To addresses the issues of low contrast and inaccurate segmentation of tiny vessels in retinal images,a U-shaped network incorporating multi-level residuals and three-space attention mechanism is proposed.In encoding stage,a multi-level residual module is added after inputting original images for preserving image features,and additionally,batch normalization and Dropout are integrated into the residual module to prevent vanishing gradient and feature data redundancy within the deep network.In decoding stage,a three-space attention mechanism is adopted to assign different weights to the features from the original images,down-sampled images,and up-sampled images,thus enhancing feature texture and position information,and achieving precise segmentation of tiny blood vessels.Experimental results on a public color fundus image dataset demonstrate that the proposed algorithm achieves higher accuracy(0.985),specificity(0.991),sensitivity(0.829),and AUC(0.985)than the existing algorithms.Moreover,the vessel maps obtained by the comparison with the gold standard are of significant reference value in clinic.

To address the challenge of unclear features and difficulties in pulmonary nodule CT image detection,an efficient attention feature pyramid network is proposed.The network firstly employs a feature pyramid of multi-scale feature fusion as the backbone network for effectively preserving both low-and high-level features,and uses the depthwise separable convolutional neural network to extract feature information.Then,the attention mechanism is integrated into the backbone network for assigning weights to salient feature information.Finally,the proposed algorithm is applied to Lung-PET-CT-Dx dataset and Luna16 dataset,and the experimental results demonstrate that the proposed algorithm has higher precision,recall rate and mAP value than the existing comparative algorithms,substantiating its superiority in pulmonary nodule detection.

[Objective]To summarize the thought process behind Chief QIU Shengliang's decision to dispel dampness in order to fortify the spleen and tonify the spleen Yang in clinical treatment of distention and fullness.[Methods]The clinical applications of the aforementioned dampness dispelling technique were compiled for future reference through experience gained via apprenticeship,gathered medical cases,Chief QIU's verbal account on the matter and relevant references.Proven clinical cases were also attached at the end of the report for verification.[Results]Living environment,fast-paced jobs and irregular diet nowadays are making people more prone to spleen-stomach dysfunction and inhibition of Qi movement throughout the middle-Jiao,which in turn leads to distention and fullness.Chief QIU often clinically treats distention and fullness using the aforementioned dampness dispelling technique,for which remarkable efficacy has been achieved.In the medical case reported in this study,the patient was admitted due to recurrent abdominal distension and frequent loose stool.the patient was diagnosed with abdominal distension featuring spleen deficiency and dampness excess by Chief QIU.After treated by strengthening the spleen,dispelling dampness,warming the spleen Yang,promoting digestion and tranquilizing the mind,the patient showed significantly improved condition.[Conclusion]Chief QIU treats distention and fullness by dispelling dampness with the view to fortify the spleen and tonifying the spleen Yang,whose therapeutic efficacy is worth extensive share and popularization.

Objective:To discuss the clinical efficacy of laparoscopic radical cystectomy in the treatment of bladder cancer after partial cystectomy.Methods:The clinical data of 30 patients who underwent laparoscopic radical cystectomy after PC in Sichuan Provincial People's Hospital from March 2016 to August 2020 were retrospectively analyzed. Including 24 males and 6 females with an average age was 62.5 (45.5-82.5)years.6 out of 30 cases underwent pelvic lymph node dissection during PC. All patients had definite pathological diagnosis for the high-grade urothelial carcinoma after PC, and the tumor staging was pT 2-3bN 0M 0.5 patients received postoperative adjuvant chemotherapy with gemcitabine and cisplatin, 6 received postoperative adjuvant radiotherapy, 13 received postoperative adjuvant radiotherapy and chemotherapy, and all patients were received maintenance intravesical instillation. Median time for local tumor recurrence after PC was 9(5-29) months, all patients had pathological diagnosis for the high-grade papillary urothelial carcinoma, cT 2-4N 0M 0 stage.The average tumor diameter was 3.5(2.5-4.5)cm, an average number of tumors was 2(1-3). Laparoscopic salvage cystectomy was performed after recurrence.General anesthesia, supine position, 5 ports were inserted through the abdominal approach. Standard pelvic lymph node dissection (PLND) was used to clean the pelvic lymph nodes. Those who had underwent PLND no longer clean the obturator and peripheral iliac vessels, but including the common iliac vessel and the bifurcation of the abdominal aorta and lymphatic tissues around the inferior vena cava, as well as the presacral lymph nodes. Results:All 30surgeries were successfully performed. The average operative time was 270(240-310)min, average estimated intraoperative blood loss was 180(50-300)ml, and there was no blood transfusion during the perioperative period.The average number of lymph nodes dissected was 18 (10-27). There were 4 cases with positive lymph nodes, of which 3 cases were positive for 2 obturator lymph nodes, and 1 case was positive for 3 obturator and external iliac lymph nodes. No serious intraoperative complications occurred.No lymphatic leakage occurred. The average drainage duration was 4(3-7) d, and postoperative hospital stays was 9(7-20)d. The postoperative pathology was invasive high-grade papillary urothelial carcinoma, and pathological TNM stage was pT 2-4aN 0-2M 0.13 patients received postoperative adjuvant chemotherapy. The average postoperative follow-up time was 23(3-31) months. There were 2 cases of pelvic recurrence and 1 case of retroperitoneal lymph node metastasis. These 3 cases received adjuvant chemotherapy and radiotherapy. Conclusions:Radical cystectomy should be the primary treatment for recurrence of bladder cancer after partial cystectomy.

Objective: To investigate the in vitro and in vivo effects of apatinib in esophageal squamous cell carcinoma and the underlying mechanisms. Methods: The esophageal cancer cells, KYSE-150 and ECA-109, were divided into control group and apatinib treatment group at the concentrations of 2.5, 5, 10, 20 and 40 μmol/L respectively. All of experiments were performed in triplicate. MTT and colony formation assays were used to measure cell proliferation. Transwell assay was used to determine the migration capacity. The effect of apatinib on cell cycle and apoptosis was analyzed by flow cytometry. The expression of VEGF and VEGFR-2 was measured by real-time quantitative PCR (qRT-PCR). The concentration of VEGF in the cell supernatant was assessed by enzyme-linked immunosorbent assay (ELISA). The expression levels of MEK, ERK, p-MEK, p-ERK, JAK2, STAT3 and p-STAT3 after VEGF stimulation were detected by Western blot. Furthermore, the nude mice xenograft model was established. The tumor-bearing mice were randomly divided into control group, apatinib low dose treatment group (250 mg) and apatinib high dose treatment group (500 mg), respectively. Tumor inhibition rates of different groups were calculated. And then the expressions of VEGF and VEGFR2 were detected in xenograft tissues by immunohistochemical staining. Results: In the presence of 20 μmol/L and 40 μmol/L of apatinib for 24 hours, the migration cell numbers of KYSE-150 and ECA-109 were 428.67±4.16 and 286.67±1.53 as well as 1 123.67±70.00 and 477.33±26.84, respectively, that were significantly lower than control group (P<0.05 for all). In addition, after treatment with 10 μmol/L, 20 μmol/L and 40 μmol/L of apatinib for 7 days on KYSE-150 and ECA-109, the colony formation rates were (65.12±25.48)%, (58.19±24.73)% and (29.10±22.40)% as well as (70.61±15.14)%, (61.12±17.21)% and (43.09±11.13)%, respectively. The colony formation rates of 20 μmol/L and 40 μmol/L of apatinib treatment groups were significantly lower than control group (100.00±0.00, P<0.05). The cell cycle ratio of G₂/M phase and apoptosis rate of control group and 20 μmol/L apatinib group in KYSE-150 cells were (12.14±2.13)% and (3.49±0.74)% as well as (26.27±3.30)% and (15.65±1.54)%, respectively. The corresponding ratios in ECA-109 cells were (3.44±0.57)% and (6.31±1.43)% as well as (22.64±2.36)% and (49.26±1.62)%, respectively. The results show that apatinib suppressed cell cycle progression at G₂/M phase and induced cell apoptosis in both KYSE-150 and ECA-109 cells (P<0.05 for all). In the presence of 20 μmol/L and 40 μmol/L of apatinib in KYSE-150 cells, the relative levels of VEGF mRNA were (42.57±10.43)% and (25.69±1.24)%, and those of VEGF-2 mRNA were (36.09±10.82)% and (13.99±6.54)%, which were all significantly decreased compared to control group (100.00±0.00, P<0.05 for all). For ECA-109 cells, the relative expression of VEGF and VEGFR2 showed similar tendency (P<0.05 for all). Moreover, after treatment with 20 μmol/L and 40 μmol/L of apatinib in KYSE-150 cells, the VEGF concentrations were (766.48±114.27) pg/ml and (497.40±102.18)pg/ml, which were significantly decreased compared to control group [(967.41±57.75) pg/ml, P<0.05)]. The results in ECA-109 were consistent (P<0.05). Furthermore, after treatment with 40 μmol/L of apatinib in KYSE-150 and ECA-109, the relative expression of p-MEK and p-ERK were 0.49±0.05 and 0.28±0.03 as well as 0.63±0.03 and 1.22±0.15, which were significantly lower than control group (1.23±0.19 and 0.66±0.07 as well as 1.03±0.20 and 1.76±0.20; P<0.05). The relative expression of STAT3, p-STAT3 in control group and experimental group were 0.96±0.15 and 0.85±0.16 as well as 0.62±0.09 and 0.36±0.13, respectively. The results showed that the protein levels of STAT3 and p-STAT3 were significantly lower than the control group (P<0.05 for all). The inhibition rates of apatinib in xenograft nude mice were 29.25% and 19.96% for 250 mg and 500 mg treatment groups. The concentration of VEGF were (25.11±4.12) pg/ml, (16.40±2.81) pg/ml and (15.04±4.88)pg/ml for control, 250 mg and 500 mg treatment groups, respectively. Conclusions Apatinib can inhibit cell proliferation, induce apoptosis and suppress migration of esophageal cancer cells in vitro and in vivo. This effect was mainly mediated via the alterations of Ras/Raf/MEK/ERK pathway and JAK2/STAT3 pathway.

Objective To investigate the in vitro and in vivo effects of apatinib in esophageal squamous cell carcinoma and the underlying mechanisms. Methods The esophageal cancer cells, KYSE?150 and ECA?109, were divided into control group and apatinib treatment group at the concentrations of 2.5, 5, 10, 20 and 40 μmol／L respectively. All of experiments were performed in triplicate. MTT and colony formation assays were used to measure cell proliferation. Transwell assay was used to determine the migration capacity. The effect of apatinib on cell cycle and apoptosis was analyzed by flow cytometry. The expression of VEGF and VEGFR?2 was measured by real?time quantitative PCR (qRT?PCR). The concentration of VEGF in the cell supernatant was assessed by enzyme?linked immunosorbent assay (ELISA). The expression levels of MEK, ERK, p?MEK, p?ERK, JAK2, STAT3 and p?STAT3 after VEGF stimulation were detected by Western blot. Furthermore, the nude mice xenograft model was established. The tumor?bearing mice were randomly divided into control group, apatinib low dose treatment group (250 mg) and apatinib high dose treatment group (500 mg), respectively.Tumor inhibition rates of different groups were calculated.And then the expressions of VEGF and VEGFR2 were detected in xenograft tissues by immunohistochemical staining. Results In the presence of 20 μmol／L and 40 μmol／L of apatinib for 24 hours, the migration cell numbers of KYSE?150 and ECA?109 were 428.67±4.16 and 286.67±1.53 as well as 1 123.67±70.00 and 477.33± 26.84, respectively, that were significantly lower than control group ( P＜0.05 for all). In addition, after treatment with 10 μmol／L, 20 μmol／L and 40 μmol／L of apatinib for 7 days on KYSE?150 and ECA?109, the colony formation rates were ( 65.12± 25.48)%, ( 58.19± 24.73)% and (29.10± 22.40)% as well as (70.61±15.14)%, (61.12±17.21)% and (43.09±11.13)%, respectively. The colony formation rates of 20 μmol／L and 40 μmol／L of apatinib treatment groups were significantly lower than control group (100.00±0.00, P＜0.05). The cell cycle ratio of G2／M phase and apoptosis rate of control group and 20 μmol／L apatinib group in KYSE?150 cells were (12.14±2.13)% and (3.49±0.74)% as well as (26.27±3.30)% and (15.65± 1.54)%, respectively. The corresponding ratios in ECA?109 cells were (3.44±0.57)% and (6.31±1.43)%as well as (22.64±2.36)% and (49.26± 1.62)%, respectively. The results show that apatinib suppressed cell cycle progression at G2／M phase and induced cell apoptosis in both KYSE?150 and ECA?109 cells (P＜0.05 for all). In the presence of 20 μmol／L and 40 μmol／L of apatinib in KYSE?150 cells, the relative levels of VEGF mRNA were (42.57± 10.43)% and ( 25.69± 1.24)%, and those of VEGF?2 mRNA were (36.09±10.82)% and (13.99±6.54)%, which were all significantly decreased compared to control group (100.00±0.00, P＜0.05 for all). For ECA?109 cells, the relative expression of VEGF and VEGFR2 showed similar tendency (P＜0.05 for all). Moreover, after treatment with 20 μmol／L and 40 μmol／L of apatinib in KYSE?150 cells, the VEGF concentrations were ( 766.48± 114.27) pg／ml and ( 497.40± 102.18) pg／ml, which were significantly decreased compared to control group [(967.41± 57.75) pg／ml, P＜0.05)]. The results in ECA?109 were consistent (P＜0.05). Furthermore, after treatment with 40 μmol／L of apatinib in KYSE?150 and ECA?109, the relative expression of p?MEK and p?ERK were 0.49±0.05 and 0.28±0.03 as well as 0.63±0.03 and 1.22±0.15, which were significantly lower than control group (1.23±0.19 and 0.66± 0.07 as well as 1.03±0.20 and 1.76±0.20; P＜0.05). The relative expression of STAT3, p?STAT3 in control group and experimental group were 0.96 ± 0.15 and 0.85 ± 0.16 as well as 0.62 ± 0.09 and 0.36 ± 0.13, respectively. The results showed that the protein levels of STAT3 and p?STAT3 were significantly lower than the control group (P＜0.05 for all). The inhibition rates of apatinib in xenograft nude mice were 29.25% and 19.96% for 250 mg and 500 mg treatment groups. The concentration of VEGF were (25.11±4.12) pg／ml, (16.40 ± 2.81) pg／ml and ( 15.04 ± 4.88) pg／ml for control, 250 mg and 500 mg treatment groups, respectively. Conclusions Apatinib can inhibit cell proliferation, induce apoptosis and suppress migration of esophageal cancer cells in vitro and in vivo. This effect was mainly mediated via the alterations of Ras／Raf／MEK／ERK pathway and JAK2／STAT3 pathway.

Objective To investigate the in vitro and in vivo effects of apatinib in esophageal squamous cell carcinoma and the underlying mechanisms. Methods The esophageal cancer cells, KYSE?150 and ECA?109, were divided into control group and apatinib treatment group at the concentrations of 2.5, 5, 10, 20 and 40 μmol／L respectively. All of experiments were performed in triplicate. MTT and colony formation assays were used to measure cell proliferation. Transwell assay was used to determine the migration capacity. The effect of apatinib on cell cycle and apoptosis was analyzed by flow cytometry. The expression of VEGF and VEGFR?2 was measured by real?time quantitative PCR (qRT?PCR). The concentration of VEGF in the cell supernatant was assessed by enzyme?linked immunosorbent assay (ELISA). The expression levels of MEK, ERK, p?MEK, p?ERK, JAK2, STAT3 and p?STAT3 after VEGF stimulation were detected by Western blot. Furthermore, the nude mice xenograft model was established. The tumor?bearing mice were randomly divided into control group, apatinib low dose treatment group (250 mg) and apatinib high dose treatment group (500 mg), respectively.Tumor inhibition rates of different groups were calculated.And then the expressions of VEGF and VEGFR2 were detected in xenograft tissues by immunohistochemical staining. Results In the presence of 20 μmol／L and 40 μmol／L of apatinib for 24 hours, the migration cell numbers of KYSE?150 and ECA?109 were 428.67±4.16 and 286.67±1.53 as well as 1 123.67±70.00 and 477.33± 26.84, respectively, that were significantly lower than control group ( P＜0.05 for all). In addition, after treatment with 10 μmol／L, 20 μmol／L and 40 μmol／L of apatinib for 7 days on KYSE?150 and ECA?109, the colony formation rates were ( 65.12± 25.48)%, ( 58.19± 24.73)% and (29.10± 22.40)% as well as (70.61±15.14)%, (61.12±17.21)% and (43.09±11.13)%, respectively. The colony formation rates of 20 μmol／L and 40 μmol／L of apatinib treatment groups were significantly lower than control group (100.00±0.00, P＜0.05). The cell cycle ratio of G2／M phase and apoptosis rate of control group and 20 μmol／L apatinib group in KYSE?150 cells were (12.14±2.13)% and (3.49±0.74)% as well as (26.27±3.30)% and (15.65± 1.54)%, respectively. The corresponding ratios in ECA?109 cells were (3.44±0.57)% and (6.31±1.43)%as well as (22.64±2.36)% and (49.26± 1.62)%, respectively. The results show that apatinib suppressed cell cycle progression at G2／M phase and induced cell apoptosis in both KYSE?150 and ECA?109 cells (P＜0.05 for all). In the presence of 20 μmol／L and 40 μmol／L of apatinib in KYSE?150 cells, the relative levels of VEGF mRNA were (42.57± 10.43)% and ( 25.69± 1.24)%, and those of VEGF?2 mRNA were (36.09±10.82)% and (13.99±6.54)%, which were all significantly decreased compared to control group (100.00±0.00, P＜0.05 for all). For ECA?109 cells, the relative expression of VEGF and VEGFR2 showed similar tendency (P＜0.05 for all). Moreover, after treatment with 20 μmol／L and 40 μmol／L of apatinib in KYSE?150 cells, the VEGF concentrations were ( 766.48± 114.27) pg／ml and ( 497.40± 102.18) pg／ml, which were significantly decreased compared to control group [(967.41± 57.75) pg／ml, P＜0.05)]. The results in ECA?109 were consistent (P＜0.05). Furthermore, after treatment with 40 μmol／L of apatinib in KYSE?150 and ECA?109, the relative expression of p?MEK and p?ERK were 0.49±0.05 and 0.28±0.03 as well as 0.63±0.03 and 1.22±0.15, which were significantly lower than control group (1.23±0.19 and 0.66± 0.07 as well as 1.03±0.20 and 1.76±0.20; P＜0.05). The relative expression of STAT3, p?STAT3 in control group and experimental group were 0.96 ± 0.15 and 0.85 ± 0.16 as well as 0.62 ± 0.09 and 0.36 ± 0.13, respectively. The results showed that the protein levels of STAT3 and p?STAT3 were significantly lower than the control group (P＜0.05 for all). The inhibition rates of apatinib in xenograft nude mice were 29.25% and 19.96% for 250 mg and 500 mg treatment groups. The concentration of VEGF were (25.11±4.12) pg／ml, (16.40 ± 2.81) pg／ml and ( 15.04 ± 4.88) pg／ml for control, 250 mg and 500 mg treatment groups, respectively. Conclusions Apatinib can inhibit cell proliferation, induce apoptosis and suppress migration of esophageal cancer cells in vitro and in vivo. This effect was mainly mediated via the alterations of Ras／Raf／MEK／ERK pathway and JAK2／STAT3 pathway.

Objective To evaluate the radiosensitivity effects of apatinib on the esophageal cancer cell line ECA-109 and its cancer stem-like cells,and to investigate the underlying mechanism.Methods A serum-free medium (SFM) was used to culture esophageal cancer stem cell line ECA-109 and enrich the esophageal stem-like spheres.ECA-109 and its stem-like cells were divided into control group,drug treatment group,radiation group and drug plus radiation group.Cell proliferations of ECA-109 and its stem-like cells were detected with CCK-8 method.The concentration of vascular endothelial growth factor (VEGF) in the cell culture medium was determined by enzyme linked immunosorbent assay(ELISA).Cell cycle and apoptosis were detected by flow cytometry method.The expressions of CHK2 and P-STAT3 proteins were detected by Western blot assay.Results With the administration with apatinib for 24,48 and 72 h,the half of the inhibitory concentration (IC50) of ECA-109 stem-like cells was significantly higher than that of the parent cells (t =8.17,9.29,18.85,P ＜ 0.05) in a time dependent manner (parental cells:r2 =0.94-0.97,P ＜0.05;stem-like cells:r2 =0.94-0.98,P ＜0.05).After administration with different concentrations of apatinib (parental cells:10 and 20 μmol/L;stem-like cells:30 and 40 μmol/L) combined with different dose of X-rays (6 and 8 Gy),the proliferations of ECA-109 and its stem-like cells were significantly (t =5.20-39.68,P ＜ 0.05) inhibited compared with radiation alone group.VEGF secretion from both ECA-109 cells and its stem like cells were significantly decreased in different manner (t =7.45,P ＜ 0.05).Compared with control group,the cell apoptosis rate and the percentages of cells in G2/M phase were significantly increased in drug plus radiation group (t =8.83,11.59,P ＜ 0.05),and the expressions of CHK2 and P-STAT3 were decreased in drug group (t =3.36,4.10,P ＜ 0.05).Compared with radiation group,the expressions of CHK2 and P-STAT3 were decreased in drug plus radiation group (t =9.05,2.36,P ＜ 0.05).Conclusions Apatinib enhanced the radiosensitivity of ECA-109 cells and its stem-like cells,which was much more effective on ECA-109 cells and may be related to the radiation-induced inhibition of VEGF signal pathway that can further inhibit cell proliferation,promote cell apoptosis and induce cell cycle redistribution.The higher intrinsic level of VEGF protein may contribute to radioresistance of ECA-109 stem-like cells.

Objective To evaluate the radiosensitization effect of apatinib on esophageal cancer cell line Kyse-150, and to investigate the underlying mechanism. Methods Cells were divided into four groups:control group, apatinib treatment group, X-ray radiation group, and the combination group treated with X-rays plus apatinib. The effect of apatinib with different concentrations on the cell proliferative and radiosensitivity were evaluated by CCK-8 kit and colony formation assay. Flow cytometry method was adopted to detect the effect of apatinib on cell cycle progress and apoptosis induction. Results Apatinib inhibited the proliferation of Kyse-150 cells in time-and dose-dependent manners (r=0. 89-0. 96, P<0. 05). With the increase of apatinib concentration, D0, Dq and SF2 value of Kyse-150 cells decreased and SERD0 value increased. Compared with control group, apatinib alone group, and radiation alone group, the cell apoptosis rate significantly increased in the combination group (t=12. 36, 5. 99, 15. 47,P<0. 05). Compared with control group, the percentages of cells in G2/M phase were all significantly increased in apatinib group, radiation group and combination group (t=8. 81, 39. 69, 20. 61,P<0. 05). Compared with radiation alone group and control group, the percentage of cells in S phase significantly increased in apatinib alone group and combination group(t = 6.06, 3.82,8.81,6.24,P < 0.05). Conclusions Apatinib can increase radiosensitivity of esophageal cancer cell line Kyse-150 possibly by inhibiting cell proliferation, inducing cell apoptosis and causing redistribution of cell cycle.

Objective To study the radiation sensitive enhancement ratio (SER) of NS398 on esophageal cancer stem cells and adherent tumor cells and analyze the radioresistance related protein expressions.Methods ECA109 esophageal cancer stem cells were cultured in serum-free medium.Expression levels of cell surface maker CD44 + and CD271 + were analyzed by flow cytometry.MTT assay was used to detect cell proliferation after the treatments with NS398 and irradiation(0,4 and 8 Gy).The sensitization effects of NS398 on the parental cells and its spheroid were evaluated by clone formation assay.Western blot assay was performed to determine protein expressions.Results Serum-free medium was successfully applied to isolate the cancer stem cells with spherical properties.CD271 + in the spheroid cells was notable higher than that in the parent cells (t =3.81,P ＜ 0.05).After irradiation,the proliferation rate of parental cells was higher than that in spheroid cells.After the combination treatment of NS398 and irradiation,SF2 value of parental cells was lower than spheroid cells(t =2.91,P ＜ 0.05)and the SER of NS398 on parental cells was greater than spheroid cells.The expressions of Bmi-1,c-Myc,β-catenin and Cyclin D1 in spheroid cells were higher than those in parental cells (t =8.09,7.90,7.50,7.15,P＜0.05).Cyclin D1 expression levels under both cell situations increased after 4 Gy irradiation (t =9.74,6.67,P ＜0.05).Compared to the 4 Gy irradiation alone group,the β-catenin and Cyclin D1 expression levels in both parental cells (t =10.15,12.12,P ＜ 0.05) and spheroid cells (t =3.23,7.45,P ＜ 0.05) decreased in the combination group.Conclusions Esophageal cancer stem cells with high level of CD271 can be isolated with serum-free medium and it is radioresistant where β-catenin and its downstream proteins may be involved.