=2.62, 95% CI: 1.35-3.90, p<0.0001) in serum. However, the overall survival (OS) was not prolonged (HR=0.86, 95%CI: 0.73-1.02, p=0.09). The incidences of fatigue, diarrhea, elevated bilirubin, skin reaction of hands and feet, rash, hypertension and oral mucosal inflammation in sorafenib combined with TACE group were higher than those in TACE group (p<0.05).

Conclusion: Sorafenib combined with TACE has some clinical benefits compared with TACE alone, but it does not seem to prolong the OS of patients with HCC, and the incidence of adverse reactions is higher, so more high-quality RCTs are needed to further study the efficacy of the combination regimen.

Purpose: To determine the severity of the effects on VMAT dose calculations caused by varying statistical uncertainties (SU) per control point in a Monte Carlo based treatment planning system (TPS) and to assess the impact of the uncertainty during dose volume histogram (DVH) evaluation.

Methods: For this study, 13 archived patient plans were selected for recalculation. Treatment sites included prostate, lung, and head and neck. These plans were each recalculated five times with varying uncertainty levels using Elekta's Monaco Version 5.11.00 Monte Carlo Gold Standard XVMC dose calculation algorithm. The statistical uncertainty per control point ranged from 2 to 10% at intervals of 2%, while the grid spacing was set at 3 mm for all calculations. Indices defined by the RTOG describing conformity, coverage, and homogeneity were recorded for each recalculation.

Results: For all indices tested, one-way ANOVA tests failed to reject the null hypothesis that there is no significant difference between SU levels (p>0.05). Using the Bland-Altman analysis method, it was determined that we can expect the indices (with the exception of CIRTOG) to be within 1% of the lowest uncertainty calculation when calculating at 4% SU per control point. Beyond that, we can expect the indices to be within 3% of the lowest uncertainty calculation.

Conclusion: Increasing the SU per control point exponentially decreased the amount of time required for dose calculations, while creating minimal observable differences in DVHs and isodose lines.