Objective To evaluate the expression of KAII (CD82) gene inhibited by small interfering RNA (siRNA) in human pancreatic cancer cell line T3. Methods Four sequences of siRNA including A, B,C, D were designed, which were based on the KAI1 gene sequence using online RNA interfering designing software and lentivirus vector was built. Then they were used to transfect T3 cells by liposome 2000 and virus titer was determined. Empty vector containing siRNAd1 lentivrus particle ( MOI =5) was also used to infect T3 cells. The expression of CD82 mRNA was detected by real-time PCR. Results The expression of CD82 mRNA in normal control group, empty vector group, A group, B group, C group, D group were 1. 398 ±0.242,1. 311±0.048, 0. 664 + 0. 093, 0. 345 ± 0. 032, 0. 641 ± 0. 049 and 0. 147 ± 0. 049, respectively, the difference between the expression of CD82 mRNA in empty vector group and that of A, B, C, D groups was significant (P＜0.01 ). Conclusions RNAi was able to inhibit the expression of KAI1 gene CD82 in human pancreatic cancer cell line T3.

Objective To observe the inhibitory effect on metastasis and growth of pancreatic cancer in mice by injection of KAI1 gene in vivo. Methods Pancreatic cancer cell line MiaPaCa Ⅱ was used to construct the nude mice models bearing tumors, then the mice were divided into normal saline group, Ad group and Ad-KAI1 group. Since the 10th days of model construction, the Ad-KAI1 was injected every 7 d and repeated twice, then the tumor size, the weight of liver, lung and their pathologic changes were evaluated. Results The tumor sizes were not significantly different between the three groups. The weight of lung and liver of Ad-KAI1 group was (0.366±0.041) g and (1. 35±0.21) g, respectively; the weight of lung and liver of Ad group was (0.57±0.065) g and (1.58±1.828) g, respectively; the weight of lung and liver of control group was (0.66±0.13)g and (1.95±0.344)g, respectively. The difference between Ad-KAI1 group and control group was significantly different (t = 5.984, P < 0. 05), and there was no significant difference between Ad group and control group (t=1.089, P > 0.05). The number of pulmonary, liver and lymph node metastasis in Ad-KAI1 group was (1±1), (2±1) and (2±2), respectively; in Ad group was (6±2), (5 ±1), (10±2), respectively; in control group was (7±2), (6±2), (11±3), respectively. The difference between Ad-KAI1 group and control group was significantly different (t = 7.44, 4.34, 8. 16, P < 0.05), while the difference between Ad group and control group was not significantly different (t=0.92, 0.64, 0.42, P >0.05). Conclusions KAI1 gene directly injected into tumors of nude mice may inhibit the growth and metastasis of pancreatic cancer.

Objective To explore the sensitivity of HER-2-positive BT474 breast cancer cells to trastuzumab after knockdown or overexpression of RNA binding protein 38 ( RNPC1 ) .Methods The expressions of RNPC1 and HER-2 mRNA were detected by qRT-PCR, and the expressions of RNPC1, HER-2 and PI3K/AKT proteins were detected by Western blot after transfected with RNPC1 lentiviral vector, respectively.The experimental groups were treated with different concentration of trastuzumab, and cell apoptosis rate was analyzed by 7-AAD/APC double staining flow cytometry, and cell growth inhibition rate was tested by cell counting kit 8 ( CCK-8) .The expression of apoptosis-related proteins was detected by Western blot assay.Results The results of qRT-PCR showed that overexpression of RNPC1 increased the expressions of RNPC1 and HER-2 mRNA, and the expressions of RNPC1 and HER-2 were decreased after RNPC1 knockdown.The knockdown of RNPC1 decreased the expressions of RNPC1 and HER-2.Moreover, overexpression of RNPC1 decreased and knockdown of RNPC1 increased the levels of p-PI3K and p-AKT while the total protein expressions of both were marginally changed.The results of analysis using a cell counting CCK-8 kit showed that the RNPC1 overexpressed group had a higher growth inhibition rate [(20.33± 1.25)%,(35.38±2.05)%,(50.43±2.12)%,(65 .35±2.08)%and(76.00±2.16)%, respectively] than that of the control group [(13.67±1.24)%,(27.86±2.05)%,( 39.72±1.69)%,(53.33±1.70)%and(62.68± 2.07)%] when treated with different concentrations of trastuzumab (5, 10, 15, 20 and 25 μg/ml).The cell apoptosis rates in the RNPC1-overexpressed group [ ( 19.46 ±1.06 )%, ( 30.87 ±0.98 )%, ( 50.45 ± 1.1)3%, respectively] were also increased compared with that in the control group [(14.38±0 .64)%,(21.65± 1.24)%,(38.03±0.85)%] when treated with different concentrations of trastuzumab (0, 10, 20 and 30μg/ml) ( P<0.05 for all).Reverse results were observed in the RNPC1 knockdown experiments [ experimental groups:(9.67±1.18)%, ( 21.67 ±1.23)%, ( 30.33 ±1.25)%, ( 40.33 ±1.69)%, and ( 53.00 ± 1.63)%] compared with those of control groups:[(14.00±0.82)%, (27.67±1.25)%, (39.67±1.79)%, (53.67±1.50)%, and (63.33±1.52)%];and experimental groups:[(11.64±0.68)%, (16.60±1.01)%, and (25.14±3.12)%] compared with those of the control groups: [(14.71±0.61)%, (22.65±0.96)%, and (39.03±0.85)%].The overexpression of RNPC1 increased the expression levels of Bim and Bad and decreased the level of Bcl-xl, and reverse result was observed after knockdown of RNPC1.Conclusion RNPC1 may promote the sensitivity of breast cancer cells to trastuzumab through the increased expression of HER-2 in the BT474 breast cancer cells.

Objective To investigate the regulatory mechanism of RNA binding motif protein 38 (RNPC1) on the expression of progesterone receptor (PR) in breast cancer cell line ZR?75?1. Methods Lentiviral vector was used to induce overexpression of RNPC1 in ZR?75?1 cells. qRT?PCR and Western blot were used to assess the regulatory effect of RNPC1 on PR expression. Actinomycin was used to detect the regulatory mechanism involved. Immunohistochemical ( IHC) staining was used to determine the protein expression of RNPC1 and PR in 80 breast cancer tissues. Results IHC staining showed that the expression of RNPC1 was significantly higher in the PR positive breast cancer tissues than that in the PR negative breast cancer tissues ( P<0.05) . The qRT?PCR results showed that overexpression of RNPC1 in ZR?75?1 cells significantly upregulated the mRNA level of PR (1.764±0.028 vs. 1.001±0.037, P<0.01), whereas knockdown of RNPC1 did the opposite (0.579± 0.007 vs. 1.000±0.002, P<0.01).The Western blot results also showed that overexpression of RNPC1 up?regulated PR levels, while knockdown of RNPC1 resulted in down?regulation of PR levels in the ZR?75?1 cells. The actinomycin assay showed that overexpression of RNPC1 increased the mRNA stability of PR. The half?life of PR mRNA was increased from 4. 0 h to 6. 5 h. Knockdown of RNPC1 decreased the mRNA stability of PR and the half?life of PR transcript was decreased from 4.1 h to 3.0 h. Conclusion RNPC1 plays a crucial role in regulating the expression of PR in breast cancer ZR?75?1 cells.

Since cadmium is an indirect genotoxic carcinogen, epigenetic modifications could be one of the major mechanisms underlying cadmium?induced carcinogenesis. It has been proposed that epigenetic alterations might be associated with cadmium?induced carcinogenesis, such as disruptions of DNA methylation, histone modifications, and microRNA expression profile, which would result in abnormal expression of carcinogenesis?related genes and/or imbalance of signal transduction pathways. Other mechanisms of cadmium?induced carcinogenesis consist of disruption of gene regulation and signaling pathways, repression of DNA repair, suppression of apoptosis, induction of oxidative stress and autophagy. Here, we reviewed the research of both epigenetic and non?epigenetic mechanisms underlying cadmium?induced carcinogenesis.

Objective To explore the sensitivity of HER-2-positive BT474 breast cancer cells to trastuzumab after knockdown or overexpression of RNA binding protein 38 ( RNPC1 ) .Methods The expressions of RNPC1 and HER-2 mRNA were detected by qRT-PCR, and the expressions of RNPC1, HER-2 and PI3K/AKT proteins were detected by Western blot after transfected with RNPC1 lentiviral vector, respectively.The experimental groups were treated with different concentration of trastuzumab, and cell apoptosis rate was analyzed by 7-AAD/APC double staining flow cytometry, and cell growth inhibition rate was tested by cell counting kit 8 ( CCK-8) .The expression of apoptosis-related proteins was detected by Western blot assay.Results The results of qRT-PCR showed that overexpression of RNPC1 increased the expressions of RNPC1 and HER-2 mRNA, and the expressions of RNPC1 and HER-2 were decreased after RNPC1 knockdown.The knockdown of RNPC1 decreased the expressions of RNPC1 and HER-2.Moreover, overexpression of RNPC1 decreased and knockdown of RNPC1 increased the levels of p-PI3K and p-AKT while the total protein expressions of both were marginally changed.The results of analysis using a cell counting CCK-8 kit showed that the RNPC1 overexpressed group had a higher growth inhibition rate [(20.33± 1.25)%,(35.38±2.05)%,(50.43±2.12)%,(65 .35±2.08)%and(76.00±2.16)%, respectively] than that of the control group [(13.67±1.24)%,(27.86±2.05)%,( 39.72±1.69)%,(53.33±1.70)%and(62.68± 2.07)%] when treated with different concentrations of trastuzumab (5, 10, 15, 20 and 25 μg/ml).The cell apoptosis rates in the RNPC1-overexpressed group [ ( 19.46 ±1.06 )%, ( 30.87 ±0.98 )%, ( 50.45 ± 1.1)3%, respectively] were also increased compared with that in the control group [(14.38±0 .64)%,(21.65± 1.24)%,(38.03±0.85)%] when treated with different concentrations of trastuzumab (0, 10, 20 and 30μg/ml) ( P<0.05 for all).Reverse results were observed in the RNPC1 knockdown experiments [ experimental groups:(9.67±1.18)%, ( 21.67 ±1.23)%, ( 30.33 ±1.25)%, ( 40.33 ±1.69)%, and ( 53.00 ± 1.63)%] compared with those of control groups:[(14.00±0.82)%, (27.67±1.25)%, (39.67±1.79)%, (53.67±1.50)%, and (63.33±1.52)%];and experimental groups:[(11.64±0.68)%, (16.60±1.01)%, and (25.14±3.12)%] compared with those of the control groups: [(14.71±0.61)%, (22.65±0.96)%, and (39.03±0.85)%].The overexpression of RNPC1 increased the expression levels of Bim and Bad and decreased the level of Bcl-xl, and reverse result was observed after knockdown of RNPC1.Conclusion RNPC1 may promote the sensitivity of breast cancer cells to trastuzumab through the increased expression of HER-2 in the BT474 breast cancer cells.

Objective To investigate the regulatory mechanism of RNA binding motif protein 38 (RNPC1) on the expression of progesterone receptor (PR) in breast cancer cell line ZR?75?1. Methods Lentiviral vector was used to induce overexpression of RNPC1 in ZR?75?1 cells. qRT?PCR and Western blot were used to assess the regulatory effect of RNPC1 on PR expression. Actinomycin was used to detect the regulatory mechanism involved. Immunohistochemical ( IHC) staining was used to determine the protein expression of RNPC1 and PR in 80 breast cancer tissues. Results IHC staining showed that the expression of RNPC1 was significantly higher in the PR positive breast cancer tissues than that in the PR negative breast cancer tissues ( P<0.05) . The qRT?PCR results showed that overexpression of RNPC1 in ZR?75?1 cells significantly upregulated the mRNA level of PR (1.764±0.028 vs. 1.001±0.037, P<0.01), whereas knockdown of RNPC1 did the opposite (0.579± 0.007 vs. 1.000±0.002, P<0.01).The Western blot results also showed that overexpression of RNPC1 up?regulated PR levels, while knockdown of RNPC1 resulted in down?regulation of PR levels in the ZR?75?1 cells. The actinomycin assay showed that overexpression of RNPC1 increased the mRNA stability of PR. The half?life of PR mRNA was increased from 4. 0 h to 6. 5 h. Knockdown of RNPC1 decreased the mRNA stability of PR and the half?life of PR transcript was decreased from 4.1 h to 3.0 h. Conclusion RNPC1 plays a crucial role in regulating the expression of PR in breast cancer ZR?75?1 cells.

Since cadmium is an indirect genotoxic carcinogen, epigenetic modifications could be one of the major mechanisms underlying cadmium?induced carcinogenesis. It has been proposed that epigenetic alterations might be associated with cadmium?induced carcinogenesis, such as disruptions of DNA methylation, histone modifications, and microRNA expression profile, which would result in abnormal expression of carcinogenesis?related genes and/or imbalance of signal transduction pathways. Other mechanisms of cadmium?induced carcinogenesis consist of disruption of gene regulation and signaling pathways, repression of DNA repair, suppression of apoptosis, induction of oxidative stress and autophagy. Here, we reviewed the research of both epigenetic and non?epigenetic mechanisms underlying cadmium?induced carcinogenesis.

Objective: To summarize the experience of diagnosis and treatment of superior mesenteric artery compression syndrome (SMACS) secondary to chronic constipation according to the concept of Lee′s triad syndrome. Methods: The concept of Lee′s triad syndrome: (1) clinical symptoms: triad of constipation, malnutrition, upper gastrointestinal obstruction (vomiting, difficulty in eating); (2) anatomical manifestations: with triple anatomy anomaly of transverse colon sagging, elevated spleen flexure, and mesentery arterial compression; (3) treatment: with triple treatment of enteral nutrition support, chest-knee posture and fecal microbiota transplantation. A descriptive cohort study was performed. According to Lee′s triad syndrome criteria, clinical data of 78 patients with superior mesenteric artery compression syndrome secondary to chronic constipation in the Tenth People′s Hospital of Tongji University and General Hospital of Eastern Theater Command from June 2004 to November 2018 were prospectively collected, including basic information, symptoms and signs, imaging findings, nutritional indicators, gastrointestinal quality of life index (GIQLI) and Wexner defecation score. The above parameters based on Lee′s triad syndrome criteria were followed up and recorded at 1, 3, 6, 12 months after comprehensive treatment. Results: All the patients had Lee′s triple symptoms of constipation, malnutrition, upper gastrointestinal obstruction (vomiting, eating difficulties), and triple anatomy anomaly of transverse colon sagging, elevated spleen curvature, and mesentery arterial compression before treatment. After triple treatment of enteral nutrition support, chest-knee posture, and fecal microbiota transplantation, 69 (88.5%) patients had a significant improvement of symptoms, and 9 patients had no significant improvement of symptoms and then eventually received surgery. The 69 cases without operation received follow-up for 12 months. All the patients eventually returned to normal eating, and upper gastrointestinal angiography and superior mesenteric artery imaging showed duodenal compression disappeared. After 1 month, the constipation-related indexes were improved. After 12 months, the number of autonomous defecation per week increased from 1.0±0.8 to 5.0±1.6 (P<0.001). The GIQLI score increased from 52.7±8.5 to 93.2±7.5 (P<0.001), and the Wexner score decreased from 19.1±2.5 to 6.2±2.1 (P<0.001). After 1 month, nutritional indexes were improved gradually. After 12 months, the BMI increased from (17.9±1.8) kg/m² to (21.0±1.3) kg/m², total protein increased from (65.2±5.7) g/L to (68.3±4.2) g/L, albumin increased from (32.1±5.1) g/L to (40.4±3.0) g/L, prealbumin increased from (163.2±53.7) mg/L to (259.1±45.6) mg/L, fibrinogen increased from (1.9±0.5) g/L to (2.4±0.5) g/L, whose differences were statistically significant (all P<0.001). Upper gastrointestinal angiography and superior mesenteric artery imaging showed duodenal compression were relieved. The angle between superior mesenteric artery and abdominal aorta increased from (17.4±3.8)° to (37.8±5.8)° (t=-22.26, P<0.001). Conclusion When patients with SMACS secondary to chronic constipation have Lee′s triple symptoms and triple anatomy anomaly, the triple combination treatment of enteral nutrition support, chest-knee posture and fecal microbiota transplantation should be applied.