Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The bisindole alkaloids vinblastine, vincristine, and N-formyl-leurosine were nitrated and subsequently converted to amino derivatives. In the case of compounds 5e and 5b cytotoxic activity has been found for non-small cell lung cancer and breast cancer in the concentration range tested (10(-5)-10(-9) M). 5b also showed potency in the screen for colon cancer and leukemia.
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PMID:Synthesis of vinca alkaloids and related compounds, Part XCVI. Nitration study of vinblastine-type bisindole alkaloids. 1185 36

Flavopiridol is a synthetic flavonoid inhibitor of cyclin-dependent kinases, which is under development by Aventis Pharma (formerly Hoechst Marion Roussel) and the National Cancer Institute (NCI) for the potential treatment of cancer and proliferative disorders. By May 2001, the product was in phase IIa trials and had achieved proof-of-concept in phase I/IIa trials as a monotherapy. At this time, Aventis expected a global submission to take place in 2003 [409257]. By July 1999, the compound had entered phase II trials for gastric cancer and leukemia, and phase I/II trials for esophageal tumor and non-small cell lung cancer (NSCLC) [277372], [325929], [331850]. Phase II trials for colon and renal cancer [411684], [411769] and phase I trials for prostate cancer [279466] have also been reported. Analysts Merrill Lynch predicted in September and November 2000 that the product would be launched by 2003, with sales of EUR 50 million in that year, rising to EUR 100 million in 2004 [383742], [391426]. In April 1999, ABN Amro predicted annual sales of DM 100 million in 2002 [328676].
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PMID:Flavopiridol. National Cancer Institute. 1189 28

Protodioscin (NSC-698 796) is a furostanol saponin isolated from the rhizome of Dioscorea collettii var. hypoglauca (Dioscoreaceae), a Chinese herbal remedy for the treatment of cervical carcinoma, carcinoma of urinary bladder and renal tumor for centuries. To systematically evaluate its potential anticancer activity, protodioscin was tested for cytotoxicity in vitro against 60 human cancer cell lines in the NCI's (National Cancer Institute, USA) anticancer drug screen. As a result, protodioscin was cytotoxic against most cell lines from leukemia and solid tumors in the NCI's human cancer panel, especially selectively against one leukemia line (MOLT-4), one NSCLC line (A549/ATCC), two colon cancer lines (HCT-116 and SW-620), one CNS cancer line (SNB-75), one melanoma line (LOX IMVI), and one renal cancer line (786 - 0) with GI50 < or = 2.0 microM. In the general view of mean graphs, leukemia, colon cancer and prostate cancer are the most sensitive subpanels, while ovarian cancer is the least sensitive subpanel. Based on an analysis of COMPARE computer program with protodioscin as a seed compound, no compounds in the NCI's anticancer drug screen database have cytotoxicity patterns (mean graphs) similar to those of protodioscin, indicating that a potential novel mechanism of anticancer action is involved.
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PMID:Protodioscin (NSC-698 796): its spectrum of cytotoxicity against sixty human cancer cell lines in an anticancer drug screen panel. 1198 50

ST7 is a tumor suppressor gene, which is clustered with WNT2 gene in human chromosome 7q31 region. WNT2 gene is homologous to WNT2B gene. WNT2B gene encodes two isoforms due to alternative splicing of alternative promoter type. WNT2 and WNT2B isoform 2 (WNT2B2) are positive regulators of the WNT - beta-catenin - TCF signaling pathway. Here, a novel ST7-related gene ST7R (ST7-like, ST7L) was identified by using bioinformatics, and ST7R cDNAs were isolated by using cDNA-PCR. ST7R gene encoded 575-amino-acid polypeptide with leucine zipper domain and 3 tyrosine-phosphorylation sites. Human ST7R was homologous to human ST7 (72.1% total-amino-acid identity) and Drosophila CG3634 (56.8% total-amino-acid identity). Leucine zipper domain was unique to ST7R. Tyr 268 and Tyr 441 of ST7R were conserved in ST7 and CG3634. ST7R-homologous domains (S7H1, S7H2, and S7H3) were conserved among ST7R, ST7, and CG3634. ST7R gene consisted of at least 15 exons, and four ST7R isoforms were transcribed due to alternative splicing. ST7R and WNT2B genes, located in human chromosome 1p13 region, were clustered in tail-to-tail manner with an interval of less than 5.0-kb. ST7R-WNT2B and ST7-WNT2 gene clusters might be generated due to duplication of an ancestral gene cluster. Because allelic loss or rearrangements of human chromosome 1p13 region are reported in breast cancer, germ cell tumors, squamous cell carcinoma of head and neck, non-small cell lung cancer, gastrointestinal stromal/smooth muscle tumors (GIST), meningioma, melanoma, acute megakaryoblastic leukemia (M7), and Kaposi's sarcoma, ST7R might be a novel tumor suppressor gene on human chromosome 1p13.
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PMID:Molecular cloning and characterization of ST7R (ST7-like, ST7L) on human chromosome 1p13, a novel gene homologous to tumor suppressor gene ST7 on human chromosome 7q31. 1201 6

Methyl protoneodioscin (NSC-698791) is a furostanol saponin isolated from the rhizome of Dioscorea collettii var. hypoglauca (Dioscoreaceae), a Chinese herbal remedy for the treatment of cervical carcinoma, carcinoma of the urinary bladder and renal tumor for centuries. In order to systematically evaluate its potential anticancer activity, methyl protoneodioscin cytotoxicity was tested in vitro against 60 human cancer cell lines in the NCI's (National Cancer Institute, USA) anticancer drug screen. As a result, methyl protoneodioscin was cytotoxic against all the test cell lines from leukemia and solid tumors in the NCI's human cancer panel, especially selectively against one non-small cell lung cancer (NSCLC) line (A549/ATCC), one colon cancer line (HCT-116), two central nenous system (CNS) cancer lines (SF-539 and SNB-75), one melanoma line (M14), one renal cancer line (CAKI-1), one prostate cancer (DU-145) and two breast cancer lines (HS 578T and MDA-MB-435) with GI50 < or = 2.0 microM. The selectivity between these nine most sensitive lines and the least sensitive line (TK-10) was from 22- to 30- fold. In the same cancer subpanel, a selectivity at GI50 level of more than 15-fold was observed between A549/ATCC and EKVX (NSCLC), between CAKI-1 and TK-10, A498 (renal cancer), respectively. In general the CNS cancer was the most sensitive subpanel, while renal cancer was the least sensitive subpanel. Based on an analysis of COMPARE computer program with methyl protoneodioscin as a seed compound, no compounds in the NCIs anticancer drug screen database have similar cytotoxicity patterns (mean graphs) to that of methyl protoneodioscin, indicating a potential novel mechanism of anticancer action involved.
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PMID:The cytotoxicity of methyl protoneodioscin (NSC-698791) against human cancer cell lines in vitro. 1201 16

Janssen is developing tipifarnib (formerly known as R-1 15777), an inhibitor of RAS farnesylation, for the potential treatment of neoplasia [287030], [289610]. Janssen commenced clinical trials in the US, in conjunction with the National Cancer Institute, in April 1997 [287030], [289610], and by May 1999, phase II trials in patients with advanced non-small cell lung cancer were being planned [325960]. By February 2001, phase III trials for the potential treatment of pancreatic cancer and leukemia had been initiated [399065], and by June 2001, it was in phase II trials for RAS-dependent solid tumors [412618]. In November 2001, Credit Lyonnais Securities predicted NDAfilings in 2002 and 2003 for pancreatic cancer and other cancers, respectively, and projected US introductions for these indications in 2004 and 2005, respectively [436939].
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PMID:Tipifarnib (Janssen Pharmaceutica). 1202 65

The treatment of advanced non-small cell lung cancer requires histologic proof of diagnosis, careful staging, and assessment of each patient's performance status and comorbidities. For patients with stage IIIB (pleural effusion) and stage IV disease who have a Cancer and Leukemia Group B performance status (PS) of 0 to 1, appropriate management consists of combination chemotherapy with a platinum (either cisplatin or carboplatin) combined with paclitaxel, gemcitabine, vinorelbine, docetaxel, or CPT-11. Dosages and schedules previously established by large phase II or phase III studies should be followed. Variations in the toxicity patterns, schedules of administration, and economic considerations should guide the selection of the specific regimen. For patients who maintain a good performance status after first-line chemotherapy, second-line treatment may be considered. Current evidence supports the use of docetaxel as second-line treatment if the patient has not previously received this drug. Gemcitabine and paclitaxel may also have activity in this setting. Vinorelbine, ifosfamide, and CPT-11 appear to be inactive as second-line therapy for patients who have previously received platinum-based chemotherapy. For patients with a PS of 2, single-agent chemotherapy with vinorelbine, gemcitabine, or a combination of the two should be considered. Patients with poor performance status should be treated with supportive measures designed to relieve pain and acute complications because any tumor-directed therapy has limited benefit. Special situations exist in which curative therapy for metastatic disease is a possibility. Patients who present with solitary sites of metastatic disease, particularly after a long disease-free interval and in the CNS may undergo definitive surgery or radiotherapy with curative intent. Some have also reported favorable outcomes for patients with solitary adrenal or bone metastases as well. Surgical treatment or definitive radiotherapy should not be employed unless a thorough restaging evaluation is performed that includes computed tomography scan of the chest and abdomen through adrenals, brain magnetic resonance imaging, and positron emission tomography scan. A plethora of new agents targeting angiogenesis, tumor invasiveness, the hypoxic environment of tumors, and the cell cycle are currently in development.
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PMID:Advanced non-small cell lung cancer. 1205 40

Cisplatin based chemotherapies have increased the survival in nonsmall cell lung cancer. A mechanism for identifying tumors resistant to cisplatin would be useful in avoiding unnecessary toxicity of platinum regimens. Mutation of p53 has been shown to induce chemotherapy resistance in vitro. We hypothesized that tumors staining for p53 would be resistant to cisplatin. In Cancer and Leukemia Group B protocol 8935, patients with stage IIIA (N2 node positive) nonsmall cell lung cancer received chemotherapy followed by surgery, then post-operative chemotherapy and/or radiation. All patients underwent pre-treatment staging mediastinoscopy. Twenty-five out of forty-nine pre-treatment mediastinal lymph node specimens stained positively for p53. Positive staining did not correlate with response to chemotherapy or survival. It did predict a slightly higher complete or partial resection rate compared to negative staining (76 vs. 45%) (p = 0.042). A trend toward longer median survivals was seen in patients with positive p53 staining. This study does not support the ability of p53 staining to predict chemotherapy resistance.
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PMID:Aberrant p53 staining does not predict cisplatin resistance in locally advanced non-small cell lung cancer. 1219 24

A new series of 5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones (3a-k) obtained by condensation of 5-nitro-1H-indole-2,3-dione (1) with N-substituted-thiosemicarbazides (2a-k) were treated with morpholine or piperidine and formaldehyde to yield 1-morpholino/piperidinomethyl-5-nitroindole-2,3-dione-3-thiosemicarbazones (4a-m). The structures of all the compounds were determined by analytical and spectral (IR, 1H-NMR, EIMS) methods. Compounds 3b, 3c, 3f, 3k, 4a, 4c, 4f and 4l chosen as prototypes were evaluated in the National Cancer Institute's 3-cell line, one dose in vitro primary cytotoxicity assay. All the compounds that passed the criteria for activity in this assay were scheduled automatically for evaluation against the full panel of 60 human tumour cell lines at a minimum of five concentrations at 10-fold dilutions. Sulphorhodamine B (SRB) protein assay was used to estimate cell stability or growth. The most active compound was found to be 1-morpholinomethyl-5-nitroindole-2,3-dione-3-N-(chlorophenyl)thiosemicarbazone (4l). This compound demonstrated the most marked effects in the National Cancer Institute's 60 human tumour cell line in vitro screen on a non-small cell lung cancer cell line (HOP-62, log(10)GI(50) value <-8.00) and on leukaemia cell lines (HL-60(TB), log(10)GI(50) value -6.30; MOLT-4, log(10)GI(50) value -6.18).
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PMID:Synthesis and primary cytotoxicity evaluation of new 5-nitroindole-2,3-dione derivatives. 1244 50

A nihilistic approach to the treatment of patients with medically inoperable, early stage non-small cell lung cancer (NSCLC) is not warranted. Despite the frequency of comorbid medical illness in patients with medically inoperable NSCLC, lung cancer progression is the major cause of morbidity and death. Although expectations for cure are reduced compared to good-risk patients (eg, adequate pulmonary reserve), modest long-term survival rates of patients have been reported, after definitive therapy. A comparison of radiotherapy and limited resection is difficult because of the lack of randomized data and the selection bias inherent in retrospective reports. For example, patients treated with surgery have peripheral lesions, undergoing rigorous staging compared to patients treated with radiotherapy. In a multidisciplinary thoracic program, patients are counseled on the options of sublobar resection and conformal radiotherapy. The efficacy of adjuvant radiotherapy, after limited resection, in reducing local recurrence in patients with medically inoperable NSCLC is unclear. However, adjuvant radiotherapy may be considered if a postoperative target volume can be defined, particularly if resection margins are narrow. Considering the benefit of chemoradiotherapy for patients with locally advanced disease, combination therapy is administered to patients with good performance status and large (eg, > 4 cm) primary lesions, although combined therapy may increase the potential for pulmonary toxicity in patients with baseline pulmonary dysfunction. Prospective data are becoming available to define the value of treatment alternatives for patients with medically inoperable NSCLC. The Cancer and Leukemia Group B completed a phase II study of thoracoscopic wedge resection and postoperative radiotherapy, whereas a phase I trial of dose-intensive accelerated conformal radiotherapy is ongoing. Trials involving systemic therapy for patients with medically inoperable NSCLC should be developed.
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PMID:Early stage medically inoperable non-small cell lung cancer. 1252 82


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