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Gynecologic Oncology Dec 2004The objective of this study was to evaluate the response rate and survival of patients with locally advanced uterine cervical cancer who were treated with intraarterial... (Clinical Trial)
Clinical Trial
Neoadjuvant high-dose intraarterial infusion chemotherapy under percutaneous pelvic perfusion with extracorporeal chemofiltration in patients with stages IIIa-IVa cervical cancer.
OBJECTIVE
The objective of this study was to evaluate the response rate and survival of patients with locally advanced uterine cervical cancer who were treated with intraarterial infusion chemotherapy under percutaneous pelvic perfusion with extracorporeal chemofiltration (PPPEC).
METHODS
Twenty-three untreated patients with stages IIIa-IVa cervical cancer were enrolled in the study. PPPEC was administered twice at 2 weeks interval using high-dose cisplatin alone (140-250 mg/m(2)) or high-dose cisplatin plus mitomycin C (7 mg/m(2)), pepleomycin (7 mg/m(2)) and 5-fluorouracil (700 mg/m(2)). Eighteen patients in whom the tumor downstaging was confirmed underwent radical surgery following PPPEC, whereas in the remaining five patients, radiotherapy was administered.
RESULTS
Two weeks after the second PPPEC, the median volumetric tumor reduction and tumor response were 76% and 87%, respectively. Histologic response was 96%, while the tumor downstaging reached 83%. The curative surgery rate achieved was 89%. Five-year progression-free survival was 47% and 5-year survival rate was 74%.
CONCLUSION
High-dose intraarterial infusion chemotherapy under PPPEC effectively achieved tumor downstaging and resulted in the favorable performance of the subsequent radical surgery and improved the 5-year survival rate of patients with locally advanced uterine cervical cancer.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; Cisplatin; Dose-Response Relationship, Drug; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Middle Aged; Mitomycin; Neoadjuvant Therapy; Neoplasm Staging; Peplomycin; Uterine Cervical Neoplasms
PubMed: 15581966
DOI: 10.1016/j.ygyno.2004.08.027 -
Acta Pharmacologica Sinica Dec 2004To investigate the mechanism of peplomycin (PEP)-induced apoptosis in liver carcinoma cell line (Bel-7402).
AIM
To investigate the mechanism of peplomycin (PEP)-induced apoptosis in liver carcinoma cell line (Bel-7402).
METHODS
Growth inhibition by PEP was analyzed using 3- 4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptotic cells were detected using Hoechest 33258 staining, and confirmed by flow cytometric analysis and DNA fragmentation analysis. The expression of cyclin A and B1 were determined by flow cytometry and Western blot. Annexin V assay was measured by flow cytometric analysis.
RESULTS
PEP induced apoptosis and then inhibited cell proliferation in liver carcinoma cell line Bel-7402. Cells treated with PEP 50 mumol/L for 15 h were arrested in G2-phase with dramatical expression of cyclin A and a little change in cyclin B1. Almost all the apoptosis occurred in cells undergoing the G1-phase after treatment for 24 h.
CONCLUSION
Peplomycin induced G1-phase specific apoptosis in Bel-7402 involving G2-phase arrest.
Topics: Antibiotics, Antineoplastic; Apoptosis; Carcinoma, Hepatocellular; Cell Line, Tumor; Cyclin A; Cyclin B; G1 Phase; G2 Phase; Humans; Liver Neoplasms; Peplomycin
PubMed: 15569418
DOI: No ID Found -
Cancer Science Aug 2004We examined the influence of ROS on the phosphorylation and complex formation of Bcl-2 family proteins in Mn-superoxide dismutase (SOD) antisense-transfected squamous...
We examined the influence of ROS on the phosphorylation and complex formation of Bcl-2 family proteins in Mn-superoxide dismutase (SOD) antisense-transfected squamous cell carcinoma cells, OSC-4 cells. The increase of intracellular ROS level induced by cis-diamminedichloroplatinum (CDDP) and gamma-ray treatment was greater in antisense-transfected cells than in control vector-transfected cells, and apoptosis was more extensively induced in the former. Antisense-transfected cells expressed high levels of Bax and Bak, but low levels of Bcl-2 and Bcl-XL when treated with CDDP, peplomycin, 5-fluorouracil or gamma-rays. After treatment with these agents, the phosphorylation of protein kinase A, Bcl-2 (Thr56) and Bad (Ser155) was increased, especially in antioxidant (N-acetylcysteine and pyrrolidine dithiocarbamate)-pretreated control cells, but the phosphorylation levels were very low in the antisense-transfected cells. Bcl-2 ubiquitination was increased, but ubiquitination of Bad and Bax was decreased in the antisense-transfected cells, although their ubiquitination was increased by the antioxidants. These results reveal that ROS induce apoptosis by regulating the phosphorylation and ubiquitination of Bcl-2 family proteins, resulting in increased proapoptotic protein levels and decreased antiapoptotic protein expression.
Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Squamous Cell; Cisplatin; Humans; Mouth Neoplasms; Phosphorylation; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Transfection; Tumor Cells, Cultured; Ubiquitins
PubMed: 15298726
DOI: 10.1111/j.1349-7006.2004.tb03323.x -
The British Journal of Dermatology Jun 2004
Review
Topics: Aged; Antineoplastic Agents; Bleomycin; Carcinoma, Squamous Cell; Humans; Lip Neoplasms; Male; Peplomycin; Scleroderma, Diffuse
PubMed: 15214916
DOI: 10.1111/j.1365-2133.2004.05969.x -
Anticancer Research 2004The sensitivity of human hepatoma (HepG2) and oral squamous cell carcinoma (HSC-2) cell lines against various apoptosis-inducing agents was compared. HepG2 cells were...
The sensitivity of human hepatoma (HepG2) and oral squamous cell carcinoma (HSC-2) cell lines against various apoptosis-inducing agents was compared. HepG2 cells were generally more resistant to an oxidant (H2O2), antioxidants (sodium ascorbate, gallic acid, epigallocatechin gallate) and anticancer drugs (doxorubicin, methotrexate, cisplatin (CDDP), etoposide, 5-fluoro-2,4(1H,3H)-pyrimidinedione (5-FU), peplomycin sulfate) as compared to HSC-2 cells. Lower concentrations of CDDP, but not other anticancer drugs, induced comparable cytostatic effects on both HSC-2 and HepG2 cells. CDDP induced internucleosomal DNA fragmentation and activation of caspases 3, 8 and 9 in HepG2 cells. On the other hand, CDDP did not induce DNA fragmentation and activated caspase 3 only marginally in HSC-2 cells. Combination treatment with CDDP (10 microM) and 5-FU (100 microM) additively activated all three caspases in HepG2 cells, but not in HSC-2 cells. The present study demonstrated the chemotherapeutic potential of combined treatment of CDDP and 5-FU against hepatoma cells and the considerable variation of drug sensitivity between cancer cell lines.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Carcinoma, Hepatocellular; Carcinoma, Squamous Cell; Caspases; Cell Line, Tumor; Cisplatin; DNA Fragmentation; Drug Screening Assays, Antitumor; Enzyme Activation; Fluorouracil; Humans; Liver Neoplasms; Mouth Neoplasms
PubMed: 15161008
DOI: No ID Found -
Life Sciences Apr 2004Although superselective continuous intra-arterial infusion has advantages for cancer therapy, intra-arterial chemotherapy is often interrupted by arterial damage due to...
Although superselective continuous intra-arterial infusion has advantages for cancer therapy, intra-arterial chemotherapy is often interrupted by arterial damage due to arteritis. Therefore, an animal model must be developed to elucidate the mechanism of arteritis associated with continuous anti-cancer drug infusion. We developed a new rat model with which to investigate the causal mechanism(s) of vascular damage associated with continuous catheterization chemotherapy. Chemotherapeutic agents (fluorouracil (5-FU) or peplomycin (PEP)) were continuously administered for 7 days into the abdominal aorta of male Sprague-Dawley rats through a catheter fixed in situ. We found that the incidence of apoptotic endothelial cells of the aorta was higher nearer the tip of the catheter. The incidence of apoptosis was higher in the group treated with 5-FU than with PEP. This animal model will be useful to improve arterial damage among patients undergoing chemotherapy using continuous catheterization.
Topics: Animals; Antineoplastic Agents; Aorta, Abdominal; Apoptosis; Arteritis; Catheterization; Endothelium, Vascular; Fluorouracil; In Situ Nick-End Labeling; Infusions, Intra-Arterial; Male; Models, Animal; Peplomycin; Rats; Rats, Sprague-Dawley
PubMed: 15051425
DOI: 10.1016/j.lfs.2003.11.017 -
Anticancer Research 2003We have recently found that sodium fluoride (NaF) induced apoptotic cell death in tumor cell lines. We investigated here whether 6 popular antitumor compounds modify the... (Comparative Study)
Comparative Study
We have recently found that sodium fluoride (NaF) induced apoptotic cell death in tumor cell lines. We investigated here whether 6 popular antitumor compounds modify the cytotoxic activity of NaF against human squamous cell carcinoma (HSC-2) and human promyelocytic leukemia (HL-60) cell lines. Cytotoxic concentrations of cisplatin, etoposide, doxorubicin or peplomycin (tentatively termed as Group I compounds), but not methotrexate and 5-FU (tentatively termed as Group II compounds), enhanced the cytotoxic activity of NaF. NaF and Group I compounds induced internucleosomal DNA fragmentation in HL-60 cells, whereas Group II compounds were inactive even in the presence of NaF. Most Group I compounds except doxorubicin (which induced DNA fragmentation less effectively than others) activated caspase 3 more efficiently than Group II compounds. Caspase 8 (involved in non-mitochondrial extrinsic pathway) and caspase 9 (involved in mitochondrial intrinsic pathway) were also activated, but to a much lesser extent. NaF reduced the glucose consumption at early stage, possibly by inhibition of glycolysis, whereas cisplatin and etoposide reduced the glucose consumption at later stage, suggesting that early decline of glucose consumption is rather specific to NaF.
Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Squamous Cell; Cell Survival; Cisplatin; Doxorubicin; Etoposide; Fluorouracil; Glycolysis; HL-60 Cells; Humans; Kinetics; Methotrexate; Peplomycin; Sodium Fluoride; Tumor Cells, Cultured
PubMed: 14981920
DOI: No ID Found -
Acta Crystallographica. Section D,... Jan 2004Crystals of the self-complementary oligonucleotide d(CCAGGCCTGG) [Heinemann & Alings (1989), J. Mol. Biol. 210, 369-381] complexed with the hydroperoxide of...
Crystals of the self-complementary oligonucleotide d(CCAGGCCTGG) [Heinemann & Alings (1989), J. Mol. Biol. 210, 369-381] complexed with the hydroperoxide of cobalt-pepleomycin (CoPEP) were obtained by the hanging-drop vapour-diffusion method at 298 K. An X-ray diffraction data set was collected to 2.8 A at 100 K. The crystal belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 34.52, b = 59.88, c = 72.93 A.
Topics: Antibiotics, Antineoplastic; Cobalt; Crystallization; Crystallography, X-Ray; DNA; Oligonucleotides; Peplomycin
PubMed: 14684911
DOI: 10.1107/s0907444903021917 -
International Journal of Oncology Oct 2003Apoptotic cell death is frequently suppressed by NF-kappaB transcription factor. We examined the effects of NF-kappaB on the sensitivity to anti-cancer drugs by using...
Apoptotic cell death is frequently suppressed by NF-kappaB transcription factor. We examined the effects of NF-kappaB on the sensitivity to anti-cancer drugs by using two NF-kappaB-inhibitory molecules, IkappaBalpha-super-repressor (IkappaBalpha-SR) and dominant negative IKKbeta (IKKbeta-DN). Ha-ras-transformed NIH3T3 (ras-NIH3T3) mouse fibroblasts were stably transfected with these cDNAs, and suppression of NF-kappaB activity was confirmed by electrophoretic mobility shift assays. Cell viability analysis revealed that IkappaBalpha-SR- or IKKbeta-DN-transfected cells were more resistant to peplomycin, mitomycin C, and camptothecin. Flow cytometric analysis indicated partial G1 arrest of these transfected cells. Consistently, elevated expression of IkappaBalpha-SR and IKKbeta-DN was accompanied by increased levels of p21 but not of Bax. Transfection of p21 into ras-NIH3T3 cells caused similar reduced chemosensitivity to the anti-cancer drugs. These results collectively indicate that constitutive suppression of NF-kappaB activity reduced the chemosensitivity to anti-cancer drugs via enhanced expression of p21.
Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Blotting, Western; Camptothecin; Cell Line, Transformed; Cell Nucleus; Cell Survival; Coloring Agents; DNA; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Fibroblasts; Flow Cytometry; Mice; Mitomycin; NF-kappa B; NIH 3T3 Cells; Peplomycin; Tetrazolium Salts; Thiazoles; Transfection
PubMed: 12963987
DOI: No ID Found -
Ai Zheng = Aizheng = Chinese Journal of... Jul 2003Intraoperatively,the routine method to differentiate malignant lung neoplasms from benign lesions is by the judgment of naked eye or frozen section. It is not accurate...
BACKGROUND & OBJECTIVE
Intraoperatively,the routine method to differentiate malignant lung neoplasms from benign lesions is by the judgment of naked eye or frozen section. It is not accurate to judge by naked eye and will take long time by frozen section. Using a gamma-detecting probe (GDP) to accurately detect the tumors and the metastases, the operators could decide the resection range and the treatment plan. This study was preliminary clinical practice of tumor imaging and radioimmunoguided surgery (RGS) using (99m)Tc-PPM (peplomycin) as a tumor tracer.
METHODS
Thirty-seven patients were administered with injection of (99m)Tc-PPM. The images were taken preoperatively. Region of interest (ROI) method was performed and tumor-to- normal-tissue (T/NT) ratio was calculated on the image. The radioactivity of the specimens resected from the patients was detected using GDP at the time of surgery. T/NT ratio was obtained by comparing the radioactivity of the tumor tissue with the normal lung tissue.
RESULTS
The uptake ratios (T/NT) of (99m)Tc-PPM were different between malignant and benign lesion (P< 0.01). The ratio (T/NT, x+/-2s) was regarded as the threshold for differentiation of malignant and benign lesions. The sensitivity, specificity, and accuracy of identifying malignant lesion were 90%, 87.5%, and 89.3%, respectively; GDP could be used to accurately detect the invasive range of the tumors, with the sensitivity, specificity, and accuracy of identifying lymph node metastases of 91%, 88%, and 90%, respectively.
CONCLUSION
(99m)Tc-PPM is a useful agent in differentiating malignant lung neoplasm from benign lesions, and as a tumor tracer can be used in detecting tumor by GDP intraoperatively. The RGS is a simple method that can help the surgeon in the intraoperative assessment of the tumor and the lymph node metastases.
Topics: Adult; Aged; Antibiotics, Antineoplastic; Female; Gamma Rays; Humans; Lung Neoplasms; Male; Middle Aged; Peplomycin; Radionuclide Imaging; Technetium
PubMed: 12866969
DOI: No ID Found