A Chinese multi-center study on the significance of monitoring imatinib plasma concentration in patients with gastrointestinal stromal tumor before and after administration / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the factors which may influence the imatinib plasma concentration in Chinese patients with gastrointestinal stromal tumor(GIST), and to illuminate the significance of monitoring imatinib plasma concentration in adjuvant therapy for patients with GIST.</p><p><b>METHODS</b>A cross-sectional study with 60 GIST patients who accepted the imatinib therapy after surgery was conducted. They were respectively administrated in 10 domestic hospitals from December 2014 to April 2016, including The First Affiliated Hospital of Nanjing Medical University(n=28), The Affiliated Hospital of Nantong University(n=9), The Affiliated Hospital of Xuzhou Medical College(n=6), Nanjing Drum Tower Hospital(n=5), The Second Affiliated Hospital of Nanjing Medical University (n=2), Jingling Hospital (n=2), The Second People's Hospital of Lianyungang(n=2), Shandong Provincial Hospital(n=2), Jiangsu Province Tumor Hospital(n=2), and The First Affiliated Hospital of Zhejiang University(n=2). Some specific time points for collecting blood sample before and after taking imatinib were determined, then liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used for monitoring imatinib plasma concentration in patients with GIST. Linear regression analysis was used for the correlation analysis of imatinib plasma concentration with dosage, clinicopathologic feature and side effect.</p><p><b>RESULTS</b>Patients who could not tolerate 400 mg imatinib per day(n=3) received 300 mg per day. There was no significant difference in imatinib plasma concentration between patients with 300 mg and those with 400 mg imatinib(n=53)(P=0.527). However, the imatinib plasma concentration in patients with 600 mg imatinib per day (n=4) was significantly higher as compared to those with 400 mg(P=0.000). Linear regression analysis indicated a negative correlation between the imatinib plasma concentration in patients with 400mg imatinib per day for 90 days continuously and body surface area(R=0.074, P=0.035), but no significant correlations of with age, creatinine clearance and serum albumin concentration were observed (all P>0.05). The differences in imatinib plasma concentration were not statistically significant between patients of different gender and those taking proton-pump inhibitor (PPI) or not (both P>0.05). Difference in imatinib plasma concentration between patients with different surgery was significant (P=0.026). Compared to patients who underwent wedge resection, enterectomy and other surgeries, the imatinib plasma concentration of patients with subtotal gastrectomy or total gastrectomy decreased significantly (all P<0.05). After 90 days of taking imatinib continuously, linear regression analysis revealed a negative correlation between imatinib plasma concentration in patients with 400 mg imatinib per day and white blood cell count (R=0.103, P=0.013), and a positive correlation with serum alanine aminotransferase (ALT) concentration (R=0.076, P=0.033).</p><p><b>CONCLUSIONS</b>The imatinib plasma concentration in patients with larger body surface area, subtotal gastrectomy or total gastrectomy may be lower. For these patients, dosage of imatinib should be considered to increase in order to achieve effective plasma concentration. Excessive imatinib plasma concentration can result in some side effects, such as decrease of white blood cells and liver damage. Therefore, it is significant for receiving optimal clinical therapeutic efficacy to monitor imatinib plasma concentration, adjust imatinib dosage timely and keep imatinib plasma concentration in effective and safe range.</p>

The expression and significance of Nanog and CD44 in spheroid body-forming cells of gastric cancer cell line MKN-45 / 天津医药

Objective To detect the expression of stem-cell related factors Nanog and CD44 in spheroid body-form?ing cells of gastric cancer cell line MKN-45. Methods The gastric cancer cell line MKN-45 was used to culture spheroid bodies in non-adherent condition in a serum-free medium supplemented with epidermal growth factor (EGF) and basic fibro?blast growth factor (bFGF). Using Western blot analysis, immunofluorescence staining and quantitative real time polymerase chain reaction(qRT-PCR), the expression levels of stem cell-related genes Nanog and CD44 were studied. Results In this study, we observed that MKN45 cells formed spheroid bodies in non-adherent condition in a serum-free medium, and the levels of Nanog and CD44 mRNA expression in spheroid body-forming cells were 2.34 ± 0.22 and 1.18 ± 0.04,respectively, which were higher than those in parental cells (1.00±0.00 and 1.00±0.05). The levels of Nanog and CD44 protein expression in spheroid body-forming cells were 0.18±0.02 and 0.24±0.04, respectively, which were significantly higher than those in pa?rental cells (0.07±0.02 and 0.18±0.01, P<0.05). Nanog protein was positively stained within the perinuclear and cytoplasm of the spheroid body-forming cells, and CD44 was positively stained mainly in the membrane. Dual staining of Nanog/CD44 indicated that the embryonal protein Nanog was co-localized with CD44 in the spheroid body-forming cells. Conclusion Spheroid body-forming cells developed from human gastric cancer cell line MKN-45 in serum-free medium supplemented with EGF and bFGF show characteristics of cancer stem cell (CSC). The cells co-expressed of CD44 and Nanog maybe a phe?notype of gastric CSCs.

Metastasis of axillary node in clinical T1 -T2 N0M0 breast cancer patients / 国际外科学杂志

Objective To study the metastasis of lymph node of breast cancer patients in clinical T1-T2 N0 M0 and its clinical significance in (sentinel lymph node biopsy, SLNB). Methods A total of 276 pa-tients of breast cancer were enrolled in the study (T1 N0M0 cases =115 ; T2N0M0 cases = 161 ). The metas-tasis and distribution of axillary node by virtue of the location of primary tumor, ages and pathologic status were analyzed. Results The metastasis rate of axillary node in T1 N0M0 patients was less than T2 N0 M0 (P =0.027), while that in the central and lower outer quadrant's was higher than in other' s parts(P =0.004).When the tumor located in outer quadrant, the axillary node metastasis rate of Berg I was highest in the cen-tral, outer and inner quadrant(P =0.000). But the metastasis rate of Berg Ⅲ was lowest in the three quad-rants (P = 0. 000). For the pathologic status, the metastasis rate of invasive carcinoma-not otherwise speci-fied(NOS) was higher than early breast carcinoma and other pathologic categories (P =0.000). More than 2 groups axillary node metastasis was found in 6 of 9 patients with carcinoma simplex. The 90 cases with axilla-ry node metastasis were analyzed by age. Axillary node was easier for metastasis in those cases aged above 50years than those below 50 years(68.9% vs 31.1% )(P =0. 000). Two eases with skip metastasis were in T2 No Mo (invasive ductal carcinoma disease = 1, carcinoma simplex disease = 1 ). Conclusion The distri-bution of the metastasis of lymph node in clinical T1 ,T2 N0M0 breast cancer plays an important role in SLNB and formulating reasonable treatment protocols.

Immunogenicity and intensity of homegraft decelluladzed scaffolds without pretreatment / 中国组织工程研究

BACKGROUND:Pretreatment is a dominant way to increase the histocompatibility of biomaterials,but many pretreatments are not satisfactory due to some reactions,such as calcification,cytotoxic reaction and reducing the tension resistance.OBJECTIVE:To investigate the effect of immunogenicity,scaffold tension and cell growth factor on the non-pretreated scaffold biomaterials,and to prepare the homograft decellularized scaffolds.DESIGN:Contrast observation for the histomorphology.SETTING:The experiments were carried out in the Department of General Surgery,Affiliated Hospital of Nantong University from June 2006 to March 2007.MATERIALS:Wistar rats of SPF grade were adopted in this study.Sodium dodecyl sulfate from BioteehGrade Company(U.S.A.);basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) from Peprotech Company(UK);dynamometer from Suzhou Electrical Element First Factory (China).METHODS:The vena cava inferior from rats were selected as experimental materials,we decellularized the epithelial cells from vein according to the improved Booth's methods with low osmotic Tris buffer containing sodium dodecyl sulplate,and then reserved the extracellular matrix.After fixing,the decellularized scaffold was stained by hematoxylin and eosin,the collagen fibers were observed and photographed by light microscope and scanning electron microscope.Changes of the intensity of the scaffolds were measured before and after decellularization.The deceilularized scaffolds were transplanted subcutaneously at homogeneity rats to observe whether the scaffolds had induced immunological rejection.In combination with bFGF and/or VEGF,the scaffolds were transplanted subcutaneously at homogeneity rats and took out two weeks later,in order to exam the new vessels in the scaffolds by immunohistochemistry.Dynamometer was applied to compare the change of the intensity of the scaffolds before and after transplantation.MAIN OUTCOME MEASURES:Change of the intensity of the scaffolds after decellularization and transplantation.Formation of new vessels in scaffolds.Local rejection of the scaffold subcutaneously transplanted into rats.RESULTS:The endothelial cells of the vein were completely removed when incubated with Tris buffer containing 0.03% sodium dodecyl sulfate for 48 hours.Results of hematoxylin and eosin staining,light microscope and scanning electron microscope showed that,the main components of extracellular matrix (collagen fiber) were reserved.There was no significant difference in the morphological structure and the intensity of collagenous scaffolds before and after decellalarization (P＞0.05).There was no apparent reject reaction at the embedded site,local incisions healed well.New vessels could be observed in the scaffolds two weeks later.There was no significant difference in the intensity of collagenons scaffolds before and after inoculation (P＞0.05).CONCLUSION:The low osmotic Tris buffer containing 0.03% sodium dodecyl sulfate is suitable for decellularizing the vein.The homograft collagenous scaffolds exhibit no rejection after transplantation,and the intensity of the scaffolds does not descend.VEGF and bFGF can improve the growth of new vessels in the decellularized scaffolds,and have a synergistic effect.

Experimental Study of the Choice of Vital Dyes for Sentinel Lymph Node Biopsy in Gastric Cancer / 医学研究杂志

0.05).The average fading time of the lymph nodes stained by PB and MB+PB was 13.06min and 82.13min,we observed the lymph nodes stained by MB 120 min,they were still stained deeply.There were dramatically differences among three groups(P=0.000).Conclusion Application of MB and PB possess their advantage and disadvantage in sentinel node biopsy.The mixture of patent blue and methylene blue could overcome the shortage of the two vital dyes in the experimental study and be an ideal tracer for the use.

Application and Immune Effect of Nutrison-5Fu on Perioperative Patients with Progressive Gastrointestinal Cancer / 中国医师杂志

Objectives To investigate and evaluate the effect of Nutrison-5Fu on immune function of perioperative patients with progressive gastrointestinal cancer,and simultaneously we also recommended the methods of application of Nutrison-5Fu.Methods Seventy eight cases were equally divided at random into three groups,26 cases in each group.⑴Nutrison-5Fu group:the patients were treated with Nutrison-5Fu.⑵Chemotherapy group:the patients only received 5-Fu.⑶Control group:there were not any chemotherapy and immunetherapy during the perioperation.The values of CD 3,CD 4,CD 8 and NKCC were determined in all cases.Results Values of CD 3,CD 4,CD/CD 8 ratio and NKCC in most patients were distinctly low,but the condition rapid improved by giving them Nutrison-5Fu.On the contrary,the values declined further after chemotherapy alone.Conclusion The treatment of Nutrison-5Fu not only can repress the development of the tumor,but also can improve the dystrophic status and immune function of the patients with cancer.

Surgical excision of tumors in the body and tail of pancreas / 中国普通外科杂志

Objective To explore the methods of surgical treatment of patients with tumors in the body and tail of pancreas. Methods We analyzed the clinical data from 45 patients with tumors in the body and tail of pancreas who underwent surgical excision between 1984 and 2002 in our hospital. The 45 cases consisted of malignant tumors(n=33) and benign tumors(n=12). Operations performed included resection of the body and tail of pancreas(17 cases), combined-organ excision (24 cases) and local tumor resection(4 cases ). Results Pathological classification:carcinoma (33 cases), islet cell tumors (8 cases ), cystic adenoma (8 cases), epithelioid fibroma (1 case) and cystic teratoma (1 case). The average diameter-size of excised tumor was determined as follows: carcinoma in the body or tail of pancreas was(8.0?2.6)cm, and that of islet cell tumors was(6.5?2.4)cm. There were no operative deaths, but operation resulted in the following complications: pancreatic fistula (2 cases), subdiaphragmatic abscess (2 cases), pancreatic pseudocyst (1 case ), upper gastrointestinal bleeding(1 case) and infection or poor healing of incisional wound (3 cases). All of the complications were cured with conservative therapy. Conclusions Excision of the body and tail of pancreas is an effective method for the treatment of patients with tumors in the distal half of pancreas.Before operation, it is necessary to be routinely prepared to perform combined organ excision. Regarding the surgical handling of pancreatic stump, we select the use of ligation of main pancreatic duct plus mattress suture, which we believe could effectively prevent pancreatic fistula.

Expression of bax and bcl-2 gene in mucous adenocarcinoma of the rectum / 中国普通外科杂志

ObjectiveTo determine the relationship between the expression of bax and bcl-2 gene in mucous adenocarcinoma of rectum and patient′s prognosis.MethodsImmunohistochemical method was used to evaluate monoclone antibody of bax and bcl-2 protein in 38 cases of mucous adenocarcinoma of the rectum. ResultsThe positive-staining rate of bax was 77.8% in Dukes′ A and B stage compared to 45.0% in Dukes′ C stage( ? 2=4.260,P=0.039).The intensity of positive-staining of bax over bcl-2 was significantly correlated with tumor stage(P=0.04) and the survival (P=0.001).ConclusionThe expression rate of bax and bcl-2 gene was very high in mucous adenocarcinoma of large bowel, and it might have a prognosis implications in patients with colonic mucous adenocarcinoma.