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Short-term effects of chemotherapy with combination of hydroxycamptothecine and oxaliplatin in the treatment of advanced digestive tract cancers.

Yuan-jue SUN ; Hui ZHAO ; Yue-wu GUO ; Feng LIN ; Xun CAI ; Xiao-chun TANG ; Yang YAO

Chinese Journal of Oncology.2004;26(12):749-752.

OBJECTIVETo evaluate the short-term therapeutic effects and side effects of combined hydroxycamptothecine and oxaliplatin in the treatment of advanced digestive tract cancers.

METHODSThirty patients suffering from advanced digestive tract tumors including gastric cancer 8, colorectal cancer 20, cholecystic cancer 1 and malignant fibroadenoma 1 were studied. They were treated with hydroxycamptothecine plus oxaliplatin for 2 cycles with interval of 21 days.

RESULTSThe complete response, partial response, stable disease and progressive disease rates were 3.3% (1/30), 36.7% (11/30), 53.3% (15/30) and 6.7% (3/30) respectively with an overall response rate (CR + PR) of 40.0% (12/30). In the whole 77 cycles, leukocytopenia was observed in 34 cycles (44.2%) and 19 cycles (55.9%) at grades III and IV. Diarrhea developed in 42 cycles (54.5%) and 20 cycles (47.6%) grades III and IV. The other side effects were fever, alopecia, nausea and vomiting, constipation, hepatic and renal function abnormity and neuritis.

CONCLUSIONSatisfactory response rate is obtainable in advanced colorectal cancer as treated by hydroxycamptothecine plus oxaliplatin. The toxicity consists of severe leukocytopenia and diarrhea.

Adenocarcinoma ; drug therapy ; secondary ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Camptothecin ; administration & dosage ; analogs & derivatives ; Colorectal Neoplasms ; drug therapy ; pathology ; Diarrhea ; chemically induced ; Female ; Humans ; Leukopenia ; chemically induced ; Liver Neoplasms ; drug therapy ; secondary ; Lung Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds ; administration & dosage ; Remission Induction ; Stomach Neoplasms ; drug therapy ; pathology ; Treatment Outcome

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Oxaliplatin plus capecitabine as a second line chemotherapy for patients with advanced gastric cancer.

Jun QIAN ; Shu-kui QIN ; Jing-feng MEI ; Ying-xia CHEN ; Zhi-jian SHAO ; Ze-ming HE

Chinese Journal of Oncology.2004;26(12):746-748.

OBJECTIVETo evaluate the effect and toxicity of oxaliplatin combined with capecitabine (Xeloda) as a second-line chemotherapy regimen for patients with advanced gastric cancer.

METHODSTwenty-four patients with advanced gastric cancer who had been treated by multiple chemotherapy regimens presenting poor responses were allotted. LX regimen (oxaliplatin 85 mg/m(2) in 2-hour infusion on D1 and D15, capecitabine 1250 mg/m(2)/d divided in two daily doses given from D1 to D14) was adopted. The cycles were repeated every 28 days. All patients received two or more cycles.

RESULTSAll 24 patients were evaluated after having received 2 to 6 cycles of chemotherapy, totally 92 cycles. The overall response rate was 29.2% (including 2 CR, 5 PR, 10 NC and 7 PD). The time to tumor progression (TTP) was 2 to 18 months (median 5 months), and duration of remission was 4 to 14 months (median 8 months). The major toxicities were bone marrow suppression and nausea/vomiting.

CONCLUSIONOxaliplatin combined with capitabine is effective as a secondary line regimen for patients with advanced gastric cancer. This protocol is active and well tolerated. Further clinical studies are warranted.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Capecitabine ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Drug Administration Schedule ; Female ; Fluorouracil ; analogs & derivatives ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Staging ; Neutropenia ; chemically induced ; Organoplatinum Compounds ; administration & dosage ; Remission Induction ; Stomach Neoplasms ; drug therapy ; pathology

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IRESSA in the treatment of advanced non-small-cell lung cancer patients who failed to respond previous chemotherapy.

Bin WANG ; Xiang-ru ZHANG ; Da-tong CHU

Chinese Journal of Oncology.2004;26(12):742-745.

OBJECTIVETo evaluate the antitumor efficacy, time to tumor progression (TTP) and toxicity of Iressa (ZD1839)-a selective epidermal growth factor receptor tyrosine kinase inhibitor in advanced non-small-cell lung cancer (NSCLC) patients who have failed to respond previous chemotherapy.

METHODSFifty-two patients with grade IV NSCLC previously treated with chemotherapy (77.0% of patients after second line therapy) received 250 mg of Iressa orally once daily until disease progression or development of intolerable toxic reaction. They were required to receive tumor-evaluation before the treatment, one month after Iressa administration and every other month thereafter.

RESULTSWithout complete regression being observed, partial response (PR) rate was 21.2% (11/52), stable disease (SD) 32.7% (17/52), disease control rate (PR + SD) 53.8%, progression of disease (PD) 46.2% (24/52); median time to tumor progression (TTP) was 3.5 month. Among them, 22 patients were followed up over one year and the 1-year survival rate was 31.8%. Symptomatic improvement rate was 52.9%. The most common adverse effects were skin reactions and diarrhea which were generally mild (grade 1 or 2). Only one patient withdrew from the trial because of grade III hepatic toxicity with increase in ALT and AST.

CONCLUSIONIressa has significant antitumor activity in advanced NSCLC patients who have previously failed in second or third line chemotherapy. It greatly alleviates tumor related symptoms. Adverse effects are generally tolerable. IRESSA is suitable for patients with poor performance status (ECOG > 2).

Adult ; Aged ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Diarrhea ; chemically induced ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Quinazolines ; adverse effects ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Remission Induction

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Clinical trial on ibandronate in patients with tumor-associated hypercalcemia.

Tao WANG ; San-tai SONG ; Ze-fei JIANG ; Shou-geng BIAN ; Ya-jie WANG ; Li-qing LI ; Jun ZHU

Chinese Journal of Oncology.2004;26(12):739-741.

OBJECTIVEIbandronate, a third generation bisphosphonate, inhibits bone resorption in human and animal studies. This study is to evaluate the efficacy and safety of ibandronate as a single agent in patients with tumor-associated hypercalcemia.

METHODSAn open, multicenter, non-controlled clinical trial was conducted in 22 patients. The patients received 2 mg ibandronate intravenously if the corrected calcium was less than 3.0 mmol/L but more than 2.7 mmol/L; they received 4 mg ibandronate iv if corrected calcium was more than 3.0 mmol/L.

RESULTSThere was 100% efficacy in these two dose groups but the calcium correcting effect was more pronounced in the 4-mg dose group than the 2-mg dose group. The most common adverse reactions were fever and skin itching with an incidence of 4.5%.

CONCLUSIONIbandronate is active in patients with tumor-associated hypercalcemia and the adverse effects are well tolerated.

Bone Neoplasms ; complications ; secretion ; Breast Neoplasms ; complications ; pathology ; Calcium ; blood ; Diphosphonates ; administration & dosage ; therapeutic use ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Fever ; chemically induced ; Humans ; Hypercalcemia ; blood ; drug therapy ; etiology ; Lung Neoplasms ; complications ; pathology ; Male ; Middle Aged ; Multiple Myeloma ; complications ; Phosphorus ; blood ; Pruritus ; chemically induced

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Correlation study of expression levels of prostate-specific membrane antigen and prostate-specific antigen with Gleason score of prostate carcinoma.

Jia-qiang REN ; Zhong-qing CHEN ; Li ZHENG ; Qi CHEN ; Hua LI ; Hong-guang ZHU

Chinese Journal of Oncology.2004;26(12):735-738.

OBJECTIVETo study the correlation of prostate-specific membrane antigen (PSMA) and prostate-specific antigen (PSA) expression with Gleason score of prostate carcinoma.

METHODSMonoclonal antibodies against epitopes of PSMA extracellular domain were prepared, with which the expression of PSMA of prostate carcinoma (PC) was determined by immunohistochemical staining. Correlation of its expression with Gleason score of PC was statistically analyzed, and compared with that of PSA.

RESULTSEight hybridoma cell lines secreting monoclonal antibodies specific for PSMA were prepared. PSMA expression level was positively correlated with Gleason score. In poorly differentiated prostate carcinoma, the expression intensity of PSMA was higher than that of medium-and well-differentiated prostate carcinoma (P < 0.01). However, there was no correlation between level of PSA expression and Gleason score (P > 0.05).

CONCLUSIONPSMA expression level may be used as a useful surrogate marker in Gleason grading of prostate carcinoma. It may be a more suitable target than PSA in antibody mediated immunotherapy against poorly differentiated prostate carcinoma which is usually not sensitive to hormonal therapy.

Antigens, Surface ; metabolism ; Biomarkers, Tumor ; metabolism ; Glutamate Carboxypeptidase II ; metabolism ; Humans ; Male ; Prostate-Specific Antigen ; metabolism ; Prostatic Neoplasms ; metabolism ; pathology

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Influence of chemotherapy on Th1/Th2 cytokine switching in stomach cancer patients.

Yan LI ; Jing LIANG ; Wen-bo LIU ; Xiao-qun XU ; Yue-ran ZHAO

Chinese Journal of Oncology.2004;26(12):732-734.

OBJECTIVETo observe the influence of chemotherapy on the switching of Th1/Th2 cytokines in stomach cancer patients.

METHODSTh1/Th2 cytokine genes expressed by peripheral blood mononuclear cells of stomach cancer patients before and after chemotherapy were detected by RT-PCR.

RESULTSThe expression of Th2 cytokines was dominant in patients before chemotherapy, and the dominancy became less marked after chemotherapy.

CONCLUSIONThe immune deviation with Th2 predominance in stomach cancer patients has a tendency to become reversed after chemotherapy.

Adenocarcinoma ; drug therapy ; immunology ; metabolism ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Female ; Fluorouracil ; administration & dosage ; Humans ; Interferon-gamma ; metabolism ; Interleukins ; metabolism ; Leucovorin ; administration & dosage ; Male ; Middle Aged ; Organoplatinum Compounds ; administration & dosage ; Stomach Neoplasms ; drug therapy ; immunology ; metabolism ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism

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Changes in gene expression profiles of hydatidiform mole and choriocarcinoma as compared with trophoblast hyperplasia.

Jin-quan CUI ; Yi-fu SHI ; Huai-jun ZHOU ; Juan-qing LI

Chinese Journal of Oncology.2004;26(12):727-731.

OBJECTIVETo study the relationship of changes in gene expression profiles of hydatidiform mole and choriocarcinoma with hyperplasia of trophoblasts.

METHODSThe differentially expressed genes were analyzed in two pairs of tissues of hydatidiform mole versus normal villi, and in two pairs of normal primary culture trophoblasts versus JAR cell line of chariocarcinoma, using cDNA microarray containing 4096 genes. To confirm the results of cDNA microarray analysis, expressions of some up-regulated genes related to DNA synthesis in normal villi, hydatidiform mole, and 2 choriocarcinoma cell lines (JAR and JEG-3) were examined by immunohistochemistry, immunoblotting and RT-PCR.

RESULTSA total of 89 genes were differentially expressed in all hydatidiform moles, accounting for 2.2% of the genes arrayed. Of the 89 genes, 24 were up-regulated and 65 were down-regulated. Compared with normal primary trophoblasts, there were 433 genes up-regulated and 380 genes down-regulated in JAR cell line. Forty six genes were up-regulated in both hydatidiform mole and choriocarcinoma, while 13 genes were down-regulated. Some genes associated with cell proliferative inhibition were significantly down-regulated, whereas those associated with cell proliferation, malignant transformation, metastasis and drug resistance were highly up-regulated. The expressions of thymidine kinase 1, the small subunit of ribonucleotide reductase (RRM2) were significantly increased in hydatidiform mole, JAR and JEG-3 cells.

CONCLUSIONAbnormal expression of genes exists in hydatidiform mole and choriocarcinoma. Hyperplasia of trophoblasts may be related to over-expression of genes coding for synthetic enzymes.

Adult ; Cell Line, Tumor ; Cell Proliferation ; Cell Transformation, Neoplastic ; Choriocarcinoma ; genetics ; metabolism ; pathology ; Drug Resistance, Neoplasm ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Hydatidiform Mole ; genetics ; metabolism ; Hyperplasia ; Neoplasm Metastasis ; Oligonucleotide Array Sequence Analysis ; Pregnancy ; Reverse Transcriptase Polymerase Chain Reaction ; Ribonucleoside Diphosphate Reductase ; metabolism ; Thymidine Kinase ; metabolism ; Trophoblasts ; pathology ; Uterine Neoplasms ; genetics ; metabolism ; pathology

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Inhibitory effect of ginsenoside-Rg3 on lung metastasis of mouse melanoma transfected with ribonuclease inhibitor.

Ji-wei LIU ; Jun-xia CHEN ; Li-hua YU ; Yu-xiang TIAN ; Xiu-yun CUI ; Qiu YAN ; Li FU

Chinese Journal of Oncology.2004;26(12):722-725.

OBJECTIVETo investigate the effect of ginsenoside-Rg3 on lung metastasis of ribonuclease inhibitor (RI) gene-transfected mouse B16 melanoma.

METHODSC57BL/6 mice were iv injected with parental or RI-transfected B16 melanoma cells. Lung metastasis was assessed by the number of surface tumor nodules. Mice were divided into 6 groups. Group I, II and III of mice were given parental, mock-transfected and RI-transfected B16 melanoma cells, respectively while in group IV, V and VI, Rg3 (1.5 mg/kg, iv q.o.d. x 10) was given to mice bearing parental, mock-transfected and RI-transfected B16 melanoma, respectively. Micovessel density (MVD) of the lung metastatic tumor was assessed by immunohistochemical staining of factor VIII-R expression.

RESULTSThe number of tumor nodules was significantly decreased in mice injected with RI-transfected B16 melanoma (Gp III, compared to Gp I and II). Rg3 treatment per se could also decrease the number of lung tumor nodules but to a lesser extent (Gp IV and V compared to Gp III). However, Rg3 synergized with RI transfection resulting in most significant inhibition of lung metastasis (Gp VI). Mice in Gp I and II died within 26 days of the experiment, whereas all the mice in Gp VI were alive during the observation period of one and one half month. MVD was significantly decreased in the lung tumor nodules in mice injected with RI-transfected B16 melanoma. It was further decreased when additional Rg3 was given (Gp VI).

CONCLUSIONTransfection of ribonuclease inhibitor gene significantly reduces the metastatic potential of B16 melanoma. Ginsenoside-Rg3 has a synergistic effect.

Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Line, Tumor ; Ginsenosides ; isolation & purification ; pharmacology ; Lung Neoplasms ; pathology ; secondary ; Male ; Melanoma, Experimental ; genetics ; pathology ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Panax ; chemistry ; Placental Hormones ; genetics ; Transfection

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Growth inhibitory effect of adriamycin conjugated to single-chain antibody on human lung adenocarcinoma in vitro.

Wen-tao YUE ; Bai-tang LAI ; Hui WANG ; Xu-ping ZHAN ; Yue WANG

Chinese Journal of Oncology.2004;26(12):718-721.

OBJECTIVETo evaluate the growth inhibitory effect of adriamycin (ADM) conjugated to an anti-lung cancer single-chain antibody (ScFv) 2A7-1 on lung adenocarcinoma cell line A2 in vitro.

METHODS2A7-1 cell culture medium was concentrated by ultra-filtration (with Amicon P10Z filter), and soluble ScFv was purified using RPAS purification kit. ADM was conjugated to 2A7-1 by glutaraldehyde. A(280) and A(490) of the conjugate 2A7-1-ADM were determined by spectrophotometry and the molar ratio of 2A7-1 to ADM was calculated. Immunoreactivity of the conjugate was detected by immunohistochemistry. Its growth inhibitory effect on lung adenocarcinoma cell line A2 was determined by colony formation assay in vitro.

RESULTSThe molar ratio of 2A7-1 to ADM was 1:3.2. The conjugate strongly reacted with A2 cell. Its growth inhibitory effect on A2 cells was 4 times as potent as ADM.

CONCLUSIONAdriamycin conjugated to anti-lung cancer single-chain antibody 2A7-1 has much higher cytotoxic activity than unconjugated adriamycin against human lung adenocarcinoma.

Adenocarcinoma ; immunology ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Colony-Forming Units Assay ; Doxorubicin ; administration & dosage ; pharmacology ; Humans ; Immunoconjugates ; pharmacology ; Immunoglobulin Variable Region ; chemistry ; pharmacology ; Lung Neoplasms ; immunology ; pathology

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Effect of RNA interference on EGF receptor expression of non-small-cell lung cancer A549 cell line.

Min ZHANG ; Xin ZHANG ; Chun-xue BAI ; Jie CHEN ; MinQ WEI

Chinese Journal of Oncology.2004;26(12):713-717.

OBJECTIVETo investigate changes in biologic properties of non-small-cell lung cancer (NSCLC) A549 cells whose EGF receptor (EGFR) expression was suppressed by short interference RNA (siRNA).

METHODSA549 cells were transfected with synthetic EGFR sequence-specific siRNA by Lipofectamine. EGFR expression was examined by Western blot and flow cytometry. The biological features of the transfected A549 cells were assessed by cell cycle analysis, colony formation and chemosensitivity assay.

RESULTSSequence-specific siRNAs targeting EGFR significantly down-regulated its expression in A549 cells. Cell growth and colony formation were inhibited by 85.0% and 63.3%, respectively, as compared to the non-sequence-specific siRNA treated cells. Decreased EGFR expression was accompanied by 12.7% increase in A549 cells in G(0)-G(1) phase and 6.6% decrease in S-phase. The EGFR sequence-specific siRNA transfected A549 cells were much more sensitive to the cytotoxic effect of cisplatin with a 77.2% decrease in IC(50) compared to the non-sequence-specific iRNA transfected A540 cells.

CONCLUSIONDown regulation of EGFR expression of NSCLC by sequence-specific siRNA may be considered as an additional option in the treatment of EGFR over-expressing cancers, including NSCLC.

Antineoplastic Agents ; administration & dosage ; pharmacology ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; drug effects ; Cisplatin ; administration & dosage ; pharmacology ; Humans ; Inhibitory Concentration 50 ; Lung Neoplasms ; metabolism ; pathology ; RNA Interference ; RNA, Double-Stranded ; genetics ; RNA, Small Interfering ; genetics ; Receptor, Epidermal Growth Factor ; genetics ; metabolism ; Transfection

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