Efficacy and Safety of Radiotherapy Combined with Pyrotinib in the Treatment of HER2-Positive Breast Cancer with Brain Metastases.

Purpose: To explore the efficacy and safety of pyrotinib combined with different radiotherapy modes in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) patients with brain metastasis (BM). Patients and Methods: This study is a retrospective analysis of patients diagnosed with BM who underwent treatment with pyrotinib between November 2018 and April 2023. A total of 66 patients were administered radiotherapy in conjunction with pyrotinib (Group A), while 26 patients received pyrotinib as a standalone treatment (Group B). Within Group A, 18 patients underwent conventional fractionated radiotherapy (2Gy/F), while 48 patients received hyperfractionated radiotherapy (HFRT) (≥3Gy/F). The primary endpoints were intracranial progression-free survival (IC-PFS) and overall survival (OS). The secondary endpoints were objective response rate (ORR) and clinical benefit rate (CBR). Results: The ORR of Group A was 54.5% (36/66), while the ORR of Group B was 34.6% (9/26) (P= 0.047). The CBR of Group A was 89.4% (59/66) and that of Group B was 69.2% (18/26) (P= 0.041). The IC-PFS between Group A and Group B were 12 months and 8 months, respectively (P< 0.001), and the OS were 20 months and 16 months, respectively (P= 0.065). In Group A, the IC-PFS and OS between the conventional fractionation radiotherapy group and the HFRT group were 10 months and 12 months, respectively (P= 0.001) and 16 months and 24 months, respectively (P< 0.001). No serious adverse reactions were observed in Group A and Group B. Conclusion: For HER2-positive BC patients with BM, it is recommended to adopt the treatment mode of HFRT combined with pyrotinib, which can improve the local control and survival of patients.

Analysis of the prognostic factors of simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) in 220 cases of locally advanced squamous esophageal cancer: a retrospective cohort study.

Background: Esophageal cancer is one of the most common malignant tumors in China. Patients with advanced esophageal cancer often cannot be treated by surgery; in these cases, radiation therapy is usually applied. However, there are currently few studies on the clinical efficacy of this treatment method. The present study aimed to investigate and observe the clinical efficacy and related prognostic factors of simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) in esophageal squamous carcinoma, and to provide a reference for clinicians in radiotherapy (RT) departments. Methods: The clinical and follow-up data of 220 patients with esophageal squamous carcinoma admitted to the First Affiliated Hospital of Bengbu Medical College from January 2017 to December 2018 were retrospectively analyzed to assess the relevant prognostic factors and analyze their effects on 3-year overall survival (OS) and progression-free survival (PFS). The prognostic influencing factors were analyzed using the log-rank test and Cox multi-factor regression analysis. Results: The median follow-up time was 56.0 months (3.0 to 66.0 months). The 1-, 2-, and 3-year survival rates were 68.6%, 49.1%, and 36.3%, respectively, for the entire cohort, and the 1-, 2-, and 3-year PFS rates were 52.3%, 37.7%, and 25.5%, respectively. The median OS time was 24 months [95% confidence interval (CI): 19.16-28.84 months] and the median PFS time was 15 months (95% CI: 11.04-18.96 months). The multifactorial analysis results showed that gender, RT dose, treatment modality, absolute lymphocyte count (ALC), and gross tumor volume (GTV) were independent prognostic factors affecting 3-year OS (P<0.05); while gender, N-stage, RT dose, and GTV were independent prognostic factors affecting 3-year PFS (P<0.05). Conclusions: In the SIB-IMRT era, the survival of esophageal squamous cell carcinoma (ESCC) patients treated with radical (chemo)radiotherapy is relatively satisfactory. As a single-institution study on radiation therapy for esophageal cancer, this study yielded accurate results that help to provide references for subsequent related studies and clinicians' selection of treatment options.

Analysis of Immunotherapy Combined with Radiotherapy in Patients with Brain Metastasis of Driver Gene-Negative Non-Small-Cell Lung Cancer.

Purpose: To observe the remission rate and side effects of immunotherapy combined with radiotherapy in patients with brain metastasis of driver gene-negative non-small-cell lung cancer (NSCLC). Methods: 152 patients with NSCLC brain metastasis admitted to our hospital from January 2019 to December 2021 were selected as the research objects. Patients were divided into a single group (85 cases) and a combined group (67 cases) according to treatment methods. The therapeutic effects and side effects of the single group and combined group were compared. In addition, the patients who received immunotherapy combined with radiotherapy were divided into three subgroups: A, B, and C, and the therapeutic effects and side effects of different radiotherapy modes were compared among group A [whole brain radiotherapy (WBRT)], group B (WBRT combined with local radiotherapy) and group C (local radiotherapy). Results: The objective response rate (ORR) and disease control rate (DCR) in the combined group were higher than those in the single group (P < 0.05). The incidence of reactive capillary hyperplasia and immune-related pneumonia in the combined group were higher than that in the single group (P < 0.05). There was no significant difference in the incidence of other side effects between the two groups (P > 0.05). ORR and DCR in group B were higher than those in group A (P < 0.05). There was no significant difference in the incidence of side effects among the three groups (P > 0.05). Conclusion: Immunotherapy combined with radiotherapy is effective in patients with brain metastasis of driver gene-negative NSCLC, which can improve the disease control rate without increasing the side effects. In addition, WBRT combined with local push radiotherapy is effective and safe. Clinical Study Registration Number. The Clinical study registration number is K2019086.

Significance of intratreatment tumor volume change during chemoradiotherapy for potentially resectable thoracic esophageal squamous cell carcinoma.

OBJECTIVE: The purpose of this study was to investigate the clinical significance of tumor response assessment at a twentieth fraction of radiotherapy when predicting the survival of patients with potentially resectable esophageal squamous cell carcinoma (ESCC). METHODS: A total of 123 ESCC patients with clinical stages II to IVa were enrolled and analyzed. Gross tumor volume (GTV) of the esophagus (GTVe) and GTV of the metastatic lymph node (GTVnd) were manually contoured by at least 2 senior professional radiotherapists on the simulated computed tomography (CT) images in a process that followed the delineating rules for ESCC. RESULTS: The GTVe reduction ratio (RR) and GTVnd RR were calculated based on the evaluation of the tumor volume at a twentieth fraction of radiotherapy. Univariate analysis showed that GTVe and GTVnd before treatment, and GTVe RR and GTVnd RR at the twentieth fraction of radiotherapy were all significantly associated with complete clinical response (cCR) and overall survival (OS). The Kaplan-Meier method was used to estimate OS and locoregional recurrence-free survival (LRRFS). CONCLUSIONS: The GTVe RR ≥27.92% and GTVnd RR ≥21.49% at a twentieth fraction of radiotherapy are positive predictive factors of LRRFS, and according to multivariate analysis, only GTVe RR at the twentieth fraction of radiotherapy ≥27.92% is prognostic for a favorable OS.

Efficacy and Prognostic Analysis of 315 Stage I-IVa Esophageal Cancer Patients Treated with Simultaneous Integrated Boost-Intensity-Modulated Radiation Therapy.

PURPOSE: Use of simulated integrated boost-intensity-modulated radiation therapy (SIB-IMRT) is rarely reported in the treatment of esophageal cancer. This study was performed to observe the curative effect and prognostic factors associated with concurrent chemoradiotherapy for esophageal cancer using modern radiotherapy (RT) techniques. PATIENTS AND METHODS: In total, 315 patients with esophageal squamous cell carcinoma who received SIB-IMRT between 2015 and 2018 were included in this retrospective study. Median doses were planning target volume (PTV) 5400 cGy, 30 times (180cGy/fraction); planning gross tumor volume (PGTV) 6000 cGy, 30 times (200 cGy/fraction), once a day and 5 times a week. The entire period of RT was 6 weeks. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse reactions were observed. Univariate analysis was performed, and factors with P<0.15 were included in multivariate analysis. Cox regression analysis was used for multivariate prognostic analysis. P<0.05 was considered statistically significant. The incidence of adverse reactions under single chemotherapy concurrent chemoradiotherapy (sCCRT) and double chemotherapy concurrent chemoradiotherapy (dCCRT) was analyzed. RESULTS: Two-year, 3-year OS and PFS of the entire group were 49.5%, 40.2% and 40.3%, 34.0%, and the median survival time was 23.5 months. Univariate and multivariate analyses showed that T-stage (P=0.049), N-stage (P=0.024), clinical stage (P=0.041), short-term efficacy (P<0.001), and use of concurrent chemotherapy (P<0.001) were the influencing factors for OS. ORR was 87.6%. Adverse reactions were significantly increased with increasing chemotherapy dose. CONCLUSION: The adverse reactions of SIB-IMRT in esophageal cancer can be tolerated. T-stage, N-stage, clinical stage, short-term curative effect, and concurrent chemotherapy are the prognostic factors affecting survival. Because it has lower toxicity and is as effective as dCCRT, sCCRT should be considered in the management of esophageal cancer.

[Bioaccumulation and Translocation Characteristics of Heavy Metals in a Soil-Maize System in Reclaimed Land and Surrounding Areas of Typical Vanadium-Titanium Magnetite Tailings].

A total of 86 soil samples, 86 corn kernel samples, 50 tailings samples, and 33 ore rock samples were collected in reclaimed land and surrounding areas of typical vanadium-titanium magnetite tailings located in the Chengde Central Region and analyzed for 14 elements (P, Fe, Cu, Ni, Cd, Cr, Pb, Zn, Hg, Ti, Mn, and Mo) and speciation of heavy metals. This study investigated the bioaccumulation and translocation characteristics of heavy metals in a soil-maize system based on a descriptive statistical analysis, a geological accumulative index, bioconcentration factors, and a redundancy analysis. The results showed that the average accumulation index of surface soil followed an order of P > Cu > Fe2O3 > Cr > Ti > V > Ni > Mn > Cd > Zn > Mo > As > Pb > Hg, while the accumulation level of heavy metals was generally categorized as either no accumulation or moderate accumulation. Compared to China's soil environmental quality standard risk screening values (GB15618-2018), the over-standard rates of Cr and Cu were 2.32% and 1.16%, respectively. The content of Fe, Ti, As, Pb, and Mn in the corn kernels of the tailings and surrounding areas was relatively high, and the content of Mo, Ni, Cu, Zn, Cd, and Cr in the control area was relatively high. The over-standard rates of Ni, Zn, and Cu in the corn kernels were 13.61%, 13.23%, and 5.17% respectively, according to China's national food safety standard limits for contaminants in food (GB 2762-2017). The bioconcentration factors of Fe, Ti, As, Pb, and Mn in the corn kernels of the tailings and the surrounding areas were relatively higher, while the bioconcentration factors of Mo, Ni, Cu, Zn, Cd, and Cr were lower than in control area. The bioactive components of Cd accounted for 50.17%, which was the highest, followed by Ni, Zn, and Cu with average ratios of 13.61%, 13.23%, and 5.17%, respectively. Compared to the control area, the Pb, As and Hg elements in the soil samples of the reclaimed land showed a lower total amount but a higher bioavailability content and soil pH value, while the Cu and Hg elements showed a higher total amount but lower bioavailability content and soil pH value. These differences in total heavy metal concentrations, bioavailability amounts, and soil pH values made the bioconcentration intensity of As and Pb in the tailings reservoir and surrounding area relatively higher. When studying the ecological risk of heavy metal pollution or determining the remediation target value of reclaimed land in a mine tailings reservoir and the soil around the mine area, the bioavailable state limit of heavy metals should be should be taken into account as the evaluation standard.

GPR120 promotes radiation resistance in esophageal cancer via regulating AKT and apoptosis pathway.

The aim of the study is to investigate the role of GPR120 on the biological behavior of esophageal cancer cells in the setting of radiation and explore the mechanism. GPR120 knockdown was fulfilled by siRNA-mediated effects in two esophageal cancer cell lines Eca109 and EC9706. Colony formation, survival fraction calculation, viable cell evaluation by cell counting kit-8 assay and cell apoptosis analysis by phycoerythrin annexin V and 7-amino-actinomycin (7-AAD) staining and the flow cytometry examination was evaluated in Eca109 and EC9706 under the treatment of different radiation dosage. The mechanisms were explored by the evaluation of the Akt pathway and apoptosis protein level. Significantly decreased GPR120 mRNA and protein after GPR120 siRNA treatment compared to control siRNA treatment. Significantly decreased colony formation was found in GPR120 siRNA-treated Eca109 and EC9706 cells compared to control siRNA-treated cells at the radiation dosage of 2, 4, 6 and 8 Gy. Moreover, decreased survival fraction number with increased sensitive enhancing ratio was also found in GPR120 siRNA-treated Eca109 and EC9706 cells compared to control siRNA-treated cells. Decreased cell viability and increased cell apoptosis in GPR120 siRNA-treated esophageal cancer cells. GPR120 siRNA decreased the Akt phosphorylation and anti-apoptotic Bcl-2 expression level, but increased pro-apoptotic Bim expression level in esophageal cancer cell lines. GPR120 regulated the biological behavior of the esophageal cancer cells via affecting Akt pathway and apoptosis molecules. Moreover, GPR120 siRNA combined radiation treatment could be a therapeutic choice for esophageal cancer.

[Source of Groundwater Nitrate in Luanping Basin Based on Multi-environment Media Nitrogen Cycle and Isotopes].

The multi-environment media of water, surface soil and vadose zone soil samples were collected in the upstream of Miyun Reservoir, in the Luanping Basin of Chengde City, Hebei Province. The aim was to identify the pollution source, ratio, spatial distribution, migration, and transformation characteristics of nitrogen in groundwater. Hydrogeochemistry, soil total nitrogen, and dissolved nitrate nitrogen of vadose zone soil analysis and a multi isotope tracer technique of δ15 N-NO3 and δ18O-NO3, δ34S-SO4 and δ18O-SO4, δ14 C, combined with land-use type analysis and geostatistics, were used in the study. The results showed that nitrate was the main form of nitrogen in the groundwater of the Luanping Basin. The NO3- concentration of groundwater was significantly correlated with the land-use types of residential land and cultivated land where the nitrate pollution of shallow groundwater was mainly distributed. Of the groundwater samples, 13.79% exceeded the National Standard Ⅲ for Groundwater (GB/T 14848-2017) of NO3- concentration value, while the excess multiple was 1.04-3.86, and 37.93% of the groundwater samples exceeded the World Health Organization NO3- concentration standard value. The excess multiple was 1.08-6.83. The spatial variation of groundwater NO3- concentration, soil total nitrogen and surface soil dissolved nitrate nitrogen of vadose zone was affected by the combination of natural structural factors and anthropogenic factors. The source of groundwater nitrate was mainly from livestock manure and domestic sewage, followed by chemical fertilizer leaching. The nitrogen cycle in the aeration zone-groundwater-dominated nitrogen circulation in the groundwater runoff area of the piedmont basin was nitrification. These findings are highly significant for the prevention and remediation of groundwater pollution when viewing the basin system as an independent unit, and for studying the sources and fate of nitrate pollution in the water environment.

Chemoradiotherapy with extended nodal irradiation and/or erlotinib in locally advanced oesophageal squamous cell cancer: long-term update of a randomised phase 3 trial.

BACKGROUND: To report the long-term outcomes of a phase III trial designed to test two hypotheses: (1) elective nodal irradiation (ENI) is superior to conventional field irradiation (CFI), and (2) chemoradiotherapy plus erlotinib is superior to chemoradiotherapy in locally advanced oesophageal squamous cell cancer (ESCC). METHODS: Patients with locally advanced ESCC were randomly assigned (1:1:1:1 ratio) to one of the four groups: A: radiotherapy adoption of ENI with two cycles of concurrent TP chemotherapy (paclitaxel and cisplatin) plus erlotinib; B: radiotherapy adoption of ENI with two cycles of concurrent TP; C: radiotherapy adoption of CFI with two cycles of concurrent TP plus erlotinib and D: radiotherapy adoption of CFI with two cycles of concurrent TP. A total of 60 Gy of radiation doses was delivered over 30 fractions. We explored the impact of epidermal growth factor receptor (EGFR) expression on the efficacy of erlotinib plus chemoradiotherapy. RESULTS: A total of 352 patients (88 assigned to each treatment group) were enrolled. The 5-year survival rates were 44.9%, 34.8%, 33.8% and 19.6% in groups A, B, C and D, respectively (P = 0.013). ENI significantly improved OS compared with standard CFI (median, 38.5 vs 22.6 months; HR, 0.74; P = 0.018). The addition of erlotinib significantly improved OS (median, 39.4 vs 27.4 months; HR, 0.75; P = 0.025). Patients with overexpressing EGFR treated with erlotinib had a better OS and PFS than those without erlotinib. CONCLUSIONS: Concurrent chemoradiotherapy with ENI and/or erlotinib improved long-term survival in locally advanced ESCC. CLINICAL TRIAL REGISTRATION: Trial registration: NCT00686114.

Fibroblast Activation Protein-α Expressing Fibroblasts Promote Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma.

BACKGROUND AND OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) remains one of the most common malignancies in China and has a high metastasis rate and poor prognosis. Fibroblast activation protein-α (FAP-α) is a serine peptidase the expression of which in cancer-associated fibroblasts has been associated with a higher risk of metastases and poor survival. This study aimed to analyze the correlation of FAP-α expression with the lymph node metastasis and prognostic significance in ESCC. METHODS: FAP-α expression was examined in 121 resected ESCC specimens and 10 adjacent normal tissue using immunohistochemistry. FAP-α expression was scored in the stromal fibroblasts adjacent to neoplastic nests. A chi-square test was used to analyze the correlation between FAP-α expression in tumors stromal and lymph node metastasis of ESCC. The association between FAP-α expression and prognosis was evaluated using univariable and multivariable statistical modeling. RESULTS: FAP-α expression was absent in the benign controls. FAP-α expression was evident in the stromal 37% (45/121) of ESCC. Expression of FAP-α level is significantly associated with lymph node metastasis (p=0.023), but it is not correlated to age, gender, and tumor location in ESCC patients. Stromal FAP-α expression was significantly associated with poor survival in univariable (HR 2.009; 95% CI 1.259-3.205; p=0.003) and multivariable analysis (HR 1.833; 95% CI 1.144-2.937; p=0.012). CONCLUSION: FAP-α may be an important regulator in lymph node metastasis of ESCC and may provide a novel therapeutic target in ESCC.

Progress of clinical study on hypofractionated radiotherapy after breast-conserving surgery.

Whole-breast radiotherapy after breast-conserving surgery (BCS) can improve patient survival while reducing local tumor recurrence. Although standard breast radiotherapy can achieve good tumor control and cosmetic effects with low toxicity, the 5- to 7-week treatment time is relatively long for patients and can result in wasted medical resources. Therefore, there is a growing trend toward hypofractionated radiotherapy (HFRT), which accelerates partial-breast irradiation. Both short-course radiotherapy and conventional fractionated radiotherapy are safe and effective treatment modes, with similar survival and local tumor control effects as those of conventional radiotherapy (CRT), and adverse reactions can be tolerated. Compared with conventional fractionated radiotherapy, short-course radiotherapy saves medical resources and has a shorter total treatment time, reduced treatment costs, and an improved quality of life for patients.

Matrine induces apoptosis in acute myeloid leukemia cells by inhibiting the PI3K/Akt/mTOR signaling pathway.

Matrine has been demonstrated to exert anticancer effects on acute myeloid leukemia (AML) cell lines. However, the mechanisms of matrine in AML remain largely unknown. The present study investigated the anticancer effects and underlying mechanisms of matrine on human AML cells in vitro. THP-1 cell lines were cultured and treated with different doses of matrine (0.4, 0.8, 1.2, 1.6 and 2.0 g/l). The effects of matrine on the cell proliferation were assessed by the Cell Counting Kit-8 assay. The apoptotic effects were evaluated by DAPI and annexin V/propidium iodide staining assays. The effects of the drug on phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ mechanistic target of rapamycin kinase (mTOR) protein expression were studied by western blot analysis. The results of the present study demonstrated that matrine suppressed the viability of THP-1 cells. The anticancer effects were identified to be dose-dependent and the IC50 value was 1.2 g/l in THP-1 cells. Matrine inhibited cell viability and induced cell apoptosis of AML cell lines in a dose- and time-dependent manner. In addition, it was observed that matrine decreased the expression of phosphorylated (p)-PI3K, p-Akt and p-mTOR in a concentration-dependent manner. However, the expression levels of PI3K, Akt and mTOR remained almost unaltered. These findings indicated that matrine may inhibit cell proliferation and induce apoptosis of AML cells and may be a novel effective chemotherapeutic agent against AML.

[Matrine inhibits proliferation and promotes autophagy and apoptosis in non-small cell lung cancer cells by deactivating PI3K/AKT/mTOR pathway].

OBJECTIVE: To investigate the inhibitory effect of matrine on the proliferation of human non-small cell lung cancer (NSCLC) and explore the possible molecular mechanism. METHODS: Cultured human NSCLC A549 cells were treated with 0.4, 0.8, 1.2, 1.6, and 2.0 g/L matrine for 24, 48 or 72 h. CCK-8 assay was used for measuring the changes in A549 cell viability. The morphological changes of the cells were observed under a fluorescence microscope, and flow cytometry was employed for analyzing the cell apoptosis. The effects of matrine and the PI3K specific inhibitor LY294002 (10 nmol/L) on AKT pathway and autophagy-related proteins in A549 cells were investigated using Western blotting. RESULTS: Matrine significantly inhibited the proliferation of A549 cells in a time- and dose-dependent manner (P < 0.05). At the concentration of 1.6 g/L or higher, matrine caused obvious cell shrinkage and fragmentation and significantly increased floating cells; autophagy vacuoles could be observed in the cells after acridine orange staining. Within the concentrations range of 0.8-1.6 g/L, matrine time- and dosedependently increased the cell apoptosis. Treatment of the cells with 1.6 g/L matrine and 10 nmol/L LY294002 resulted in significantly lowered expressions of p-AKT and p-mTOR proteins and increased the expression of light chain 3B (LC 3B), an autophagy-related protein, as compared with those in the control cells (P < 0.05). CONCLUSIONS: We demonstrate that matrine inhibits the proliferation and induces autophagy and apoptosis of A549 cells by deactivating AKT pathway, suggesting the potential of matrine as an anti-cancer agent for lung cancer.

Factors relevant to the prognosis of patients with esophageal cancer who received intensity-modulated radiotherapy.

BACKGROUND: The aim of this study was to evaluate the clinical factors relevant to the prognosis of patients with esophageal cancer who received intensity-modulated radiotherapy (IMRT). METHODS: The data of 60 patients admitted to our hospital from January 2014 to December 2015 with pathologically confirmed esophageal cancer were retrospectively reviewed. All patients received IMRT. Patients were divided into groups according to two-year survival: those who survived > 2 years after treatment, and those who died within 2 years of treatment. The potential clinical factors relevant to prognosis were evaluated by logistic regression analysis. RESULTS: Single factor analysis showed that lesion length (P < 0.05), tumor diameter (P < 0.05), T stage (P < 0.05), N stage (P < 0.05), and combined chemotherapy (P < 0.05) were associated with the prognosis of esophageal cancer patients who received IMRT. Logistic regression analysis demonstrated that T stage (odds ratio = 3.62; P < 0.05) and N stage (odds ratio = 2.98; P < 0.05) were independent factors relevant to prognosis. CONCLUSION: T stage and N stage influence the long-term curative effects of IMRT for esophageal cancer. The higher the stage, the lower the two-year survival rate.

G­protein­coupled receptor 120 regulates the development and progression of human esophageal cancer.

The aim of the present study was to investigate the role of G­protein coupled receptor 120 (GPR120) in esophageal cancer and explore the related mechanisms. The expression of GPR120 in esophageal cancer tissues was examined by immunohistochemistry. Correlation analysis was performed to investigate the association between the level of GPR120 and clinical parameters. The expression of GPR120 was evaluated in esophageal cancer cell lines and the effects of GPR120 on cell proliferation, clone formation, migration and invasion were evaluated in an in vitro cell model and an in vivo ectopic tumor nude mice model. In addition, the effect of GPR120 on epithelial­mesenchymal transition (EMT), PI3K and I­κB pathway, as well as angiogenesis and inflammation­related cytokines was explored in order to elucidate the underlying mechanisms. Significantly increased expression of GPR120 was observed in esophageal cancer tissues compared to normal tissues. The expression of GPR120 was significantly related with histological grade, TNM stage and lymph node metastasis. GPR120 knockdown significantly decreased cell proliferation, clone formation, migration and invasion in vitro and decreased tumor growth in vivo. Furthermore significantly increased levels of E­cadherin and decreased levels of N­cadherin and vimentin, decreased level of Akt phosphorylation and I­κB phosphorylation, as well as decreased levels of vascular endothelial growth factor (VEGF), interleukin­8 (IL­8) and cyclooxygenase­2 (Cox­2) and its corresponding protein PGE2 were observed as the underlying mechanisms. In conclusion, we observed an increased level of GPR120 in esophageal cancer tissues, which served as a positive regulator of the development and progression of esophageal cancer. Multiple mechanisms including EMT, PI3K and I­κB pathway, as well as angiogenesis and inflammation­related cytokines were involved.

Randomised phase III trial of concurrent chemoradiotherapy with extended nodal irradiation and erlotinib in patients with inoperable oesophageal squamous cell cancer.

BACKGROUND: This randomised phase III study was conducted to investigate the efficacy of extended nodal irradiation (ENI) and/or erlotinib in inoperable oesophageal squamous cell cancer (ESCC). PATIENTS AND METHODS: Patients with histologically confirmed locally advanced ESCC or medically inoperable disease were randomly assigned (ratio 1:1:1:1) to one of four treatment groups: group A, radiotherapy adoption of ENI with two cycles of concurrent TP chemotherapy (paclitaxel 135 mg/m2 day 1 and cisplatin 20 mg/m2 days 1-3, every 4 weeks) plus erlotinib (150 mg per day during chemoradiotherapy); group B, radiotherapy adoption of ENI with two cycles of concurrent TP; group C, radiotherapy adoption of conventional field irradiation (CFI) with two cycles of concurrent TP plus erlotinib; group D, radiotherapy adoption of CFI with two cycles of concurrent TP. RESULTS: A total of 352 patients (88 assigned to each treatment group) were enrolled. The 2-year overall survival rates of group A, B, C and D were 57.8%, 49.9%, 44.9% and 38.7%, respectively (P = 0.015). Group A significantly improved 2-year overall survival compared with group D. The ENI significantly improved overall survival in patients with inoperable ESCC (P = 0.014). The addition of erlotinib significantly decreased loco-regional recurrence (P = 0.042). Aside from rash and radiation oesophagitis, the incidence of grade 3 or greater toxicities did not differ among 4 groups. CONCLUSION: Chemoradiotherapy with ENI and erlotinib might represent a substantial improvement on the standard of care for inoperable ESCC. ENI alone should be adopted in concurrent chemoradiotherapy for ESCC patients.

The role of radiation therapy in the modern management of oligometastatic disease.

Multimodal treatment approaches are indispensable for patients with advanced-stage cancer, while radiation therapy has been established as essential part of therapeutic approaches and has been introduced as a better option to face challenges, such as, local relapse or oligometastatic disease. The mere insight of the concept of oligometastases, proposed for the first time in the middle 1990s, led to the hypothesis that this condition may be cured using local ablative weapons. This hypothesis has already been demonstrated by surgical ablative techniques. Even though been considered a gold-standard approach for ablation of metastatic lesions, surgery limitations, technical obstacles, or patients refusal, or advanced age, or associated comorbidities, or advancements in radiation delivery and imaging technology, all have allowed the progressive implementation of radiation therapy as an alternative local ablative weapon. The advanced technique of stereotactic body radiation therapy has been shown to be safe and effective, and achieved high local control rates, and long-term survival. Despite its good results, stereotactic radiotherapy still faces significant clinical challenges, including selection of candidate patients most likely to being in oligometastatic state and most likely to being in the therapeutic technique. In this article, we will make an overview of the oligometastatic disease and review the growing clinical literature of patients suffering from this condition and treated with radiation therapy.

Patterns of failure after involved field radiotherapy for locally advanced esophageal squamous cell carcinoma.

PURPOSE: To retrospectively analyze the patterns of failure and the treatment effects of involved-field irradiation (IFI) on patients treated with locally advanced esophageal squamous cell carcinoma (ESCC) and to determine whether IFI is practicable in these patients. METHODS: A total of 79 patients with locally advanced ESCC underwent three dimensional conformal (3D)CRT) or intensity modulated radiotherapy (IMRT) using IFI or elective nodal irradiation (ENI) according to the target volume. The patterns of failure were defined as local/regional, in-field, out)of)field regional lymph node (LN) and distant failure. With a median follow)up of 32.0 months, failures were observed in 66 (83.6%) patients. RESULTS: The cumulative incidence of local/regional failure (55.8 vs 52.8%) and in)field regional lymph node failure (25.6 vs 19.4%) showed no statistically significant difference between the IFI and the ENI group (p=0.526 and 0.215, respectively). Out)of)field nodal relapse rate of only 7.0% was seen in the IFI group. Three)year survival rates for the ENI and IFI group were 22.2 and 18.6%, respectively (p=0.240), and 3)year distant metastasis rates were 27.8 and 32.6%, respectively (p=0.180). The lung V10, V20, V30 and mean lung dose of the ENI group were greater than those of the IFI group, while the mean lung dose and V10 had statistically significant difference. CONCLUSIONS: The patterns of failure and survival rates in the IFI group were similar as in the ENI group; the regional recurrence and distant metastasis are the main cause of treatment failure. IFI is feasible for locally advanced ESCC. Further investigation is needed to increase local control and decrease distant metastasis in these patients.

Downregulation of cell division cycle 25 homolog C reduces the radiosensitivity and proliferation activity of esophageal squamous cell carcinoma.

Radiation therapy is one of the most important methods of contemporary cancer treatment. Cells in the G2 and M phases are more sensitive to radiation therapy, and cell division cycle 25 homolog C (CDC25C) is essential in shifting the cell cycle between these two phases. In this study, the knockdown of CDC25C in human esophageal squamous carcinoma EC9706 cells was mediated by transfecting shRNA against human CDC25C-subcloning into pGV248. The levels of CDC25C mRNA and protein expression were assessed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting, respectively. Moreover, cell proliferation and radiosensitivity were measured. Stable CDC25C-knockdown EC9706 cell lines were successfully established. Furthermore, the proliferation of both control and CDC25C-shRNA-EC9706 cells was inhibited after the cells were treated with increasing X-ray doses, and the proliferation of the control cells was affected more significantly (p<0.05). Moreover, cell colony formation assays allowed us to reach the same conclusion. Taken together, our experiments demonstrated that the knockdown of CDC25C can reduce both the radiotherapy sensitivity and the proliferation activity of EC9706 cells. Thus, CDC25C might be a potential biomarker for radiotherapy treatment.

[Effect of Qingfei Quyu Decoction in Prevention of Radiation Pneumonitis Induced by Concurrent Chemoradiotherapy for Esophageal Carcinoma Patients].

OBJECTIVE: To assess the effect of Qingfei Quyu Decoction (QQD) in preventing radiation pneumonitis in esophageal carcinoma patients by concurrent using it with chemoradiotherapy. METHODS: A total of 120 patients with mid-late stage esophageal carcinoma were randomly assigned to the treatment group (60 cases) and the control group (60 cases). All patients received concurrent radiochemotherapy. Patients in the treatment group additionally took QQD, one dose per day for 8 successive weeks. The incidence of radiation pneunonitis was compared between the two groups. The improvement rates of short-term benefit rate, Karnofsky performance scale (KPS), and body weight (BW) improvement rate were calculated between the two groups. The 1-and 2-year overall survival rates were compared between the two groups. RESULTS: The incidence of radiation pneunonitis was 8.93% (15/56) in the treatment group and 18.64% (11/59) in the control group (P < 0.05). The short-term benefit rate was 92.86% (52/56) in the treatment group and 69.49% (41/59) in the control group (P < 0.05). Besides, the KPS and BW improvement rate were higher in the treatment group [89.29% (50/56) and 83.05% (49/59) ] than in the control group [80.36% (45/56) and 66.10% (39/59)] (P < 0.05). The 1-and 2-year overall survival rate were 66.07% and 35.71% in the treatment group, higher than those of the control group (61.02% and 30.51%; P > 0.05). CONCLUSION: Concurrent using QQD with chemoradiotherapy for treating esophageal carcinoma patients could lower the incidence of radiation pneumonitis, attenuate the degree of radiation induced lung injury, improve clinical benefit rate, and elevate their QOL.