Objective To investigate the mechanisms of inhibitory effect of Erlotinib,an epidermal growth factor(VEGF) receptor inhibitor,on angiogenesis of pancreatic carncer.Methods①In a tube formation assay,Erlotinib(100?mol/L) was applied to the culture media and compared to the serum free media.The expression of vascular endothelial growth factor(VEGF) in BxPC-3 cells treated with Erlo- tinib at different concentrations(5,50,100,200?mol/L) was determined by RT-PCR.②The xeno grafts derived from BxPC 3 cancer cells were inoculated into the BALB/C nude mice.The mice were treated with either Erlotinib(100 mg/kg of Erlotinib oral lavage daily) or saline for four weeks.The vol- ume of the xenografts was measured and the tumor growth rate was calculated.The microvessel density (MVD) of tumor tissue was determined by immunohistochemistry with an antibody against factorⅧ. Results There were less endothelium cells and close hollow tubular structures in grlotinib treated group compared to the control group in the tube formation assay.The mean weight of xenografts in Erlotinib treated group[(0.397?0.550)g] was significantly lower than that in the control group[(1.570?1.060)g] with a inhibitary rate of 74.5%.The expression of VEGF mRNA in Ertotinib treated groups (=50?mol/L) were decreased comparing to the control group.The VEGF expression in xeno- grafts tumor tissues was also markedly down-regulated.The MVI) was significantly decreased in Erlotinib treated group( 1.86?0.43)than that in the control group (5.98?1.27,P

Objective To investigate the antitumor therapeutic effect of combined therapy of magnetic induction heating by nano-magnetic particles, herpes simplex virus thymidine kinase gene(HSV-tk suicide gene) and internal radiation in mice bearing MCF-7 breast carcinoma. Methods The transfection reagents, plasmids heat shock protein-HSV-tk (pHSP-HSV-tk), ferroso-ferric oxide nano-magnetic fluid flow and 188Re-ganciclovir-bovine serum albumin-nanopaticles (GCV-BSA-NP) were prepared. The heating experiments in vivo were carried out using ferroso-ferric oxide nano-magnetic fluid flow. Sixty mice tumor models bearing MCF-7 breast carcinoma were established and randomly divided into six groups. Group A was the control group, B was gene transfection therapy group, C was hyperthermia group, D was gene transfection therapy combined with radionuclide brachytherapy group, E was gene therapy combined with hyperthermia group, and F was gene therapy, hyperthermia combined with radionuclide brachytherapy group. The tumor growth, tumor mass and histopathological changes were evaluated. The expression of HSV-tk in the groups of B, D, E and F was detected by RT-PCR. Poisson distribution and one-way analysis of variance (ANOVA) were used for statistical analysis by SPSS 10.0 software. Results In the animal heating experiments, the temperature of tumor increased up to 39.6 ℃, 43.2 ℃, and 48.1 ℃ quickly with different injected doses (2, 4 and 6 mg respectively) of nano-magnetic particles and maintained for 40 min. The temperature of tumor tissue reduced to 36.8 ℃, 37.5 ℃ and 37.8 ℃ in 10 min when alternating magnetic field (AMF) stopped. The tumor mass in Groups C ((452.50 ±30.29) mg), D ((240.98 ±35.32)mg), E((231.87 ±27.41) mg) and F ((141.55 ±23.78) mg) were much lower than that in Group A ((719.12±22.65) mg) (F=800.07, P＜0. 01), with the most significant treatment effect in Group F.The tumor mass in Group B((684.05 ±24.02) mg) was higher than that in Group D (t =32. 805, P ＜0. 05). Semi-quantitative RT-PCR analysis showed that the expression of HSV-tk in Groups B and D (0.33 ±0. 13 and 0. 46 ±0.12) was significantly different from that in Groups E and F (0.66 ±0.13 and 0.74 ±0. 11)(F = 21. 573, P ＜ 0.05). Conclusion Combined use of hyperthermia, gene therapy and radionuclide brachytherapy could effectively depress the growth of MCF-7 breast carcinoma, thus possessing treatment potential for this tumor.

OBJECTIVETo explore the effect of Jinwu Jiangu Recipe (JJR) on the expression of synovial cells' nuclear factor-kappaB (NF-kappaB) and serum interleukin 17 (IL-17) in collagen induced arthritis (CIA) rats.

METHODSTotally 60 Wistar rats were randomly divided into 6 groups, i.e., the blank control group, the model group, high, middle, and low dose JJR treatment groups, and the tripterygium control group, 10 in each group. Except rats in the blank control group, CIA model was established in rats of the rest 5 groups. Then they were treated from the 7th day of modeling. After 4 weeks of medication they were sacrificed, serum collected, and synovium of joints were isolated. The expression of serum IL-17 was detected in synovium of joints by enzyme linked immunosorbent assay (ELISA). And the expression of NF-kappaB/P65, Ikappabetaalpha and NF-KappaB/P50 were detected by Western blot.

RESULTSCompared with the blank control group, the serum IL-17 level increased in the model group (P <0. 01). Compared with the model group, the serum IL-17 level obviously decreased in high and middle dose JJR groups and the tripterygium control group (P < 0.01). Results of Western blot showed, when compared with the blank control group, protein activities of NF-kappaB/P65 and NF-kappaB/P50 were significantly enhanced in the model group (P < 0.01). Compared with the model group, protein activities of NF-kappaB/P65 and NF-kappaB/P50 significantly decreased in high and middle dose JJR groups and the tripterygium control group (P < 0.05, P < 0.01). All indices mentioned above were higher in the low dose JJR group than in the tripterygium control group (P < 0.05, P < 0.01).

CONCLUSIONJJR could lower the expression of serum IL-17 in CIA model rats, and inhibit protein activities of NF-kappaB/P65 and NF-kappaB/P50.

Animals ; Arthritis, Experimental ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; chemistry ; Interleukin-17 ; blood ; NF-kappa B ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Synovial Membrane ; drug effects ; metabolism ; Tripterygium ; chemistry

OBJECTIVETo investigate whether patients presenting with self-reported olfactory disorders demonstrates significant side difference in odour recognition by measuring separately for each nostril.

METHODSOne hundred and four patients with chief complaint of hyposmia were evaluated by medical history, physical examination, T&T olfactory testing and medical imaging. Smell was tested using T&T olfactometry in each nostril separately.

RESULTSBased on the history and results from the clinical examination, unilateral sinonasal diseases and abnormal nasal structure were excluded. In almost one eighth of all presenting patients (13.46%), a side difference was detected. Especially, six of the patients were identified with lateralized hyposmia.

CONCLUSIONSOlfactory testing could be performed in each nostril separately. The above findings suggested that testing each nostril separately was necessary so as not to miss unilateral hyposmia as a special clinical manifestation of olfactory disorder.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Olfaction Disorders ; diagnosis ; physiopathology ; Olfactory Mucosa ; Sensory Receptor Cells ; Smell ; physiology ; Young Adult

OBJECTIVETo investigate clonal evolution of abnormal Philadelphia chromosome-negative cells (Ph- CE) after imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML).

METHODSBone marrow cells G-banding karyotype was evaluated every 3 months in 100 patients with Ph+ CML after achieving hematologic responses on the course of imatinib therapy. There were 54 patients in chronic phase (CP), 37 in accelerated phase (AP) and 9 in blast phase (BP).

RESULTSAfter a median follow-up of 32 months (ranged 25-34 months), 11 patients, including 5 cases in CP, 5 in AP and 1 in BP, developed transient, interrupted or continuous Ph- CE after 3 - 29 months on imatinib therapy. Ph- CE emerged at the beginning of Ph+ cells decreasing or after Ph+ cells disappearing. The proportion of Ph- CE, was negatively correlated with the proportion of Ph+ cells (P < 0.05). Ph- CE commonly included +8 (45.5%) and +Y (27.3%). Five patients had additional cytogenetic abnormalities besides Ph+ in Ph- CE. Seven of the patients with Ph- CE achieved a major cytogenetic response while 9 of them achieved a complete hematologic response. One patient with Ph- CE in AP progressed to BP 20 months after the initiation of the therapy while the rests remained in hematologic or cytogenetic responses.

CONCLUSIONPh- CE occurred in about 11% of the patients with Ph+ CML who achieved major or minor cytogenetic responses on imatinib therapy. After a median follow-up of more than 2 years, most of the patients with Ph- CE were in a stable status with no disease progression.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Benzamides ; Clone Cells ; drug effects ; metabolism ; pathology ; Female ; Follow-Up Studies ; Humans ; Imatinib Mesylate ; Karyotyping ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; pathology ; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative ; drug therapy ; genetics ; pathology ; Male ; Middle Aged ; Philadelphia Chromosome ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use ; Treatment Outcome

OBJECTIVETo investigate the relationship between the biological features and the treatment efficacy and prognosis in acute myeloid leukemia subtype M2 (AML-M2) patients with chromosome 8 and 21 translocation.

METHODSBy using Cox regression model and Kaplan-Meier analyses, prognostic factors in 54 cases of de novo adult AML with t(8;21) in our institute from 1990 to 2003 were retrospectively analyzed.

RESULTThe complete remission (CR) rates were 81.9% for all M2 patients, 82.4% for patients with normal karyotype, 88.5% for patients with t(8;21) [P > 0.05 for normal karyotype vs t(8;21)], 100.0% for 28 patients with t(8;21) alone and 75.0% for 24 patients with additional chromosome abnormalities (P < 0.01). The actuarial 3 year overall survival(OS) was 26% for M2 patients with normal karyotype, 25% for patients with t(8;21) [P > 0.05 for normal karyotype vs t(8;21)], in whole t(8;21) group, 46.4% for patients with t(8;21) alone and 0% for patients with additional chromosome abnormalities (P < 0.01). Multivariate analysis of prognostic factors showed that chromosome abnormalities besides t(8;21) was the only factor affecting CR, disease-free survival (DFS) and OS. DFS of allogeneic hematopoietic stem cell transplantation (HSCT) and intermediate-dose cytarabine/high dose cytarabine (IDAC) groups were better than the group received routine dose cytarabine as postremission therapy (P < 0.01).

CONCLUSIONAML with t(8;21) is not a single defined AML subset, and patients with additional chromosome abnormalities have a worse prognosis. HSCT and IDAC could improve the outcome. HSCT is the best choice for patients with high risks, especially with additional chromosome abnormalities.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Chromosomes, Human, Pair 21 ; genetics ; Chromosomes, Human, Pair 8 ; genetics ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; surgery ; therapy ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Translocation, Genetic

Ph chromosome occurs in nearly all patients with CML, and eliminating Ph-positive clone is a major target in the treatment of CML. IFN-alpha is a well-known effective treatment in chronic phase CML. The cytogenetic response and the prognostic factors in 128 CML patients treated with IFN-alpha were retrospectively studied. IFN-alpha administered singly at a dose of 3 million U/day for 2 - 3 times a week or in combination with either hydroxyurea (Hu), busulfan (Bu), low dose Ara-C or harringtonine. Karyotyping was examined by G-banding before and after IFN-alpha-based treatment. The results showed that all patients achieved complete hematological remission. Cytogenetic response occurred in 36 of 118 patients with standard t (9;22) translocation; 3 of these 36 patients had a complete cytogenetic response (Ph = 0), 13 had major cytogenetic responses (Ph < 35%) and 20 had minimal response (Ph > 35%). The total cytogenetic effectiveness was 13.6% (16/118). Four of seven patients with complicated variant translocation also achieved cytogenetic response, 2 of them had a major cytogenetic response and 2 had minimal response. Factors influenced the prognosis associated with cytogenetic response included sex, patient status at diagnosis and IFN-alpha administered singly or in combination with other chemotherapeutic agents. IFN-alpha could not prevent the progression of CML. It is concluded that Ph(+)CML patients with both standard and variant translocation had major cytogenetic response to IFN-alpha treatment at a dose of 6 - 9 million U/week in single or combination with Hu/Bu, however, IFN-alpha treatment could not prevent disease progression. Long term survival was also observed in patients with variant translocation treated with IFN-alpha. Regular cytogenesis examination in CML patients is necessary during IFN-alpha therapy, which is useful to reflect curative effect and progression of the disease.
Adolescent ; Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Chromosome Aberrations ; Chromosomes, Human, Pair 22 ; genetics ; Chromosomes, Human, Pair 9 ; genetics ; Cytogenetic Analysis ; Female ; Humans ; Interferon-alpha ; therapeutic use ; Karyotyping ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; pathology ; Leukemia, Myeloid, Chronic-Phase ; drug therapy ; genetics ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Translocation, Genetic ; Treatment Outcome

The purpose of this study was to explore the significance of abnormal karyotype in diagnosis and prognosis estimation of myelodysplastic syndrome (MDS). Chromosome analysis were performed in 306 cases of MDS using the short-term culture of bone marrow cell and G-banding technique, and in partial cases FISH technique was used for this analysis. 93 out of 306 cases were followed up. The results showed that 144 cases (47.1%) had clonal chromosome aberrations. The most common chromosomal aberrations included +8, translocation, complex or high complex karyotype, -7/7q-, 20q-/-20, trisomy 1 or partial trisomy 1, +11/+11q-, -9/9q-, +9/9q+, -Y, dup(1q), +21. The rate of abnormal karyotype in refractory anemia with erythroblasts (RAEB) and refractory anemia with erythroblasts-transformation (RAEBT) were much higher than in refractory anemia (RA) and refractory anemia with sideroblasts (RAS) (P < 0.05). The rate of abnormal karyotype among those cases with mutagen contact history were higher than those in cases without mutagen contact history. The patients with abnormal karyotype had a mean survival time much shorter than patients with normal karyotype (P < 0.005) and had a higher risk transforming into acute leukemia (P < 0.05). The worst outcome was observed in those patients with a complex or high complex karyotype, -7/7q- and trisomy 11. In conclusion, MDS is highly heterogeneous disorders and karyotype analysis is helpful for its diagnosis, treatment selection and prognosis estimation.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Chromosome Aberrations ; Female ; Humans ; Karyotyping ; Male ; Middle Aged ; Myelodysplastic Syndromes ; genetics ; mortality ; Prognosis

To investigate the cytogenetic and clinical characteristics in patients with abnormalities at the short arm of chromosome 12, chromosome specimens were prepared by 24-hour culture of bone marrow cells and undergone karyotype analysis by G-banding technique. The results showed that aberration at the short arm of chromosome 12 were detected in 16 cases with 12p balanced translocation, in 10 cases with 12p deletion, 6 cases with 12p addition, and in 1 case with inversion 12. By complex karyotype classification, 12p translocation included 6 simple aberrations, 6 complex aberrations, and 4 highly complex aberrations; while 12p deletion were mainly composed of highly complexity of aberration. Patients consisted of acute leukemia, myelodysplastic syndrome, chronic myelogenous leukemia and so on. Clinical follow-up data were available in 14 patients, in which 8 cases of acute leukemia were treated with conventional chemotherapy only. Three of them attained complete remission, and the median survival time in 8 patients was 5.5 months. In conclusion, the aberrations at short arm of chromosome 12 were involved in a broad spectrum of haematological malignancies, and the karyotypes showed most complexity of aberration with low remission rate and short survival in clinic.
Adolescent ; Adult ; Aged ; Child ; Chromosome Aberrations ; Chromosomes, Human, Pair 12 ; Female ; Humans ; Leukemia ; genetics ; Male ; Middle Aged ; Multiple Myeloma ; genetics ; Myelodysplastic Syndromes ; genetics

Aged ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; diagnosis ; immunology ; Prognosis ; T-Lymphocyte Subsets ; immunology