Effect of Survivin Down-Regulation by Egr1-Survivin shRNA Combined with Radiotherapy on Radiosensitivity of Esophageal Squamous Carcinoma / Efecto de la Regulación Negativa de Survivina por shRNA de Egr1-Survivina Combinado con Radioterapia sobre la Radiosensibilidad del Carcinoma Escamoso de Esófago

SUMMARY: This study is to investigate the effect of survivin down-regulation by Egr1-survivin shRNA combined with radiotherapy on the apoptosis and radiosensitivity of esophageal squamous cell carcinoma ECA109 and KYSE150 cells. ECA109 and KYSE150 cells were transfected with Egr1-survivin shRNA, and then treated with radiotherapy. After 24 h, the mRNA and protein levels of Egr1-survivin were detected by qPCR and Western-Blot. Cell cycle and apoptosis were detected by flow cytometry. Western blot also detected levels of cleavaged Caspase 3 and Caspase 9. YM155 was used as a positive control to inhibit survivin expression. The levels of survivin mRNA and protein in ECA109 and KYSE150 cells treated with Egr1-survivin shRNA combined with radiotherapy were significantly lower than those of the blank control group, the empty vector control group, and, the YM155 + radiotherapy group (P<0.05). Meanwhile, after survivin down-regulation, the ratio of G2 to S phase of ECA109 and KYSE150 cells increased significantly, leading to significant G2 and S phase arrest. Additionally, apoptosis of ECA109 and KYSE150 cells increased significantly (P <0.01). Further, protein levels of cleavaged Caspase 3 and Caspase 9 significantly increased in Egr1-survivin shRNA combined with radiotherapy group. Egr1-survivin shRNA combined with radiotherapy can down-regulate survivin expression, which further increases the apoptosis, and enhances the radiosensitivity of ECA109 and KYSE150 cells.

Este estudio tuvo como objetivo investigar el efecto de la regulación negativa de survivina por el shRNA de Egr1-survivina combinado con radioterapia sobre la apoptosis y la radiosensibilidad del carcinoma de células escamosas de esófago Células ECA109 y KYSE150. Las células ECA109 y KYSE150 se transfectaron con shRNA de survivina Egr1 y luego se trataron con radioterapia. Después de 24 h, los niveles de ARNm y proteína de Egr1-survivina se detectaron mediante qPCR y Western-Blot. El ciclo celular y la apoptosis se detectaron mediante citometría de flujo. La transferencia Western también detectó niveles de Caspasa 3 y Caspasa 9 escindidas. Se usó YM155 como control positivo para inhibir la expresión de survivina. Los niveles de ARNm y proteína de survivina en células ECA109 y KYSE150 tratadas con shRNA de survivina Egr1 combinado con radioterapia fueron significativamente más bajos que los del grupo control en blanco, el grupo control de vector vacío y el grupo de radioterapia YM155 + (P <0,05). Mientras tanto, después de la regulación negativa de survivina, la proporción entre las fases G2 y S de las células ECA109 y KYSE150 aumentó significativamente, lo que llevó a una detención significativa de las fases G2 y S. Además, la apoptosis de las células ECA109 y KYSE150 aumentó significativamente (P <0,01). Además, los niveles de proteína de Caspasa 3 y Caspasa 9 escindidas aumentaron significativamente en el shRNA de Egr1- survivina combinado con el grupo de radioterapia. El shRNA de survivina de Egr1 combinado con radioterapia puede regular negativamente la expresión de survivina, lo que aumenta aún más la apoptosis y mejora la radiosensibilidad de las células ECA109 y KYSE150.

The prognostic effect of immunohistochemical staining rates in patients with non–muscle-invasive bladder cancer

Context: Despite the follow-up protocols developed in non–muscle-invasive bladder cancer patients, progression and recurrence could not be prevented. Aims: We aimed to investigate whether proteins such as OCT-4, CD47, p53, Ki-67, and Survivin, which increase in bladder cancer cells, can be used as prognostic markers for patients with non–muscle-invasive bladder cancer. Settings and Design: The study included a total of 89 patients with newly diagnosed non–muscle-invasive bladder cancer between January 2015 and December 2020. Materials and Methods: Levels of OCT-4, CD47, p53, K?-67, and Survivin proteins in cancer cells were determined with a semi-quantitative immunohistochemical experiment. Pathological data and survival rates were compared according to the staining rates. Statistical Analysis Used: Data obtained in the study were analyzed statistically with SPSS 22.0 (SPSS, Chicago, IL, USA). Results: The mean age of the patients was 64.25 ± 9.91 years, and the median follow-up period was 55 months. Recurrence rate was determined to be 36% (n = 32), and the rate of progression at 40.4% (n = 36). The staining rates were stronger for each marker in the progression group and advanced-stage tumors (p < 0.001). The findings of the multivariate analysis carried out as part of the study showed that older age and higher tumor stage were independent risk factors for recurrence-free survival (HR = 1.048 and 7.074, respectively; P = 0.02). Also, higher tumor stages, diameters, and grades were associated with reduced progression-free survival (HR = 0.105, 0.395, 0.225, respectively; P < 0.05). Conclusions: Although immunohistochemical staining rates are promising, it is more appropriate to use tumor characteristics when assessing survival rate in patients with non–muscle-invasive bladder cancer.

Survivin expression as a prognostic marker for breast cancer

SUMMARY OBJECTIVE: Due to the speed of development observed in breast cancer, several studies aimed at discovering new biomarkers have been carried out in order to arrive at an early diagnosis. As survivin plays a fundamental role in the evasion of apoptosis in tumor cells, the aim of this study was to verify the expression profile of the survivin gene in paraffin-embedded breast tumor samples and associate it with the clinical characteristics of the patients. METHODS: This is a cross-sectional study, for which 100 tumor samples were obtained from cancer patients treated throughout the year 2019 at Instituto de Mama do Cariri (Juazeiro do Norte, in the state of Ceará). This study included women over 30 years old who had confirmed breast cancer through anatomopathological examination but excluded those with non-neoplastic breast comorbidities, other neoplasms, or chronic diseases. Survivin gene expression was assessed by quantitative polymerase chain reaction. RESULTS: The expression of survivin is associated with the lack of expression of estrogen (p=0.027) and progesterone (p>0.0005) receptors. It means that survivin expression is higher in patients in which labeling was absent for estrogen receptor and progesterone receptor. CONCLUSION: Our data reinforce that survivin expression is higher in estrogen receptor-patients, thus representing an additional prognostic tool.

A novel nano-formulation of olmesartan medoxomil with improved delivery and efficacy in the treatment of indomethacin-induced duodenitis in rats

There are few studies addressing duodenal inflammation. This study was designed to investigate the effects of a recently developed biotechnological product, a nano-formulation of olmesartan medoxomil (OM) - olmesartan medoxomil zeinmersomes (OMZ) - for the treatment of indomethacin-induced duodenitis in rats. Adult male Wistar rats were given indomethacin (10 mg/kg/day) for four weeks. They were divided into a positive control group (PC, untreated) and two groups treated orally with 3 mg/kg per day of OM or OMZ for the last two weeks of the 4-week indomethacin-treatment. At end of the four weeks, blood and duodenum were collected. Duodenal homogenate was used for measurement of levels of myeloperoxidase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde, reduced glutathione (GSH), and cleaved caspase-3. Duodenal sections were stained with H&E. Gene expressions of nuclear factor kappa B (NF-κB p65), Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2) by RT-PCR, and protein expression of survivin by western blot were assessed. Plasma and duodenal olmesartan concentrations were measured by high performance liquid chromatography mass spectrometry. The duodenitis rats showed significantly higher duodenal levels of myeloperoxidase, TNF-α, IL-6, malondialdehyde, and cleaved caspase-3, a significantly lower GSH level, and histopathological alterations. Moreover, they showed upregulated gene expressions of NF-κB p65 and Bax, downregulated gene expression of Bcl-2, decreased Bcl-2/Bax ratio, and lower protein expression of survivin. OMZ was more effective in protecting the duodenum from indomethacin-induced injuries compared to OM due to improved delivery, higher bioavailability, and better anti-inflammatory, antioxidant, and antiapoptotic effects. OMZ could be a better choice for hypertensive patients with non-steroidal anti-inflammatory drugs-induced duodenitis.

Expressions of survivin, p53 and human epidermal growth factor receptor 2 in breast cancer tissues and their prognostic value / 肿瘤研究与临床

Objective:To investigate the expressions of apoptosis-related factors survivin, p53 and human epidermal growth factor receptor 2 (HER2) in breast cancer tissues and their prognostic value.Methods:A total of 131 patients undergoing radical mastectomy for breast cancer who were admitted to Tangshan Maternal and Child Health Care Hospital from February 2015 to January 2019 were selected as the research subjects. During the operation, the cancer tissues and adjacent tissues (normal tissues >3 cm from the tumor margin) were collected from the patients. Expressions of survivin, p53 and HER2 in cancer tissues and adjacent tissues of patients were detected by using immunohistochemistry. The prognoses of patients were recorded after the follow-up for 3 years; the recurrence, metastasis and death treated as the poor prognosis, the rest prognoses of patients were treated as the good prognosis group. The difference of clinicopathological characteristics between the poor prognosis group and the good prognosis group was compared. Multivariate logistic regression was used to analyze risk factors for prognosis of breast cancer patients. The result of prognosis of breast cancer was taken as the golden standard. The receiver operating characteristic (ROC) curve was used to analyze the value of survivin pasitive, p53 pasitive, HER2 pasitive alone, the combination of both and the combination of the there in the judgement of poor prognosis of breast cancer.Results:The positive expression rates of survivin [49.6% (65/131) vs. 7.6% (10/131)], p53 [60.3% (79/131) vs. 13.0% (17/131)] and HER2 [79.4% (104/131) vs. 16.8% (22/131)] in cancer tissues were higher than those in adjacent tissues (all P<0.001). A total of 131 breast cancer patients were followed up for 3 years without any loss of follow-up, and the follow-up rate was 100%. Within the follow-up for 3 years, there were 15 (11.5%) cases of recurrence, 8 (6.1%) cases of metastasis, and 10 (7.6%) cases of death, the incidence of poor prognosis was 25.2% (33/131); and the remaining 98 cases had good prognosis. The proportions of patients with TNM stage Ⅲ, lymph node metastasis, poorly differentiated histology, tumor diameter ≥3 cm, survivin, p53, and HER2 positive expressions in the poor prognosis group were higher than those in the good prognosis group (all P<0.05). Multivariate logistic regression analysis showed that TNM stage Ⅲ [ OR = 5.323 (95% CI 2.190-12.936)], lymph node metastasis [ OR = 4.773 (95% CI 1.964-11.600)], tumor diameter ≥3 cm [ OR = 3.582(95% CI 1.474-8.706)], positive survivin [ OR = 2.740 (95% CI 1.127-6.659)], positive p53 [ OR = 3.271 (95% CI 1.346-7.949)], and positive HER2 [ OR = 3.873 (95% CI 1.594-9.412)] were independent risk factors for prognosis of breast cancer (all P<0.001). The ROC curve results showed that the area under the curve (AUC) values of survivin positive, p53 positive,HER2 positive, and the combination of any two were more than 0.80 (all P<0.001); the AUC of the combination of the three was 0.944 (95% CI 0.890-0.977) ( P<0.001). Conclusions:The expressions of survivin, p53, and HER2 are highly expressed in breast cancer tissues. The expressions of the three can be used to judge the prognosis of breast cancer patients, and the combination of the three has a higher judgement value.

Anti-proliferating effect of Ocimum sanctum and Centella asiatica plant extract on growth of human glioblastoma cells: An in vitro study

Glioblastoma is aggressive brain tumour with poor prognosis with conventional chemotherapy, hence there is need to find alternative targets for developing newer treatment. Advent of new treatment methods involving medicinal plants have shown to reduced Cancer mortalities and prevents development of drug resistance for chemotherapy. Present study aimed at investigates the anti-proliferating activity of two promising medicinal plants, Ocimum sanctum and Centella asiatica. We studied the effect of their plant extract on U87MG Glioblastoma cells proliferation, survival effect and apoptosis. Cytotoxic activity was assessed, after the plant extract treatment on U87MG using MTT assay with dose of 1 mg/mL to 25mg/mL and apoptosis assess was done using Annexin V assay with the three dose (1.5 mg/mL, 2 mg/mL and 2.5 mg/mL). Survivin gene expression was studied using QRT-PCR (Rotar gene Q, Qiagene) has a marker of proliferation. Ocimum sanctum and Centella asiatica treatment of U87MG cells with dosage of 1.5 mg/mL, 2.0 mg/mL, 2.5 mg/mL showed increase in mean apoptotic cells 2.8 %, 4.9%, 10 % and 3.1%, 5.8% and 7.2%, respectively, compared to untreated U87MG cells. Survivin gene analysis of U87MG cells showed down-regulation in gene expression and differences was significant in comparison to untreated control group with both the plant extract, Centella asiatica showed more down-regulation (97% with 2.5 mg/mL) than Ocimum sanctum. Ocimum sanctum and Centella asiatica exhibited promising anti-proliferating activity and induces apoptosis by down regulation of survivin gene expression

Dehydroabietic acid chemosensitizes drug-resistant acute lymphoblastic leukemia cells by downregulating survivin expression

Objective: To explore the mechanism of drug resistance in acute lymphoblastic leukemia and the anti-tumor effect of combination therapy of dehydroabietic acid and vincristine against acute lymphoblastic leukemia cells. Methods: Acute lymphoblastic leukemia cells REH and CCRF- CEM were employed to detect the anti-tumor effect of vincristine and doxorubicin on proliferation and apoptosis using EdU assay, human active caspase-3 Quantikine ELISA kit, and flow cytometry. Vincristine-resistant REH cells (REH-R), survivin knockdown and overexpressing REH cells were established to verify the role of survivin in drug resistance. Additionally, in vitro and in vivo assays were performed to determine the effect of dehydroabietic acid on the cytotoxicity of vincristine. Results: Vincristine and doxorubicin markedly suppressed proliferation and induced apoptosis of REH and CCRF-CEM cells. Survivin expression was upregulated in REH-R cells compared with REH cells. Knockdown of survivin expression obviously restored the sensitivity of REH-R cells to vincristine. Akt phosphorylation was also increased in REH-R cells compared to REH cells. In addition, LY294002, a PI3k/Akt pathway blocker, inhibited survivin expression and enhanced cytotoxicity of vincristine to REH-R cells. Dehydroabietic acid effectively reduced survivin expression in REH-R cells, thereby enhancing the therapeutic effect of vincristine on drug-resistant cells. Survivin overexpression markedly reduced the effect of dehydroabietic acid on enhancing the anti-proliferation and inducing apoptosis effect of vincristine. Moreover, the combination of dehydroabietic acid with vincristine significantly extended the survival rate in a mouse xenograft model of acute lymphoblastic leukemia, compared with vincristine treatment alone. Conclusions: Dehydroabietic acid may be used as a potential candidate for the treatment of acute lymphoblastic leukemia in combination with vincristine.

Influence of buccal acupuncture on analgesic effect, immune indicators, and expression of Survivin and Livin proteins in patients with advanced-stage primary liver cancer / 针灸推拿医学（英文版）

Objective: To investigate the effects of buccal acupuncture on analgesia, immune indicators, and expression levels of Survivin and Livin proteins in patients with advanced-stage primary liver cancer. Methods: Eighty patients with advanced-stage primary liver cancer were selected and divided into control and treatment groups according to the difference in treatment modalities, with 40 patients in each group. The control group received transcatheter arterial chemoembolization (TACE), and the treatment group received buccal acupuncture in addition to TACE. The recent efficacy, analgesic effect, liver function, serum tumor markers, Survivin and Livin protein expression levels in liver cancer tissue, and immune indexes were analyzed and compared between the two groups. Results: The objective response rate (ORR) and disease control rate (DCR) of the treatment group were 37.5％ and 77.5％, respectively, which were significantly higher than those of the control group (22.5％ and 52.5％), and the recent efficacy of the treatment group was significantly better than that of the control group (P<0.05). The onset of analgesia in the treatment group was significantly faster than that in the control group (P<0.05), the duration of analgesia was significantly longer than that in the control group (P<0.05), and the numeric rating scale (NRS) score of pain after treatment was significantly lower than that in the control group (P<0.05). In the treatment group, the aspartate aminotransferase (AST), alanine aminotransferase (ALT), and albumin/globulin (A/G) were significantly lower than those in the control group (P<0.05), and the serum levels of alpha-fetoprotein (AFP), alpha-L-fucosidase (AFU), and carcinoembryonic antigen (CEA) were significantly lower than those in the control group (P<0.05), and the expression levels of Survivin and Livin in liver cancer tissue were significantly lower than those in the control group (P<0.05); CD4+ and CD4+/CD8+ in the treatment group were significantly higher than those in the control group, and CD8+ was significantly lower than that in the control group after treatment (P<0.05). Conclusion: Buccal acupuncture can reduce the degree of pain and liver function damage in patients with advanced- stage primary liver cancer and lower the serum tumor marker levels, and its mechanism of action may be related to the down-regulation of Survivin and Livin protein expression levels in the liver cancer tissue and the regulation of the immune function.

Effect of Huoxue Jiedu Runzao Prescription on Expression of Apoptosis Inhibitor Survivin in Submandibular Gland Cells of Sjögren's Syndrome Mice / 中国实验方剂学杂志

Objective:To investigate the effect of Huoxue Jiedu Runzao prescription on the morphology， apoptosis， and function of submandibular gland in the mouse model of Sjögren's syndrome （SS） and its functioning mechanism， we analyzed the expression of the apoptosis inhibitor Survivin in the submandibular gland cells of SS mice. Method:Female BALB/c57 mice were selected as the normal group. The naive non-obese diabetic （NOD/Ltj） female mice were selected as the SS model， which were randomly assigned into the model group， Paeoniae Radix Alba total glucosides capsule （0.234 g·kg^-1） group， and low-， medium-， and high-dose （15.6， 31.2， 62.4 g·kg^-1， respectively） Huoxue Jiedu Runzao prescription groups. Each group had 15 mice. The morphological and functional changes of submandibular gland and the Survivin expression were observed and measured after 8 weeks of drug intervention. Survivin expression was determined by immunohistochemistry （IHC）， Western blot， and reverse transcription-polymerase chain reaction （RT-PCR）. Result:Compared with normal group， salivary flow and submandibular gland index in model group were significantly decreased （<italic>P</italic><0.01）， and histopathological score of submandibular gland was significantly increased （<italic>P</italic><0.01）. Western blot showed that Survivin protein expression was significantly decreased （<italic>P</italic><0.05）. IHC showed that， Survivin mRNA expression was significantly decreased （<italic>P</italic><0.01）， and RT-PCR results showed that Survivin mRNA expression was significantly decreased （<italic>P</italic><0.01）. Compared with model group， salivary flow and submandibular gland index of mice in Huoxue Jiudu Runzao prescription groups and Paeoniae Radix Alba total glucosides capsules groups were significantly increased （<italic>P</italic><0.05）， histopathological score of submandibular gland was significantly decreased （<italic>P</italic><0.05）， IHC results showed that Survivin expression was significantly increased （<italic>P</italic><0.01）. Western blot and RT-PCR results showed that Survivin protein and mRNA expression of Huoxue Jiudu Runzao prescription high-dose group and Paeoniae Radix Alba total glucosides capsule group were significantly increased （<italic>P</italic><0.05）. Conclusion:Huoxue Jiedu Runzao prescription can improve the secretion function of submandibular acinus， increase the submandibular gland index， and saliva secretion of SS mice by up-regulating survivin in submandibular gland cells of SS mice.

Expression and its clinicopathological significance of Survivin, MSH2 and MSH6 in colorectal cancer / 中国医师杂志

Objective To analyze the changes of Survivin,MSH6 and MSH2 expression in colorectal cancer and explore their relationship with clinical and pathological parameters.Methods 197 cases of colorectal adenocarcinoma and 20 cases of inflammatory intestinal mucosa were detected by immunohistochemistry with Survivin,MSH6 and MSH2,and the correlation between Survivin,MSH6 and MSH2 expression was analyzed.Results In the control group of 20 cases with inflammatory non-tumor intestinal mucosa,the positive expression rate of MSH2,MSH6,Survivin were 95％,95％,10％,respectively.While the positive expression rate of MSH2,MSH6,Survivin were 88.3％,74.1％ and 84.3％ in 197 cases of colorectal cancer.Survivin positive expression rate in colorectal cancer group was significantly higher than that in inflammatory control group (P ＜ 0.05).Survivin expression was correlated with invasion depth and lymph node metastasis in colorectal cancer tissue (P ＜ 0.05),but not with gender,age,tumor size,gross type or degree of differentiation (P ＞ 0.05).MSH2 expression was correlated with tumor size and lymph node metastasis (P ＜ 0.05),but not with gender,age,gross type,depth of infiltration and degree of differentiation (P ＞ 0.05).MSH6 expression was related to gender and lymph node metastasis (P ＜ 0.05),but not to age,tumor size,gross type,infiltration depth and differentiation (P ＞ 0.05).Colorectal cancer tissues showed positive correlation between MSH6 and MSH2 (r =0.326,P ＜ 0.01),positive correlation between MSH2 and Survivin positive expression (r =0.277,P ＜ 0.01),and positive correlation between MSH6 and Survivin positive expression (r =0.435,P ＜ 0.01).Conclusions The positive expression rate of Survivin in colorectal cancer is high.MSH2,MSH6 and Survivin in colorectal cancer play an important role in the development and progression of colorectal cancer,and can provide evidence for the detection of these three factors,including metastasis risk,prognosis assessment and clinical treatment.In particular,Survivin gene may provide evidence for gene therapy.

Correlation of Survivin gene and UHRF1 gene expressions with sensitivity to cervical cancer in cervical cancer / 西安交通大学学报(医学版)

Objective: To study the expressions of Survivin mRNA and UHRF1 mRNA in cervical cancer tissues and their relationship with radiosensitivity to cervical cancer. Methods We recruited 112 patients with cervical cancer who underwent radical radiotherapy in our hospital. The expression levels of tumor Survivin mRNA and UHRF1 mRNA were detected by RT-PCR. We analyzed the correlation of expression levels of Survivin mRNA and UHRF1 mRNA, as well as clinical characteristics such as age, stage, tumor differentiation and tumor diameter with radiosensitivity. The independent predictors related to radiosensitivity were analyzed by Logistics. Results: After radiotherapy in 112 patients with cervical squamous cell carcinoma, 48 patients received radiotherapy and 64 patients received radiotherapy. Compared with radiosensitivity group, the degree of differentiation was lower and the tumor diameter was larger, and the expression levels of Survivin mRNA and UHRF1 mRNA were higher in the radioresistance group (P0.05), but Univariate and multivariate logistic analysis showed that Survivin mRNA and UHRF1 mRNA expression levels were the independent predictors of radiosensitivity in the cervical cancer patients. Patients with low expressions of Survivin mRNA and UHRF1 mRNA had higher sensitivity to radiotherapy. Conclusion: The expressions of Survivin mRNA and UHRF1 mRNA are negatively correlated with the sensitivity to cervical squamous cell carcinoma. The lower the expression, the higher the sensitivity of radiotherapy.

Inhibitory effect of ursolic acid on proliferation of TPC-1 cells in thyroid carcinoma / 医学研究生学报

ObjectiveAt present, there are relatively few studies on the inhibitory effect of ursolic acid (UA) on the proliferation of thyroid cancer cells. This paper intends to explore the inhibitory effect and mechanism of ursolic acid on the proliferation of TPC-1 cells in thyroid papillary carcinoma.MethodsAfter adhering TPC-1 cells to the wall, the original medium was discarded and added ursolic acid medium without fetal bovine serum (0, 2, 4, 8, 16, 32 μmol/L, respectively, with 0 μmol/L as the control), and then the culture medium without cells was used as blank. The proliferation inhibition rate of TPC-1 cells was detected by CCK8 reagent at different times (24 h, 48 h); Flow cytometry was used to detect the apoptosis rate; JC1 kit was used to detect the changes of mitochondrial membrane potential (MMP) of TPC-1 cells after ursolic acid was applied; Fluorescent probe DCFH-DA was used to detect reactive oxygen species in TPC-1 cells after ursolic acid intervention; Flow cytometry was used to detect the protein expression of survivin and vascular endothelial growth factor (VEGF) in cells. RT-PCR assay detected the expression of survivin and VEGF mRNA in TPC-1 cells after the intervention of ursolic acid at different concentrations.ResultsThe inhibitory rate of 2, 4, 8, 16 and 32 mol/L ursolic acid on TPC-1 cells was significantly higher than that of 0 mol/L (P<0.01), and the inhibitory rate of 48 h ursolic acid on TPC-1 cells was significantly higher than that of 24 h (P<0.05). Therefore, the TPC-1 cell inhibition rate was positively correlated with ursolic acid concentration and the time (P<0.05). The apoptosis rates of 0 mol/L, 4 mol/L and 8 mol/L ursolic acid were (4.13±0.61)%, (6.53±0.65)% and (13.13±1.59)%, respectively. With the increase of the concentration, the apoptosis rate of TPC-1 cells increased gradually (P<0.05). The relative expression levels of survivin, VEGF protein and mRNA of 4 and 8 mol/L ursolic acid were significantly lower than those of 0 mol/L (P<0.05), and the expression levels of 8 mol/L ursolic acid was significantly lower than that of 4 mol/L (P<0.05).ConclusionUrsolic acid can effectively inhibit the proliferation and induce the apoptosis of TPC-1 cells, and its inhibitory induction pathway is related to the expression of survivin and VEGF in cells.

The association between survivin −31G>C polymorphism and susceptibility to sporadic colorectal cancer in a Southern Chinese population

Background: The case–control study aimed to investigate the association between the −31G>C polymorphism in the promoter of survivin gene and the susceptibility to sporadic colorectal cancer (CRC) in a Southern Chinese population. Materials and Methods: The study was carried out on 711 healthy controls and 702 CRC cases of a Southern Chinese population. Survivin gene −31G>C genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. The association between CRC risk and −31G>C genetic polymorphism was estimated using an unconditional logistic regression model. Results: The number of CC genotype carried in CRC patients was much higher than those of controls (P < 0.001). Compared with CC genotypes, GC, GG genotypes and −31G wild-type genotypes (i.e., GC + GG) had a significantly decreased risk of CRC (P < 0.001). In addition, survivin −31G wild-type genotypes were not associated with decreased risk of sporadic CRC patients with body mass index (BMI) ≥28.0 kg/m2, family cancer history, and premenopausal. Conclusion: Survivin −31G>C polymorphism is associated with sporadic CRC risk in the Southern Chinese population. The −31G wild-type genotypes and GC, GG genotypes are the independent protective factors against sporadic CRC excluding those with a BMI ≥28.0 kg/m2, family cancer history, and premenopausal

CAFs conditioned medium up-regulates the expression of survivin gene in human intrahepatic cholangiocarcinoma HCCC-9810 cells / 肿瘤

Objective: To investigate the effect of carcinoma-associated fibroblasts (CAFs) conditioned medium on the expression of survivin gene in human intrahepatic cholangiocarcinoma HCCC-9810 cells. Methods: The effect of CAFs conditioned medium on the proliferation of HCCC-9810 cells was detected by MTT assay. The effect of CAFs conditioned medium on the cell cycle distribution of HCCC-9810 cells was detected by FCM. The effects of CAFs conditioned medium on the expression levels of survivin mRNA and protein were detected by realtime fluorescent quantitative PCR and Western blotting, respectively. Results: CAFs conditioned medium significantly promoted the proliferation of HCCC-9810 cells (P 0.05). The expression levels of survivin mRNA and protein in HCCC-9810 cells were up-regulated by CAFs conditioned medium (both P < 0.05). Conclusion: CAFs conditioned medium can promote the proliferation and cell cycle progression of HCCC-9810 cells. This effect is related to the up-regulaion of survivin mRNA and protein expressions.

Effect of insulin-like growth factor-I receptor on radiosensitivity of HepG2 cells / 中华肝胆外科杂志

Objective@#To explore the effect of insulin-like growth factor-Ⅰ (IGF-Ⅰ) receptor on radiosensitivity of HepG2 cells and the underlying mechanism.@*Methods@#HepG2 cells were divided into the following groups: negative control group, siRNA group, irradiation group and combined group. HepG2 cells were transfected with IGF-Ⅰ receptor siRNA combined with irradiation therapy to investigate the effect on cell proliferation by methyl thiazolyl tetrazolium and cell cycle using flow cytometry. Expression of IGF-Ⅰ receptor, proliferating cell nuclear antigen (PCNA), cyclin-dependent kinases 1(CDK1) and Survivin were detected using Western blotting and Q-PCR.@*Results@#The expression of IGF-Ⅰ receptor in HepG2 cells was decreased significantly after siRNA transfection compared with the control group. After the combinational therapy, cell viability was decreased significantly according with control group [(1.02±0.08) vs. (1.08± 0.10) vs. (0.60±0.07)]; In addition, cell cycle was arrested in G2/M[(20.3±0.3)% vs. (22.6±0.4)% vs. (34.7±0.5)%] and CDK1 expression was reduced significantly. The relative expression of Survivin in siRNA group was lower than negative control group, the difference was statistically significant (P<0.05).@*Conclusion@#Inhibition of IGF-Ⅰ receptor can enhance the radiosensitivity of HepG2 cells through cell cycle arrest.

Expression of survivin, fibronectin-1, VEGF and ezrin in thyroid tumors and their relationship with tumor pathological characteristics / 中国肿瘤生物治疗杂志

@# Objective: To investigate the expression of survivin, fibronectin-1, vascular endothelial growth factor (VEGF) and ezrin in thyroid tumors and their relationship with the pathological characteristics of thyroid tumors. Methods: Ninety patients with thyroid tumors admitted to the third affiliated hospital of Zunyi Medical University and the first hospital during Oct. 2016 and Oct. 2018 were selected as the observation group. Seventy-five patients with normal thyroid confirmed by pathology in the same period were selected as the control group. The protein levels of survivin, fibronectin-1, VEGF and ezrin were detected by immunohistochemical method. Results: The positive rates of survivin, fibronectin-1, VEGF and Ezrin in the control group were 2.67%, l4.00%, 1.33% and 1.33%, which were lower than 97.78%, 96.67%, 93.33% and 95.56% in the observation group, respectively (all P<0.05 or P<0.01). The expressions of survivin, fibronectin-1, VEGF and ezrin were significantly correlated with TNM staging, tumor diameter, extrathyroid invasion and lymphatic metastasis (all P<0.05). Conclusion: Survivin, fibronectin-1, VEGF and ezrin proteins are all involved in the occurrence and development of thyroid tumors. The combined detection of these four indicators is of great significance in the diagnosis, treatment and prognosis of thyroid tumors.

Gene Expression of Molecules Regulating Apoptotic Pathways in Glioblastoma Multiforme Treated with Umbilical Cord Stem Cell Conditioned Medium

@#Background: Glioblastoma multiforme (GBM) is the most malignant primary brain tumour and there is no definite cure. It has been suggested that there are significant interactions among mesenchymal stem cells (MSCs), their released factors and tumour cells that ultimately determine GBM’s growth pattern. This study aims to analyse the expression of molecules involved in GBM cell apoptotic pathways following treatment with the MSC secretome. Methods: A conditioned medium of umbilical cord-derived MSCs (UCMSC-CM) was generated by culturing the cells on serum-free αMEM for 24 h. Following this, human GBM T98G cells were treated with UCMSC-CM for 24 h. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was then performed to measure the mRNA expression of survivin, caspase-9, TNF-related apoptosis-inducing ligand (TRAIL), DR4 and DcR1. Results: mRNA expression of caspase-9 in CM-treated T98G cells increased 1.6-fold (P = 0.017), whereas mRNA expression of survivin increased 3.5-fold (P = 0.002). On the other hand, TRAIL protein expression was upregulated (1.2-fold), whereas mRNA expression was downregulated (0.4-fold), in CM-treated cells. Moreover, there was an increase in the mRNA expression of both DR4 (3.5-fold) and DcR1 (1,368.5-fold) in CM-treated cells. Conclusion: The UCMSC-CM was able to regulate the expression of molecules involved in GBM cell apoptotic pathways. However, the expression of anti-apoptotic molecules was more upregulated than that of pro-apoptotic molecules.

Predictive Value of Serum Survivin Level for Clinical Efficacy of Tumor Necrosis Factor-α Inhibitor Treatment in Patients with Rheumatoid Arthritis / 中国医科大学学报

Objective To investigate the predictive value of serum survivin for clinical efficacy of tumor necrosis factor-α (TNF-α) inhibitor treatment in rheumatoid arthritis (RA) patients. Methods This study enrolled 63 consecutive patients with moderate or severe RA who received TNF-α inhibitor via subcutaneous injection 2 times/week, 25 mg/dose, for 24 weeks. According to disease activity, patients were also administered a disease-modifying antirheumatic drug. Serum survivin level was measured by enzyme-linked immunosorbent assay. The Disease Activity Score 28 was assessed, and clinical response and clinical remission were investigated. Results After treatment, 41 patients had a clinical response and 22 had no response. Baseline serum survivin level was reduced in the responder group compared to that in the non-responder group (P = 0.004). Receiver operating characteristic curve analysis showed that survivin level had good predictive value for non-response to TNF-α inhibitor treatment in RA patients (area under the curve:0.717, 95％ confidence interval:0.583-0.852). High survivin level (≥672.75 pg/mL) was an independent predictor of non-response to TNF-α inhibitor treatment in RA patients (P = 0.011), while a high C-reactive protein (CRP) level was an independent predictor of a better response to TNF-α inhibitor treatment (P = 0.011). High survivin level predicted non-response to TNF-α inhibitor treatment, independent of CRP level. However, baseline survivin level showed no difference between remission (16 cases) and non-remission groups (47 cases) (P = 0.265). A high survivin level did not affect remission in RA patients after TNF-α inhibitor treatment. Conclusion Baseline serum survivin level can predict the response of RA patients to TNF-α inhibitor treatment.

High Survivin and Low Zinc Finger of the Cerebellum 1 Expression Indicates Poor Prognosis in Triple-negative Breast Carcinoma / 한국유방암학회지

PURPOSE: Triple-negative breast carcinoma (TNBC) is accompanied with high risk of metastasis and recurrence. The present study aimed to explore the clinicopathological and prognostic roles of putative tumor-related genes in patients with TNBC. METHODS: Thirty pairs of frozen-thawed tumors were used to select reliable indicators via real-time quantitative polymerase chain reaction (RT-qPCR). Then, 150 pathology specimens were used to evaluate the expression of proteins in TNBC through immunohistochemistry. In addition, Kaplan-Meier curves and Cox regression analysis were also performed to analyze the overall survival and disease-free survival. RESULTS: RT-qPCR results indicated that among all the proteins analyzed using fresh-frozen TNBC samples, the expression levels of only Survivin and zinc finger of the cerebellum 1 (ZIC1) were obviously different from those in the corresponding normal tissues. Survivin and ZIC1 expression had opposite effects on the clinicopathological diagnosis and prognostic assessment in TNBC patients. Further, there was a negative correlation between Survivin and ZIC1 expression. In addition, the “Survivin-positive ZIC1-negative group” was associated with histologic grade, lymph node metastasis, and TNM staging (p < 0.001) and this was also an independent factor for evaluating the prognosis of TNBC in patients. CONCLUSION: In summary, the expression levels of Survivin and ZIC1 in TNBC are different from those in normal tissues and are negatively correlated mutually. The combined detection of Survivin and ZIC1 expression levels could allow better comprehensive diagnosis and prognostic evaluation for TNBC patients.

Inhibitory effect of exopolysaccharide from Rhizopus nigricans combined with oxaliplatin on dimethylhydrazine-induced colon cancer in rats and its effect on Survivin/caspase-3/caspase-7 / 中国药理学通报

Aim To study the inhibitory effect of ex-opolysaccharide from Rhizopus nigricans ( EPS) combined with oxaliplatin on colon cancer in rats and its mechanism. Methods Colon cancer model in rats was established by subcutaneous injection of 1,2-dime-thylhydrazine ( DMH). The experimental rats were randomly divided into five groups: Control group, model group, EPS group (150 mg • kg-1 ) , oxaliplatin group (10 mg • kg-1 ) and EPS + oxaliplatin group. The his-topathological changes of colon tissues in rats were observed by HE staining. The expression levels of Sur-vivin, caspase-3 and caspase-7 proteins in colon tissues were detected by Western blot and immunohisto-chemistry. Results HE staining results showed that the damage degree of colon tissues could be significantly improved in treatment groups. Compared with model group, the expression of Survivin protein in treatment groups decreased significantly, and the expression of caspase-3 and caspase-7 proteins increased ( P < 0. 05). Conclusions Both EPS and oxaliplatin inhibit colon cancer in rats, and the synergistic effect is more remarkable. Its mechanism may be through inhibiting the expression of Survivin protein and increasing the expression of caspase-3 and caspase-7 proteins, thereby promoting the apoptosis of tumor cells and inhibiting the occurrence and development of tumors.