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)

Previous studies by our laboratory have reported that the T cell receptor (TCR) TCR/CD3 complex could mediate activation as well as apoptosis of T lymphocytes. Two tyrosine residues in the ITAM (immuno-receptor tyrosine-based activation motifs) of CD3 epsilon were required for apoptosis signalling of Jurkat T lymphocytes. Stable cell lines TJK and T3JK produced from CD8(-) Jurkat T lymphocytes by transfection with wild-type and mutant CD8 epsilon (fusion of the extracellular and transmembrane domains of human CD8 alpha to the intracellular domain of mouse CD3 epsilon), were used with CD8(-) Jurkat T lymphocytes for studying the role of single intact CD3 epsilon. 5-Fluorouracil (5-FU), a chemotherapeutic drug can induce cell death of many tumour cell lines. In the present experiments, we examined the expression of caspase-3, p53 and Bid in the three cell lines induced by 5-FU and/or anti-CD8 antibody. We found high expression of p53 during activation-induced cell death of TJK cells mediated by anti-CD8 antibody and apoptosis of TJK and T3JK induced by 5-FU, implicating p53 involvement in apoptosis of leukemia cells induced by anti-CD8 antibody and 5-FU. We also detected the active form of caspase-3 and Bid in apoptotic leukemia cells after treatment with 5-FU and/or anti-CD8 antibody, indicating that the drug and antibody induced cell death through caspase-3 and the signal pathway may involve the Bcl-2 protein family. Our results showed that combined treatment with 5-FU and anti-CD8 antibody could enhance the rate of apoptosis induced by 5-FU or anti-CD8 antibody through increased expression of p53 and by promoting activation of caspase-3 and Bid. This suggests that the combination of 5-FU and anti-CD8 antibody may play an important role in inducing apoptosis of leukemia cells.
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PMID:5-Fluorouracil enhances apoptosis sensitivity of T lymphocytes mediated by CD3 epsilon. 1512 84

The use of hepatic arterial infusion (HAI) chemotherapy in patients with liver-only colorectal metastases is based on the pharmacologic principle that the regional administration of some drugs can lead to higher drug concentrations at the site of the metastases and avoid systemic toxicity. Early randomized trials resulted in high response rates but did not lead to a survival advantage with HAI. More recent trials have utilized improved surgical techniques and strict guidelines regarding dose reduction or cessation of HAI chemotherapy, resulting in a significant reduction in toxicity. In patients with unresectable liver metastases, two recent European trials using HAI fluorouracil (5-FU) again failed to demonstrate an improvement in survival, but both were plagued by a high complication rate with an associated high proportion of patients failing to receive the assigned treatment. In contrast, the preliminary results of a recent Cancer and Leukemia Group B trial did demonstrate a survival advantage with HAI floxuridine when compared to systemically administered 5-FU. Trials investigating the use of HAI chemotherapy in the adjuvant setting have yielded mixed results. Moreover, in light of improved response rates and overall survival with newer more active chemotherapeutic and novel agents, the absolute role of HAI chemotherapy remains undefined.
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PMID:Defining the role of hepatic arterial infusion chemotherapy in metastatic colorectal cancer. 1521 95

Esophageal cancer is a rare but highly virulent malignancy in the United States, and adenocarcinoma of the esophagus has had the most rapid rate of increase of any solid tumor malignancy. Systemic metastatic disease is present in 50% of patients at diagnosis. In the remaining 50% presenting with local regional disease, systemic metastatic disease will develop in the vast majority of these patients. The limited efficacy and toxicity of conventional fluorouracil (5-FU)/cisplatin-based chemotherapy has prompted the evaluation of newer agents. Irinotecan (Camptosar) has shown promising single-agent activity in a number of gastrointestinal cancers, including colorectal, pancreatic, and esophagogastric cancer. The phase II evaluation of the combination of weekly irinotecan and cisplatin has shown encouraging response rates exceeding 30% to 50% in esophageal and gastric cancer. Hematologic toxicity using a schedule of 4 consecutive weeks of therapy followed by 2 weeks of rest prompted interest in a multicenter trial evaluation of a change in therapy delivery to 2 weeks on and 1 week off. Cisplatin at 30 mg/m2 was administered with irinotecan at 65 mg/m2, days 1 and 8, on an every-21-day schedule. Thirty-nine patients were entered on study, with 36 evaluable for toxicity and 31 evaluable for response. Grade 3/4 neutropenia was observed in only 22% of patients, reduced from 49% in a prior phase II trial employing 4 consecutive weeks of therapy. Confirmed major responses were observed in 36% of patients (10 of 28). A change to a day 1, day 8 schedule of weekly irinotecan and cisplatin appears to reduce hematologic toxicity but maintain antitumor activity in patients with esophageal and gastroesophageal junction cancer. A randomized phase II trial in gastric and esophageal cancer comparing weekly irinotecan and cisplatin to epirubicin, cisplatin, and 5-FU, and to infusional 5-FU in combination with irinotecan, will be conducted by the Cancer and Leukemia Group B (CALGB). A phase II trial combining this schedule of weekly cisplatin and irinotecan and concurrent radiotherapy given as preoperative therapy will also be conducted by the CALGB as a pilot trial.
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PMID:Phase II trial of weekly irinotecan/cisplatin in advanced esophageal cancer. 1568 30

Over the last 20 years, the increase in the cure rate of childhood cancer and leukemia of almost 80% has facilitated the observation of middle and long-term sequelae, particularly of cardiovascular origin; such after-effects are the consequence of cytotoxic damage to the cells of the cardiovascular system, in particular by anthracyclines and radiotherapy, and all the more so by their combined use. Such destructive lesions to myocytes greatly hinder the capacity of the cardiac muscle to hypertrophy to meet the needs of bodily growth, pregnancy and certain intense sports activities. Endothelial cells also accelerate an early arteriosclerotic process, a potential cause of sudden death in the case of ostial stenosis. All such phenomena build up over time, together with the usual adult cardio-vascular risk factors. Finally, no cardiac tissue, pericardial, valvular endocardium or autonomic nervous tissue escapes these cytotoxic effects, giving rise to pericarditis, calcification, valvular leaks and arrythmias and conduction abnormalities. The resulting excessive cardiac mortality is one of the major concerns of paediatric oncologists, along with secondary tumours and leukaemia. This article analyses physiopathological consequences that are often asymptomatic or clinical, together with diagnostic, screening and follow-up methods for these patients, encouraging lifestyle modifications where appropriate or, when possible, treatment before the appearance of cardiac failure, myocardial infarction or sudden death. Other cytotoxic drugs such as high-dose cyclophosphamide, amsacrin, 5-FU and tubulin acting agents are also mentioned as a result of their cardiac toxicity, but this is not usually dose-cumulative.
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PMID:[Cardiac toxicity of cancer treatment regimes in children and adolescents: physiopathology, clinical data and the paediatric oncologist's point of view]. 1589 26

Anti-proliferative activity of essential oil from 17 Thai medicinal plants on human mouth epidermal carcinoma (KB) and murine leukemia (P388) cell lines using MTT assay were investigated. An amount of 1 x 10(4)cells/well of KB cell line and 1 x 10(5) cells/well of P388 cell line were treated with the oil samples at different concentrations ranging from 0.019 to 4.962 mg/ml. In KB cell line, Guava (Psidium guajava L.) leaf oil showed the highest anti-proliferative activity with the IC(50) value of 0.0379 mg/ml (4.37 times more potent than vincristine) whereas Sweet Basil (Ocimum basilicum L.) oil gave the highest anti-proliferative activity with the IC(50) value of 0.0362 mg/ml (12.7 times less potent than 5-FU) in P388 cell line. The results demonstrated the potential of essential oil from Thai medicinal plants for cancer treatment.
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PMID:Anti-proliferative activity of essential oil extracted from Thai medicinal plants on KB and P388 cell lines. 1597 35

Survival for patients with pancreatic cancer remains abysmal. Standard treatment for resected and locally advanced disease usually consists of 5-fluorouracil (5-FU, either bolus or continuous infusion) and external beam radiation. However, recent studies have shown the role of gemcitabine either used alone or incorporated with 5-FU and external beam radiation in this setting. Gemcitabine and erlotinib (Tarceva) are currently the only standard chemotherapeutic agents approved by FDA for the treatment of advanced pancreatic cancer. Combination chemotherapy trials incorporating gemcitabine with other agents such as 5-FU, oxaliplatin, or capecitabine generally show improved outcomes in objective response rates but with little or no improvement in survival in phase III trials. In this article, the author summarizes the key studies in pancreatic cancer presented at the 2007 Gastrointestinal Cancers Symposium (Orlando, FL, USA; January, 2007). The studies discussed here include preliminary results of the Cancer and Leukemia Group B (CALGB) phase III trial of gemcitabine plus bevacizumab and activity of other targeted agents including sorafenib, cetuximab, retrospective and population-based studies evaluating the role of chemo-radiotherapy and radiotherapy, an analysis of 3,306 patients from the Surveillance, Epidemiology and End Results (SEER) database evaluating the predictive role of lymph nodes in survival following pancreatectomy and the assessment of novel agents, such as Genexol-PM and S-1.
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PMID:Pancreatic cancer: are we moving forward yet? Highlights from the Gastrointestinal Cancers Symposium. Orlando, FL, USA. January 20th, 2007. 1735 39

Stem bromelain (EC 3.4.22.32) is a major cysteine proteinase, isolated from pineapple ( Ananas comosus) stem. Its main medicinal use is recognized as digestive, in vaccine formulation, antitumoral and skin debrider for the treatment of burns. To verify the identity of the principle in stem fractions responsible for the antitumoral effect, we isolated bromelain to probe its pharmacological effects. The isolated bromelain was obtained from stems of adult pineapple plants by buffered aqueous extraction and cationic chromatography. The homogeneity of bromelain was confirmed by reverse phase HPLC, SDS-PAGE and N-terminal sequencing. The in vivo antitumoral/antileukemic activity was evaluated using the following panel of tumor lines: P-388 leukemia, sarcoma (S-37), Ehrlich ascitic tumor (EAT), Lewis lung carcinoma (LLC), MB-F10 melanoma and ADC-755 mammary adenocarcinoma. Intraperitoneal administration of bromelain (1, 12.5, 25 mg/kg), began 24 h after tumor cell inoculation in experiments in which 5-fluorouracil (5-FU, 20 mg/kg) was used as positive control. The antitumoral activity was assessed by the survival increase (% survival index) following various treatments. With the exception of MB-F10 melanoma, all other tumor-bearing animals had a significantly increased survival index after bromelain treatment. The largest increase ( approximately 318 %) was attained in mice bearing EAT ascites and receiving 12.5 mg/kg of bromelain. This antitumoral effect was superior to that of 5-FU, whose survival index was approximately 263 %, relative to the untreated control. Bromelain significantly reduced the number of lung metastasis induced by LLC transplantation, as observed with 5-FU. The antitumoral activity of bromelain against S-37 and EAT, which are tumor models sensitive to immune system mediators, and the unchanged tumor progression in the metastatic model suggests that the antimetastatic action results from a mechanism independent of the primary antitumoral effect.
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PMID:In vivo antitumoral activity of stem pineapple (Ananas comosus) bromelain. 1789 36

In patients with colon cancer who undergo resection for potential cure, 40% to 60% have advanced locoregional disease and are classified as either stage II or stage III. The role of adjuvant therapy in stage III colon cancer is well defined. The results from the MOSAIC trial (Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer) and the National Surgical Adjuvant Breast and Bowel Project C-07 trial confirm a definite disease-free survival (DFS) benefit with the addition of oxaliplatin to either infusional or bolus 5-fluorouracil/leucovorin (5-FU/LV). The Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) trial showed capecitabine to be of equivalent clinical benefit to bolus 5-FU/LV. However, adjuvant trials with irinotecan, including Cancer and Leukemia Group B (CALGB 89803), the Pan-European Trial in Adjuvant Colorectal Cancer 3 (PETACC-3), and the French ACCORD trial, have not shown a significant DFS advantage. In contrast, in patients with stage II disease, a small survival benefit of 1% to 5% exists with chemotherapy. Perhaps the analysis of molecular markers in combination with high-risk histopathologic features will help increase patient specificity and identify subsets of patients with stage II colon cancer who will derive a survival benefit with adjuvant therapy. The current Intergroup study stratifying stage II patients based on presence of microsatellite instability and loss of heterozygosity 18q allele will help us better understand the risk versus benefit observed.
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PMID:Adjuvant therapy for colon cancer. 1799 44

5-Fluorouracil (5-FU) is an important chemotherapeutic agent for nasopharyngeal carcinoma (NPC). However, drug resistance may occur after several cycles of 5-FU-based chemotherapy. The oncogene B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI-1) has been shown to be involved in the protection of cancer cells from apoptosis. In this study, 5-FU treatment could increase the percentage of apoptotic NPC cells among BMI-1/RNAi-transfected cells than that among cells transfected with the empty vector. The 50% inhibitory concentration (IC(50)) values of 5-FU were significantly decreased to a greater extent in the cells transfected with BMI-1/RNAi. Most importantly, the expression of phospho-AKT and the anti-apoptotic protein BCL-2 were downregulated in the cells in which BMI-1 expression was inhibited, whereas the apoptosis-inducer BAX was observed to be upregulated. Abrogation of AKT pathway by a PI3K inhibitor could not further increase the sensitivity to 5-FU in the cells with reduced BMI-1 expression. Taken together, BMI-1 depletion enhanced the chemosensitivity of NPC cells by inducing apoptosis; which is associated with inhibition of the PI3K/AKT pathway.
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PMID:Downregulation of BMI-1 enhances 5-fluorouracil-induced apoptosis in nasopharyngeal carcinoma cells. 1845 7

Triphenyltin coumarin-3-carboxylate and its coordination complexes with ethanol, triphenylphosphine oxide, triphenylarsine oxide, diphenylcyclopropenone and quinoline N-oxide exhibited high in vitro cytotoxicity (LC(50) values in the range 0.25-3.4 mug/mL) when tested against EBV-DNA positive Raji cells and P-388 leukaemia cells, compared to the standard drug 5-Fluorouracil, which showed LC(50) values of 11 and >50 mug/mL, respectively, against these cells. Additional tests performed on the Raji cells incubated with the quinoline N-oxide complex in the presence of the tumour promoters, TPA and sodium butyrate, revealed that the diffused and restricted protein components of the early antigen complex were suppressed relative to the control containing only the promoters, indicating impaired function of the genes involved as transactivators in the early lytic cycle of the EBV. The failure of the restriction enzymes Eco R1 and Hind III to cleave the extracted DNA from such treated cells in contrast to the control, coupled with the amplification of the BMLF-1 gene by the PCR technique which was realised only with the DNA of the control and not of the treated sample, point to a punitive interaction of the organotin with the nuclear DNA of the Raji cells.
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PMID:High In-Vitro Antitumour Activity of Triphenyltin Coumarin 3-Carboxylate and its Coordination Complexes With Monodentate Oxygen Donor Ligands Against the Epstein Barr Virus (EBV)-DNA Positive Raji and the P-388 Murine Leukaemia Cell Lines, and Evidence for the Suppression by Organotin of the Early Antigen Complex in the EBV Lytic Cycle. 1847 52


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