allopurinol and Lung-Neoplasms

No systematic synthesis of all cases of spontaneous tumor lysis syndrome (STLS) in adult patients with solid tumors is available to date. Herein, we aim to recognize specific STLS characteristics and parameters related to a worse prognosis. We conducted a systematic search for randomized controlled trials, cohorts, case-control studies, and case reports. The primary endpoints were death and the need for renal replacement therapy (RRT) due to STLS. We estimated crude odds ratios (ORs) with 95% confidence intervals (95%CI) via univariate binary logistic regression. We included one cohort of 9 patients and 66 case reports of 71 patients [lung cancer 15(21.1%)]. Regarding the case reports, most patients [61(87.1%)] had metastatic disease [liver 46(75.4%)], developed acute kidney injury [59(83.1%)], needed RRT [25(37.3%)], and died due to STLS [36(55.4%)]. Metastatic disease, especially in the liver [p = 0.035; OR (95%CI): 9.88 (1.09, 89.29)] or lungs [p = 0.024; 14.00 (1.37, 142.89)], was significantly associated with STLS-related death compared to no metastasis. Cases resulting in death had a significantly higher probability of receiving rasburicase monotherapy than receiving no urate-lowering agents [p = 0.034; 5.33 (1.09, 26.61)], or the allopurinol-rasburicase combination [p = 0.023; 7.47 (1.40, 39.84)]. Patients receiving allopurinol were less likely to need RRT compared to those not receiving it or those receiving rasburicase. In conclusion, current anecdotal evidence demonstrated that metastatic disease, especially in the liver and lungs, may be associated with STLS-related death compared to no metastatic status. Careful surveillance of high-risk cases within larger studies is essential to identify markers predicting morbidity or mortality.

Topics: Acute Kidney Injury; Adult; Allopurinol; Humans; Liver; Lung Neoplasms; Tumor Lysis Syndrome

To study the protective effect of dexmedetomidine against perioperative inflammation and on pulmonary function in patients undergoing radical resection of lung cancer.. From May, 2014 to May, 2016, 124 patients with lung cancer receiving radical surgeries were randomized into experimental group (n=62) and control group (n=62). The patients in the control group received a single anesthetic agent for anesthesia, and additional dexmedetomidine was given in the experimental group. The levels of serum interleukin-1β (IL-1β), IL-10, and tumor necrosis factor-alpha (TNF-α) were measured before the operation (T. At the time points of T. Anesthesia with dexmedetomidine in lung cancer patients undergoing radical surgery can effectively reduce the inflammatory response of the lungs and protect the lung function of the patients.

Topics: Anesthesia; Dexmedetomidine; Enzyme-Linked Immunosorbent Assay; Humans; Inflammation; Interleukin-10; Interleukin-1beta; Lung; Lung Neoplasms; Malondialdehyde; Partial Pressure; Peroxidase; Tumor Necrosis Factor-alpha; Xanthine Oxidase

Thirty patients with a diagnosis of metastatic adenocarcinoma of the lung were entered on a trial to evaluate the antitumor efficacy of 5-fluorouracil 370 mg/m2 daily for 5 days every four weeks in combination with folinic acid 200 mg/m2, 60 min prior to 5FU. All patients had a good performance status, bidimensionally measurable disease, and weight loss less than or equal to 5% of preillness weight. Of the 29 evaluable patients, only two (7%) had partial responses (95% confidence limits 1-24%). Eleven (38%) had stable disease and 16 (55%) progressed. The two responding patients survived 12 and 60+ weeks. The median survival of all evaluable patients was 25 weeks (range 7-60+) and that of the stable patients was 26 weeks. The principal toxicities observed were diarrhea and stomatitis. Myelosuppression was rarely dose limiting. In contrast to the results of treatment with 5FU and folinic acid in metastatic colorectal cancer and breast cancer, the results of treatment with this combination of agents have been much less encouraging in adenocarcinoma of the lung.

Topics: Adenocarcinoma; Adult; Aged; Allopurinol; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Fatigue; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Nausea; Nervous System; Stomatitis

Objective To investigate the effects of Astragalus polysaccharide (APS) on autophagy and expression of microtubule-associated protein 1 light chain 3B (LC3B), mammalian target of rapamycin (mTOR) and beclin1 in xanthine oxidase (XOD)-induced autophagic model of non-small cell lung cancer A549 cells. Methods A549 cells were divided into five groups: control group, model group, 100, 200 and 400 μg/mL APS-treated group. Except for control group, all groups were administered XOD for 24 hours to establish autophagic models. Morphology of autophagosome was detected by transmission electron microscopy (TEM) and the number was counted by monodansylcadaverine (MDC) staining. The expression levels of LC3B, beclin1 and mTOR were detected by Western blot analysis. Results Compared with the control group, the number of autophagosome in the model group increased; the expression of LC3B and beclin1 significantly increased; while the expression of mTOR significantly decreased. Compared with the model group, the number of autophagosome decreased remarkably; the expression of LC3B and beclin1 severely decreased, and the expression of mTOR obviously increased in 200 or 400 μg/mL APS-treated group. Conclusion APS reduces the level of autophagy, down-regulates the expression of LC3B and beclin1, and increases mTOR expression in the autophagic model of A549 cells induced by XOD.

Topics: A549 Cells; Astragalus Plant; Autophagy; Autophagy-Related Proteins; Beclin-1; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Microtubule-Associated Proteins; Polysaccharides; TOR Serine-Threonine Kinases; Xanthine Oxidase

The ability to predict responsiveness to drugs in individual patients is limited. We hypothesized that integrating molecular information from databases would yield predictions that could be experimentally tested to develop transcriptomic signatures for specific drugs. We analyzed lung adenocarcinoma patient data from The Cancer Genome Atlas and identified a subset of patients in which xanthine dehydrogenase (XDH) expression correlated with decreased survival. We tested allopurinol, an FDA-approved drug that inhibits XDH, on human non-small-cell lung cancer (NSCLC) cell lines obtained from the Broad Institute Cancer Cell Line Encyclopedia and identified sensitive and resistant cell lines. We utilized the transcriptomic profiles of these cell lines to identify six-gene signatures for allopurinol-sensitive and allopurinol-resistant cell lines. Transcriptomic networks identified JAK2 as an additional target in allopurinol-resistant lines. Treatment of resistant cell lines with allopurinol and CEP-33779 (a JAK2 inhibitor) resulted in cell death. The effectiveness of allopurinol alone or allopurinol and CEP-33779 was verified in vivo using tumor formation in NCR-nude mice. We utilized the six-gene signatures to predict five additional allopurinol-sensitive NSCLC cell lines and four allopurinol-resistant cell lines susceptible to combination therapy. We searched the transcriptomic data from a library of patient-derived NSCLC tumors from the Jackson Laboratory to identify tumors that would be predicted to be sensitive to allopurinol or allopurinol + CEP-33779 treatment. Patient-derived tumors showed the predicted drug sensitivity in vivo. These data indicate that we can use integrated molecular information from cancer databases to predict drug responsiveness in individual patients and thus enable precision medicine.

Topics: Allopurinol; Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Survival; Drug Resistance, Neoplasm; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genomics; Humans; Janus Kinase 2; Lung Neoplasms; Mice, Nude; Phenotype; Protein Kinase Inhibitors; Pyridines; Systems Analysis; Triazoles; Xenograft Model Antitumor Assays

Acquired ichthyosis is a rare condition that can reveal an unsuspected haematological malignancy, thus allowing early diagnosis and management. If ichthyosis regresses under treatment for the haematological disorder, its recurrence reflects a turning point in the course of the disease and implies worsening of the prognosis.. The patients were examined at a joint dermatology/haematology consultation. The diagnosis of ichthyosis was based on clinical examination alone with no patients undergoing skin biopsy.. Our series included three men and two women aged 38 to 65 years consulting for a variety of reasons including asthenia, anaemia and adenopathy. Ichthyosis occurred 2 to 9 months after the initial symptoms of the blood disease. Lesions consisted of diffuse brown scales. The disease was associated with lymphadenopathy and biological inflammatory syndrome. Two patients were presenting non-Hodgkin lymphoma, one had Hodgkin's disease, one had chronic myeloid leukaemia in progression and one had an undifferentiated lymphomatous process. Treatment was based on chemotherapy and emollients. The ichthyosis progressed in step with the underlying malignancy in all cases, with regression being complete in three cases, partial in one case and absent in one case.. In rare cases, acquired ichthyosis reveals systemic disease, and may be of infectious, endocrine or drug origin; it may also be idiopathic. However, it is most often a paraneoplastic syndrome with cutaneous expression encountered during haematological malignancies. Because of the variety of causative blood dyscrasias, ichthyosis cannot be used to guide their diagnosis, although it remains a reliable monitoring tool.. Acquired ichthyosis should prompt the clinician to search for a neoplastic condition, primarily a haematological disorder, guided by other associated signs, given that in our study, skin lesions generally appear to precede signs of the blood disease.

Topics: Adult; Aged; Allopurinol; Anemia; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Bleomycin; Cyclophosphamide; Doxorubicin; Etoposide; Female; Hematologic Neoplasms; Hodgkin Disease; Humans; Ichthyosis; Imatinib Mesylate; Leukemia, Myeloid, Accelerated Phase; Lung Neoplasms; Lymphoma, B-Cell; Male; Middle Aged; Paraneoplastic Syndromes; Parotid Neoplasms; Piperazines; Platelet Aggregation Inhibitors; Prednisone; Procarbazine; Pyrimidines; Retrospective Studies; Rituximab; Schizophrenia; Stomach Neoplasms; Vincristine

In this study, we examined oxidative stress and B vitamins status in non-small cell lung cancer (NSCLC) patients at different stages. NSCLC patients were divided into 2 groups, stage III (IIIA + IIIB, n = 27) and stage IV (n = 23). A total of 16 healthy control subjects were included for comparison. Plasma levels of alpha-tocopherol, beta-carotene, vitamin C, Se, Cu, Zn, reduced glutathione (GSH), oxidized glutathione (GSSG), lipid oxidation and the activities of glutathione peroxidase (GPX), superoxide dismutase (SOD), catalase, and xanthine oxidase (XO) were determined for evaluating oxidative status in these subjects. B vitamins (B(1), B(2), B(6), B(12), folate) in blood and plasma ghrelin level in these subjects were analyzed. Results showed that plasma level of ghrelin and lipid oxidation in NSCLC patients were significantly greater than control groups (P < 0.05). The activity of GPX, SOD, or catalase was significantly reduced, but XO activity was significantly elevated in NSCLC patients (P < 0.05). Plasma level of GSH was significantly lower, but GSSG level was significantly increased in NSCLC patients (P < 0.05). Vitamins B(2) and B(6) levels in red blood cells (RBC) from NSCLC patients were significantly lower (P < 0.05), and both were negatively correlated with plasma ghrelin. The correlation coefficients were -0.788 and -0.752, respectively. These data suggest that plasma GSH level may be a proper biomarker for evaluating oxidation status for NSCLC patients. RBC levels of vitamins B2 and B6 were reduced in NSCLC patients; thus, the importance of vitamins B(2) and B(6) for NSCLC patients could not be ignored.

Topics: Adult; Aged; Aged, 80 and over; alpha-Tocopherol; Ascorbic Acid; beta Carotene; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Case-Control Studies; Catalase; Erythrocytes; Female; Ghrelin; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Health Status; Humans; Lipid Peroxidation; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Nutritional Status; Oxidation-Reduction; Oxidative Stress; Superoxide Dismutase; Vitamin B Complex; Xanthine Oxidase

Lung cancer is a common pathology with high mortality due to late diagnosis. Glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), catalase (CAT), xanthine oxidase (XO), Cu-Zn superoxide dismutase (Cu-Zn SOD) activities, total glutathione (TGSH), nitric oxide (NO*), and malondialdehyde (MDA) levels were investigated in erythrocytes of patients with non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), and healthy control group. We aimed to investigate serum GSH, GSH-dependent enzymes activities (GSH-Px and GST), XO, CAT, Cu-Zn SOD activity, and NO*, and MDA levels in patients with NSCLC and with SCLC and correlate with the cancer stage. Erythrocyte MDA, NO*, TGSH levels and erythrocyte SOD, CAT and XO activities were significantly higher in patients with NSCLC and SCLC than in controls. Slightly increased erythrocyte GSH-Px and GST activities were not significantly different from the controls. Erythrocyte MDA level positively correlated with erythrocyte NO* levels in patients with early stage (I+II) in NSCLC groups. Erythrocyte MDA level positively correlated with erythrocyte XO activity in patients with advanced stage (III+IV) in NSCLC groups. However, no other correlation could be found among the parameters in healthy controls and patients with NSCLC and with SCLC. Results obtained in this study indicate significant changes in antioxidant defence system in NSCLC and SCLC patients, which may lead to enhanced action of oxygen radical, resulting in lipid peroxidation.

Topics: Adult; Aged; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Case-Control Studies; Catalase; Erythrocytes; Female; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Humans; Lipid Peroxidation; Lung Neoplasms; Male; Malondialdehyde; Middle Aged; Nitric Oxide; Oxidative Stress; Oxidoreductases; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Xanthine Oxidase

Accumulating evidence has suggested that cellular production of superoxide acts as an intracellular messenger to regulate gene expression and modulate cellular activities. In this report, we set out to investigate the role of active H-ras-mediated superoxide production on tumor cell malignancy in a SV-40 transformed human lung WI-38 VA-13 cell line. Stable transfection and expression of constitutively active mutant V12-H-ras (V12-H-ras) dramatically increased intracellular production of superoxide. The expression of V12-H-ras significantly enhanced cell proliferation, migration and resistance to TNF-alpha treatment compared to that of parental and vector control cells, while expression of wild type H-ras (WT-H-ras) only had modest effects. Upon scavenging by superoxide dismutase and other molecules that decrease the intracellular level of active H-ras mediated superoxide production, cell proliferation, migration and resistance to TNF-alpha were significantly reduced. Furthermore, we demonstrated that the activation of membrane NADPH oxidase activity by expression of active H-ras contributed to the intracellular superoxide production. The causal relationship between membrane superoxide production and increased cell proliferation, migration, and resistance to TNF-alpha by the expression of active H-ras, has provided direct evidence to demonstrate that superoxide acts as an intracellular messenger to cascade ras oncogenic signal relay and to modulate tumor malignant activity.

Topics: Acetophenones; Allopurinol; Cell Division; Cell Line, Transformed; Cell Movement; Drug Resistance; Enzyme Activation; Genes, ras; Genistein; Humans; Lung Neoplasms; Membrane Proteins; Models, Biological; NADPH Oxidases; Onium Compounds; Oxypurinol; Protein Kinase Inhibitors; Rotenone; Superoxides; Tumor Necrosis Factor-alpha

Topics: Adenosine Deaminase; Adult; Aged; Aged, 80 and over; Bronchoalveolar Lavage Fluid; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pneumonia; Prospective Studies; Purines; Xanthine Oxidase

The enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) expressed by the parasite Trypanosoma brucei (Tb) can convert allopurinol, a purine analogue, to corresponding nucleotides with greater efficiency than its human homologue. We have developed a retroviral system that expresses the parasitic enzyme and tested its capacity to activate the prodrug allopurinol to a cytotoxic metabolite. Cytotoxicity assays demonstrated that five non-small cell lung carcinoma cell lines transduced with the construct were sensitized to the prodrug by 2.1- to 7.6-fold compared with control values. This selectivity was not observed in seven other cell lines also expressing the construct, such as breast carcinoma. Assays indicated that enhanced cytotoxicity to allopurinol correlated with induction of apoptosis in lung cancer cells. The selectivity of this suicide gene was not explained either by the TbHGPRT expression or by the allopurinol accumulation. Our study shows that this novel system may represent a therapeutic tool for gene prodrug targeting of lung cancer, considering the fact that allopurinol is well tolerated in humans.

Topics: Allopurinol; Animals; Apoptosis; Blotting, Western; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Genes, Lethal; Genes, Protozoan; Genetic Therapy; Humans; Hypoxanthine Phosphoribosyltransferase; Lung Neoplasms; Microscopy, Fluorescence; Organ Specificity; Prodrugs; Time Factors; Transduction, Genetic; Trypanosoma brucei brucei; Tumor Cells, Cultured; Vesicular stomatitis Indiana virus

To examine the effect of 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid (TEI-6720), an inhibitor of xanthine oxidase, on purine metabolism in the lung cancer cell line A549, the activities of adenosine deaminase, purine nucleoside phosphorylase, adenine phosphoribosyltransferase, hypoxanthine guanine phosphoribosyltransferase, xanthine oxidase, and guanase together with pyrimidine nucleoside phosphorylase were measured with or without the addition of TEI-6720, and the extracellular concentrations of hypoxanthine, xanthine, inosine, uracil, and uridine were measured after the addition of inosine or uridine to the incubation medium with or without TEI-6720. Moreover, the Na-independent nucleoside transport was determined in A549 cells with or without TEI-6720. TEI-6720 inhibited the activity of xanthine oxidase in A549 cells, but did not affect other enzymes. During incubation, TEI-6720 not only prevented a decrease in the inosine concentration in inosine-containing medium, but also a decrease in the uridine concentration in uridine-containing medium. Furthermore, the Na-independent transport of uridine was inhibited by TEI-6720 with a K(i) value of 4.1 micromol/l. These results indicate that TEI-6720 is an inhibitor of the Na-independent nucleoside transport of uridine and inosine, as well as xanthine oxidase.

Topics: Allopurinol; Biological Transport; Carrier Proteins; Drug Interactions; Enzyme Inhibitors; Febuxostat; Humans; Hypoxanthine; Inosine; Lung Neoplasms; Membrane Proteins; Nucleoside Transport Proteins; Nucleosides; Pentosyltransferases; Purines; Pyrimidine Phosphorylases; Thiazoles; Tumor Cells, Cultured; Uracil; Uridine; Xanthine; Xanthine Oxidase

Topics: Adenosine; Allopurinol; Cell Membrane; Cell Membrane Permeability; Cells, Cultured; Digitonin; Glucose; Glutathione; Humans; Insulin; Lung Neoplasms; Mannitol; Mitochondria; Organ Preservation Solutions; Oxygen Consumption; Potassium Chloride; Procaine; Raffinose; Reperfusion Injury; Rotenone; Tumor Cells, Cultured; Umbilical Veins

Nitric oxide release is induced in many cells, including vascular endothelium, as part of the host response to inflammation. Nitric oxide synthase activity is increased in patients with sepsis, associated with increased oxidant demands and decreased antioxidant protection. We used a human vascular endothelial cell line to investigate the influence of antioxidants on nitric oxide synthase activity. Cells were cultured to confluence and incubated with interferon gamma, tumor necrosis factor, and lipopolysaccharide in the combined presence of the antioxidants ascorbic acid, Trolox, catalase, or superoxide dismutase, singly and in combination, for 48 h. Additionally, some cells were incubated with hypoxanthine-xanthine oxidase or a nitric oxide donor. Nitric oxide synthase activity was upregulated by cytokine exposure (p < .0005). Ascorbic acid and superoxide dismutase/ catalase resulted in decreased enzyme activity (p < .05). Superoxide anion release from xanthine oxidase caused increased activity (p < .05) and exogenous nitric oxide tended to suppress synthase activity. We suggest that antioxidants scavenge superoxide anion, enabling feedback inhibition of nitric oxide synthase activity by nitric oxide, and thus reducing enzyme activity. Exogenous nitric oxide also has a similar effect. Superoxide generation suppresses this feedback inhibition. This study has important implications in patients with sepsis in whom nitric oxide synthase inhibitor therapy is currently under investigation.

Topics: Animals; Antioxidants; Cattle; Cells, Cultured; Chromans; Endothelium, Vascular; Humans; Hybrid Cells; Interferon-gamma; Kinetics; Lipopolysaccharides; Lung Neoplasms; Nitric Oxide Synthase; Recombinant Proteins; Superoxide Dismutase; Tumor Necrosis Factor-alpha; Umbilical Veins; Xanthine Oxidase

Solid tumors induce an angiogenic response by the host blood vessels to form a new vascular network for the supply of fresh nutrients and oxygen responsible for tumor growth. Furthermore, tumor growth and metastatic spread is abrogated or markedly reduced in the absence of neovascularization. Spleen T lymphocytes from tumor-bearing mice elicit a strong neovascular response. It is well known that certain T cell responses require the presence of active oxygen radicals. Because these metabolites are produced during tumor growth, we studied whether oxygen free radicals play a role in the angiogenesis induction by lymphocytes. In this study, we demonstrated that the administration of a free radical scavenger (EGb-761) to tumor-bearing mice, blocked the angiogenic response and decreased the lung metastatic incidence. On the other hand, when normal lymphocytes were incubated with the xanthine-xanthine oxidase system (X-XO), a known superoxide anion generator, this elicited a dose-response positive angiogenic reaction in normal recipient mice. No angiogenic response was observed in the absence of X-XO, or when EGb-761 or superoxide dismutase (SOD) plus catalase (CAT) were added to the incubation medium. These results suggest that free radicals are involved in some step of the angiogenic process, and that the EGb-761 treatments block this response due to the free radical scavenging activity of this compound.

Topics: Adenocarcinoma; Animals; Catalase; Free Radical Scavengers; Ginkgo biloba; Lung Neoplasms; Male; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Neovascularization, Pathologic; Plant Extracts; Spleen; Superoxide Dismutase; T-Lymphocytes; Xanthine; Xanthine Oxidase; Xanthines

Selected immunotherapies (tumor necrosis factor, interleukin-1, interleukin-2, and gamma interferon), chemotherapeutic agents (mitomycin, platinum, doxorubicin [Adriamycin], and bleomycin), and radiation therapy have been described to exert cytotoxicity through the generation of reactive oxygen species, including superoxide and hydrogen peroxide. Tumor necrosis factor, however, has been shown to impart increased resistance in vitro and in vivo against reactive oxygen species stress, including radiation therapy and oxygen toxicity, possibly because of the induction of increased cellular buffering capacities. It is unknown whether the sensitivity of a lung cancer cell to reactive oxygen species therapy is altered by tumor necrosis factor through the induction of free radical scavenging enzymes such as manganese superoxide dismutase. This question was investigated as follows: A549 lung adenocarcinoma cells, exposed for 24 hours to 0, 0.1, 1.0, or 10 micrograms/ml concentrations of tumor necrosis factor, were exposed to hypoxanthine plus xanthine oxidase, a superoxide generating system, for varying intervals. The number of cells surviving 5 days after the stress was determined, and cells exposed to tumor necrosis factor were examined by Northern Blot analysis for induction of the manganese superoxide dismutase gene. The hypoxanthine-xanthine oxidase stress alone caused a time-dependent decrease in survival; however, pretreatment with tumor necrosis factor increased cell survival significantly. Moreover, the cells exposed to tumor necrosis factor had a fivefold increase in the number of manganese superoxide dismutase transcripts. These findings suggest that tumor necrosis factor may confer resistance of lung cancer cells to subsequent reactive oxygen species-based therapies, and the resistance of these cells may be due to increased expression of manganese superoxide dismutase. Clinical treatment failures may result, especially if tumor necrosis factor is given concurrently with other therapies.

Topics: Adenocarcinoma; Cell Division; Enzyme Induction; Humans; Lung Neoplasms; Superoxide Dismutase; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha; Xanthine Oxidase

Topics: Adenocarcinoma; Aged; Allopurinol; Arteritis; Coformycin; Drug Hypersensitivity; Humans; Lung Neoplasms; Male; Necrosis; Pentostatin; Ribonucleosides

Allopurinol has been shown to ameliorate the myelotoxicity of 5-fluorouracil (5-FU) given as an infusion. To study the potential effectiveness of allopurinol in modifying the toxicity of 5-FU given as a bolus, 8 adult patients with metastatic malignancies were given 11 courses of bolus 5-FU with allopurinol. Allopurinol was administered at a dose of 900 mg/day orally beginning a week prior to the 5-FU therapy and continued a week after the last dose of 5-FU was administered. Three patients received a total of 5 courses of 600 mg/m2 of 5-FU via bolus injection for 4 consecutive days every 28 days. Six patients were given 6 courses of 800 mg/m2 of 5-FU via bolus injection in the same schedule. Gastrointestinal toxicity was mild and no significant neurotoxicity was documented. However, severe myelosuppression occurred at the 800 mg/m2 dosage which led to marked leukopenia in 5 of the 6 patient courses and thrombocytopenia in 1. Gram-negative sepsis developed in 3 of the leukopenic patients with 2 resultant deaths. Allopurinol does not appear to allow clinically significant dose escalation of bolus 5-FU given on this schedule.

Topics: Adenocarcinoma; Adult; Allopurinol; Carcinoma, Squamous Cell; Colonic Neoplasms; Drug Administration Schedule; Fluorouracil; Gallbladder Neoplasms; Gastrointestinal Diseases; Hematologic Diseases; Humans; Lung Neoplasms; Neoplasm Metastasis; Rectal Neoplasms

Topics: Aged; Allopurinol; Antineoplastic Agents; Carcinoma, Small Cell; Humans; Lung Neoplasms; Male; Syndrome

Using two case-histories it is shown that atypical radiological findings caused the delay in diagnosis of pulmonary embolism depsite clinical signs (such as fever and intermittent dyspnoea; cyanosis, haemoptoe and cough reflex were absent). The exact diagnosis was finally established after having excluded all diseases, which were of greater probability on the grounds of the x-ray findings.

Topics: Adult; Allopurinol; Diagnosis, Differential; Digitalis Glycosides; Female; Heparin; Humans; Lung; Lung Neoplasms; Male; Middle Aged; Pulmonary Embolism; Radiography; Radionuclide Imaging; Spironolactone

Topics: Adenocarcinoma; Adult; Aged; Fanconi Syndrome; Fasting; Female; Humans; Hypoparathyroidism; Kidney; Lung Neoplasms; Male; Middle Aged; Multiple Myeloma; Obesity; Osteomalacia; Uric Acid; Xanthine Oxidase; Xanthines

Topics: Adenocarcinoma; Adult; Allopurinol; Antineoplastic Agents; Calcium; Cyclophosphamide; Fluorouracil; Humans; Hypercalcemia; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Lymphoma; Male; Middle Aged; Neoplasms; Plicamycin; Vincristine

Topics: Allopurinol; Child; Child, Preschool; Dactinomycin; Female; Humans; Lung Neoplasms; Male; Neoplasm Metastasis; Nephrectomy; Preoperative Care; Sulfates; Vincristine; Wilms Tumor