1.Gefitinib in the treatment of refractory non-small cell lung cancer.
Jian-Fang XU ; Cai-Cun ZHOU ; Ai-Wu LI
Chinese Journal of Oncology 2007;29(12):938-940
OBJECTIVETo observe the efficacy, median survival time, time to progression, quality of life and adverse effect of gefitinib (IRESSA) in the treatment for refractory advanced non-small cell lung cancer (NSCLC).
METHODSForty-one patients with stage III b to IV NSCLC who had previously treated with 2-7 cycles of platinum-based chemotherapy were enrolled into the study, 85.4% of the patients had received second line chemotherapy. The regimen was oral intake of gefitinib 250 mg once daily until the disease progression or intolerable toxic reaction occurred. The patients were required to receive tumor assessment before the treatment, one month, two months and every three months after IRESSA administration.
RESULTSAll 41 patients were evaluable for therapeutic effect. Partial response rate (PR), stable disease (SD) and progression of disease (PD) was 43.9% (18/41), 34.1% (14/41) and 22.0% (9/41), respectively. No complete regression was observed. The overall response rate was 43.9% (18/41) with a rate of 42.1% in the male and 45.5% in the female (P > 0.05). The disease control rate (PR + SD) was 78.0% (32/41). Twenty-two of the 41 patients (53.7%, 22/41) were still alive with MST of 10.1 months when the follow-up ended in Nov. 2006. TP and MST of dead patients was 2.7 and 5.0 months, respectively. The rate of symptom improvement was 78% for all patients with MST of 13.3 months for PR patients. The performance status (Karnofsky) was improved (20 +/- 5) after 28-day treatment. III-IV degree toxicity was not observed.
CONCLUSIONIRESSA is effective and safe for the advanced NSCLC patients with poor performance status who previously failed in the second or third line chemotherapy.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Bone Neoplasms ; secondary ; Brain Neoplasms ; secondary ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Diarrhea ; chemically induced ; Disease-Free Survival ; Exanthema ; chemically induced ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Quality of Life ; Quinazolines ; adverse effects ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Remission Induction ; Survival Rate
2.Study on the genetic polymorphism of mec Ⅰ in the clinical isolates of methicillin-resistantStaphylococcus aureus
Fang-You YU ; Zeng-Qiang CHEN ; Cun-Li LIU ; Xue-Qing ZHANG ; Fan CHEN ; Zhan-Guo CHEN ; Mei-Lan LI ; Tie-Li ZHOU ; Sai-Fang WANG
Chinese Journal of Laboratory Medicine 2003;0(07):-
Objective To investigate the genetic polymorphism of mec Ⅰ in the clinical isolates of methicillin-resistant Staphylococcus anreus(MRSA).Methods 40 isolates(MRSA)carrying mecA gene were selected randomly from the clinical isolates of Staphylococcus anreus from Jan,2005 to Aug,2006 in our hospital.The mec Ⅰ gene was detected by PCR followed with sequencing.Staphylococcal cassette chromosome mec(SCCmec)in MRSA were detected by multiplex-PCR.Agar dilution method was used for determining the MICs of oxacillin against MRSA.Results 35 of 40(87.5%)MRSA carried mec Ⅰ gene.All isolates carrying mec Ⅰ gene have mecI 202C→T substitution,which resulted in Gln at 68 aminophenol position replaced by stop condon.32 isolates carried single point mutation.3 isolates carried double-point mutation,including additonal A at 3 positon,A→C at 41 position and C→T at 142 position beside C→T at 202 position,respectively.Among 35 isolates carrying mec Ⅰ gene,there were 27 isolates of SCCmec Ⅲ, 7 isolates of SCCmec Ⅲ A and 1 isolate of SCCmec Ⅱ.Among 5 isolates with deletion of mec Ⅰ gene,there were 3 isolates of SCCmecⅣ,1 isolate of SCCmec Ⅰ and 1 isolate of non-known SCCmec tpye.The MICs of oxacillin were 256-512 ?g/ml,≥512 ?g/ml and 8-256 ?g/ml in 31 isolates with single point mutation at 202 position in mec Ⅰ gene,3 isolates with double-point mutation in mecI gene and 5 isolates with deletion of mec Ⅰ gene,respectively.1 isolate with single point mutation in mec Ⅰ gene had contrary result(MIC
3.Clinical characteristics and diagnosis of pulmonary mucosa-associated lymphoid tissue-derived (MALT) lymphoma: a retrospective analysis of 29 cases.
Ai-wu LI ; Jian-fang XU ; Cai-cun ZHOU ; Chun-yan WU ; Yan-li WANG
Chinese Journal of Oncology 2012;34(5):390-393
OBJECTIVETo study the clinical manifestations and radiological characteristics, diagnostic methods and outcomes of pulmonary mucosa-associated lymphoid tissue-derived(MALT) lymphoma.
METHODSA retrospective review of clinical, radiological and follow-up data of 29 pulmonary MALT lymphoma cases at Shanghai Pulmonary Hospital affiliated to Tong Ji University from January 2002 to June 2010 was performed.
RESULTSAmong these patients, there were 19(65.5%) males and 10 (34.5%) females aged from 27 to 73 (median 53) years old. Common clinical manifestations were cough (51.7%), fever (20.7%), apnea (17.2%), chest pain (17.2%), fatigue (13.8%) and weight loss (13.8%), while 9(31.0%) cases had no symptoms at diagnosis. The characteristics of the chest CT showed that 22 (75.9%) of the cases had patch infiltration or consolidation of the lung, 7(24.1%) of the cases had mass, and 15 (51.7%) unilateral and 14(48.3%) bilateral lesions. Their diagnosis duration varied between 0.5 and 96 months. 18(62.1%) cases were confirmed by surgery (15 open lung and 7 video-assisted thoracic surgery, VAST), 4 (13.8%) by percutaneous lung biopsy, 5 (17.2%) by bronchoscopic biopsy, and 2 (6.9%) by peripheral lymph node biopsy. The treatment methods included surgery, combined chemotherapy, radiotherapy and Chinese herbal medicine. The 1- and 3-year-survival rates were 92.3% and 87.4%, respectively.
CONCLUSIONSPulmonary MALT lymphoma is atypical in clinical manifestations and radiological characteristics, and easy to be misdiagnosed. Local diseases are mainly treated by operation while extensive diseases receive combined chemotherapy. A proper diagnosis is mainly based on pathological biopsy. Patients with MALT lymphoma have a favorable outcome. Poor prognosis may be connected with poor performance status and long diagnosis duration.
Adult ; Aged ; Antigens, CD20 ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Combined Modality Therapy ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Lung ; pathology ; Lung Neoplasms ; diagnosis ; diagnostic imaging ; pathology ; therapy ; Lymphoma, B-Cell, Marginal Zone ; diagnosis ; diagnostic imaging ; pathology ; therapy ; Male ; Middle Aged ; Neoplasm Staging ; Pneumonectomy ; methods ; Prednisone ; therapeutic use ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Retrospective Studies ; Survival Rate ; Thoracic Surgery, Video-Assisted ; Tomography, X-Ray Computed ; Vincristine ; therapeutic use
4.Effects of weikangning contained serum on growth of gastric cancer cell, expression of vascular endothelial growth factor and its receptors including KDR and fit-1.
Qing-ming LI ; Fang-ju KAN ; Cun-yun MIN
Chinese Journal of Integrated Traditional and Western Medicine 2006;26 Suppl():88-92
OBJECTIVETo observe the effect of drug-containing serum of Chinese traditional herbal decoction Weikangning (WKN) on growth of gastric cancer cell, expression of vascular endothelial growth factor (VEGF) and its receptors including KDR and Flt-1.
METHODSA total of 120 male Wistar rats were given high, medium and low-dose WKN. After the drug-containing serum was prepared, the gastric cancer cells MGC-803 of different dose groups were cultured with the drug-containing serum, respectively. The gastric cell growth was observed by using light microscope and flow cytometer,the expression of VEGF and its receptor Flt-1 was detected with SABC immunohistochemistry method and the mRNA expression levels of VEGF and its receptors including KDR and Flt-1 of different groups were detected with reverse transcription-polymerase chain reaction (RT-PCR), respectively.
RESULTSThe gastric cancer cell growth and cell cycle of the three medicated groups were significantly improved as compared with those of the control group (P <0. 01) ,the proportion of cells in G0 - G1 phase was increased,while the cells in S phase were decreased. It was shown that the apoptotic rates were increased in the medicated groups in a dose-dependent manner. The gray scales ( microm(2) ) of VEGF and Flt-1 in high, medium and low dose groups was 182. 44 +/-0. 54,178. 65 +/-0. 56,174. 80 +/-0. 81 and 168. 51 +/- 0. 81,162. 01 +/-0. 52,148. 20 +/-0. 69, respectively vs 147.82 +/-0. 15(P <0.01) and 144.31 +/-0.71 (P <0.01) in the control group. The mRNA expression of VEGF and its receptors significantly decreased in gastric cancer cells after cultured with WKN contained serum (P < 0. 01 ).
CONCLUSIONWKN has inhibitory effects on gastric cancer cell growth and mRNA expression of VEGF as well as its receptors KDR and Flt-1.
Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; therapeutic use ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Rats ; Rats, Wistar ; Stomach Neoplasms ; drug therapy ; enzymology ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism
5.EGR-1 mRNA expression during 12-0-tetradecanoylphorbol-13-acetate-induced K562 cell differentiation.
Ding-zhu FANG ; Qing-kui LIAO ; Jiu GAO ; Xian-jun YANG ; Li-xing YUAN ; Guo-cun JIA
Chinese Journal of Pediatrics 2004;42(7):495-498
OBJECTIVE12-0-tetradecanoylphorbol-13 acetate (TPA) plays an important role in precipitating cell differentiation for various tumor cells, especially leukemic cells. Changes of many genes may be involved in this process. The purpose of this study was to observe the relationship between the EGR1mRNA expression and cell differentiation during TPA-induced K562 cell differentiation.
METHODSIncubation of human K562 cells in vitro was applied to cultivate K562 cells. The cells were treated in two different ways. K562 cells of experiment group were treated with TPA and those of control group were treated without TPA. Using morphology (Wright's staining and NSE staining) and flow cytometry (FCM), the investigators observed the differentiation characteristics of K562 cells, cell-cycle and the differentiation antigen expressions of CD33 and CD14 on cell membranes. RT-PCR was carried out to assay EGR1 mRNA expression.
RESULTSAfter treated with TPA for 7 d, the morphology of K562 cells obviously tended to mature differentiation, like monocytes. The differentiation rate of induced K562 cells was up to 95% in experiment group and 4.5% in control group, respectively. Using SPSS software, the above result showed statistical significance (P < 0.01). Using NSE staining, K562 cells showed positive reaction. Some of them were densely stained. The positive rate was up to 86%. More than half of the positive cells could be inhibited by NaF. The inhibiting rate of NaF was up to 58.72%, showing statistical difference when compared with that of control group. FCM analysis showed that most of K562 cells stimulated by TPA underwent G1/S phase cell-cycle arrest. The composing rate of cell-cycle in TPA-treated group showed that (53.7 +/- 1.25)% of cells were at G0 + G1 phase and (44.3 +/- 1.32)% were at S phase (P < 0.05). The level of CD33 expression on cell membranes was mildly decreased from 0.997% to 0.893% (P > 0.05). However, the level of CD14 expression was significantly increased from 0.049% to 0.387% (P < 0.05).
CONCLUSIONK562 cells could express EGR1mRNA during TPA-induced differentiation, which suggested that EGR1mRNA might participate in the process of K562 cells differentiating into monocyte/macrophages, and might play an important role in precipitating and maintaining cell differentiation for leukemic cells.
Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Carcinogens ; pharmacology ; Cell Cycle ; drug effects ; genetics ; Cell Differentiation ; drug effects ; genetics ; Cell Division ; drug effects ; genetics ; Cell Membrane ; chemistry ; drug effects ; DNA-Binding Proteins ; genetics ; Early Growth Response Protein 1 ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Immediate-Early Proteins ; genetics ; K562 Cells ; Lipopolysaccharide Receptors ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sialic Acid Binding Ig-like Lectin 3 ; Tetradecanoylphorbol Acetate ; pharmacology ; Transcription Factors ; genetics
6.Expression of proline-rich tyrosine kinase-2 in human primary colorectal carcinoma and its prognostic implication.
Zong-nai ZHANG ; Xin WANG ; Ting LI ; Hong-fang YIN ; Yuan-lian WAN ; Yu-cun LIU ; Jing ZHU
Chinese Journal of Surgery 2008;46(6):440-442
OBJECTIVETo investigate the expression of proline-rich tyrosine kinase-2 (Pyk2) in human primary colorectal carcinoma (CRC) and it's prognostic significance.
METHODSThe expression of Pyk2 was retrospectively examined with immunohistochemistry (IHC) in 108 tissues of primary CRC. The correlation of Pyk2 expression to prognosis and relevant clinical factors were analyzed.
RESULTSThe rate of Pyk2 low-expression in CRC was 56.5% (61/108). The expression of Pyk2 correlated significantly to the histological grade (P < 0.05) and the TNM stage (P < 0.05), while no correlation between Pyk2 expression and age, tumor size (P > 0.05). Patients with Pyk2 over-expression had significantly higher 5-year survival rate (66.0%) than those with Pyk2 low-expression (31.4%). Pyk2 expression, together with carcinoma histologic grade and TNM stage were prognostic factors to CRC on the multivariate analysis.
CONCLUSIONSPyk2 expression can be a prognostic factor to the CRC patients together with other predictors.
Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; enzymology ; pathology ; Female ; Focal Adhesion Kinase 2 ; metabolism ; Humans ; Male ; Middle Aged ; Prognosis
7.Effects of endostatin and doxycycline on microcirculation patterns in melanoma and their relevant molecular mechanisms.
Bao-cun SUN ; Shi-wu ZHANG ; Li-sha QI ; Dann-fang ZHANG ; Hua GUO ; Xiu-lan ZHAO
Chinese Journal of Oncology 2007;29(7):500-504
OBJECTIVETo investigate the effects of endostatin and doxycycline on microcirculation patterns in melanoma and their molecular mechanisms.
METHODSTo establish mouse B16 melanoma model by subcutaneous injection of B16 melanoma cell suspension. The mice were divided into 3 experimental groups and 1 control group. To treat the mice in the 3 experimental groups with endostatin, doxycycline, endostatin and doxycycline, respectively, and the control group without any treatment. The tumor volume was measured and recorded to make comparison of their growth rate. To assess the expression of MMP-2, MMP-9 and TIMP-2 by immunohistochemical staining. The three microcirculation patterns of endothelium-dependent vessels, mosaic vessels and vasculogenic mimicry were counted. The activity of MMP-2, MMP-9 between different groups was examined by gelatin zymography.
RESULTSTumor growth in the three experimental groups was statistically significantly slower than that in the control group. The expression of MMP-2, MMP-9 and TIMP-2 in each treated group was significantly different with that in the control group. The amount of three microcirculation patterns in three experimental groups was less than that of the control group, and the amount of MV and VM in each experimental group was significantly less than that in the control group. By gelatin zymography, the enzyme activity of MMP-9, actived-MMP-2 and MMP-2/proMMP-2 in ES, DOX and ES + DOX group was lower than that in the control group, but the enzyme activity of pro-MMP-2 among the four groups was not significantly different.
CONCLUSIONThe combined use of doxycycline and endostatin in melanoma can inhibit the expression of MMPs, influencing the formation of different microcirculation patterns in melanoma.
Animals ; Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Doxycycline ; pharmacology ; Drug Combinations ; Drug Synergism ; Endostatins ; pharmacology ; Female ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Melanoma, Experimental ; blood supply ; enzymology ; pathology ; Mice ; Mice, Inbred C57BL ; Microcirculation ; drug effects ; Microvessels ; pathology ; Neoplasm Transplantation ; Tissue Inhibitor of Metalloproteinase-2 ; metabolism ; Tumor Burden ; drug effects
8.The influence of different microenvironments on melanoma invasiveness and microcirculation patterns.
Shi-Wu ZHANG ; Bao-Cun SUN ; Dan-Fang ZHANG ; Yan LI ; Zhe RONG ; Xiu-Lan ZHAO
Chinese Journal of Pathology 2007;36(12):832-837
OBJECTIVETo investigate the influence of different microenvironments on tumor microcirculation patterns and invasive capability.
METHODSMelanoma B16 cells were injected into the peritoneal cavity and skeletal muscle of C57 mice synchronously. CK18 expression in melanoma was assessed to distinguish the malignant phenotype of tumors in the peritoneal cavity from that in the skeletal muscle. HIF-1alpha, MMP-2 and MMP-9 protein and mRNA expression were compared in the two microenvironments. Cells positive for each immunohistochemical stain and the vessels representative of each type of microcirculation pattern were evaluated in two microenvironments.
RESULTSCK18 and HIF-1alpha expression in melanoma were significantly higher in the skeletal muscle than in the peritoneal cavity (t = 8.142, t = 3.645, P < 0.05). Compared with the peritoneal cavity, melanoma cells in the skeletal muscle overexpressed MMP-2 and MMP-9 (t = 4.916, t = 7.782, P < 0.05). Real time-PCR results also showed that MMP-2 and MMP-9 mRNA levels in melanoma were higher in the skeletal muscle than in the peritoneal cavity (t = 36.814, t = 26.025, P < 0.05). Vasculogenic mimicry channels and endothelium-dependent vessels were the major microcirculation patterns in the skeletal muscle and in the peritoneal cavity respectively.
CONCLUSIONSDifferent microenvironments affect invasiveness and blood supply patterns of melanoma. Different microenvironment induced tumor cell secretion of more invasion-related proteins and affect invasiveness and blood supply patterns of melanoma.
Animals ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; Matrix Metalloproteinase 2 ; genetics ; Matrix Metalloproteinase 9 ; genetics ; Melanoma ; blood supply ; genetics ; metabolism ; pathology ; Mice ; Mice, Inbred C57BL ; Microcirculation ; Muscle, Skeletal ; blood supply ; metabolism ; pathology ; Neoplasm Invasiveness ; Peritoneal Cavity ; blood supply ; pathology ; Polymerase Chain Reaction ; RNA, Messenger ; genetics ; metabolism
9.Establishment of an animal model of open tibial fractures with infection in New Zealand rabbits
Fang GENG ; Li-Cun PAN ; Zi-Hui ZHOU
Chinese Journal of Tissue Engineering Research 2018;22(8):1223-1228
BACKGROUND: Open facture is easy to induce infection, which is an urgent problem in clinic. Establishing a reliable animal model of open fracture with infection is of great significance for drug and instrument development and application. OBEJCTIVE: To develop an open fracture with infection model in New Zealand white rabbits, and to identify the available number of bacteria that can cause infection. METHODS: The amount of bacteria was determined by establishing open fracture structure and verifying the concentration of bacterial colonies. Thirty New Zealand white rabbits were randomly divided into control group and four experimental groups, and a transverse fracture at the middle part of tibia was established in all rabbits,followed by the injection of 1 mL of normal saline or 1mL of Staphylococcus aureus suspension at the concentrations of 1×105, 1×106, 5×106, and 1×107CFU/mL. Afterwards, the optimal concentration of 1 mL of bacteria liquid causing infection was determined by gross observation, body temperature analysis and body mass measurement, white blood cell and C-reactive protein detection, bacterial culture and pathological observation. RESULTS AND CONCLUSION: Rabbits in the 5×106CFU/mL group were all infected and had higher survival rate. In the 1×105and 1×106CFU/mL groups, some rabbits showed no infection. One rabbit died due to infection in the 1×107CFU/mL group. In summary, the reliable infection model of open fracture can be induced by injected with 1 mL of Staphylococcus aureus at the concentration of 5×106CFU/mL in New Zealand white rabbits, which can be used as an effective model to guide drugs and instruments related anti-infective research.
10.The value of 18F-FDG PET/CT in the diagnosis of secondary malignant peripheral nerve lesion
Lei, FANG ; Shi-cun, WANG ; Bo, PAN ; Feng-lin, ZHAN ; Qiang, XIE ; Ji-kui, XIE ; Jiu-lin, LI ; Sai-juan, SHEN
Chinese Journal of Nuclear Medicine 2010;30(4):222-225
Objective To investigate the characteristics and diagnostic value of 18F-fluorodeoxyglucose (FDG) PET/CT in patients with secondary malignant peripheral nerve lesions. Methods 18F-FDG PET/CT studies of 8 cases of secondary malignant peripheral nerve lesions confirmed by histopathology or follow-up were analyzed retrospectively. The maximum standardized uptake value ( SUVmax ) of infiltrating peripheral nerves and contralateral normal peripheral nerves was measured and compared with their morphological appearances on CT. Paired student t-test was performed by SPSS 10.0. Results Twelve secondary malignant peripheral nerve lesions with high 18F-FDG metabolism were found in 8 cases. On PET imaging,the lesions distributed along the neurovascular tissues or intervertebral foramina with appearances resembling those of fibre bundles,radices or nodes on PET but no density differences with the surrounding soft tissue or fat planes on CT. The SUVmax was 6.86 ± 3.87. The contralateral normal peripheral nerves showed no abnormal 18F-FDG uptake with a SUVmax of 1.10 ±0.46,which was significantly different from that of the secondary malignant peripheral nerve lesions (t = 9.231,P < 0.001 ). Conclusion 18 F-FDG PET/CT may be useful in locating the secondary malignant peripheral nerve lesions and in assessing its regional infiltration.