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)

Antibodies directed against the central nervous system were looked for by indirect immunohistochemistry in the sera of 8 patients with paraneoplastic neurological syndrome (group 1), 21 cancer patients without neurological signs, 23 patients with miscellaneous neurological diseases and 63 normal subjects (groups 2 to 4). Four patients in group 1 had very high titres of antibodies. In 2 patients with small-cell lung carcinoma associated with sensory neuropathy the antibody recognized the cytoplasm and nucleus of all neurons. A 37 Kd protein was recognized by Western blot. A woman with cancer of the ovary and cerebellar syndrome exhibited an antibody against Purkinje's cell cytoplasm with a band of about 50-55 Kd at Western blot. In a woman with chronic uveitis and cerebellar atrophy with disappearance of Purkinje's cells the antibody (in blood and CSF) recognized certain layers of the retina as well as glial cells and cells present in the subependymal areas of the brain. Two bands of 46 and 59 Kd were revealed by Western blot. Immunoglobulins were detected in the cytoplasm of white matter cells in the cerebellum and brain stem. Among the other groups, one patient with lung cancer had a moderate titre of neuronal antinuclear antibody. The Western blot test was negative. The relevance of these antibodies for the diagnosis and treatment is discussed.
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PMID:[Autoantibodies in paraneoplastic polioencephalomyelitis: 8 cases]. 129 56

The clonal growth of cell lines from some human solid tumours can be stimulated by haematopoietic growth factors such as recombinant human (rh) interleukin-3 (IL-3) and rh granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. Among these cell lines are the human colorectal adenocarcinoma cell line HTB 38 and the human small-cell lung cancer cell line HTB 119. Here we report on a series of experiments studying the influence of subcutaneously administered rhIL-3 and rhGM-CSF on the in vivo growth of HTB 38 and HTB 119 cell lines as xenografts in athymic nu/nu BALB/c mice. Beginning 1 day after transplantation of the tumour the cytokines were administered daily for 20 days as a subcutaneous bolus distant from the tumour lesion at dose levels up to 1 mg/m2/day. The cytokines caused no significant and reproducible growth modulation of the tumours in vivo.
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PMID:Effect of interleukin-3 and granulocyte-macrophage colony-stimulating factor on growth of xenotransplanted human tumour cell lines in nude mice. 131 97

We have investigated the kinetics of myeloid cell proliferation in the marrow of patients with small-cell lung cancer and treated with 10 daily subcutaneous injections of granulocyte/macrophage colony-stimulating factor (GM-CSF). Bone marrow, obtained before and during treatment with the growth factor, was labelled in vitro with tritiated thymidine (3H-TdR). A 3rd bone-marrow sample was obtained 1 hr following an intravenous injection of 3H-TdR. Subsequent daily blood samples were also collected, and 3H-TdR labelling was assessed on these and the marrow preparations by autoradiography. GM-CSF treatment increased the peripheral granulocytic cells nearly 5-fold, but this included significant eosinophilia, so that the neutrophilic granulocytes increased only 3.3-fold. These cells were released from the marrow over a normal time scale, but their peripheral half-life was about 6 times longer than normal and they were probably functionally defective. Furthermore, significant numbers of immature cells were released from the marrow. Neutrophil production stimulated by GM-CSF was thus overestimated by measurement of the apparent peripheral granulocytosis. Increased labelling indices and grain counts in the proliferating granulocytic cells of the marrow indicate shortened cell-cycle times, and the excess granulocyte production appears to be the result of extra amplification divisions in the proliferative compartments.
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PMID:Haemopoietic cell kinetics in humans treated with rGM-CSF. 137 Feb 26

The study was aimed to evaluate the feasibility of dose-intensive chemotherapy given on a weekly basis for 12 weeks. Seventeen [7 with limited disease (LD) and 10 with extensive disease (ED)] previously untreated patients with small-cell lung cancer (SCLC) were treated with the cisplatin, vincristine, doxorubicin, and etoposide (CODE) regimen. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was given to eight patients for the purpose of increasing the dose intensity. Overall response rate was 88%, with a 29% complete response. The median survival times were greater than 20.5 months for LD patients and 8.1 months for ED patients. Overall actual dose intensity was 88% of planned protocol. The major toxicity was myelosuppression. Fifteen patients (88%) had grade 3 or 4 leukopenia. Other problems were weight loss and worsening of performance status during the treatment. RhG-CSF significantly reduced leukopenic nadirs and shortened the neutropenic period. Our preliminary results indicate that 12 cycles of the CODE regimen on a weekly schedule is effective for SCLC, but is also associated with significant toxicity.
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PMID:Weekly dose-intensive chemotherapy in patients with small-cell lung cancer: a pilot study. 137 63

A phase II study examining the effects of human recombinant granulocyte-colony-stimulating factor (G-CSF) on the growth of colony-forming unit-granulocyte macrophage (CFU-GM) in the bone marrow and in the peripheral blood was performed in lung cancer patients treated with cisplatin-containing regimens. Treatment with G-CSF following chemotherapy significantly increased the absolute granulocyte count. No significant effect of G-CSF on either the platelet or the red blood cell count was observed. Treatment with G-CSF did not affect the CFU-GM levels in the bone marrow, but did have a significant effect on peripheral blood CFU-GM levels 14 days after initiation of chemotherapy (P less than 0.05). Four patients demonstrated a rebound increase in the level of peripheral blood CFU-GM during the first course of chemotherapy without G-CSF. In contrast, eight patients displayed increase in peripheral blood CFU-GM levels during the second course of chemotherapy with G-CSF treatment. These findings demonstrate that G-CSF is a potent stimulator of granulocyte proliferation as well as a potent agent for promoting transport of hematopoietic progenitors from the bone marrow into the peripheral blood.
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PMID:Granulocyte-colony-stimulating factor enhances the circulating hematopoietic progenitors in lung cancer patients treated with cisplatin-containing regimens. 138 42

In three consecutive pilot studies the effect of recombinant human granulocyte/macrophage-colony-stimulating factor (rhGM-CSF) on haematopoetic recovery after chemotherapy in patients with small-cell lung cancer was investigated. In study I, 20 patients received AIO chemotherapy (A, Adriamycin 25 mg/m2 on days 1 + 2; I, ifosfamide 2 g/m2 on days 1-5; O, vincristine 2 mg on day 1) at 4-week intervals either with or without rhGM-CSF (250 micrograms/m2 sc) from day 8 until recovery of leucocytes. Neither the degree nor the duration of myelosuppression was markedly influenced by rhGM-CSF. Suggesting that these disappointing results were caused by the late onset of GM-CSF application, in the following study we shortened chemotherapy to 3 days and started with GM-CSF on day 4. The main objective of this study was to test whether the earlier administration of GM-CSF allowed treatment intervals to be reduced or the dose to be escalated. After 10 patients had received a starting dose of AIO (A, 50 mg/m2 on day 1; I, 2 g/m2 on days 1-3; 0,2 mg on day 1) alternating with cisplatin (90 mg/m2 on day 1) and etoposide (150 mg/m2 on days 1-3), the dose of ifosfamide and etoposide was escalated to 2.5 g/m2 on days 1-3 and 200 mg/m2 on days 1-3 in the next 10 patients. Treatment was given at 2-week intervals when leucocytes were greater than 3500/mm3 and thrombocytes were greater than 100,000 mm3 on day 14. At each dose level patients were randomized to receive either rhGM-CSF 250 micrograms/m2 s.c. on days 4-12 or no GM-CSF. In this study, rhGM-CSF markedly shortened the duration of leukopenia. Reinstitution of chemotherapy on day 15 was possible at dose level 1 in 1/4 patients without and in 3/4 patients with GM-CSF, and at dose level 2 in 0/5 patients without and in 5/5 patients with GM-CSF. However, the degree of myelosuppression was not improved by GM-CSF. In a third study we tried to apply rhGM-CSF simultaneously with chemotherapy. After 3 patients had received GM-CSF starting on day 1 concurrent to AIO chemotherapy, we noticed an increase of myelosuppression with prolonged neutropenia and thrombocytopenia and stopped this investigation. Considering all patients included in these three consecutive pilot studies, there is no difference in response rates and survival between patients with and without rhGM-CSF treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of rhGM-CSF on haematopoietic reconstitution after chemotherapy in small-cell lung cancer. 166 93

The therapeutic evaluation of rG.CSF has been studied on neutropenic patients receiving lung cancer chemotherapy with focusing the change in the absolute neutrophil counting (ANC) in the patients during chemotherapy and subsequent rG.CSF treatment by daily dosing either at 0.4, 2.0, 5.0 and 10.0 micrograms/kg intravenously or at 2.0 and 5.0 micrograms/kg subcutaneously. The daily rG.CSF dosing for 14 consecutive days was performed on the patients upon completion of the 28-day chemotherapy for lung cancer. As a result, remarkable recovery of ANC was observed in the patients administered at doses of more than 5 and 2.0 micrograms/kg intravenously and subcutaneously, respectively. Additionally, the shortening of the neutropenia (ANC: below 1,000/cmm) was observed in the patients at doses of not less than 2.0 micrograms/kg in both administration routes. In conclusion, rG.CSF treatment demonstrates the completion and/or shortening of the chemotherapy cycle for lung cancer at a subcutaneous dose of 2.0 micrograms/kg and at a intravenous dose of 5.0 micrograms/kg. No adverse drug effects were observed in all patients during the study.
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PMID:[Clinical effect of recombinant human G-CSF on neutropenia induced by chemotherapy for lung cancer. rG.CSF Cooperation Study Group]. 168

In an attempt to evaluate rG-CSF for preventing and reducing the period of chemotherapy-induced neutropenia, phase II studies of the agent, KRN 8601, have been conducted in patients receiving chemotherapy for lung cancer. In the cooperative study, 53 patients with lung cancer were fully evaluated. The chemotherapy regimen for the patients enrolled in the study was not specified, but an identical regimen with an identical dose and schedule was mandatory for the first cycle in which the patients did not receive the rG-CSF, and for the following cycles in which they received it after completion of chemotherapy for 14 days consecutively. Patients were allocated to receive the agents either at a dose of 100, 200 or 400 micrograms/m2 via intravenous drip infusion; or at as ub cutaneous dose of 25, 75, or 125 micrograms. In the author's study, all the 9 patients with non-small cell lung cancer received a 3-drug combination of vindesine, ifosfamide, and cisplatin(VIP) at an identical dose throughout the cycles. The rG-CSF was administered on the second and the following cycles at a dose of 100 micrograms/m2, subcutaneously, in the same manner as the above. Myelogram and neutrophil functions, i.e., superoxide anion production, chemotactic, and phagocytic activity, were serially determined in these patients. With intravenous dose of 100 micrograms/m2, the rG-CSF considerably elevated the nadir count of neutrophils and significantly reduced the duration of neutropenia. Subcutaneously administered rhG-CSF at 75 micrograms doses did as with intravenous infusion. The optimal dose of the agent in conventional chemotherapy was estimated to be 100 micrograms/m2 when infused intravenously, and 75-125 micrograms subcutaneously. Subcutaneously administered rG-CSF at a dose of 100 micrograms/m2 did not contribute to spare the nadir count of neutrophils, but contributed toward reducing the period of neutropenia induced by the 3-drug combination which was much more myelosuppressive than conventional regimens. Thus, the optimal dose of the agent should be determined according to the dose-intensity of chemotherapy. Peripheral neutrophils obtained after recovery from VIP-induced neutropenia showed a normal activity in superoxide anion production and mobility when combined with rG-CSF, although the activity showed a trend to remain subnormal in the recovered neutrophils without rG-CSF. In conclusion, rG-CSF considerably reduces the neutropenia and possibly reduces infections caused by intensive chemotherapy. Hereafter, clinical trials must determine whether rG-CSF improve the therapeutic outcomes of patients receiving chemotherapy in terms of response rate and patient survival.
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PMID:[Effect of recombinant human granulocyte colony-stimulating factor (rG-CSF) on chemotherapy-induced neutropenia in patients with lung cancer]. 169 62

Dose intensity (DI) is defined as the amount of drugs administered per unit time (mg/m2/wk). Recently this concept is thought to be one of the most important tactics to improve the chemotherapeutic results. In this article, we summarized the reports about the impact of dose intensity chemotherapy on various malignancies and the experimental results in animal models. As the application of this concept for the treatment of lung cancer, we conducted the following trials. For the patients with small-cell lung cancer (SCLC), weekly intensive chemotherapy employing cisplatin, oncovin, doxorubicin, and etoposide (CODE regimen) was performed. Fifteen (88%) of 17 patients responded to this regimen, including 5 (29%) complete responders. The median survival time for all patients was 45 weeks. For the patients with non-small cell lung cancer (NSCLC), short interval (3 weeks) MVP (mitomycin, vindesine, and cisplatin) therapy using with recombinant human granulocyte-colony stimulating factor (rhG-CSF) was performed. This study was aimed at improving the therapeutic result by reducing the cycle length of MVP regimen through the use of rG-CSF. Thirty-two out of 40 patients could receive two or more cycles of MVP regimen on schedule. These results in SCLC and NSCLC suggest that does intensity chemotherapy can improve the outcome for patients with these disease.
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PMID:[Dose intensity chemotherapy in lung cancer]. 169 98

The activity of endogenous colony stimulating factor (CSF) in pleural effusions of patients with lung cancer was measured quantitatively by colony-forming bioassay. Before treatment malignant effusions contained various levels of CSF activities. Anti-GM-CSF and anti-M-CSF antibodies neutralized approximately 60% and 70% of CSF activities in malignant effusions, respectively. Significant increase in the CSF activity in malignant effusion was seen during intrapleural injections of recombinant interleukin-2 (IL-2). Thus, in vivo treatment with IL-2 can induce production of endogenous CSF which may be responsible for proliferation and differentiation of mononuclear phagocytes.
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PMID:[Colony-stimulating factor activity in malignant pleural effusions and its augmentation by local administration of interleukin 2]. 192 Sep 77


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