2.Establish a gemcitabine-resistant pancreatic cancer cell line SW1990/GZ and research the relationship between SW1990/GZ and pancreatic cancer stem cell.
Yong AN ; Jie YAO ; Ji-Shu WEI ; Zi-Peng LU ; Hui-Hua CAI ; Cun-Cai DAI ; Zhu-Yin QIAN ; Ze-Kuan XU ; Yi MIAO
Chinese Journal of Surgery 2010;48(13):999-1003
OBJECTIVESTo establish a gemcitabine-resistant pancreatic cancer cell line SW1990/GZ, and to explore the relationship between drug-resistant cell line SW1990/GZ and pancreatic cancer stem cell.
METHODSGemcitabine-resistant pancreatic cancer cell line SW1990/GZ was obtained by treating parental cell line SW1990 in vitro with increasing dosage of gemcitabine in culture medium intermittently for 24 weeks. Stable cultures were obtained which were 77.2-fold increased in resistance relative to parental cells. Gene expressions of ABCB1/MDR1, ABCC1/MRP and ABCG2/BCRP were determined by real-time PCR. Tumorigenic potential was performed by nude mice xenograft transplant experiments. Side population analysis and CD24CD44 positive cells explore were determined by flow cytometry to examine cancer stem cell proportion.
RESULTSGemcitabine-resistant cell line SW1990/GZ underwent obvious morphological and functional changes. Compared with the parental cell line, SW1990/GZ cell was small and turned into round shape. SW1990/GZ had a higher gene expression level of ABCB1/MDR1, ABCC1/MRP and ABCG2/BCRP than SW1990 (P < 0.01). Nude mice xenograft transplant experiments showed that only 1 × 10(5) SW1990/GZ cells were sufficient for tumor formation, whereas an injection of 1 × 10(5) SW1990 cells did not initiate tumors. Flow cytometry analysis showed that SP proportion in SW1990/GZ was (11.0 ± 1.0)%, whereas in parental SW1990 it was (4.6 ± 0.9)%, CD44CD24 positive cells was (8.73 ± 0.81)% in SW1990/GZ, whereas (1.1 ± 0.4)% in SW1990.
CONCLUSIONSGemcitabine-resistant cell line SW1990/GZ has a higher proportion of pancreatic cancer stem cells compared to its parental cell line SW1990. CD44 is mainly responsible for acquired drug resistance, which can be a potential target to overcome acquired drug resistance in pancreatic cancer.
Animals ; Antimetabolites, Antineoplastic ; pharmacology ; Cell Line, Tumor ; Deoxycytidine ; analogs & derivatives ; pharmacology ; Drug Resistance, Neoplasm ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplastic Stem Cells ; drug effects ; pathology ; Pancreatic Neoplasms ; drug therapy ; metabolism ; pathology ; Xenograft Model Antitumor Assays
3.Preliminary application experience of GuidezillaTM guide extension catheter during complex coronary percutaneous coronary intervention procedure
xun Bing WANG ; yuan Zhi SONG ; zhong Wan PENG ; cai Zeng MA ; Tao GENG ; gang Yong YUAN ; Hua LIU ; sheng Ze XU
Chinese Journal of Interventional Cardiology 2017;25(9):502-506
Objective To evaluate the clinical safety and efficacy of GuidezillaTM guide extension catheter during complex coronary percutaneous coronary intervention(PCI). Methods A total of 13 patients were included in the studywho presented with complex coronary lesions during PCI. Stents or balloons could not be delivered to these complex lesions with conventional approach and GuidezillaTM guide extension catheters were used. Results Among these 13 patients,there were 7 CTO lesions,7 calcified lesions, 6 tortuous lesions,8 diffuse lesions,8 distal lesions and 8 lesions with pre-existing stents. PCI success rate was 100% .In one patient,GuidezillaTM guide extension catheter was obstructed which were relieved after stent implantation. There was no major adverse cardiac event(MACE) during follow-up.Conclusions The GuidezillaTM guide extension catheter was safe and effective for PCI of complex coronary artery lesions.
4.Integrin beta1 mediates hepatocellular carcinoma cells chemotaxis to laminin.
Bian-hong FU ; Ze-zhi WU ; Hai-yan ZHANG ; Jian QIN ; Shao-xi CAI ; Yun-peng WU ; Cheng DONG
Chinese Journal of Hepatology 2003;11(10):605-608
OBJECTIVETo study the effects of integrin beta1 on the chemotaxis of hepatocellular carcinoma (HCC) cells to laminin (LN).
METHODSA micropipette technique was adopted to investigate the effect of integrin beta1 blockade on pseudopod protrusion of HCC cells in response to LN stimulation. Chemotactic pseudopod protrusion of a HCC cell was evaluated using a dual-pipette set-up, in which two pipettes filled with LN solution were positional in close contact with the same cell, and pseudopod protrusion into each pipette was viewed dynamically and recorded with a tape recorder. The lengths of pseudopods were measured, then plotted against time to obtain a pseudopod growth curve. The integrin beta1 subunit on the surfaces of HCC cells was analyzed by flow cytometry.
RESULTSIn dual pipette chemotaxis experiment, when the two pipettes were filled with LN (50microg/ml, 200microg/ml), pseudopods extended from the HCC cells into each of the pipettes nearly symmetrically. Upon addition of anti-CD29 (20microg/ml) to one of the pipettes, the pseudopod protrusion was blocked almost completely, while the pseudopod protrusion into the opposite pipette became more evidently, with larger maximum length. The expression rate of integrin beta1 on the cells was up to 95.78%.
CONCLUSIONIntegrin beta1 subunit is the important receptor for mediating HCC cells chemotaxis to laminin.
Carcinoma, Hepatocellular ; pathology ; Cell Adhesion ; Cell Line, Tumor ; Chemotaxis ; Humans ; Integrin beta1 ; immunology ; metabolism ; physiology ; Laminin ; metabolism ; Liver Neoplasms ; pathology
5.Long-term therapeutic outcome of patients with acute promyelocytic leukemia.
Li ZHANG ; Rui LI ; Da-peng LI ; Yong-ze LIU ; Shi-cai XU ; Yu-shu HAO ; Zhi-jian XIAO
Chinese Journal of Hematology 2007;28(1):15-18
OBJECTIVETo analyze the long-term therapeutic outcome of patients with acute promyelocytic leukemia(APL).
METHODSNewly diagnosed APL patients were treated with ATRA as induction therapy followed by 3-4 courses of combined consolidation chemotherapy and 2 year maintenance therapy with ATRA and 6-MP + methrotrexate, alternatively. Patients were regularly monitored with nested RT-PCR for PML-RARalpha fusion transcript at the end of consolidation chemotherapy and in the following 4 to 5 years.
RESULTSA total of 81 patients with APL were entered the trial, 75 (92.6%) patients achieved CR. Early death (ED) rate was 6.6%. ED patients had significantly higher WBC count and higher percentage of peripheral promyelocyte than those achieved CR. Of 65 patients received consolidation, 60 (92.3%) were proved PML-RARalpha fusion gene negative at the end of the 3rd courses and 3 (4.6%) the end of the 4th courses of consolidation. The mean follow-up was 21.2 (8-64) months, 6 patients relapsed (relapse rate 9.2%). The 5-year Kaplan-Meier estimates of overall survival (OS) rate was (86.6 +/- 4.6)%. For 65 patients received consolidation therapy, the 5-year relapse-free survival (RFS) rate was 82.7%. COX-regression analyses showed only high WBC count (>10 x 10(9)/L) had an adverse prognostic influence on OS.
CONCLUSIONMore than 80% of APL patients treated with systemic therapy could experience long-term relapse-free survival.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Female ; Follow-Up Studies ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Middle Aged ; Remission Induction ; Treatment Outcome ; Tretinoin ; administration & dosage
6.Value of lymph node micrometastasis detected by RT-PCR assay in determining the stage of gastric carcinoma.
Ze-yu WU ; Wen-hua ZHAN ; Jing-hua LI ; Yu-long HE ; Jian-ping WANG ; Ping LAN ; Jun-sheng PENG ; Shi-rong CAI
Chinese Journal of Gastrointestinal Surgery 2006;9(3):217-220
OBJECTIVETo detect micrometastasis in regional lymph nodes using RT- PCR assay and evaluate the significance of the new assessment of nodal status in determining pN staging in gastric carcinoma.
METHODSIn addition to HE,RT- PCR assay for cytokeratin-20 gene marker was used to detect micrometastasis in 850 lymph nodes from 30 patients with gastric carcinoma who underwent gastrectomy with lymphadenectomy from Dec. 2003 to Apr. 2004.
RESULTSThe detection rate of HE staining was 27.1% (233/850), the detection rate of RT-PCR assay was 36.5% (310/850) (Pa< 0.01). Lymph node micrometastasis was further detected in 77 nodes from 14 patients. The detection rate of RT- PCR assay from the routine negative lymph nodes was 12.5% (77/617). Seven of those patients were up- staged (from IB stage to II stage, from IB stage to III A stage, from I stage to III A stage, from III A stage to III B stage, from III A stage to IV stage in one patient respectively, and from III B stage to IV stage in 2 patients).
CONCLUSIONRT- PCR assay can increase the detection rate of lymph node metastasis and have a significant impact on the staging system of gastric carcinoma.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Reverse Transcriptase Polymerase Chain Reaction ; Stomach Neoplasms ; pathology
7.Quality control of human chorionic gonadotrophin subunit dissociation
Qin-pei DENG ; Ran AN ; Tong-ze XU ; Li-xiu HE ; Meng-mei SUN ; Jia-ming YANG ; Yu-cai PENG
Acta Pharmaceutica Sinica 2017;52(3):430-435
Human chorionic gonadotrophin (hCG), a glycohormone widely used in treatment of infertility, is a heterodimer composed of an alpha-and a beta-subunit. The heterodimer could be dissociated during production and storage with an impact on its bioactivity. A CE-SDS method for quantitative analysis of hCG subunit dissociation was established in this study by optimization of a variety of method conditions including sample preparation buffer compositions, incubation temperature, separation voltage, and capillary temperature. This method was validated for good sensitivity, linearity, precision, and accuracy for both α-and β-subunit. CE-SDS also showed much better precision and accuracy than SDS-PAGE. The method was successfully used in both recombinant hCG (r-hCG) produced by cell culture and hCG (u-hCG) derived from urine. The CE-SDS method was used in the study of hCG development and stability. Therefore, it is an useful tool for the quality control of hCG.
8.Feasibility of a single-port thoracoscopy-assisted five-step laparoscopic procedure via transabdominal diaphragmatic approach for No.111 lymphadenectomy in patients with Siewert type II esophageal gastric junction adenocarcinoma.
Ze Yu LIN ; Hai Ping ZENG ; Ji Cai CHEN ; Wen jun XIONG ; Li Jie LUO ; Yan Sheng ZHENG ; Jin LI ; Hai Peng HUANG ; Wei WANG
Chinese Journal of Gastrointestinal Surgery 2023;26(4):339-345
Objective: We aimed to explore the feasibility of a single-port thoracoscopy- assisted five-step laparoscopic procedure via transabdominal diaphragmatic(TD) approach(abbreviated as five-step maneuver) for No.111 lymphadenectomy in patients with Siewert type II esophageal gastric junction adenocarcinoma (AEG). Methods: This was a descriptive case series study. The inclusion criteria were as follows: (1) age 18-80 years; (2) diagnosis of Siewert type II AEG; (3) clinical tumor stage cT2-4aNanyM0; (4) meeting indications of the transthoracic single-port assisted laparoscopic five-step procedure incorporating lower mediastinal lymph node dissection via a TD approach; (5) Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1; and (6) American Society of Anesthesiologists classification I, II, or III. The exclusion criteria included previous esophageal or gastric surgery, other cancers within the previous 5 years, pregnancy or lactation, and serious medical conditions. We retrospectively collected and analyzed the clinical data of 17 patients (age [mean ± SD], [63.6±11.9] years; and 12 men) who met the inclusion criteria in the Guangdong Provincial Hospital of Chinese Medicine from January 2022 to September 2022. No.111 lymphadenectomy was performed using five-step maneuver as follows: superior to the diaphragm, starting caudad to the pericardium, along the direction of the cardio-phrenic angle and ending at the upper part of the cardio-phrenic angle, right to the right pleura and left to the fibrous pericardium , completely exposing the cardio-phrenic angle. The primary outcome includes the numbers of harvested and of positive No.111 lymph nodes. Results: Seventeen patients (3 proximal gastrectomy and 14 total gastrectomy) had undergone the five-step maneuver including lower mediastinal lymphadenectomy without conversion to laparotomy or thoracotomy and all had achieved R0 resection with no perioperative deaths. The total operative time was (268.2±32.9) minutes, and the lower mediastinal lymph node dissection time was (34.0±6.0) minutes. The median estimated blood loss was 50 (20-350) ml. A median of 7 (2-17) mediastinal lymph nodes and 2(0-6) No. 111 lymph nodes were harvested. No. 111 lymph node metastasis was identified in 1 patient. The time to first flatus occurred 3 (2-4) days postoperatively and thoracic drainage was used for 7 (4-15) days. The median postoperative hospital stay was 9 (6-16) days. One patient had a chylous fistula that resolved with conservative treatment. No serious complications occurred in any patient. Conclusion: The single-port thoracoscopy-assisted five-step laparoscopic procedure via a TD approach can facilitate No. 111 lymphadenectomy with few complications.
Male
;
Female
;
Humans
;
Adolescent
;
Young Adult
;
Adult
;
Middle Aged
;
Aged
;
Aged, 80 and over
;
Diaphragm/surgery*
;
Retrospective Studies
;
Feasibility Studies
;
Esophagogastric Junction/surgery*
;
Lymph Node Excision/methods*
;
Stomach Neoplasms/pathology*
;
Laparoscopy/methods*
;
Gastrectomy/methods*
;
Esophageal Neoplasms/pathology*
;
Adenocarcinoma/pathology*
;
Thoracoscopy
9.Naringenin inhibits thoracic aortic aneurysm formation in mice with Marfan syndrome.
Zhi Qing LI ; Bing YU ; Ze Yu CAI ; Ying Bao WANG ; Xu ZHANG ; Biao ZHOU ; Xiao Hong FANG ; Fang YU ; Yi FU ; Jin Peng SUN ; Wei LI ; Wei KONG
Journal of Peking University(Health Sciences) 2022;54(5):896-906
OBJECTIVE:
To identify whether naringenin plays a protective role during thoracic aneurysm formation in Marfan syndrome.
METHODS:
To validate the effect of naringenin, Fbn1C1039G/+ mice, the mouse model of Marfan syndrome, were fed with naringenin, and the disease progress was evaluated. The molecular mechanism of naringenin was further investigated via in vitro studies, such as bioluminescence resonance energy transfer (BRET), atomic force microscope and radioligand receptor binding assay.
RESULTS:
Six-week-old Fbn1C1039G/+ mice were fed with naringenin for 20 weeks. Compared with the control group, naringenin significantly suppressed the aortic expansion [Fbn1C1039G/+ vs. Fbn1C1039G/++naringenin: (2.49±0.47) mm, n=18 vs. (1.87±0.19) mm, n=22, P < 0.05], the degradation of elastin, and the expression and activity of matrix metalloproteinase 2 (MMP2) and MMP9 in the ascending aorta of Fbn1C1039G/+ mice. Besides, treatment with naringenin for 6 weeks also attenuated the disease progress among the 20-week-old Fbn1C1039G/+ mice with established thoracic aortic aneurysms [Fbn1C1039G/+ vs. Fbn1C1039G/++naringenin: (2.24±0.23) mm, n=8 vs. (1.90±0.17) mm, n=8, P < 0.05]. To understand the underlying molecular mechanisms, we examined the effects of naringenin on angiotensin Ⅱ type 1 receptor (AT1) signaling and transforming growth factor-β (TGF-β) signaling respectively, which were the dominant signaling pathways contributing to aortopathy in Marfan syndrome as previously reported. The results showed that naringenin decreased angiotensin Ⅱ (Ang Ⅱ)-induced phosphorylation of protein kinase C (PKC) and extracellular regulating kinase 1/2 (ERK1/2) in HEK293A cell overexpressing AT1 receptor. Moreover, naringenin inhibited Ang Ⅱ-induced calcium mobilization and uclear factor of activated T-cells (NFAT) signaling. The internalization of AT1 receptor and its binding to β-arrestin-2 with Ang Ⅱ induction were also suppressed by naringenin. As evidenced by atomic force microscope and radioligand receptor binding assay, naringenin inhibited Ang Ⅱ binding to AT1 receptor. In terms of TGF-β signaling, we found that feeding the mice with naringenin decreased the phosphorylation of Smad2 and ERK1/2 as well as the expression of TGF-β downstream genes. Besides, the serum level of TGF-β was also decreased by naringenin in the Fbn1C1039G/+ mice. Furthermore, we detected the effect of naringenin on platelet, a rich source of TGF-β, both in vivo and in vitro. And we found that naringenin markedly decreased the TGF-β level by inhibiting the activation of platelet.
CONCLUSION
Our study showed that naringenin has a protective effect on thoracic aortic aneurysm formation in Marfan syndrome by suppressing both AT1 and TGF-β signaling.
Angiotensin II/metabolism*
;
Animals
;
Aortic Aneurysm, Thoracic/prevention & control*
;
Calcium/metabolism*
;
Disease Models, Animal
;
Elastin/metabolism*
;
Fibrillin-1/metabolism*
;
Flavanones
;
Marfan Syndrome/metabolism*
;
Matrix Metalloproteinase 2
;
Matrix Metalloproteinase 9
;
Mice
;
Mice, Inbred C57BL
;
Protein Kinase C/metabolism*
;
Receptor, Angiotensin, Type 1/metabolism*
;
Transforming Growth Factor beta/metabolism*
;
Transforming Growth Factors/metabolism*
;
beta-Arrestins/metabolism*
10.Relationship between two blood stasis syndromes and inflammatory factors in patients with acute coronary syndrome.
Cai-Yun MA ; Jing-Hua LIU ; Jian-Xun LIU ; Da-Zhuo SHI ; Zhen-Ye XU ; Shao-Ping WANG ; Min JIA ; Fu-Hai ZHAO ; Yue-Rong JIANG ; Qin MA ; Hong-Yu PENG ; Yuan LU ; Ze ZHENG ; Feng-Xue REN
Chinese journal of integrative medicine 2017;23(11):845-849
OBJECTIVETo investigate the relationship between inflammatory factors and two Chinese medicine (CM) syndrome types of qi stagnation and blood stasis (QSBS) and qi deficiency and blood stasis (QDBS) in patients with acute coronary syndrome (ACS).
METHODSSixty subjects with ACS, whose pathogenesis changes belongs to qi disturbance blood stasis syndrome, were divided into 2 groups: 30 in the QSBS group and 30 in the QDBS group. The comparative analysis on them was carried out through comparing general information, coronary angiography and inflammatory factors including intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40) and lipoprotein-associated phospholipase A2 (Lp-PLA2).
RESULTSCompared with the QSBS group, Lp-PLA2 and YKL-40 levels in the QDBS group showed no-significant difference (P>0.05); ICAM-1 was significantly higher in the QDBS group than in the QSBS group in the pathological processes of qi disturbance and blood stasis syndrome of ACS (P<0.05).
CONCLUSIONSInflammatory factor ICAM-1 may be an objective basis for syndrome typing of QSBS and QDBS, which provides a research direction for standardization research of CM syndrome types.