Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a phase II study 40 patients with non-small-cell lung cancer were treated with 100 mg/m2 cis-diamminedichloroplatinum (II) (DDP) i.v. on day 1, combined with VP 16-213 (VP) in a dose of either 80 mg/m2 daily i.v. on days 1, 2 and 3 or 120 mg/m2 daily by mouth on days 3, 4, 5 and 6. The course was repeated every 3 weeks. In 30 evaluable patients, 10 partial remissions were recorded with a median duration of 3 months. Eleven patients had stable disease and 9 showed progression under treatment. Leukopenia was more pronounced with intravenous administration of VP than with oral VP (median leukocyte nadir 2400/mm3 and 3700/mm3 respectively). Two patients had thrombocytopenia under 50,000/mm3. All patients suffered from moderate to marked nausea and vomiting. All patients had alopecia. Nine patients had serum creatinine elevations over 1.4 mg/dl. Six patients with renal toxicity were treated in one institution with incorrectly applied forced diuresis during DDP administration. DDP and VP are an active regimen for remission induction in non-small-cell lung cancer. Due to cumulative and marked gastrointestinal intolerance this regimen cannot be given over prolonged periods of time.
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PMID:[Chemotherapy of non-small-cell bronchial cancer with a combination of Cis-diamminedichloroplatinum (II) and VP 16-213]. 719 2

The efficacy of cisplatin [cis-diamminedichloroplatinum (II); DDP] is hampered by acquired or de novo resistance of malignant cells to its cytotoxic effects. We have previously reported that cisplatin resistance parallels glutathione S-transferase (GST) activity in several human small-cell lung cancer cell lines. In the presently described studies, we used sulphasalazine, an inhibitor of GSTs, to evaluate the relative role of GSTs in mediating cisplatin resistance in two human small-cell lung cancer cell lines, NCI H-69 and H-2496. The H-69 cell line, which contained relatively higher GST activity than the H-2496 cell line (317 +/- 7 vs 9 +/- 1 mU mg-1 protein respectively), also displayed a greater degree of cisplatin resistance (IC50 values of 25.0 +/- 3.9 vs 4.5 +/- 1.0 microM respectively). Western blot and Northern blot analyses of purified GSTs revealed the expression of only the pi-class GST in both cell lines. Sulphasalazine inhibited the purified GSTs (IC50 of 10 microM for H-69 and 12 microM for H-2496) from both lines in a competitive manner with similar Ki values (6.5 and 7.9 microM for the H-69 and H-2496 cell lines respectively). Cytotoxicity studies revealed that sulphasalazine increased the cytotoxicity of cisplatin towards both cell lines. Isobologram analysis showed that sulphasalazine synergistically enhanced the cytotoxicity of cisplatin towards both cell lines, the magnitude of synergy being remarkably higher in H-69 cells than in H-2496 cells. Our studies indicate that clinically achievable concentrations of sulphasalazine may be useful in modulating cisplatin resistance in malignancies with increased GST-pi content.
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PMID:Modulation of cisplatin cytotoxicity by sulphasalazine. 791 20

The development of resistance to cisplatin (DDP) occurs rapidly both in vitro and in vivo, and constitutes a major obstacle to effective therapy. We have previously demonstrated that there is a highly synergistic interaction between tamoxifen (TAM) and DDP against cell lines representative of three different human cancers: melanoma, ovarian carcinoma and small-cell lung cancer. The purpose of these studies was to determine if TAM interferes with the development of resistance to DDP. T-289 melanoma cells and 2008 ovarian cancer cells were cultured with increasing concentrations of DDP +/- TAM in an attempt to induce resistance to DDP. At various time points the cells were removed from culture and the degree of resistance to DDP was quantitated. Concurrent exposure to TAM and DDP decreased both the rate and the absolute magnitude of resistance to DDP in both melanoma and ovarian cancer cell lines. In the T-289 cell line the rate was decreased by a factor of 3.4 +/- 1.4 (P < 0.05), while in the 2008 cell line the rate was decreased by a factor of 2.4 (P < 0.01). TAM decreases the rate as well as the absolute magnitude of in vitro resistance to DDP in both melanoma and ovarian cancer cell lines. These data suggest that the concurrent administration of TAM and DDP may result in a delay in the development of resistance to DDP which may have important clinical implications in the design of DDP-containing regimens.
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PMID:Tamoxifen delays the development of resistance to cisplatin in human melanoma and ovarian cancer cell lines. 808 Jul 29

The effect of calmodulin antagonist trifluoperazine (TFP) on in vitro drug sensitivity of primary cultured lung cancer cells was studied in 28 cases with MTT assay. TFP was found to enhance significantly the anticancer activities of VCR, ADR and VP16 (P < 0.01 or < 0.05). But TFP could not sensitize tumor cells to DDP. TFP may therefore be useful as an adjunct in chemotherapy of lung cancer.
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PMID:[Effect of calmodulin antagonist on chemosensitivity of primary cultured lung cancer cells]. 869 72

A total of 55 patients with measurable colorectal metastatic carcinoma were studied to evaluate the impact on toxicity, response, and survival of protracted venous infusion (PVI) 5-FU 200 mg/m2 per day with Cis-DDP 80 mg/m2 or carboplatin 300 mg/m2 every 3 weeks, 1-hour infusion. Patients received continuous uninterrupted therapy until there were signs or symptoms of toxicity. Both 5-FU and cisplatin were withheld when patients experienced grade II stomatitis and diarrhea, severe nausea or vomiting not controlled by standard antiemetic therapy, and clinically significant hand-foot syndrome. The toxicity was neurological (20% grade 2 and 3) hematological (13% grade 2) and dermatological (11% grade 2). The overall response (CR+PR) was 24% with a median survival of 13 months. The results of our study show that there is no improvement in response rate, response duration or survival compared with historical trials. However, this study does confirm the valuable palliative role of the protracted 5-FU infusion treatment. Colorectal carcinoma is one of the most common neoplasms in Western societies, being second only to lung cancer as a cause of death from malignancy. The management of nonmetastatic primary disease in surgical, with adjuvant chemotherapy for those at high risk of relapse. However, for those with metastatic disease at diagnosis or recurrent disease after resection, cytotoxic chemotherapy is the treatment of choice and fluorouracil (5-FU) is the most active cytotoxic agent in this disease, with a response rate of approximately 20%. Efforts to improve the response rate have focused on the use of agents to modulate 5 FU. The Southwestern Oncology Group (SWOG) study reported by Leichman et al. (1) and a study from the United Kingdom by Hill et al. (2) compared conventional FU to modulated FU and found no improvement in response rate or survival. In the SWOG study, two different schedules of bolus FU and LV were compared with bolus FU alone and to continuous infusion FU administered alone or modulated by LV or PALA. In this study, the results obtained with bolus FU were superior to most of the studies in the literature: The response rate was 26%, and the median survival was 14 months. The high- and low-dose LV and FU groups showed response rates and survival similar to bolus FU alone. However, in 12 previously reported randomized studies comparing FU and LV or FU alone, nine reported that the combination of FU and LV produced significant increases in response rates and two reported significant increase in survival (3, 4). Many of these trials used the dose schedules reported in the SWOG trial. Protracted venous infusion (PVI) 5-FU has been shown to have superior efficacy with less toxicity in colorectal cancer when compared to bolus 5-FU and synergy between cisplatin and 5-FU has been demonstrated in vitro. Consequently, we have investigated the efficacy of the combination of bolus cis or carboplatin and PVI 5 FU in 55 patients with advanced colorectal cancer using survival, response rate, symptomatic response, and toxicity as study endpoints.
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PMID:First-line protracted venous infusion fluorouracil with CisDDP or carboplatin in advanced colorectal cancer. 922 28

Circulating myeloid (CFU-GM) and erythroid (BFU-E) progenitor levels were evaluated weekly throughout 3 courses of treatment with vinorelbine (VNB) ifosfamide (IFO) and filgrastim (G-CSF) with or without addition of cisplatin (DDP) in 20 stage IIIB or IV non small-cell lung cancer patients. In IFO, VNB, DDP-treated patients, BFU-E mobilization in peripheral blood following chemotherapy and G-CSF was completely lacking, in contrast with the patients treated with IFO, VNB plus G-CSF. CFU-GM release, however, was of the same order in the 2 groups of patients. Further investigations are needed to explain why presence of DDP in this chemotherapeutic protocol hinders erythroid progenitor release in peripheral blood.
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PMID:Cisplatin inhibits erythroid committed progenitor (BFU-E) mobilization in peripheral blood. 968 95

Resistance to chemotherapeutic agents is the major reason for treatment failure of cancer chemotherapy. Some chemotherapeutic drugs induce the activation of NF-kappaB in cancer cells that results in their resistance to anticancer drugs. But the role of NF-kappaB in acquired resistance has not been well investigated. In this study, we transferred the "super-repressor" form of the NF-kappaB inhibitor by adenoviral vector (ad-IkappaBalpha) to human lung cancer cell lines with resistant to cisplatin (PC-14-DDP) and adriamycin (PC-14-ADR), and observed the sensitivity change. Electrophoretic mobility shift assay showed that ad-IkappaBalpha blocked the activation of NF-kappaB induced by cisplatin and adriamycin. Transduction with ad-IkappaBalpha restored the sensitivity of cisplatin and adriamycin resistant lung cancer cell lines (PC-14-DDP and PC-14-ADR) to a level compatible to the parental cell lines. Annexin-V analysis suggested that the enhancement of chemosensitivity was probably a result of the induction of apoptosis. These data demonstrated that ad-IkappaBalpha blockade of chemotherapeutic induced NF-kappaB activation increased apoptosis induction and the chemosensitivity of lung cancer cell lines with acquired resistance to cisplatin and adriamycin. Therefore, gene transfer of IkappaBalpha-SR seems to represent a new therapeutic strategy for the solution of low sensitivity and lung cancer resistance to anticancer drugs.
Lung Cancer 2003 Aug
PMID:The effect of adenovirus-IkappaBalpha transduction on the chemosensitivity of lung cancer cell line with resistance to cis-diamminedichloroplatinum(II)(cisplatin) and doxorubicin(adriamycin). 1287 83

To study the effects of cyclooxygenase 2 selective inhibitor Nimesulide (NIM) combined with Cisplatin (DDP) on human lung cancer and the possible mechanisms, the proliferation and apoptosis of human lung cancer cell line A549 were evaluated by MTT reduction assay and flow cytometry respectively. The inhibitory effect on neoplasia in vivo was tested on nude mice subcutaneously implanted tumor. Our results showed that NIM and DDP could inhibit A549 cell proliferation in a concentration-dependent pattern; this action was enhanced when NIM (25 micromol/L) was given in combination with DDP and they worked in a synergistic or additive pattern as DDP concentration > or = 1 microg/ml. NIM and DDP could induce A549 cells apoptosis and the action was augmented when used in combination (P<0.01). NIM and DDP could inhibit the growth of subcutaneously implanted tumors on nude mice (P<0.05, P<0.01) and the inhibitory rate of NIM combined with DDP was significantly higher than that of NIM or DDP group (P<0.01, P<0.01). It is concluded that combined use of NIM and DDP has significant synergistic antitumor effects on lung cancer cell line A549 and in animals in vivo. The synergy may be achieved by growth inhibition and apoptosis induction.
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PMID:The effects of nimesulide combined with cisplatin on lung cancer. 1531 58

Lung cancer remains one of the most common causes of cancer-related death worldwide. Approximately 80% is histologically non-small cell lung carcinoma (NSCLC) and in about 70% of patients it is an unresectable type. Clinical studies indicated that application of platinum derivatives caused good results and combinations of platinum with other agents could improve median survivals. In view of the central problem of sufficient efficiency of drugs in chemotherapy, efforts have focused on the development of alternative platinum-based analogues that can be more effective in cancer treatment. cis-bis(3-aminoflavone)dichloroplatinum(II) (cis-Pt(II) complex of 3-aminoflavone) represents a novel class of platinum-based potential antitumour agents. In order to evaluate the degree of apoptosis, acridine orange/ethidium bromide and Hoechst 33258/propidum iodide double staining as well as RT-PCR (P53 and BAX expression evaluation) were used in lung cancer cell line A549 after treatment with this compound in comparison with cis-diamminedichloroplatinum(II) (cis-DDP). Apoptotic cells at early and late stages and also necrotic ones were observed after usage of cis-Pt(II) complex of 3-aminoflavone and the percentage of these cells outnumbered the values obtained after cis-DDP application. The former compound induced a higher percentage of P53 and BAX expression in A549 cells in comparison with the latter one. Results indicate the beneficial properties of cis-Pt(II) complex of 3-aminoflavone as a potential antitumor drug.
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PMID:Enhanced P53 and BAX gene expression and apoptosis in A549 cells by cis-Pt(II) complex of 3-aminoflavone in comparison with cis-DDP. 1601 88

Bcl-XL is overexpressed in a variety of human tumors and is involved in tumorigenesis and chemoresistance. This study investigated the inhibitory effect of the hairpin Bcl-XL small interfering RNA (siRNA) on the expression of the Bcl-XL gene in the cisplatin (DDP)-resistant human lung adenocarcinoma cell line A549/DDP, and the effect of Bcl-XL siRNA on drug sensitization in A549/DDP cells. Bcl-XL siRNA and negative siRNA plasmids were constructed and stably transfected into A549/DDP cells. Reverse transcription-polymerase chain reaction and Western blot analysis were used to detect the target gene expression. Spontaneous apoptosis of cells was detected by acridine orange and ethidium bromide staining. Drug sensitivity of the cells to DDP was analyzed with dimethylthiazol-diphenyltetrazolium bromide (MTT) and flow cytometry. Expression levels of Bcl-XL mRNA and protein in siRNA stable transfectants were clearly reduced as compared with negative siRNA transfectants and untreated cells. MTT results indicated that Bcl-XL transfectants had a higher cell inhibition rate than the negative vector or untreated cells after treatment with 0.2-200 micarog/ml DDP. Flow cytometry revealed increased apoptosis in Bcl-XL siRNA cells. After the addition of 20 microg/ml DDP, siRNA targeting of the Bcl-XL gene specifically down-regulated gene expression in A549/DDP cells, increased spontaneous apoptosis, and sensitized cells to DDP. The results showed that Bcl-XL siRNA contributed to an increase of DDP-induced cell death in non-small-cell lung cancer and sensitized cells to DDP, leading to increased the effectiveness of the drug in treating non-small-cell lung cancer.
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PMID:Bcl-XL small interfering RNA sensitizes cisplatin-resistant human lung adenocarcinoma cells. 1749 31


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