摘要:

For many decades, invasive cervical cancer has been considered more or less chemoresistant and chemotherapy has been limited to patients presenting with overt metastatic disease or those suffering from pelvic recurrences which could not be advised to secondary local treatments. However, more than 20 different single agents are considered active in cervical cancer. Recent cooperative clinical trials have demonstrated the superiority of multi-modality strategies for patients with high-risk cervical cancer. These studies integrating chemotherapy as part of the primary therapeutic concept have provided the most significant improvement of locally advanced disease in more than three decades. This review summarizes current standards of chemotherapy for invasive cervical cancer and shows new developments which may improve systemic treatment of the disease.

ISSN:0959-4973    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Due to its pivotal role in signal transduction, the universal tumor suppressor PTEN (also termed MMAC or TEP) is one of the putative candidates for involvement in tumorigenesis of several tissues. Although involvement of PTEN in tumorigenesis was shown in different tissues, no data are available concerning PTEN activity in response to antineoplastic agents. Therefore, we assayed the PTEN activity exposed to either blank medium or the commonly used anti-cancer drugs cisplatin, adriamycin or paclitaxel, respectively, in three different concentrations. PTEN activity was determined using the Malachite Green assay basing upon dephosphorylation of phosphatidylinositol-3,4,5-triphosphate (PIP3) by the PTEN enzyme and subsequent determination of inorganic phosphate released. Although the three different anti-cancer drugs assayed act with different cellular modes, the antineoplastics influenced PTEN activity in a similar manner: at low concentrations tested all three antineoplastics significantly increased PTEN activity. However, increasing drug concentrations exhibited a decline but not a total loss of PTEN activity. The data indicate that PTEN activity is increased following cytotoxic drug exposure and, thereby, exhibits its suppressive function. However, the decrease of PTEN activity in response to increasing drug concentrations suggests an aberration of total functional activity. As far as the regulative checkpoint PTEN is abolished, tumor cells might evade cell death pathways resulting in increased proliferation of cancer cells. This might be a general event in refractory tumor cells surviving chemotherapy.

ISSN:0959-4973    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

There is no well-defined curative treatment for advanced and unresectable hepatocellular carcinoma. The widely used transarterial chemoembolization (TACE) with a doxorubicin-Lipiodol emulsion has not been shown to improve survival in randomized studies. Further, obstruction of the hepatic artery used in the procedure is badly tolerated in patients with cirrhosis. Drugs with a more rapid penetration into the cancer cells are likely to eliminate the need for obstruction of the hepatic artery. We therefore compared the cytotoxicity of another anthracycline pirarubicin with that of the commonly used doxorubicin. In this report, we show that pirarubicin has a greaterin vitrocytotoxic effect than doxorubicin on the HepG2 and Hu-H7 human hepatoma cell lines. Pirarubicin emulsion with Lipiodol is more stable at 37°C than doxorubicin-Lipiodol. Moreover, pirarubicin accumulates at a greater extent in the oil phase, permitting Lipiodol to act as a slow-releasing vector for the anthracycline. Further, amiodarone, a multidrug resistance inhibitor, was shown to decrease the intrinsic resistance of HepG2 and Hu-H7 cells to both anthracyclines, and the presence of polysorbate 80 in the amiodarone preparation increased the stability of the anthracycline-Lipiodol emulsions. We therefore conclude that pirarubicin is a better candidate for TACE than doxorubicin. The rapid and increased cytotoxicity of pirarubicin on hepatoma cancer cells and the stability of the pirarubicin-Lipiodol amiodarone emulsion could avoid the complete obstruction of the hepatic artery by Gelfoam sponges, and provide a better tolerated method of TACE in patients with latent liver insufficiency.

ISSN:0959-4973    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Anthracene-1,4-dione and 6,7-dichloro-1,4-anthracenedione (code names AQ1 and AQ4, respectively) are cytostatic (IC50: 53 and 110 nM, respectively) and cytotoxic (IC50: 100 and 175 nM, respectively) in wild-type drug-sensitive HL-60-S tumor cells at day 4in vitro. Therefore, the antitumor effects of these drugs were assessed and compared to those of daunorubicin (DAU) in HL-60-RV and HL-60-R8 tumor cells, which are, respectively, P-glycoprotein-positive and -negative multidrug-resistant (MDR) sublines. In contrast to DAU, which loses its cytostatic [resistance factors (RFs): 30.3-31.8] and cytotoxic (RFs: 48.8-58.1) activities in MDR sublines, AQ1 inhibits cell proliferation (RFs: 0.9-1.3) and cell viability (RFs: 1.4-1.6) as effectively in HL-60-RV and HL-60-R8 as in HL-60-S cells. Similarly, DAU decreases the rate of DNA synthesis less effectively in MDR sublines (RFs: 8.0-13.3) but AQ1 inhibits the incorporation of [3H]thymidine into DNA to the same degree in HL-60-S as in HL-60-RV and HL-60-R8 cells (RFs: 0.9-1.1). In contrast to DAU, which is ineffective, the advantage of AQ1 is its ability to block the cellular transport of purine and pyrimidine nucleosides in HL-60-S cells, an effect which persists in the MDR sublines (RFs: 1.1). AQ4, which mimics to a lesser degree all the antitumor effects of AQ1, except the inhibition of adenosine transport, also retains its effectiveness in MDR sublines (RFs: 1.1-3.1). The peaks of DNA cleavage caused by DAU and AQ1 in HL-60-S cells shift to lower concentrations with increasing times of drug exposure but DAU loses most of its ability to induce DNA fragmentation in MDR sublines, whereas the levels of AQ1-induced DNA cleavage at 16 and 24 h are nearly equivalent in HL-60-S, HL-60-RV and HL-60-R8 cells. Because they not only mimic the antitumor effects of DAU in the nM range but also block nucleoside transport and remain effective in tumor cells that have developed different mechanisms of MDR, AQ1 and AQ4 analogs might be valuable to develop new means of polychemotherapy.

ISSN:0959-4973    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

CHS 828 is a pyridyl cyanoguanidine that has shown promising preclinical anticancer activity against various experimental tumor models and is presently being tested in a phase II trial in man. In the present study the fluorometric microculture cytotoxicity assay was used forin vitroevaluation of CHS 828 activity in primary cell cultures from hematological and solid tumors. In total, 156 samples from various diagnoses were tested with 72-h continuous drug exposure. CHS 828 showed high relativein vitroactivity against tumor cells from chronic lymphocytic leukemia as well as from acute leukemia and high-grade lymphoma. Activity was also observed in several solid tumor cell samples, although the group as a whole appeared less responsive. CHS 828 was significantly more active against hematological malignancies compared to normal lymphocytes. Correlation analysis with standard drugs revealed low to moderate correlation coefficients. The results show that CHS 828 has potent antitumor activity against primary cultures of human tumor cells from patients and might have a unique mechanism of action.

ISSN:0959-4973    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Human colon cancer SW480 cells express the c-mycgene. On the other hand, SW480DDP cell lines resistant to cisplatin exhibited decreased c-mycgene expression, but their cell growth rates remained similar to those of their parental cells. Antisense oligonucleotides to c-mycinhibited c-mycexpression and induced increased resistance to cisplatin in SW480 cells. In contrast, SW480DDP cells showed increased c-mycexpression and reversed sensitivity to cisplatin when these cells were transfected with c-myccDNA from the pLNCX plasmid. Moreover, SW480DDP cells transfected with c-myccDNA induced apoptosis when exposed to cisplatin, but not SW480 cells transfected with an antisense sequence for c-myc. Transfection either with a c-mycantisense sequence or c-myccDNA to these cells did not change their growth rates. Thus enforced expression of c-mycin SW480 and SW620 lines sensitizes cells to cisplatin-induced apoptosis, whereas the down-regulation of c-mycin SW480DDP and SW620DDP increases cisplatin resistance when using antisense strategy.

ISSN:0959-4973    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Thirty-one different 5-(Z)-arylidene-4-imidazolidinones were tested on six AIDS-related lymphoma (ARL) tumor cell lines, one leukemia CCRF-CEM cell culture and five different lymphoma cell lines: RL, KD-488, AS283, PA682 and SU-DHL-7. The investigated compounds showed remarkable activity against ARL, compounds 3d and 5c proved to inhibit AS283 and SU-DHL-7 cell lines, respectively, both at a GI50value of 0.03 μM. The 2-(2-carboxyphenylamino) series proved to be the most active members in this investigation. Compounds 6b and 6d showed GI50(MGMID) values of 6.1 and 8.7 μM, respectively, against the studied six ARL.

ISSN:0959-4973    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Black soybean [Glycine max(L.) Merr.] has been used as a health food and herb in China for hundreds of years. In the present study, we purified a unique polysaccharide component from black soybean (PSBS) and found that it indirectly inhibits proliferation and induces differentiation of human leukemic U937 cells via activation of mononuclear cells (MNCs). We prepared conditioned media (MNC-CM) by incubating MNCs from human peripheral blood with or without PSBS (PSBS-MNC-CM and normal MNC-CM, respectively). Treatment of human leukemic U937 cells with PSBS-MNC-CM significantly inhibited proliferation of U937 cells, reducing their growth by 98.5%. Furthermore, PSBS-MNC-CM induced U937 cells to differentiate into mature monocytes/macrophages (83% by morphological examination and 90% by the nitroblue tetrazolium test). Neither PSBS alone nor normal MNC-CM had such effects. The molecular weight of PSBS was about 480 000 by gel filtration. Structural analysis of PSBS revealed that (1,6)-α-D-glucan might be its major active component. Our results suggest that the PSBS may inhibit proliferation and induce differentiation in human leukemic U937 cells by activating the immune response of MNCs.

ISSN:0959-4973    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

We previously reported that gallic acid (3,4,5-trihydroxybenzoic acid), a naturally occurring plant phenol, can induce apoptosis in four kinds of human lung cancer cell linesin vitro. The present study further investigated thein vivoanti-tumor effects of orally administered gallic acid. Gallic acid reduced cell viability of LL-2 mouse lung cancer cellsin vitrodose dependently, with a 50% inhibitory concentration (IC50) value of around 200 μM. C57Black mice were transplanted with LL-2 cells, and administered gallic acid (1 mg/ml in drinking water,ad libitum) and/or cisplatin (4 mg/kg i.p. injection, once a week). The average weight of the transplanted tumors, obtained at 29 days after transplantation, in the mice of control, gallic acid-treated cisplatin-treated and cisplatin plus gallic acid-treated groups was 4.02, 3.65, 3.19 and 1.72 g, respectively. The average tumor weight of the mice treated with cisplatin combined with gallic acid was significantly smaller than that of the control group (p<0.05). The amount of apoptotic cells in the tumor tissues of mice treated with gallic acid and/or cisplatin was significantly higher than those of the control mice. Combination of gallic acid and cisplatin increased the tumor cell apoptosis compared with the treatment with cisplatin alone. The present findings suggest that the combination of gallic acid with an anti-cancer drug, including cisplatin, may be an effective protocol for lung cancer therapy.

ISSN:0959-4973    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The usefulness of neoadjuvant chemotherapy (NAC) regimens has been reported; however, the effect of NAC for advanced stages (especially stage III-IVA) is thought to be insufficient. We conducted a phase I-II study of neoadjuvant chemoradiotherapy consisting of intra-arterial (i.a.) infusion of carboplatin and intracavitary brachytherapy in patients with locally advanced cervical cancer to achieve the new NAC method. Sixteen eligible patients included those with previously untreated stage IIB, III or IVA cancer with bulky tumor. Brachytherapy using iridium-192 was performed with concurrent i.a. chemotherapy with carboplatin (200, 300 and 400 mg/m2). Treatment was repeated every 4 weeks for a total of two cycles. Both hematologic and non-hematologic toxicities were generally mild. Grade 4 hematologic toxicity was observed in 12.5% and there were no grade III or IV non-hematologic toxicities. The optimal dose of carboplatin was determined to be 400 mg/m2. Among 16 patients, six showed complete response (37.5%) and nine showed partial response (56.3%), for an overall response rate of 93.8%. All 15 responding patients underwent radical surgery with a pelvic lymphadenectomy and postoperative radiotherapy. The combination of brachytherapy and i.a. chemotherapy with carboplatin is a promising regimen for NAC in locally advanced cervical cancer.

ISSN:0959-4973    

出版商:OVID    

年代:2001

数据来源: OVID