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Objective:To investigate the association between pelvic bone dose-volume parameters and acute bone marrow suppression in cervical cancer treated with concurrent cisplatin and intensity-modulated radiation therapy, in order to provide the limited prescription for making radiotherapeutic plan.Methods:The clinical data of 40 cervical cancer patients receiving cisplatin with concurrent intensity-modulated radiation therapy in the Affiliated Hospital of Ningde Normal College from November 2017 to January 2020 were analyzed. The correlations of the irradiated volume of pelvic bone receiving doses of 5, 10, 15, 20, 25, 30, 35, 40, 45, 50 Gy as a percentage of the total volume of pelvic bone (V 5 Gy,V 10 Gy, V 15 Gy,V 20 Gy,V 25 Gy, V 30 Gy, V 35 Gy, V 40 Gy, V 45 Gy, V 50 Gy), the maximum dose (D max), the minimum dose (D min), and the mean dose (D mean) with the occurrence of ≥grade 3 acute bone marrow suppression were analyzed. The logistic multiple regression analysis was used to study the influencing factors of ≥grade 3 acute bone marrow suppression, and the receiver operating characteristic (ROC) curve was used to determine the diagnostic efficacy of influencing factors for ≥grade 3 acute bone marrow suppression. Results:The incidence rate of ≥grade 3 acute bone marrow suppression was 47.5% (19/40). Between patients with ≥grade 3 and <grade 3 acute bone marrow suppression, the differences in pelvic bone V 5 Gy [(96.0±2.9)% vs. (93.4±3.5)%], V 10 Gy [(90.6±5.0)% vs. (87.5±4.0)%], V 15 Gy [(86.2±5.8)% vs. (83.0±4.2)%], V 20 Gy [(78.8±6.1)% vs. (74.6±4.5)%], V 50 Gy [(15.8±7.1)% vs. (10.2±7.1)%], D max [(6 376±524) cGy vs. (5 813±668) cGy] and D mean [(3 441±255) cGy vs. (3 239±240) cGy] were statistically significant (all P < 0.05). The logistic multiple regression analysis showed that pelvic bone V 5 Gy was an risk factor for the occurrence of ≥ grade 3 acute bone marrow suppression [ OR = 3.108, 95% CI 1.101-8.768, P = 0.032], and the ROC curve showed that the optimal critical value of pelvic bone V 5 Gy was 96.9%, and the area under the curve was 0.709. Conclusions:During cisplatin with concurrent intensity-modulated radiation therapy for cervical cancer, pelvic bone V 5 Gy is a risk factor for the occurrence of ≥ grade 3 acute bone marrow suppression. Setting pelvic bone V 5 Gy below 96.9% when making the radiotherapy plan can effectively reduce the occurrence of ≥ grade 3 acute bone marrow suppression.
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Objective@#To detect the expression level of YES-associated protein 1 (YAP) in hepatocellular carcinoma (HCC) cell lines and investigate its effects on the proliferation activity and the sensitivity to sorafenib in HCC cells.@*Methods@#Western blot was used to detect the protein expression levels of YAP in SMMC-7721, SK-Hep-1, HepG-2, Huh7 and the normal liver cell line L-O2. YAP specific small interfering RNA (si-YAP) or YAP expression plasmid were transfected in SK-Hep-1 or Huh7 cells, respectively. Cell counting kit-8 (CCK-8) test was used to detect the cell proliferation activity and the cell cycle test was conducted by flow cytometry. SK-Hep-1 and SK-Hep-1 si-YAP cells were subcutaneously injected into the nude mice which were sequentially treated by intragastric administration of sorafenib, and the tumor growth in vivo were observed and compared.@*Results@#The expression of YAP was upregulated in HCC cell lines. Deletion of YAP expression significantly decreased the survival rate of SK-Hep-1 cells [(78.5±0.3)% vs (92.3±0.2)%, P=0.025]. Knockdown of YAP significantly increased the percentage of G0/G1-phase cells [ (65.4±3.3) % vs (55.7±3.4) %, P=0.039]. On the contrary, upregulation of the YAP expression in Huh7 cells significantly increased the cell survival rate [(81.2±1.3)% vs (62.5±1.1)%, P=0.013] and reduced the percentage of G0/G1-phase cells [(38.2±3.8)% vs (48.8±2.9)%, P=0.019]. The survival rate of SK-Hep-1 cells treated by si-YAP combined with sorafenib was (31.13±1.79)%, significantly lower than (48.87±0.58) % of SK-Hep-1 cells treated by sorafenib alone (P=0.001), while overexpression of YAP attenuated the inhibitory effect of sorafenib on the survival of Huh7 cells [(69.98±2.94) % vs (53.53±1.93)%, P=0.001]. The tumor weights of SK-Hep-1 group, sorafenib alone group, SK-Hep-1 si-YAP group and SK-Hep-1 si-YAP combined with sorafenib group were (0.96±0.08) g, (0.62±0.08) g, (0.70±0.06) g and (0.27±0.02) g, respectively. The tumor weights of sorafenib alone group and SK-Hep-1 si-YAP group were significantly lower than that of SK-Hep-1 group (P=0.012 and P=0.031, respectively). The tumor weight of SK-Hep-1 si-YAP combined with sorafenib group was significantly lower than that of SK-Hep-1 si-YAP group (P=0.001).@*Conclusions@#The expression of YAP is upregulated in HCC cell lines, which regulates the proliferation, cell cycle, and sensitivity to sorafenib of HCC cells. YAP is a potential molecular target for HCC treatment.
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Objective@#To explore the factors affecting the prognosis of patients with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT), and to analyze the clinical value of transcatheter arterial chemoembolization (TACE) combined with iodine-125 seed implantation in such patients.@*Methods@#A retrospective analysis of 53 patients with HCC combined with PVTT was performed. In the study group, 32 cases were treated with TACE combined with iodine-125 seed implantation, and 21 cases in the control group were treated with TACE combined with sorafenib. Survival analysis was carried out on eight factors such as gender, age, Child-Pugh classification, alpha fetoprotein level, portal vein tumor thrombosis (PVTT) type, forms of liver tumor, extra-hepatic metastasis and treatment modalities. The efficacy of TACE combined with iodine-125 seed implantation and TACE combined with sorafenib was further compared. The χ 2 test was used to evaluate the efficacy of the two groups. A single factor survival analysis was calculated by Kaplan-Meier estimator and multifactor survival analysis by Cox proportional hazards model.@*Results@#All 53 patients were successfully treated. The median tumor progression time (mTTP) and median overall survival (mOS) were 8 months and 11 months, respectively. The disease control rate (DCR) of the study group for PVTT was 93.8%, which was significantly higher than that of the control group (61.9%, χ 2 = 6.448, P = 0.011). The difference was statistically significant; the objective remission rate of the study group for PVTT was 75.0%. Significantly higher than 9.5% in the control group, P < 0.05, the difference was statistically significant; the DCR of the primary tumor in the study group was 50.0%, which was lower than the 70.0% of the PVTT in the control group, P = 0.231, the difference was not statistically significant. The progression of primary HCC lesions in patients with multivariate survival analysis: Child-Pugh grade A patients were compared to grade B [Hazard ratio (HR) = 0.236, P = 0.003]; no extra-hepatic metastasis (HR = 0.258, P = 0.002); and TACE combined with iodine-125 seed implantation group compared with TACE combined sorafenib group (HR = 0.372, P = 0.002), the differences were statistically significant. Multivariate survival analysis of patients with overall survival: AFP < 400 ng/mL vs. AFP≥400 ng/mL (HR = 0.389, P = 0.030); Child-Pugh grade A vs. B (HR = 0.263, P = 0.006); and no extra-hepatic metastasis (HR = 0.306, P = 0.006), the differences were statistically significant.@*Conclusion@#TACE combined with iodine-125 seed implantation for the treatment of HCC with PVTT can effectively control the progression of PVTT and intrahepatic lesions and improve the prognosis of patients.
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The Hippo-YAP/TAZ signaling pathway is an evolutionarily conserved pathway, which has been confirmed to play an important role in organ volume control, stem cell function, tissue regeneration, and tumorigenesis. Recent research findings show that the Hippo-YAP/TAZ signaling pathway is closely associated with the development and progression of primary liver cancer, and inhibition of the activity of this pathway may be a new method for the treatment of liver cancer. This article reviews the research advances in the role of the Hippo-YAP/TAZ signaling pathway in primary liver cancer.
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Five groups were assigned to include intrahepatic cholangiocarcinoma ( ICC, n=30 ) , liver cirrhosis (LC,n=30),metastatic carcinoma (MCA,n=30) and 30 healthy subjects.The serum level of GPC3 was measured by a sandwich method of enzyme-linked immunosorbent assay ( ELISA ) and alpha-fetoprotein (AFP) by microparticle enzyme immunoassay (MEIA).The serum levels of GPC3 and AFP were significantly higher than those of other groups (P<0.05).At a cut-off value of 3.5μg/L,the sensitivity and specificity of GPC3 in the diagnosis of HCC was 83.3%and 76.7%respectively.The sensitivity of combined measurement of GPC3 and AFP was better than GPC3 or AFP alone.Detectable GPC3 was significantly correlated with the presence of viral hepatitis markers and tumor size.However there was no obvious difference in tumor thrombi in portal vein ( PVTT), tumor number, age, gender or hepatic function of HCC.Thus,as a sensitive serum diagnostic marker for HCC ,GPC3 may be a good supplement to AFP in differentiating HCC from non-malignant chronic liver diseases and other liver cancers.
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Objective To prepare a new type of chitosans nanoparticles(PEG/CS-EPI NPs),which contains epirubicin and modified by PEG.Furthermore,to investigate the anticancer activity of the NPs in vitro and in vivo.Methods The ionic gelation technique was employed to prepare the PEG/CS-EPI NPs and CS-EPI NPs.The particle size and shape were illustrated respectively by laser scattering and transmission electron microscopy.The proliferation of nasopharyngeal carcinoma cells was detected by MTT assay;The mouse model of implantation murine sarcoma cells(S-180) was applied to evaluate the anticancer effectiveness of PEG/CS-EPI NPs and CS-EPI NPs in vivo.Results The PEG modified CS NPs were discrete and uniform spheres with average diameter of 322.1 nm.The rate of drug loading and encapsulation is 13% and 74% respectively.The results of the anticancer tests showed a sustained cytotoxicity of loading drug NPs on nasopharyngeal carcinoma cells in vitro and the stealth nanoparticles was more powerful than ordinary nanoparticles on the inhibitory potency in vivo.Conclusion Stealth chitosan nanoparticles as compared with ordinary chitosan nanoparticles seems to be a potential candidate of chemotherapy drug carriers.