Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human epidermoid lung carcinoma xenografts with intrinsic and induced resistance were analyzed with regarding to different parameters. The xenografts with intrinsic resistance to vincristine (HXL 54) and induced drug-resistance sublines to vincristine (HXL 55/VCR), actinomycin D (HXL 55/AD) and cisplatin (HXL 55/DDP) were characterized in terms of the degree of resistance, cross-resistance, proliferation kinetics, tumorigenicity, keratin and P-glycoprotein expression. The results demonstrate that xenografts with intrinsic or induced resistance to vincristine or actinomycin D exhibit a similar general pattern of cross-resistance to that observed in multidrug-resistant cell lines. The resistance cannot be attributed to differences in proliferation kinetics. Development of resistance is associated with loss of tumorigenicity and features of differentiation, P-glycoprotein is little expressed in the resistant xenograft lines and corresponds well with the low grade of resistance.
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PMID:Intrinsic and acquired multidrug resistance in human lung carcinomas grown in nude mice. 197 Jul 15

Echinosporin isolated from a Streptomyces culture showed antitumor activity against rodent tumor models such as leukemia P388, P388/VCR, and fibrosarcoma Meth 1. It was marginally active against melanoma B16 and sarcoma 180. It was not active against Lewis lung carcinoma and xenograft MX-1. It inhibited the colony formation of HeLa S3 cells with a wide shoulder at low dose ranges. DNA, RNA, and protein synthesis were inhibited by echinosporin. It depressed WBC with nadir on day 3, but the recovery to the normal level after echinosporin injection was more rapid than that after mitomycin C.
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PMID:Antitumor activity of echinosporin. 400 42

From April, 1979 to November, 1981, 293 patients with small cell lung carcinoma (SCLC) were entered on a randomized, controlled study comparing the two induction regimens of high-dose CAV (HD-CAV) (cyclophosphamide [CTX] 1200 mg/m2, doxorubicin [ADR] 70 mg/m2 and vincristine [VCR] 1 mg/m2 intravenously (IV) on days 1 and 21) versus, conventional-dose CAV + VP-16 (etoposide) (CAV-VP) (CTX 1000 mg/m2, ADR 40 mg/m2, VCR 1 mg/m2 IV on days 1 and 21 with VP-16 100 mg/m2 on days 1-3, and 21-23). Responding and stable patients were continued on conventional-dose CAV for 5 consolidation courses. Prophylactic brain irradiation delivered after the first consolidation course in responders was optional. Patients were included in the study if they had extensive disease (i.e., beyond one hemithorax), no prior chemotherapy, or radiotherapy and performance status of 50 or above. After 2 induction courses, 215 cases are evaluable. Of these, 76 of 106 (72%) patients treated with HD-CAV have responded (greater than 50% regression), including 13 complete responders (CRs) versus 80 of 108 (74%) patients on CAV-VP, including 15 CRs. Of the 130 evaluable patients who have completed consolidation (HD-CAV, 65; CAV-VP, 65), an additional 22 patients achieved CR (HD-CAV, 12; CAV-VP, 10) for an overall CR rate of 24%. Median duration of remission was 33.6 weeks for HD-CAV and 35.6 weeks for CAV-VP (P = 0.61). Median duration of complete response for HD-CAV was 33.8 weeks and for CAV-VP 36.7 weeks (P = 0.81). Survival curves were similar for the two regimens, with medians of 42.1 weeks for HD-CAV and 42.3 weeks for CAV-VP (P = 0.35). Survival correlated with performance status and quality of response. As anticipated, the major toxicity for both induction regimens was leukopenia. During induction, granulocyte nadirs of less than 500/mm3 occurred in 81% of patients on HD-CAV and 77% of patients on CAV-VP. Thus, dose intensification appears to produce high response rates and modest complete response rates in extensive SCLC, but it does not appear to improve materially survival compared to prior reports of conventional-dose therapy.
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PMID:Combination chemotherapy in small cell lung carcinoma. A randomized study of two intensive regimens. 609 79

A comparison of CTX + CCNU and CTX + CCNU + procarbazine as initial systemic treatment was made in 440 evaluable patients with small-cell carcinoma of the lung. The overall response rate for patients receiving the three-drug combination was 57% (11% CR) compared with 44% (9% CR) for the two-drug combination. Median survival times were similar, 27 (with procarbazine) and 29 weeks (without procarbazine). Nonresponders to the initial treatment received ADR, ADR + VCR, and ADR + VP-16 with overall response rates of 14% (2 of 14), 27% (9 of 33), and 30% (15 of 51), respectively. Median survivals for nonresponders, as measured from day 42, were 15 weeks (ADR), 21 weeks (ADR + VCR), and 22 weeks (ADR + VP-16). Responders to the initial treatment either continued on the initial therapy or received a non-cross-resistant combination chemotherapeutic regimen (ADR + VCR) alternating with the initial therapy. There is also the suggestion that responders who received the cycled therapy after day 42 survived significantly longer than responders who did not switch treatments until relapse, 38 vs. 29 weeks.
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PMID:Phase III study of CCNU, cyclophosphamide, adriamycin, vincristine, and VP-16 in small-cell carcinoma of the lung. 627 69

Twenty-four evaluable patients with small cell carcinoma of the lung were treated with an escalating chemotherapy regimen including Cyclophosphamide, Adriamycin, Vincristine and VP16-213. The initial doses were CTX 800 mg/m2 i.v. day 1; ADR 50 mg/m2 i.v. day 1; VCR 1.4 mg/m2 day 1 weekly; and VP16-213 100 mg/m1 i.v. days 14-18 every 4 weeks, CTX and ADR were escalated by 100 and 10 mg/m2 respectively in each subsequent cycle according to blood count. Hematologic toxicity was minimal and the treatment was well tolerated. Partial responses and complete responses were 9 of 19 and 5 of 19 respectively for patients with limited disease, and 4 of 5 respectively for patients with extensive disease. The overall response rate for the whole group was 79% These results must be considered preliminary.
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PMID:Chemotherapy combination with cyclophosphamide (CTX) adriamycin (ADM), vincristine (VCR), and VP16-213 in small cell carcinoma of the lung (SCCL). 628 84

A synchronised programme consisting of VCR, CTX and MTX has been employed in 57 patients suffering fom lung carcinoma. Average survival was 10.6 months and overall tolerance was good. The best indications are intermittent long-term treatment and retreatment of patients with cancer recalcitrant to the same drugs. With the simplification of cell kinetics study techniques, more meaningful results can be expected in the application of this treatment programme.
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PMID:[Use of a synchronized protocol of cytostatic drugs in the treatment of advanced lung cancer]. 725 20

The antitumor activity of S 16020-2, a new olivacine derivative, was investigated in vivo and compared with that of Adriamycin and elliptinium acetate in a panel of murine (P388 leukemia, M5076 sarcoma, Lewis lung carcinoma, and B16 melanoma) and human (NCI-H460 non-small-cell lung and MCF7 breast carcinomas) tumor models. S 16020-2 given i.v. was active against P388 leukemia implanted i.p., s.c., or intracerebrally. The therapeutic effect of an intermittent schedule (administration on days 1, 5, 9) was superior to that of single-dose treatment, allowing the i.v. administration of high total doses of S 16020-2 and resulting in the cure of 60% of mice in the i.p. P388 model. In this model, S 16020-2 was more active than elliptinium acetate and showed a better therapeutic index than Adriamycin: > or = 8 versus 2. A good therapeutic effect of S 16020-2 was also observed in three P388 leukemia sublines displaying the classic multidrug-resistance phenotype, namely, P388/VCR, P388/VCR-20, and P388/MDRC.04, the latter being totally insensitive to vincristine and Adriamycin. However, S 16020-2 was not active against the P388/ADR leukemia, a model highly resistant to adriamycin in vivo. S 16020-2 was both more active than Adriamycin and curative in the M5076 sarcoma and Lewis lung carcinoma implanted s.c. In the B16 melanoma implanted i.p. or s.c., S 16020-2 was less active than Adriamycin. Against the NCI-H460 human tumor xenograft, S 16020-2 demonstrated activity superior to that of Adriamycin (T/C = 20% versus 43% on day 21). Against the MCF7 breast cancer xenograft, S 16020-2 was active, but less so than Adriamycin (T/C = 23% versus 9% on day 21), whereas elliptinium acetate was marginally active (T/C = 49% on day 24). The hematological toxicity of S 16020-2 given to B6D2F1 mice at pharmacological dose appeared to be less severe than that of Adriamycin, particularly in bone-marrow stem cells. These results demonstrate that S 16020-2 is a highly active antitumor drug in various experimental tumor models and is markedly more efficient than elliptinium acetate. Because of its pharmacological profile, which is globally different from that of Adriamycin, S 16020-2 is considered an interesting candidate for clinical trials.
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PMID:In vivo antitumor activity of S 16020-2, a new olivacine derivative. 882 92

Three pheophorbide-related compounds (1-3) were isolated from the leaves and stems of Clerodendrum calamitosum. The methyl ester of 3 (6) and the known (10S)-hydroxypheophytin a (7) also were isolated from leaves of the related plant Clerodendrum cyrtophyllum. Compounds 1 and 6 were isolated for the first time as naturally occurring products from a plant source. All structures were elucidated by detailed spectroscopic analysis. Biological evaluation showed that 1 and 2 exhibited strong cytotoxicity against human lung carcinoma (A549), ileocecal carcinoma (HCT-8), kidney carcinoma (CAKI-1), breast adenocarcinoma (MCF-7), malignant melanoma (SK-MEL-2), ovarian carcinoma (1A9), and epidermoid carcinoma of the nasopharynx (KB), and its etoposide- (KB-7d), vincristine- (KB-VCR), and camptothecin-resistant (KB-CPT) subclones. Compound 3 was less cytotoxic than 1 and 2. Compounds 4-6, the methyl esters of 1-3, showed strongly increased cytotoxicity compared with the parent acids. Interestingly, 6 was the most active derivative among these compounds. Compound 7 was inactive.
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PMID:Cytotoxic pheophorbide-related compounds from Clerodendrum calamitosum and C. cyrtophyllum. 1147 23

In vivo antitumoral activity, pharmacokinetics (PK) and biodistribution of a new liposomal formulation of vincristine (VCR-Lip) were compared to VCR in aqueous solution (VCR-Conv). VCR was entrapped into a vesicular phospholipid gel (VPG) consisting of densely packed liposomes. Redispersed VCR-containing VPG (VCR-Lip) consisted of 54% liposomally entrapped and 46% free VCR. In vivo efficacy of VCR-Lip versus VCR-Conv was tested using the s.c. growing human small cell lung carcinoma LXFS 650 and the human mammary carcinoma MX1. PK and biodistribution were evaluated using radiolabeled drug and lipid in LXFS 650 tumor-bearing mice. VCR-Lip at a dose of 1.0 mg/kg (dose near the maximum tolerated dose) led to partial remissions in the MX1 tumor xenograft model (T/C=3.9%). VCR-Conv at an equitoxic dose of 0.6 mg/kg produced only a tumor growth inhibition (T/C=7.0%). In LXFS 650 tumor-bearing mice, VCR-Lip was highly active at doses of 0.75 (T/C=0.7%) and 1.0 (T/C=0.0%) mg/kg, and complete tumor regressions were observed. In contrast, equitoxic doses of VCR-Conv (0.6 mg/kg) resulted only in less pronounced tumor remissions (T/C=4.1%). The PK study revealed that VCR-Lip achieved an over 10-fold higher plasma AUC (22.6 microg x h/ml) than VCR-Conv (2.16 microg x h/ml). Moreover, tumor drug levels were 2.3-fold higher when VCR was injected as VCR-Lip in comparison to VCR-Conv. In some cases, however, VCR-Lip as well as blank VPG appeared to be toxic. We conclude that VCR-Lip is an effective VCR delivery system with superior antitumor activity compared to VCR-Conv. The enhanced efficacy can be explained by sustained release and passive tumor targeting.
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PMID:Pharmacokinetics and antitumor activity of vincristine entrapped in vesicular phospholipid gels. 1239 63