Lili Qiao

Advanced research on vasculogenic mimicry in cancer

Vasculogenic mimicry (VM) is a brand‐new tumour vascular paradigm independent of angiogenesis that describes the specific capacity of aggressive cancer cells to form vessel‐like networks that provide adequate blood supply for tumour growth. A variety of molecule mechanisms and signal pathways participate in VM induction. Additionally, cancer stem cell and epithelial‐mesenchymal transitions are also shown to be implicated in VM formation. As a unique perfusion way, VM is associated with tumour invasion, metastasis and poor cancer patient prognosis. Due to VMs important effects on tumour progression, more VM‐related strategies are being utilized for anticancer treatment. Here, with regard to the above aspects, we make a review of advanced research on VM in cancer.

The relationship between vasculogenic mimicry and epithelial-mesenchymal transitions

Vasculogenic mimicry (VM) is a vascular‐like structure which can mimic the embryonic vascular network pattern to nourish the tumour tissue. As a unique perfusion way, VM is correlated with tumour progression, invasion, metastasis and lower 5‐year survival rate. Notably, epithelial‐mesenchymal transition (EMT) regulators and EMT‐related transcription factors are highly up‐regulated in VM‐forming tumour cells, which demonstrated that EMT may play a crucial role in VM formation. Therefore, the up‐regulation of EMT‐associated adhesion molecules and other factors can also make a contribution in VM‐forming process. Depending on these discoveries, VM and EMT can be utilized as therapeutic target strategies for anticancer therapy. The purpose of this article is to explore the advance research in the relationship of EMT and VM and their corresponding mechanisms in tumorigenesis effect.

Pulmonary toxicity generated from radiotherapeutic treatment of thoracic malignancies (Review)

Radiation-induced lung injury (RILI) remains a major obstacle for thoracic radiotherapy for the treatment of lung cancer, esophageal cancer and lymphoma. It is the principal dose-limiting complication, and can markedly impair the therapeutic ratio as well as a patients quality of life. The current review presents the relevant concepts associated with RILI, including the pathogenic mechanisms and the potential treatment strategies, so as to achieve a general understanding of this issue. RILI comprises an acute radiation pneumonitis phase and subsequent late lung fibrosis. The established assessment criteria are clinical manifestations, imaging changes and the necessity for medical assistance. Risk factors are also considered in order to optimize treatment planning. Due to the underlying molecular mechanisms of RILI, the present review also discusses several targeted pharmacological approaches for its treatment, as well as corticosteroid therapy.

Gene silencing of galectin-3 changes the biological behavior of Eca109 human esophageal cancer cells.

Galectin-3 is a multifunctional β-galactoside-binding lectin that is involved in multiple biological functions which are upregulated in malignancies, including cell growth, adhesion, proliferation, progression and metastasis, as well as apoptosis. A previous study has confirmed the roles of galecin-3 overexpression in the biological behavior of Eca109 human esophageal cancer (EC) cells. In the present study, small interfering (si)RNA-mediated galectin-3 silencing was performed to analyze the effects of decreased galectin-3 expression on the biological behavior of EC cells. Western blot and quantitative polymerase chain reaction analyses were utilized to confirm galectin-3 knockdown at the protein and mRNA level (P<0.05 vs. siRNA-control and untransfected groups). Cell proliferation was assessed using the Cell Counting Kit-8 assay. At 72 and 96 h after transfection, the proliferation of Eca109 cells in the siRNA-Gal-3 group was decreased compared with that in the siRNA-Control and untransfected groups (P<0.001 and P=0.004, respectively). Furthermore, Transwell assays demonstrated that inhibition of galecin-3 significantly reduced the migration and invasion of Eca109 cells compared with that in the other groups (P<0.05). Finally, apoptosis of Eca109 cells was detected using Annexin V/7-amino-actinomycin double-staining and flow cytometric analysis. Galectin-3 knockdown significantly enhanced the apoptotic rate of Eca109 cells compared with that in the siRNA-control and untreated groups (P=0.031 and P=0.047, respectively). In conclusion, following successful knockdown of galecin-3 expression in Eca109 cells, the cell proliferation, migration and invasion were reduced, while the apoptosis was enhanced, which indicates that galectin silencing may represent a therapeutic strategy for EC.

Effect of galectin-3 on the behavior of Eca‑109 human esophageal cancer cells.

Galectin-3, a β-galactoside-binding lectin, is a cell adhesion molecule involved in the regulation of tumor progression. However, the importance of galectin-3 in Eca-109 human esophageal cancer cells has not yet been elucidated. In the present study, a lentiviral vector was designed for overexpression of galectin-3 in Eca-109 cells following plasmid-mediated transfection (Eca-109/Gal-3 cells). A negative lentiviral vector was introduced into Eca-109 cells as a control (Eca-109/Neo cells). Western blot and reverse transcription-polymerase chain reaction analyses were used to measure the expression levels of galectin-3 protein and mRNA. The proliferation of Eca-109 cells was measured by a cell counting kit-8 assay. Eca-109 cell apoptosis was determined by Annexin V/7-amino-actinomycin double-staining. The migration and invasion capacity of Eca-109 cells was determined by a Transwell assay. A total of >98% Eca-109 cells were transfected with the lentiviral vector harboring galectin-3, and galectin-3 expression was detected in Eca-109 cells, Eca-109/Gal-3 cells and Eca-109/Neo cells. Compared with non-transfected and negative control Eca-109 cells, proliferation was increased significantly in the Eca-109/Gal-3 cells (P<0.05). Galectin-3 also significantly reduced Eca-109 cell apoptosis, compared with the two control groups (P=0.007 and P=0.04, respectively). Transwell migration and invasion assays revealed that significantly greater numbers of Eca-109/Gal-3 cells crossed the artificial basement membrane (55.4±3.9) compared with either the non-transfected or negative control Eca-109 cells (30.6±1.5 and 29±2.6 respectively, P<0.05). In conclusion, galectin-3 expression was significantly increased in transfected Eca-109 esophageal cancer cells, resulting in enhanced proliferation, migration and invasion, as well as reduced apoptosis. These data indicate that galectin-3 may be a potential molecular target in the treatment of esophageal cancer.

A comparative dosimetric study of volumetric-modulated arc therapy vs. fixed field intensity-modulated radiotherapy in postoperative irradiation of stage IB-IIA high-risk cervical cancer

The aim of the present study was to compare the dosimetry features of volumetric-modulated arc therapy (VMAT) and fixed field intensity-modulated radiotherapy (f-IMRT) in postoperative irradiation of stage IB-IIA high-risk cervical cancer. Fifteen patients exhibiting stage IB-IIA high-risk cervical cancer, who had been treated with postoperative adjuvant concurrent radiochemotherapy, were selected. The clinical target volume (CTV) and organs at risk (OARs) were delineated according to contrast computed tomography images. The planning target volume (PTV) was subsequently produced by using 1 cm uniform expansion of the CTV. The treatment plans were intended to deliver 50 Gy in 25 fractions. The OARs that were contoured included the bladder, rectum, small bowel and femoral heads. Dose volume histograms were used to evaluate the dose distribution in the PTV and OARs. VMAT and f-IMRT treatment plans resulted in similar dose coverage of the PTV. VMAT was superior to f-IMRT in conformity (P<0.05), and resulted in a reduction of OARs irradiated at high dose levels (V40 and V50) compared with f-IMRT (P<0.05), particularly for the bladder. However, the doses of low levels (V10 and V20) delivered to OARs with f-IMRT were slightly reduced compared with VMAT (P<0.05). For ambilateral femoral heads, VMAT demonstrated improved sparing compared with f-IMRT, with regard to D5 (P<0.05). Furthermore, VMAT treatment plans revealed a significant reduction in monitor units (MU) and treatment time. VMAT techniques exhibited similar PTV coverage compared with f-IMRT. At doses of high levels delivered to OARs, VMAT demonstrated improved sparing compared with f-IMRT, particularly for the bladder, while significantly reducing treatment time and MU number.

Docetaxel, capecitabine and concurrent radiotherapy for gastric cancer patients with postoperative locoregional recurrence.

Aims and background This study aimed to assess the efficacy of concurrent chemoradiotherapy (CCRT) with docetaxel and capecitabine versus docetaxel and capecitabine chemotherapy for gastric cancer patients with postoperative locoregional recurrence. Methods From 2008 to 2011, 81 patients with locoregional recurrence after curative resection of gastric cancer were enrolled. Thirty-nine (CCRT group) received involved-field radiotherapy with oral capecitabine (twice daily, 5 days/week) and intravenous infusion of docetaxel (once weekly). The remaining 42 patients (chemotherapy group) were treated with oral capecitabine (twice daily, days 1-14) followed by intravenous infusion of docetaxel (days 1 and 8). The overall response rate, overall symptom control rate, toxicity or adverse reactions, and overall survival (OS) were compared. Results The overall response rate (CR+PR) was significantly higher in the CCRT group (79.5%) than the chemotherapy group (54.8%). In CCRT individuals, the control rates for bleeding, pain, and dysphagia/obstruction were 87.5%, 75%, and 71.4%, respectively, versus 63.2%, 50%, and 28.6% in the chemotherapy group. CCRT patients had a better symptom control rate than the chemotherapy group (52.5% vs. 80%). Adverse reactions were non-significantly more severe in CCRT patients. Finally, median OS was longer in the CCRT vs. chemotherapy group (14.2 vs. 6.4 months). Conclusions Involved-field radiotherapy with docetaxel and capecitabine was effective and well tolerated. These findings provide further insight into the role of CCRT in gastric cancer. However, this was not a randomized controlled study and the number of patients was relatively small, suggesting that cautious interpretation of cumulative estimates is warranted.

Concurrent involved-field radiotherapy and XELOX in gastric cancer patients with postoperative oligometastatic recurrence.

PURPOSE The aim of this study was to retrospectively observe gastric adenocarcinoma patients with postoperative oligometastatic recurrence and investigated the effects of concurrent involved-field radiotherapy (RT) and XELOX on progression-free survival (PFS). PATIENTS AND METHODS From 2008 to 2011, 246 patients underwent curative resection of gastric carcinoma was enrolled. A retrospective review was performed on 34 patients with distant recurrence. Among them, 19 patients were oligometastases patients, where 13 patients received involved-field RT with a dose of 40-60 Gy by an intensity-modulated RT technique and concurrent XELOX chemotherapy, four patients were treated with XELOX chemotherapy alone (oxaliplatin 130 mg/m2, capecitabine 1000 mg/m2, twice daily, 3 week each cycle), and two patients with only brain metastasis were not included in the analysis. RESULTS The median PFS was 11 months in the 13 oligometastatic patients who received concurrent involved-field RT and XELOX. The oligometastatic patients receiving concurrent radiochemotherapy trended toward a better median PFS when compared with those receiving chemotherapy alone. CONCLUSIONS For patients with postoperative oligometastatic recurrence, concurrent involved-field RT and XELOX showed better responses and was a choice for first-line treatment.

Effect of galectin-3 on vasculogenic mimicry in esophageal cancer cells

Galectin-3 is a multifunctional β-galactoside binding lectin associated with tumor progression. Previous studies confirmed the roles of galecin-3 overexpression and silencing in the biological behavior of Eca109 human esophageal cancer (EC) cells; galectin-3 may serve a critical role in the vasculogenic mimicry (VM) of tumors. Therefore, the present study examined the effects of galectin-3 knockdown using lentivirus vectors on VM in EC. Eca109 and EC9706 EC cells were transfected with a lentiviral vector to inhibit galectin-3 expression, or a control vector. VM formation in vitro was evaluated via 3D culture. Western blotting was used to detect the expression level of galectin-3 following galectin-3 silencing and the expression levels of VE-cadherin, ephrin type-A receptor 2 precursor (EphA2) and matrix metalloproteinase 2 (MMP-2). According to the results of western blot analysis, the Eca109/galectin-3 and EC9706/galectin-3 cells exhibited effective galectin-3 silencing (P<0.05). Eca109 and EC9706 cells formed typical tubular networks; the number of tubular networks markedly decreased subsequent to galectin-3 knockdown. The expression levels of MMP-2 and EphA2 proteins in Eca109/galectin-3 and EC9706/galectin-3 cells were lower compared with those in Eca109, EC9706, and control vector-transfected Eca109 and EC9706 cells (P<0.05); however, there was no significant difference in the expression of VE-cadherin proteins. These results indicated that galectin-3 may modulate VM in EC by regulating the EphA2 expression level, which affects VM formation via MMP-2.