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1.
J Gene Med ; 22(12): e3269, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32890417

RESUMO

BACKGROUND: Thyroid carcinoma (TC) is the most common malignancy of the endocrine system. Circular RNA (circRNA) is vital in the regulation of tumor progression. Circ_0000144 serves as a novel oncogenic circRNA, and miR-217 is reported to inhibit the malignant phenotypes of cancer cells by targeting AKT3 in TC. The present study aimed to explore the regulatory mechanism of circ_0000144 and miR-217 in the progression of TC. METHODS: Circ_0000144 expression in 32 pairs of TC tissues and different TC cell lines (including BCPAP, K1, H7H83, and TPC-1) was detected by employing a quantitative real-time polymerase chain reaction (qRT-PCR). Circ_0000144 small interfering RNA was used to establish loss-of-function models. Cell counting kit-8 (CCK-8), BrdU (5-bromo-2'-deoxyuridine) and transwell assays were utilized to verify the effects of circ_0000144 on TC cell proliferation, migration and invasion, respectively. Bioinformatics, western blotting, a luciferase reporter experiment and qRT-PCR were employed to confirm the relationships among circ_0000144, miR-217 and AKT3. RESULTS: Circ_0000144 expression was remarkably elevated in TC tissues (p < 0.001) and TC cell lines. The elevation of circ_0000144 expression was markedly linked to tumor size (p = 0.015), TNM stage (p = 0.025) and lymph node metastasis (p = 0.017) of the patients. Functional studies showed that knocking down circ_0000144 repressed the malignancy of TC cells. Furthermore, miR-217 was identified as a downstream target of circ_0000144; inhibition of miR-217 could reverse the effects induced by circ_0000144 knockdown. Moreover, circ_0000144 could regulate AKT3 expression by suppressing miR-217 expression. CONCLUSIONS: Circ_0000144 exerts a cancer-promoting effect on TC cells via the miR-217/AKT3 pathway.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Circular/genética , Neoplasias da Glândula Tireoide/patologia , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Células Tumorais Cultivadas
2.
Exp Ther Med ; 13(3): 989-994, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28450931

RESUMO

The aim of the present study was to clarify whether the cell penetrating peptide of sodium-iodide symporter (NIS) has an effect on the I-131 radiotherapy of thyroid cancer. Firstly, we combined the HIV-1 TAT peptide (a cell penetrating peptide, dTAT) and established a nanoparticle vector (dTAT NP) to study the delivery efficiency of this cell-penetrating strategy for tumor-targeted gene delivery. dTAT NP was transfected into cultured TPC-1 cells as a model to study the effects of I-131 radiotherapy on thyroid cancer. Reverse transcription-quantitative polymerase chain reaction and western blotting results showed that the mRNA and protein expression levels of NIS in the transfected TPC-1 cells were substantially higher than in the negative control cells. MTT and flow cytometric analyses demonstrated that the cell growth and apoptosis rates of the TPC-1 cells were significantly inhibited and activated, respectively, by treatment with dTAT NP. The results of DAPI staining showed that treatment with dTAT NP visibly increased the nuclear apoptosis rate of the TPC-1 cells. The effect of dTAT NP on TPC-1 cells was associated with the promotion of caspase-3 and downregulation of the PI3K/Akt signaling pathway. In summary, the present data provide a pre-clinical proof-of-concept for a novel gene delivery system that efficiently delivers NIS to the targeted cancer cells and presents a satisfactory efficacy. This approach may offer an effective strategy for improving thyroid cancer gene therapy.

3.
Di Yi Jun Yi Da Xue Xue Bao ; 24(10): 1194-6, 2004 Oct.
Artigo em Zh | MEDLINE | ID: mdl-15485798

RESUMO

OBJECTIVE: To investigate the therapeutic effects of strontium-89 against osseous metastases of lung cancer. METHODS: A total of 126 patients with osseous metastases of lung cancer received strontium-89 treatment ((89)SrCl(2)) at the dose of 148 MBq given through a single intravenous injection. The analgesic effect was evaluated by the changes in the degree, frequency and scores of the pain, and the therapeutic effect assessed by observing the changes in the number and volume of osseous lesions after therapy and compared between different pathological types of lung cancer by Ka-square test. RESULTS: Within 6 months after the injection, the total pain relief rate was 70.6% (89/126), including 25 (19.8%) cases with pain vanished, suggesting significant alleviation of the pain intensity by the treatment (u=5.361, P<0.01). The frequency of pain was reduced in 78.6% (99/126) of the cases (u=4.589, P<0.01), and the average score of pain decreased significantly from 7.54+/-3.29 to 4.19+/-4.38 (t=6.865, P<0.001). The number and size of lesions decreased by more than 25% in 57 cases, showing a total efficacy rate of 45.2% (57/126). No significant difference was noted in the therapeutic effects among the 4 pathological types of lung cancer (P>0.05). CONCLUSIONS: Strontium-89 is effective for pain relief and tumor focus confinement in osseous metastases of lung cancer. No significant difference has been found in its effect between 4 different pathological types of lung cancer.


Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Neoplasias Pulmonares/radioterapia , Dor Intratável/radioterapia , Radioisótopos de Estrôncio/uso terapêutico , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adenocarcinoma/secundário , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/secundário , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade
4.
Di Yi Jun Yi Da Xue Xue Bao ; 24(10): 1184-5, 2004 Oct.
Artigo em Zh | MEDLINE | ID: mdl-15485796

RESUMO

OBJECTIVE: To evaluate the value of (99m)Tc-MIBI brain single-photon emission computerized tomography (SPECT) in diagnosis of glioma. METHODS: Fifty-nine patients with glioma, 6 with brain abscess and 9 healthy controls underwent (99m)Tc-MIBI brain SPECT, and the diagnostic indices such as the sensitivity, specificity and accuracy were calculated. The tumor to non-tumor (T/NT) ratios were calculated according to the region of interest (ROI) and compared between the glioma group, healthy control group and brain abscess group by t test. RESULTS: Among the 59 cases of glioma, 51 showed positive results in (99m)Tc-MIBI SPECT, along with one of the healthy controls and 4 of brain abscess patients. The sensitivity, specificity and accuracy of the diagnosis were 86.4%, 66.7% and 82.4%, respectively. The T/NT ratio of brain glioma group was 2.6+/-1.2, significantly higher than that of normal group (t=3.6199, P<0.001) and brain abscess group (t=2.1327, P<0.05). CONCLUSION: (99m)Tc-MIBI brain SPECT is sensitive for diagnosis of brain glioma, and can distinguish malignant from benign lesions effectively.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada de Emissão de Fóton Único , Adolescente , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
5.
Di Yi Jun Yi Da Xue Xue Bao ; 24(7): 812-4, 2004 Jul.
Artigo em Zh | MEDLINE | ID: mdl-15257911

RESUMO

OBJECTIVE: To assess the diagnostic value of bone alkaline phosphatase (B-AKP) detection in diagnosis of osseous metastases of malignant tumors. METHODS: Bone scanning and B-AKP detection were performed in 106 patients with malignancies. According to the findings in bone imaging and clinical symptoms, the patients were divided into bone metastases group (BM) and non-bone metastases group (NBM), between whom B-AKP was compared by t test. According to the number of osseous lesions on bone imaging, the patients were graded and B-AKP was compared between the 4 grades. Correlation analysis was performed between B-AKP level and the number of osseous lesions. RESULTS: Among the 106 patients, bone scanning found osseous metastases in 68 patients. For diagnosing osseous metastases, the sensitivity, specificity, PPV and NPV of B-AKP detection were 89.7%, 52.6%, 77.2% and 74.0%, respectively. B-AKP was 28.4+/-14.8 microg/L in BM group and 12.8+/-7.6 microg/L in NBM group, showing significant difference (t=6.056, P<0.001). B-AKP was 13.9+/-6.8 microg/L, 17.2+/-9.4 microg/L, 23.8+/-10.4 microg/L and 49.5+/-17.6 microg/L in patients of grade 0, 1, 2, and 3, respectively, showing significant difference by comparisons between the grades (P<0.05) except for that between grades 0 and 1 (t=1.320, P>0.05) and between grades 1 and 2 (t=1.803, P>0.05). B-AKP was 19.6+/-4.2 microg/L in patients with single hot focus and 13.1+/-3.4 microg/L in patients with single cold focus (t=2.570, P<0.05). Correlation analysis showed that there was low-degree correlation between B-AKP level and the number of osseous lesions (r=0.751, P<0.01). CONCLUSIONS: B-AKP level detection and bone imaging yield consistent results. For diagnosis of osseous metastases in patients with malignant tumor, bone scanning is the primary choice but in cases of single hot lesions, B-AKP should be performed to prevent missed diagnosis; for false positive lesions, B-AKP should also be detected to prevent misdiagnosis.


Assuntos
Fosfatase Alcalina/análise , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/secundário , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/enzimologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cintilografia
6.
Di Yi Jun Yi Da Xue Xue Bao ; 24(6): 691-3, 2004 Jun.
Artigo em Zh | MEDLINE | ID: mdl-15201092

RESUMO

OBJECTIVE: To evaluate the efficacy of (99m)Tc-methylene diphosphonate (MDP) bone scintigraphy in diagnosis of diabetic foot. METHODS: (99m)Tc-MDP three-phase bone imaging was performed in 56 patients with diabetic foot and 36 non-diabetic control subjects, each foot was analyzed independently. The radioactive concentration per pixel hence the foot to tibia ratio (R(m/t)) was calculated and the time-radioactivity curve of each region of interest generated. From the curve the perfusion time (Tp) was read and the velocity of uptake rate (V) of the foot calculated. The indices such as R(m/t), Tp and V were compared between the two groups by t test, and the diagnostic indices such as sensitivity, specificity, accuracy, positive prediction value and negative predictive value were compared using u test. RESULTS: In the control group, the Tp, V and R(m/t) were 32.9+/-9.8 s, 2.301+/-0.754 counts/s and 0.85+/-0.29, respectively, which were 36.1+/-15.3 s, 1.574+/-0.341 counts/s and 0.72+/-0.31 respectively in the diabetic group. Tp was not significantly different (t=1.693, P>0.05) between the two groups, as was V (t=8.396, P<0.001) and R(m/t)(t=2.759, P<0.01). When V was used as the index, the sensitivity, specificity, and accuracy were 80.2%, 82.8% and 81.5%, respectively, and those for R(m/t) were 65.2%, 68.8% and 67.3%, respectively. By comparison, the sensitivity (u=2.3274, P<0.05) and specificity (u=2.4068, P<0.05) of V were significantly higher than those of R(m/t). CONCLUSIONS: (99m)Tc-MDP three-phase bone imaging can identify decreased uptake rate and R(m/t) in the diabetic foot, and the former index can be more sensitive and specific to define the hemodynamics in the diabetic foot. This technique may detect hemodynamic abnormity in early stage and greatly assist the diagnoses and treatment.


Assuntos
Osso e Ossos/diagnóstico por imagem , Pé Diabético/diagnóstico por imagem , Pé Diabético/fisiopatologia , Extremidade Inferior/irrigação sanguínea , Medronato de Tecnécio Tc 99m , Adulto , Idoso , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Cintilografia , Sensibilidade e Especificidade
7.
Di Yi Jun Yi Da Xue Xue Bao ; 21(11): 839-840, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-12426187

RESUMO

OBJECTIVE: To assess the radiosensitivity of human hepatocarcinoma cell line BEL-7402. METHODS: Human hepatocarcinoma cell line BEL-7402 was cultured in vitro and then subjected to exposure to 6 MV X-ray at the doses ranging from 0 to 10 Gy. The survival rate of the cells following the exposure was assessed by determining the colony-forming units during further cell culture 12 to 14 d after the exposure, and the parameters for the radiosensitivity calculated. RESULTS and CONCLUSION: The parameters of BEL-7402 cells (D0=1.6, Dq=1.3, n=2, 4, SF2=0.63+/-0.05 Gy) demonstrates a high sensitivity of the cells to radiation.

8.
Di Yi Jun Yi Da Xue Xue Bao ; 22(11): 966-9, 2002 Nov.
Artigo em Zh | MEDLINE | ID: mdl-12433618

RESUMO

OBJECTIVE: To observe the effect of tissue-engineered bone grafts in repairing large tibial defect in goats, and assess the value of radionuclide bone imaging in monitoring the therapeutic effect of this approach. METHODS: Tibial defects measuring 2 cm was artificially made in the left tibia of 27 normal goats that were subsequently divided into 3 groups (9 each) to undergo treatment with tissue-engineered bone grafts, artificial bone grafts or without any grafts (as control group) respectively. The tissue-engineered bone grafts contained bone marrow stroma cells (BMSCs) of the goats and coral hydroxyapatite (CHAP), while the artificial bone grafts were from CHAP only. After the operations, radionuclide bone imaging was used to monitor the therapeutic effects at 2, 4 and 8 postoperative weeks. RESULTS: The 99mTc-MDP uptake of the region of interest (ROI) and the target to non-target ratios (T/NT) of the control group did not indicate any process of revascularization or bone regeneration. An increasing tendency of the revascularization and bone regeneration, in contrast, was observed in goats receiving the artificial bone grafts, a tendency that was far more obvious in the goats with tissue-engineered bone grafts. CONCLUSION: Tissue-engineered bone graft is eligible in repairing large defect in the caprine tibia, and radionuclide bone imaging may accurately monitor the revascularization and bone regeneration after the bone graft implantation.


Assuntos
Regeneração Óssea/fisiologia , Transplante Ósseo/diagnóstico por imagem , Tíbia/anormalidades , Engenharia Tecidual , Animais , Feminino , Cabras/anormalidades , Masculino , Modelos Animais , Cintilografia , Tíbia/diagnóstico por imagem
9.
Nan Fang Yi Ke Da Xue Xue Bao ; 30(11): 2463-5, 2010 Nov.
Artigo em Zh | MEDLINE | ID: mdl-21097406

RESUMO

OBJECTIVE: To evaluate the in vivo and in vitro stability of (131)I-Herceptin and its form of existence in the blood. METHODS: Herceptin was labelled with iodine-131 using the Iodogen method. (131)I-Herceptin was stored at 4 degrees celsius for 3, 24, 48, 72 and 96 h, and the radiochemical purity (RCP) was measured by high performance liquid chromatography (HPLC). Five rabbits received injections of (131)I-Herceptin and at 1, 3, 6, 24, 48, 72, 96 and 120 h after the injection, blood samples were taken to measure the RCP of (131)I-Herceptin in the serum, and the radio count of the serum and blood cells was calculated. RESULTS: The baseline RCP of (131)I-Herceptin was (94.9±2.7)%. The RCP was stable after placement at 4 degrees celsius for not over 72 h (F=15.985, P<0.001), but was significantly lowered to (82.6±2.8)% after preservation for over 72 h (t=9.971, P<0.001). Within the time of 1.0 to 96 h after injection in rabbits, (131)I-Herceptin existed mainly in the serum with a radio count of 81%-87%; 24 h after the injection, the RCP of (131)I-Herceptin in the serum was significantly lowered to (75.4±3.9)% (t=6.564, P<0.001). CONCLUSION: Storage at 4 degrees celsius for no more than 72 h does not obviously affect the activity of (131)I-Herceptin in terms of RCP. After injection in rabbits, (131)I-Herceptin exists mainly in the serum and its radiochemical purity remains stable within 24 h, after which obvious degradation occurs.


Assuntos
Anticorpos Monoclonais Humanizados/farmacocinética , Sangue/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Animais , Linhagem Celular Tumoral , Estabilidade de Medicamentos , Humanos , Radioisótopos do Iodo/farmacocinética , Coelhos , Trastuzumab
10.
Nan Fang Yi Ke Da Xue Xue Bao ; 29(12): 2477-9, 2484, 2009 Dec.
Artigo em Zh | MEDLINE | ID: mdl-20034906

RESUMO

OBJECTIVE: To study the mechanism of cardiotoxicity associated with Herceptin. METHODS: Herceptin was labeled with iodine-131 using the Iodogen method. Radioimmunoimaging was performed in 5 rabbits at 3 h to 5 days following (131)I-Herceptin injection to investigate the biodistribution of Herceptin. (131)I-Herceptin uptake in each organ or tissue relative to that in the muscular tissue (O/M ratio) was calculated and compared. On the fifth day following the injection, the organs including the heart, lung, liver and muscles were taken for measurement of the weight and radiocounts. HER2 expression was measured by immunohistochemistry in these organs and tissues. RESULTS: The O/M ratio of the heart was significantly higher than that of the lung (P=0.032) and liver (P=0.019) at 3 h after Herceptin injection, but reduced significantly at 24 h (P=0.001). The uptake of (131)I-Herceptin in the myocardium was slightly higher that that in the muscle and intestine, but lower than that in the lung and spleen. HER2 expression showed no significant difference between the myocardium and the other tissues such as the liver, lung, and kidney (H=3.236, P=0.172). CONCLUSION: Myocardium expresses low levels of HER2 and accumulates Herceptin no more than the other tissues.


Assuntos
Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais/toxicidade , Radioisótopos do Iodo/farmacocinética , Miocárdio/metabolismo , Radioimunodetecção , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Feminino , Radioisótopos do Iodo/administração & dosagem , Masculino , Coelhos , Receptor ErbB-2/metabolismo , Distribuição Tecidual , Trastuzumab
11.
Nan Fang Yi Ke Da Xue Xue Bao ; 29(6): 1257-8, 2009 Jun.
Artigo em Zh | MEDLINE | ID: mdl-19726380

RESUMO

OBJECTIVE: To analyze the radiogenic distribution in the sacrum in whole-body bone scanning. METHODS: A total of 212 patients receiving whole-body bone scanning without any explicit bone metastases were divided into different age and gender groups. The radioactive distribution in the sacrum in whole-body bone scanning was analyzed statistically. RESULTS: Of these cases, 31.1% presented with thin radioactive distribution in the sacrum and 11.3% exhibited increased radioactive distribution. Normal radioactive distribution in the sacrum was found in 57.6% of the cases. In both male and female elderly patients (>70 years), the rate of normal radioactive distribution in the sacrum was obviously reduced with increased rate of thin radioactive distribution. The female elderly patients showed higher rate of increased radioactive distribution in the sacrum than male elderly patients. CONCLUSION: The radioactive distribution in the sacrum is similar between female and male patients. Elderly male patients over 70 years have generally thin radioactive distribution in the sacrum due to the presence of osteoporosis, which is also associated with latent fracture of the sacrum to result in increased radioactive distribution in the sacrum in whole-body bone scanning.


Assuntos
Sacro/diagnóstico por imagem , Neoplasias da Coluna Vertebral/secundário , Medronato de Tecnécio Tc 99m/farmacocinética , Imagem Corporal Total , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Cintilografia , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Adulto Jovem
12.
Nan Fang Yi Ke Da Xue Xue Bao ; 29(10): 2067-9, 2009 Oct.
Artigo em Zh | MEDLINE | ID: mdl-19861268

RESUMO

OBJECTIVE: To study the overexpression of vascular endothelial growth factor (VEGF) and fluorine-18 fluorodeoxyglucose (FDG) uptake in early-stage nasopharyngeal carcinoma (NPC) and evaluate their relationship. METHODS: FDG positron emission tomography (PET) was performed in forty patients with stage I and stage II NPC. The maximum and mean standard uptake values (SUVmax and SUVmean, respectively) were measured in each patient, and the expression of VEGF was measured on paraffin sections using immunohistochemistry. RESULTS: The FDG uptake in the patients were 9.45-/+1.87 (SUVmax) and 6.04-/+1.09 (SUVmean), 8.95-/+1.91 (SUVmax) and 6.04-/+1.09 (SUVmean) in stage I patients, and 11.55-/+1.70 (SUVmax) and 7.98-/+1.1 (SUVmean) in stage II patients. The FDG uptake of stage II patients was higher than that of stage I patients. The FDG uptake of non-keratinizing differentiated carcinoma was 9.74-/+1.82 (SUVmax) and 6.82-/+1.23 (SUVmean) and 10.44-/+2.16 (SUVmax) and 6.68-/+1.35 (SUVmean) in non-keratinizing undifferentiated carcinoma, showing no significant differences between them (SUVmax: t=1.230, P>0.05; SUVmean: t=0.346, P>0.05). The VEGF-positive cells were 60.80% in the tumor. A correlation between VEGF expression and FDG uptake in he tumor was noted (r=0.460, P=0.03). CONCLUSION: VEGF overexpression is correlated to FDG uptake in patients with early-stage NPC. The SUV value reflects the glucose metabolism of NPC, and also shows the degree of oxygen insufficiency in the tumor tissue.


Assuntos
Fluordesoxiglucose F18/farmacocinética , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons/métodos , Fator A de Crescimento do Endotélio Vascular/genética , Adulto Jovem
13.
Ai Zheng ; 25(4): 443-6, 2006 Apr.
Artigo em Zh | MEDLINE | ID: mdl-16613677

RESUMO

BACKGROUND & OBJECTIVE: Herceptin plays an important role in treating metastatic breast cancer by targeting Her2/neu, therefore, combining Herceptin with iodine-131 (131I) might enhance its antitumor activity. This study was to up-regulate Her2/neu expression by interferon-gamma (IFN-gamma), and explore its effect on binding and antitumor activity of 131I-Herceptin in breast cancer cell lines MCF-7, SKBR-3 and BT-474. METHODS: MCF-7, SKBR-3 and BT-474 cells were cultured with or without IFN-gamma (500 U/ml) for 48 h. The positive rate and mean fluorescence intensity (MFI) of Her2/neu on the 3 cell lines were tested by flow cytometry. Herceptin was labeled with 131I by Iodogen method, and its radiochemical purity (RCP) was tested by size-exclusion high-pressure liquid chromatography (HPLC). The binding rate of 131I-Herceptin on cells was measured by non-competitive saturation analysis, and its killing effect was estimated by colony-forming assay. The positive rate and MFI of Her2/neu, binding rate of 131I-Herceptin, and colony-forming rate were compared between IFN-gamma-induced group and control group by t test. RESULTS: For MCF-7 cells, the positive rate and MFI of Her2/neu were significantly higher in IFN-gamma-induced cells than in control cells [(15.2+/-4.7)% vs. (8.5+/-1.9)%, t=3.515, P<0.05; 121+/-17 vs. 38+/-7, t=7.823, P<0.002]; for SKBR-3 and BT-474 cells, no obvious difference of Her2/neu positive rate was observed between IFN-gamma-induced cells and control cells [(99.7+/-0.9)% vs. (98.9+/-1.1)%, P>0.05; (99.5+/-1.2)% vs. (98.1+/-0.9)%, P>0.05], but the MFI of Her2/neu was significantly higher in IFN-gamma-induced cells than in control cells (1,608+/-201 vs. 952+/-125, t=4.802, P<0.01; 1,968+/-192 vs. 1,020+/-98, t=7.614, P<0.002). The binding rates of Her2/neu were increased from (5.2+/-1.4)% to (12.3+/-3.4)% by 2.4 folds in MCF-7 cells, from (35.8+/-4.5)% to (48.9+/-7.1)% by 1.4 folds in SKBR-3 cells, and from (37.2+/-3.6)% to (59.5+/-8.7)% by 1.6 folds in BT-474 cells after inducement with IFN-gamma. The colony-forming rates were significantly lower in IFN-gamma-induced MCF-7, SKBR-3 and BT-474 cells than in control cells [(30+/-4)% vs. (49+/-3)%, t=6.574, P<0.05; (23+/-5)% vs. (37+/-6)%, t=3.105, P<0.05; (19+/-6)% vs. (34+/-5)%, t=3.323, P<0.05]. CONCLUSION: IFN-gamma can up-regulate Her-2/neu expression and increase the binding of 131I-Herceptin, hence, improve the inhibitory effect of 131I-Herceptin on proliferation of breast cancer cells.


Assuntos
Anticorpos Monoclonais/farmacologia , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Interferon gama/farmacologia , Receptor ErbB-2/metabolismo , Anticorpos Monoclonais Humanizados , Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Radioisótopos do Iodo/farmacologia , Trastuzumab
14.
Nan Fang Yi Ke Da Xue Xue Bao ; 26(3): 361-3, 366, 2006 Mar.
Artigo em Zh | MEDLINE | ID: mdl-16546749

RESUMO

OBJECTIVE: To study the immunoactivity,biodistribution and metabolic pattern of (131)I-Herceptin in rabbits. METHODS: Herceptin was radiolabelled with (131)I and its radiochemicalpurity (RCP) measured by size-exclusion high-pressure liquid chromatography (HPLC). The binding rate to BT-474 cells was measured to evaluate the immunoactivity of (131)I-Herceptin. (131)I-herceptin (2.0 mCi/kg) was injected intravenously into New Zealand rabbits. Scintigraphy on emission computed tomography was performed at 3 h, 1, 3 and 5 days after injection, and the radiocounts of the heart, liver and kidney etc. were compared with that of the muscle to calculate the organ-to-muscle activity ratio (O/M). On the fifth day,the rabbits were killed and the blood, myocardium, lung and other organs were obtained for measuring the radiocounts on gamma-counter to calculate the uptake percentage per gram tissue (ID%/g). RESULTS: The labeling rate of (131)I-herceptin was 93% with RCP of 95% and binding rate to BT-474 cells of 36.9%. After injection of (131)I-herceptin, the heart, lung and liver displayed dense radioactive regions but not the muscles and intestines. Three hours after injection, the O/M ratio of the heart was significantly higher than that of the lung, kidney and intestine (P<0.05), but decreased significantly one day after injection (t=10.817, P<0.001) with further decrement on days 3 and 5 (P<0.05). The O/M ratio of liver on day 1, 3, and 5 reduced significantly in comparison with that at 3 h (P<0.05). The uptake percentage was higher in the blood (11.3 ID/g%) than in the liver (2.8 ID/g%) and the myocardium (1.8 ID/g%). CONCLUSIONS: (131)I-herceptin possesses high immunoactivity which distributes mainly in the blood, liver and kidney, but with low uptake in the myocardium.


Assuntos
Anticorpos Monoclonais/farmacocinética , Antineoplásicos/farmacocinética , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/metabolismo , Anticorpos Monoclonais Humanizados , Antineoplásicos/administração & dosagem , Antineoplásicos/normas , Ligação Competitiva , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Injeções Intravenosas , Radioisótopos do Iodo/administração & dosagem , Radioisótopos do Iodo/metabolismo , Radioisótopos do Iodo/farmacocinética , Masculino , Controle de Qualidade , Coelhos , Fatores de Tempo , Distribuição Tecidual , Trastuzumab
15.
Nan Fang Yi Ke Da Xue Xue Bao ; 26(2): 234-6, 2006 Feb.
Artigo em Zh | MEDLINE | ID: mdl-16503541

RESUMO

OBJECTIVE: To observe the killing effect of Herceptin and adriamycin sequentially applied on breast cancer cell line in vitro. METHODS: BT-474 human breast cancer cells in exponential growth phase were treated with Herceptin alone, adriamycin alone and their sequential administration (Herceptin before adriamycin and vice versa), respectively. Under optical microscope, the morphological changes of the cells were observed before and after drug administration. The expression rate and mean fluorescence intensity (MFI) of HER-2/neu and cell death rate were detected by flow cytometry. RESULTS: Microscopically, the cells treated with different protocols all exhibited such changes as darkening and increase of cellular debris with irregular cell morphology. Flow cytometry revealed no significant difference in the expression rate of HER-2/neu in each group before and after treatment, but the MFI of HER-2/neu and death rate of the treated cells were significant different from those of the control group (P<0.05). The cell death rate of Herceptin-pretreated cells was significantly higher than that of adriamycin-pretreated ones (P<0.05). CONCLUSION: Herceptin pretreatment enhances the killing effect of adriamycin on breast cancer cell line BT-474, which provides experimental evidence for designing clinical sequential biochemotherapy of breast cancer.


Assuntos
Anticorpos Monoclonais/farmacologia , Doxorrubicina/farmacologia , Receptor ErbB-2/biossíntese , Antibióticos Antineoplásicos/farmacologia , Anticorpos Monoclonais Humanizados , Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sinergismo Farmacológico , Feminino , Citometria de Fluxo , Humanos , Trastuzumab
16.
Ai Zheng ; 23(6): 689-92, 2004 Jun.
Artigo em Zh | MEDLINE | ID: mdl-15191672

RESUMO

BACKGROUND & OBJECTIVE: It is important and useful to evaluate the degree of malignancy for therapeutic scheme and prognosis evaluation. Traditional imaging methods such as CT and MRI play the important role in distinguishing glioma, but sometimes it was still difficult to diagnose accurately only having the aid of these anatomic information. Stereotaxic needle biopsy is an invasive method and indicates only local pathologic change, sometimes the error of sample collection will result in inaccurate grading. 18F-FDG PET can reflect the glucose metabolic rate of tumor directly and is thought as the most useful method, but the cost is too high so that it cannot be used widely at present. This study measured (99)Tc(m)-MIBI uptake in the patients with different pathological types using (99)Tc(m)-MIBI brain scan and evaluated the malignant degree of astrocytoma and its prognosis. METHODS: Fifty-two patients with glioma and 15 collators were retrospectively analyzed. (99)Tc(m)-MIBI was injected into each patient via elbow vein. SPECT was performed 20 min(early phase) and 2 h (delayed phase) after injection. (1)Diagnostic indices such as sensitivity, specificity, and accuracy were calculated. (2) The tumor to non-tumor ratios (T/N) were calculated according to ROI and compared between groups of different malignancy grading by t-test. (3) The survival time (by means of mean survival time, MST) after (99)Tc(m)-MIBI brain SPECT was follow-up surveyed. According to T/N ratios, the patients were divided into four groups. The MST was compared between four groups by t-test. RESULTS: (1) Among 52 cases of glioma, 44 showed positive and 2 collators showed false-positive on (99)Tc(m)-MIBI SPECT and the sensitivity, specificity, and accuracy were 84.6%, 86.7%, and 85.1%,respectively. (2) On early phase and delayed phase,when T/N ratio was compared, there was no significant difference between grade-I astrocytoma and grade-II astrocytoma (P >0.05), nor was between patients with ependymocytomas and patients with oligodendrogliomas (P >0.05). There was significantly different between every other two groups (P< 0.001),showing the higher the malignancy of astrocytoma,the more the T/N ratio. (3)Comparison of MST indicated that the more the T/N ratio, the shorter the MST. MST in group with T/NT ratio of 1.2-2.0 was significantly longer than that in group with T/NT ratio of 4.1-(t=5.412,P< 0.001) and that in group with T/N ratio of 3.1-4.0(t=4.418,P< 0.001). MST in group of 2.1-3.0 was significantly longer than that in group of 4.1-(t=3.382, 0.002< P< 0.005) and that in group of 3.1-4.0 (t=2.389,0.02< P< 0.05). MST showed no significant difference between the group of 1.2-2.0 and the group of 2.1-3.0 (t=1.691,P >0.05), nor did between the group of 3.1-4.0 and group of 4.1-(t=1.629,P >0.05). CONCLUSION: As a noninvasive technique, (99)Tc(m)-MIBI brain SPECT is effective to diagnose brain glioma and distinguish its malignancy degree. This method, by monitoring the T/N ratio closely, is useful to discriminate tumor viability and determine the prognosis of patients.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Glioma/diagnóstico por imagem , Compostos Radiofarmacêuticos , Tecnécio Tc 99m Sestamibi , Adulto , Idoso , Neoplasias Encefálicas/patologia , Feminino , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada de Emissão de Fóton Único
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