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Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.
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Objective To investigate the effect of downregulated activating transcription factor 3 ( ATF3) expression on proliferation of adrenocortical carcinoma cells and its mechanisms. Methods Immunohistochemistry and Western blotting were used to detect the expression of ATF3 in human adrenocortical tumor tissues and cells. Adrenocortical carcinoma cells, Sw-13, and NCI-H259R cells, were transfected with siATF3 using lipidosome 2000, and expression of ATF3 mRNA was determined using RT-PCR; expression of ATF3, cleaved caspase 3, caspase 3, cleaved PARP, and PARP proteins were detected using Western blotting; cell growth inhibition rate and apoptosis rate were monitored using MTT and AnnexinV-FITC/PI, respectively. Sw-13 and NCI-H259R cells were treated with NVP-BEZ235, Perifosine, BKM120, IWP-2, PP2, KN93, Everolimus respectively followed by detected expression of ATF3 mRNA by realtime PCR. The effect of ATF3 on cell proliferation after inhibition of related signaling pathways were detected by MTT. Results The ATF3 in human adrenocortical gland tumor tissues and cells showed high expression. The levels of ATF3 mRNA and protein in Sw-13 and NCI-F259R cells transfected with siATF3 were significantly reduced. Compared with the negative control group ( NC siRNA), siATF3 transfection significantly inhibited the proliferation of Sw-13 and NCI-F259R cells ( P＜0. 05 ), and increased the apoptosis rate ( P＜0.05). Western blotting shown that the levels of cleaved caspase 3 and cleaved PARP protein in siATF3 transfected cells increased significantly; and realtime PCR results indicated that the expression of ATF3 mRNA was dramatically inhibited by PP2, KN93, and IWP-2 in NCI-F259R cells compared with control group ( DMSO ); but ATF3 significantly promoted the proliferation activity of NCI-F259R cells which treated by PP2, KN93, and IWP-2 signaling inhibitors. Conclusion High expression of ATF3 is existed in adrenocortical carcinoma cells. Downregulated ATF3 expression may inhibit cell proliferation and activate apoptosis pathway, resulting in apoptosis in Sw-13 and NCI-F259R cells, this mechanism of action is related to activating Wnt/β-catenin, CaMKI, and SRC pathway.
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Objective To investigate the effect of FAM83A on the stem cell-like phenotype, chemosensitivity and radiosensitivity of PANC-1 cells, aiming to provide new ideas for clinical combination therapy of pancreatic cancer. Methods The PANC-1 cells with stable silencing FAM83A were constructed by using lentivirus and validated by qPCR and Western blot. Flow cytometry was used to detect the number of CD133 positive cells and cellular apoptosis; the sphere formation assay was used to test the ability of sphere formation of PANC-1 cells;the effect of gecitabine on the cell viability was detected by MTT assay;the effect of radiation on the proliferation of PANC-1 cells was detected by colony formation assay; the effect of FAM83A on Wnt/β-catenin pathway was examined by Western blot. Results The expressions of FAM83A protein ( 0.83 ± 0.08 ) and mRNA ( 0.29 ± 0.03 ) in PANC-1 cells with stable silencing FAM83A were significantly lower than those in the scrambled control group, respectively (1.95 ± 0.19, 0.98 ± 0.09;t=9.410, 12.600, P<0.05). After silencing FAM83A, the expression of stem cell marker CD133 (8.97 ± 0.62) and the sphere formation ability (8 ± 1) also decreased significantly compared with the scrambled group, respectively (21.60 ± 2.60, 25 ± 3; t=8.184, 9.311, P<0.05), and the stem cell-like phenotype of PANC-1 cells was also significantly inhibited. When PANC-1 cells were silenced by FAM83A and further treated with 50 μmol/L gecitabine at 72 h, the activity of FAM83A-silenced PANC-1 cells (32.33 ± 3.05)％ was significantly lower than that of the gecitabine alone treated group (63.06 ± 5.98)％ (t=6.378, P<0.05), and the apoptosis rate of FAM83A-silenced PANC-1 cells (76.52 ± 8.34) ％ was significantly higher than that of gemcitabine alone group (40.88 ± 4.91)％(t=7.929, P<0.05). After silencing FAM83A combined with IR irradiation, the activity of PANC-1 cells (43.25 ±4.21)％ was significantly lower than that of IR alone (78.13 ± 7.98)％ (t=6.694, P<0.05), and the apoptosis rate (44.56 ± 5.32)％ was significantly increased compared with IR alone (15.15 ±1.95)％ (t = 8.990, P < 0.05). After silencing FAM83A, the expression of Active-β-catenin was significantly decreased while the expression of p-β-catenin was significantly increased, the expression of β-catenin in the nucleus was significantly reduced, although total β-catenin had no significant change, and the activity of Wnt/β-catenin signaling pathway was significantly inhibited. Conclusions Silencing FAM83A could significantly reduce the stem cell-like traits and enhance the chemosensitivity and radiosensitivity of pancreatic cancer cells to gemcitabine and radiation via Wnt/β-catenin signaling pathway, which may provide a new target for targeted and combination therapy of pancreatic cancer.
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OBJECTIVE:To compare therapeutic efficacy and safety of lobaplatin or cisplatin combined with tegafur,gimeracil and oteracil potassium in the treatment of advanced metastatic breast cancer.METHODS:A total of 160 patients with advanced metastatic breast cancer were randomly divided into observation group and control group,with 80 cases in each group.Control group was given Cisplatin injection 30 mg/m2 intravenously,every 3 weeks Tegafur,Gimeracil and Oteracil Potassium capsules 50 mg orally after meal,twice a day,for consecutive 14 days.Observation group was given Lobaplatin for injection 30 mg/m2 intravenously,every 3 weeks+Tegafur,Gimeracil and Oteracil Potassium capsules (same usage and dosage as control group),every 3 weeks.A treatment course lasted for 3 weeks,and both groups received 2 courses.Short-term efficacies (ORR、DCR),chemotherapy effects of lymph node,lung,bone and liver,ADR and long-term efficacy were compared between 2 groups.RESULTS:After treatment,ORR(67.50％ vs.46.25％),DCR(85.00％ vs.66.25％),ORR of lymph node metastasis (71.43％ vs.47.83％),ORR of lung metastasis (60.71％ vs.40.00％),DCR of lung metastasis (78.57％ vs.56.00％),ORR of bone metastasis (28.57％ vs.16.67％),1-year survival rates (75.00％ vs.52.50％) and 2-years survival rates (42.50％ vs.17.50％) of observation group were significantly higher than control group;the incidence of chemotherapy ADR in observation group was significantly lower than control group (43.75％ vs.70.00％),with statistical significance (P＜0.05).There was no statistical significance in lymph node metastasis DCR,bone tissue metastasis DCR,liver metastasis ORR and DCR,or half year sarvival rate between 2 groups (P＞0.05).CONCLUSIONS:Compared to cisplatin combined with tegafur,gimeracil and oteracil potassium,lobaplatin combined with tegafur,gimeracil and oteracil potassium show better short-term therapeutic efficacy,therapeutic efficacy of lymph node metastasis,bone metastasis and lung metastasis,more than 1-year long-term therapeutic efficacy and safety in the treatment of advanced metastatic breast cancer.
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BACKGROUND:Breast cancer stem cels are relatively special cels in the body, which have the self-renewal and multi-differentiation ability to promote tumor formation and development, and maintain tumor growth for a long-term. Therefore, it is of great significance to analyze the expression of resistance proteins of breast cancer stem cels. OBJECTIVE:To isolate breast cancer stem cels from human breast cancer tissues, to observe their differentiation and morphology characteristics and to analyze their resistance proteins. METHODS:Thirty tumor samples of breast invasive ductal carcinoma were selected to separate single cel suspension using mechanical separation method, and breast cancer stem cels and differentiated cels were sorted with two-step immunomagnetic bead method. Two-step immunocytochemistry method was used to detect the expression of resistance proteins in breast cancer stem cels. RESULTS AND CONCLUSION:Percentage of breast cancer stem cels had no significant correlations with age, long diameter of the tumor, lymph node metastasis and histological grading (P > 0.05). P-gp and GST-π positive rates in the breast cancer stem cels were significantly higher than those in the differentiated cels (P < 0.05); while TopoII and LRP positive rates in the breast cancer stem cels were significantly lower than those in the differentiated cels (P < 0.05). To conclude, breast cancer stem cels show stronger drug resistance than the differentiated cels by highly expressing P-gp and GST-π and lowly expressing TopoII and LRP, which may be the key reason for chemotherapy resistance in breast cancer.
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Objective To evaluate the effects of comprehensive schistosomiasis control in marshlands of Pukou District Nanjing City so as to provide the evidence for developing the strategy of the disease control. Methods The information of the prevention and control of schistosomiasis was collected in Pukou District from 2004 to 2013. The variations of the infection rates of human livestock and Oncomelania hupensis snails were analyzed. Results In 2013 the area with snails in the entire dis-trict was 384.09 hm2 which was 66.24%decrease compared to 1 137.61 hm2 in 2004. Moreover after 2008 no infected-snails and schistosomiasis patients were found and both the density of live snails and serum positive rate of schistosomiasis declined with years. Conclusions After the comprehensive prevention and control is conducted the schistosomiasis situation in Pukou District is stable. However in order to consolidate the results it is still essential to continue monitoring the previous infected snail environments and implementing the comprehensive prevention and control measures.
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The Rictor/mTOR complex plays a pivotal role in a variety of cellular functions including cellular metabolism, cell proliferation and survival by phosphorylating Akt at Ser473 to fully activate the Akt kinase. However, its upstream regulatory pathways as well as whether it has additional function(s) remain largely unknown. We recently reported that Rictor contains a novel ubiquitin E3 ligase activity by forming a novel complex with Cullin-1, but not with other Cullin family members. Furthermore, we identified SGK1 as its downstream target. Interestingly, Rictor, but not Raptor or mTOR, promotes SGK1 ubiquitination. As a result, SGK1 expression is elevated in Rictor(-/-) MEFs. We further defined that as a feedback mechanism, Rictor can be phosphorylated by multiple AGC family kinases including Akt, S6K and SGK1. Phosphorylation of Rictor at the Thr1135 site did not affect its kinase activity towards phosphorylating its conventional substrates including Akt and SGK1. On the other hand, it disrupted the interaction between Rictor and Cullin-1. Consequently, T1135E Rictor was defective in promoting SGK1 ubiquitination and destruction. This finding further expands our knowledge of Rictor's function. Furthermore, our work also illustrates that Rictor E3 ligase activity could be governed by specific signaling kinase cascades, and that misregulation of this process might contribute to SGK overexpression which is frequently observed in various types of cancers.