Upregulation of PITX2 Promotes Letrozole Resistance Via Transcriptional Activation of IFITM1 Signaling in Breast Cancer Cells / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Although the interferon α (IFNα) signaling and the paired-like homeodomain transcription factor 2 (PITX2) have both been implicated in the progression of breast cancer (BCa), it remains obscure whether these two pathways act in a coordinated manner. We therefore aimed to elucidate the expression and function of PITX2 during the pathogenesis of endocrine resistance in BCa. MATERIALS AND METHODS: PITX2 expression was assessed in BCa tissues using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunohistochemistry and in experimentally induced letrozole-resistant BCa cells using RT-qPCR and immunoblotting. Effects of PITX2 deregulation on BCa progression was determined by assessing MTT, apoptosis and xenograft model. Finally, using multiple assays, the transcriptional regulation of interferon-inducible transmembrane protein 1 (IFITM1) by PITX2 was studied at both molecular and functional levels. RESULTS: PITX2 expression was induced in letrozole-resistant BCa tissues and cells, and PITX2 induction by IFNα signaling powerfully protected BCa cells against letrozole insult and potentiated letrozole-resistance. Mechanistically, PITX2 enhanced IFNα-induced AKT activation by transactivating the transcription of IFITM1, thus rendering BCa cells unresponsive to letrozoleelicited cell death. Additionally, ablation of IFITM1 expression using siRNA substantially abolished IFNα-elicited AKT phosphorylation, even in the presence of PITX2 overexpression, thus sensitizing BCa cells to letrozole treatment. CONCLUSION: These results demonstrate that constitutive upregulation of PITX2/IFITM1 cascade is an intrinsic adaptive mechanism during the pathogenesis of letrozole-resistance, and modulation of PITX2/IFITM1 level using different genetic and pharmacological means would thus have a novel therapeutic potential against letrozole resistance in BCa.

A study on the influence of blood glucose fluctuation on the ultra - structure of thyroid gland tissues in diabetes rats / 预防医学

Objective To learn the injury severity and the possible mechanism of the thyroid tissue of DM rats with different levels of glucose levels. Methods Firstly,20 Wistar rats were treated with STZ to create the experimental diabetic rats models. Then,the DM rats were divided into two groups including the persistence hyperglycemia group(n = 10),and blood glucose fluctuation group(n = 10). Another 10 Wistar rats were treated as the control group. Rats were sacrificed after 12 week treatment. The bilateral thyroid were weighted and the blood biochemistry tests were conducted for detecting glucose level,lipid levels,and thyroid functions. The ultra - structure of thyroid tissue was observed using electron microscope. Results The MBG,LAGE,and SDBG of blood glucose fluctuation group and the persistence hyperglycemia group were all higher than the control group(P ﹤ 0. 05). The MBG of blood glucose fluctuation group were lower than the persistence hyperglycemia group(P ﹤ 0. 05),the SDBG and LAGE were higher than the persistence hyperglycemia group(P ﹤ 0. 05). The TC,FPG,and HbA1c levels of DM rats were significantly higher in blood glucose fluctuation group than in control group(P ﹤ 0. 05). TC ,FPG and TG levels of the DM rats in blood glucose fluctuation group were significantly lower than the rats in persistence hyperglycemia group(P ﹤ 0. 05). No significance of the free T3 and free T4 levels was observed between the diabetes rats in persistence hyperglycemia group and blood glucose fluctuation group. However,the free T3 and T4 levels were significantly lower in both model groups than in control group(P ﹤ 0. 05). The injury of follicular epithelial cells and loss of microvilli were observed in diabetes rats in both the hyperglycemia group and blood glucose fluctuation group. Conclusion The ultra - structure changes of thyroid gland tissues indicated that abnormal glucose and lipid metabolism could result in thyroid gland tissue injury,which is the potential mechanism. However,no difference of the thyroid function and ultra - structure were observed between the hyperglycemia group and blood glucose fluctuation group.

Impact of operative and peri-operative factors on the long-term prognosis of primary liver cancer patients undergoing hepatectomy / 华中科技大学学报（医学）（英德文版）

This study examined the impact of the operative and peri-operative factors on the long-term prognosis of patients with primary liver cancer undergoing hepatectomy. A total of 222 patients with primary liver cancer who underwent hepatectomy were followed up from January 1986 to December 2010 at Chinese PLA General Hospital. The post-operative complication rate was 14.0% for all cases, 13.7% for hepatocellular carcinoma (HCC), 10.0% for cholangiocarcinoma. The 1-, 3-, 5- and 10-year overall survival rates in patients with primary liver cancer after resection were 76.6%, 57.6%, 41.4%, and 21.0%. The survival rates were significantly higher in the HCC group than in the cholangiocarcinoma group (P=0.000), in the non-anatomical resection group than in the anatomical resection group (P=0.005), in the female group than in the male group (P=0.002), in patients receiving no blood transfusion than in those who were given intra-operative blood transfusion (P=0.000), in patients whose intra-operative blood loss was less than 400 mL than in those who intra-operatively lost more than 400 mL (P=0.000). No significant difference was found in the survival rate between the HBsAg-positive group and the HBsAg-negative group (P=0.532). Our study showed that anatomical resection, blood loss and blood transfusion were predictors of poor survival after hepatectomy for primary liver cancer patients, and concomitant hepatitis B virus infection bore no relation with the post-resection survival.

Lumbar disc herniation treated with Shu-needle therapy and ozone injection of low concentration / 中国针灸

<p><b>OBJECTIVE</b>To verify the efficacy on lumbar disc herniation treated with Shu-needle therapy in combination with ozone injection of low concentration.</p><p><b>METHODS</b>One hundred and thirty cases of lumbar disc herniation were randomized into a Shu-needle therapy group and an acupotomy group, 65 cases in each one. In the Shu-needle therapy group, Shu-needle therapy was used in combination with ozone injection of low concentration. In the acupotomy group, the conventional acupotomy therapy was applied in combination with ozone injection of low concentration. The treatment was given once every 10 days, 3 treatments made one session. After one session treatment, the clinical efficacy of two groups was observed, scores of visual analogue scale (VAS) and Oswestry disability index (ODI) were counted before and after treatment. The long-term efficacy was followed up in half a year.</p><p><b>RESULTS</b>The clinical curative rate was 69.2% (45/65) and the total effective rate was 96.9% (63/65) in the Shu-needle therapy group. The curative rate was 43.1% (28/65) and the total effective rate was 84.6% (55/65) in the acupotomy group. In comparison, the efficacy of the Shu-needle therapy group was superior to that of the acupotomy group (P < 0.01, P < 0.05). The scores of VAS and ODI were reduced obviously after treatment as compared with those before treatment in two groups (all P < 0.05). The improvements in the Shu-needle therapy group were superior to those in the acupotomy group (both P < 0.05). In the follow-up observation, the recurrence rate in the Shu-needle therapy group was lower than that in the acupotomy group [17.8% (8/45) vs 46.4% (13/28), P < 0.05].</p><p><b>CONCLUSION</b>Shu-needle therapy in combination with ozone injection of low concentration achieves the superior efficacy on lumbar disc herniation as compared with the acupotomy group.</p>

Protective autophagy antagonizes oxaliplatin-induced apoptosis in gastric cancer cells / 癌症

Oxaliplatin-based chemotherapy is used for treating gastric cancer. Autophagy has been extensively implicated in cancer cells; however, its function is not fully understood. Our study aimed to determine if oxaliplatin induce autophagy in gastric cancer MGC803 cells and to assess the effect of autophagy on apoptosis induced by oxaliplatin. MGC803 cells were cultured with oxaliplatin. Cell proliferation was measured using MTT assay, and apoptosis was determined by flow cytometry. Protein expression was detected by Western blot. Autophagy was observed using fluorescent microscopy. Our results showed that the rate of apoptosis was 9.73% and 16.36% when MGC803 cells were treated with 5 and 20 μg/mL oxaliplatin for 24 h, respectively. In addition, caspase activation and poly ADP-ribose polymerase (PARP) cleavage were detected. Furthermore, when MGC803 cells were treated with oxaliplatin for 24 h, an accumulation of punctate LC3 and an increase of LC3-II protein were also detected, indicating the activation of autophagy. Phosphorylation of Akt and mTOR were inhibited by oxaliplatin. Compared to oxaliplatin alone, the combination of autophagy inhibitor chlorochine and oxaliplatin significantly enhanced the inhibition of cell proliferation and the induction of cell apoptosis. In conclusion, oxaliplatin-induced protective autophagy partially prevents apoptosis in gastric cancer MGC803 cells. The combination of autophagy inhibitor and oxaliplatin may be a new therapeutic option for gastric cancer.

Follow-up of laser peripheral iridotomy in fellow eyes with unilateral acute attack of primary angle closure glaucoma / 中华实验眼科杂志

Background Laser peripheral iridotomy(LPI) is used as the primary therapy for the eyes at risk of angle closure.But there are still 28% eyes with primary angle closure suspect occur angle closure within 2 years after LPI.It is necessary to explore the associated factors of the efficacy of LPI.Objective The aim of this study was to explore the changes of intraocular pressure(IOP) and anterior chamber angle in the fellow eyes of patients with unilateral acute attack of primary angle closure glaucoma (PACG) and analyze the relevant factors influencing the successful rate of LPI.Methods Eighty-seven fellow eyes received LPI from 87 patients with unilateral acute attack of PACG were included in this study and retrospectively analyzed.The IOP and gonioscopy were performed before and 1 week,3,6,9,12 months after LPI.Successful signs of LPI were defined as an IOP 6-21mmHg without any anti-glaucoma medication,none of glaucomatous neuropathy and the coincident visual field loss,and no need of additional glaucomatous medication or surgery.This study was approved by Ethic Committee of the First Hospital of Xinxiang Medical College,and written informed consent was obtained from each patient.Results Seventy-nine eyes of 79 cases finished the medical visit throughout the follow-up duration with the age 61.4±0.4 years and 33(41.8%) males and 46(58.2%) females.The mean IOP was lowed in various time points after LPI in comparison with before operation with the general difference among different time visiting groups(F=4.056,P＜0.01).Shaffer grade was increased in superior,temporal and nasal quadrants and significant differences were found between 1 week group,3 months group or 6 months group and before operation group (P＜0.05).LPI lessened the range of appositional angle closure (AAC) in postoperative 1 week group and 3 months group compared with pre-operative group (P＜0.05),but no statistically significant reduce was seen in range of AAC from 6 months through 12 months after LPI in comparison with pre-operation (P＞0.05).LPI was determined as successful in 61 cases (77.2%) during one-year fellow-up period.Several variables,such as preoperative IOP,Shaffer grade of each quadrant,mean Shaffer grade and the extent of AAC,were significantly different between LPI success and failure group(P＜0.01).Cox stepwise regression analysis found that the success rate was significantly associated with the extent of AAC (Wald=48.150,RR=1.963,P＜0.01) rather than pre-IOP,Shaffer grade of each quadrant,mean Shaffer grade,age and gender (P＞0.05).Conclusion LPI can widen the anterior chamber angle and low IOP in the fellow eyes of PACG attack eyes.The success rate of LPI is associated with the extent of pre-AAC,suggesting that it is necessary for LPI in consideration of the extent of pre-AAC.

Serum ECP levels in patients with allergic rhinitis and chronic rhinosinusitis / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the serum eosinophil cationic protein (ECP) levels in patients with allergic rhinitis (AR) or chronic rhinosinusitis with polyps(CRSWP), and its relations with allergic symptoms in patients with AR.</p><p><b>METHODS</b>The ECP in serum and Phadiatop tests were detected by UniCAP100 system. Blood sample was taken from 87 patients with inhaled AR, 49 patients with CRSWP and 20 healthy individuals. The serum ECP levels were detected by enzyme-linked immunosorbent assay. The allergic symptoms in patients with inhaled AR were graded.</p><p><b>RESULTS</b>Phadiatop level was 5185.0 [983.0, 14469.0] Fu in inhaled AR, 317.5 [125.0, 526.8] Fu in CRSWP with Phadiatop positive, 30.0 [28.0, 43.0] Fu in CRSWP with Phadiatop negative and 43.5 [29.0, 105.0] Fu in healthy individuals. The level of ECP in patients with inhaled AR was 24.8 [14.6, 49.1] microg/L, higher than that in CRSWP with Phadiatop positive 7.7 [3.3, 25.6] microg/L, CRSWP with Phadiatop negative 12.5 [6.7, 16.7] microg/L and control 8.8 [5.4, 20.2] microg/L. The difference was significant. There were correlations among the allergic symptoms, serum ECP and Phadiatop levels.</p><p><b>CONCLUSIONS</b>Among patients with inhaled AR, there was an up-regulated concentration of serum ECP, which had relations to allergic symptoms. The detection of serum ECP could be used as a convenient screening test for inhaled AR. Its concentration had correlation with the severity and prognosis of the disease. To the contrary, the serum ECP did not significantly increased in patients with CRSWP.</p>

Study on lymph node metastasis in 292 patients with early gastric cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the status of lymph node metastasis (LNM) and reasonable procedure in early gastric cancer (EGC).</p><p><b>METHODS</b>Two hundred and ninety-two patients with histologically proven mucosal or submucosal gastric cancer who underwent gastrectomy/lymphadenectomy were included in this study. The numbers of total dissected lymph node were all above 15 in all patients. The clinical characteristics, pathologic features, and LNM were assessed by univariate and multivariate analysis.</p><p><b>RESULTS</b>LNM were observed in 43 of 292 cases (14.7%), and 6.4% in mucosal lesions and 22.4% in submucosal lesions. The LNM was identified in 12.7% at the first level, 7.2% at the second level and 0.34% at the third level. The LNM frequency was found in the 6, 3, 4, 1, 5 lymph node (from high to low) consequently at the first level and the 7, 8a lymph node at the second level. The EGC with nodal involvement and the tumors < 2.0 cm in diameter were all depressed type. The diameter of elevated type with LNM was no less than 3.0 cm in this series. The depth of invasion and lymphatic vessel involvement were independent influencing factors in LNM on multivariate analysis (P<0.05).</p><p><b>CONCLUSIONS</b>Less extensive surgery might be considered for the elevated type EGC, and tumors <or= 2.0 cm in diameter and mucosal lesions. Gastrectomy with D1 plus No.7, 8a lymphadenectomy might be carried out in the depressed type/<or= 3.0 cm in diameter, or in the elevated type/> 3.0 cm in diameter. With respect to the depressed type EGC/tumors > 3.0 cm in diameter, gastrectomy with D2 lymphadenectomy is proper.</p>

Retrospective analysis of extended gastrectomy and lymphadenectomy in early gastric cancer patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To objectively evaluate the practical significance of different extended surgeries in early gastric cancer(EGC) patients, and to choose reasonable gastrectomies and lymphadenectomies.</p><p><b>METHODS</b>A total of 217 EGC patients were investigated undergone normalized D2 or above extended surgery and their clinicopathological data were recorded in detail. The efficiency of the extended lymphadenectomies, complications and operation causes were analyzed, and the correlation between the group 2 lymph node metastasis (LNM) and clinicopathological factors were assessed, too.</p><p><b>RESULTS</b>There was no nodal involvement in the No.5 and No.6 lymph nodes among the total gastrectomy in the upper third of the stomach, neither was in the No.10, 11p and 11d lymph nodes among the combined splenectomy, and neither was in the No.15 lymph nodes among the combined transverse mesocolon resection in the lower third of the stomach. There was no distant nodal involvement in the EGC. Above all, most of them were mistaken for advanced gastric cancer preoperatively and intraoperatively, the operation time was longer and the blood loss was more during operation. Among the resected nodes of group 2 in the lower third of the stomach, metastasis was not found in the No.11p, 12a and 14v lymph nodes. The rate of the No.7 and 8a nodal involvement in the submucosa cancer was higher than that in the mucosa cancer(P<0.05) and so did the No.7 in the lymphatic penetration positive(P<0.001). The No.1 and No.13 nodal involvement were only seen in the high risk cases, such as submucosa cancer, the lesion diameter more than 3.0 cm, depressed type and lymphatic involvement.</p><p><b>CONCLUSION</b>It is not necessary to execute total gastrectomy in the upper third of the stomach, combined organ resection (such as splenectomy, transverse mesocolon resection), and distant lymph node dissection in the EGC. In the lower third of the stomach, the No.11p 12a and 14v lymph nodes shouldn't be dissected. With respect to the high risk nodal involvement cases in the lower third of the stomach, the No.1 lymph nodes should be dissected and so does the No.13 lymph nodes if it's tumefied. It is the key point of reasonable operation to exactly diagnose the EGC before and during the surgery.</p>

Significance of hRad17 mRNA expression in human gastric cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the relationship between hRad17 mRNA expression and clinicopathologic factors and lymph node metastasis of gastric cancer, and to assess the significance of predicting the extent of lymph node metastasis and prognosis.</p><p><b>METHODS</b>hRad17 mRNA expression was examined in matched primary lesions, normal gastric mucosa and lymph node metastatic lesions among 52 gastric cancer patients by reverse transcription polymerase chain reaction (RT-PCR), polyacrylamide gel electrophoresis (PAGE) and silver stain with the relation between hRad17 mRNA expression and clinicopathologic factors analyzed. At the same time, hRad17 mRNA expressions in 5 gastric benign lesions and SGC7901 gastric carcinoma cell lines were also examined.</p><p><b>RESULTS</b>The primary tumor samples (88.4% positive) showed a significantly higher level of hRad17 expression compared with matched normal tissue (76.9% positive) (P = 0.014), so did the lymph node metastatic samples (94.2% positive) (P = 0.001). The hRad17 mRNA expression showed a low level in benign lesions, but very high in SGC7901 cell line. The hRad17 mRNA expression showed a higher level in patients with the number of lymph node metastasis above 15 than below 15 (P = 0.02), so did the diffused growth than the mass-like growth (P = 0.04).</p><p><b>CONCLUSION</b>The method of PAGE and silver stain can improve the sensitivity of RT-PCR. The degree of lymph node metastasis and invasiveness of carcinoma cells are more serious in cases with hRad17 mRNA overexpression, and extensive lymph node dissection should be carried out for these patients. Examination of hRad17 expression by RT-PCR before surgery is indicated to arrive at an optimum treatment scheme and to estimate the prognosis.</p>