Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We compared cisternal and lumbar CSF examination in 14 patients suspected of having leptomeningeal metastasis from cancer. Malignant cells were present in 12 patients--in both cisternal and lumbar CSF in nine patients and only in cisternal CSF in three. Cisternal CSF cytologic examination should be considered in patients suspected of having leptomeningeal metastasis if lumbar CSF is nondiagnostic.
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PMID:Comparison of cisternal and lumbar CSF examination in leptomeningeal metastasis. 843 22

Chronically immunosuppressed individuals are susceptible to lymphoreticular tumors. Up to 15% of patients with congenital deficiencies such as ataxia=telangiectasia may develop malignancies, mainly high-grade B cell non=Hodgkin's lymphomas (NHLs). AIDS lymphomas are comprised of NHLs including Burkitt's lymphoma (BL) and primary cerebral lymphomas (PCLs). Almost 3% of all AIDS patients (2824 of 97,258 cases) developed NHL. Epstein-Barr virus (EBV) as a co-factor in AIDS lymphomagenesis has been studied: in 12 cases of 24 AIDS lymphomas EBV by DNA in situ hybridization was found. In an analysis of 6 primary cerebral lymphomas, .5 were positive for EBV DNA by Southern blotting. In Burkitt's lymphoma the characteristic genetic alteration affects the c-myc oncogene. In 1/3 of BL p53 mutations were found but none in the 43 NHLs suggesting that p53 mutations and c-myc activation act synergistically in the pathogenesis of these tumors. Cytotoxic agents dideoxyinosine, dideoxycytosine, and zidovudine may cause secondary neoplasia. 8 of 55 AIDS patients under zidovudine treatment developed high-grade lymphoma 23.8 months subsequently; recently doses were reduced. PCL was found in 21 of 90 patients. A 5.2 months survival was associated with combined treatment with cyclophosphamide, Oncovin (vincristine), methotrexate, etoposide, and cytosine arabinoside compared with 11.3 months with chemotherapy. Colony-stimulating factors (CSFs) alleviate drug-induced myelotoxicity and zidovudine-induced neutropenia, however, l8 of 11 patients receiving granulocyte-macrophage CSF developed hematological toxicity. Interleukine-2 produced by T-helper cells enhancing tumor cells cytotoxicity has been used in AIDS-associated cryptosporidial diarrhea and in 4 patients with AIDS lymphoma with modest response, but its stimulation of the HIV-infected substrate may increase viral proliferation.
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PMID:AIDS lymphomas. 161 63

A 70-year-old woman was admitted to our hospital because of rapidly progressive cerebellar ataxia. Neurological examinations showed saccadic eye movement, downbeat nystagmus, scanning speech, proximal dominant muscle weakness and severe truncal and limb ataxia. Based on these clinical features, she was suspected to have paraneoplastic cerebellar degeneration (PCD), although the malignant tumor was not detected through clinical intensive surveys. Her serum and CSF revealed to have anti-Purkinje cell antibodies immunohistochemically, and western blot analysis showed that they reacted with 58 kd band. In view of previous reports of PCD, she was strongly suspected to have gynecological cancers. The trial laparotomy found early stage fallopian tubal cancer, which had not been detected by CT scan, ultrasonogram and MRI. It is important to detect and characterize these autoantibodies found in the PCD patients for early diagnosis and treatment of underlying cancer.
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PMID:[A case of paraneoplastic cerebellar degeneration--success in early detection of cancer by anti-Purkinje cell antibody]. 162 54

Unconjugated monoclonal antibodies (mAb) may induce tumour regression in patients. The mechanisms of action are complex. Antibody-dependent cellular cytotoxicity (ADCC) is considered one of the effector functions. Augmentation of the killing capacity of cytotoxic cells may thus be a way to increase the therapeutic potential of mAb. Granulocyte/macrophage-colony-stimulating factor (GM-CSF) has been shown to enhance this function in vitro. Eighteen patients with metastatic colorectal carcinoma received GM-CSF (250 micrograms m-2 day-1 s.c.) for 10 days and a single infusion of the anti-(colon carcinoma) mAb 17-1A (mouse IgG2A) (400 mg) on day 3 of the cycle. The cycles were repeated once a month four times. Neutrophils, eosinophils, monocytes and lymphocytes increased significantly in a biphasic way. However, at the fourth cycle the rise in white blood cells was significantly lower compared to the preceding courses. ADCC (SW948, a human CRC cell line,+mAb 17-1A) or peripheral blood mononuclear cells (PBMC) was significantly (P less than 0.05) augmented by day 6 of a cycle and then declined gradually and, at the end of a cycle, the ADCC activity had returned to the pretreatment level. The spontaneous cytotoxicity of PBMC against the natural-killer-resistant cell line, SW948, varied in a similar way. During GM-CSF treatment there was also a significant increase in FcRI+ (CD64), FcRII+ (CD32), FcRIII+ (CD16) and CD14+ cells but not of CD56+ cells.
Cancer Immunol Immunother 1992
PMID:Cytotoxic functions of blood mononuclear cells in patients with colorectal carcinoma treated with mAb 17-1A and granulocyte/macrophage-colony-stimulating factor. 163 51

Acivicin (AT-125) is a glutamine antagonist with dose-limiting, schedule-dependent CNS toxicity and predictable CSF penetration after intravenous administration. Because of these properties, a trial in CNS malignancies was initiated. Thirty-two patients with recurrent or residual malignant astrocytomas were treated with AT-125. The majority of patients had glioblastoma multiforme (24) and had received prior nitrosoureas (21). The median age was 50 years, and Southwest Oncology Group (SWOG) performance status was 2. The major determinant of response was based upon radiologic criteria using computed tomographic (CT) scanning and/or magnetic resonance imaging (MRI) scans. The tumor mass was measured in two perpendicular planes, which yielded the largest cross-sectional area. Standard solid tumor criteria for response were used. All responding patients also had a stable or tapered dose of corticosteroids with stable or improved performance status and neurologic examination. There were four objective responses (12%): one complete remission (3 1/2+ years) and three partial remissions (57, 86, and 322 days). Two patients had improvement in disease that did not meet requirements for a partial remission. Toxicity was mild and primarily consisted of nausea, vomiting, and lethargy. Two patients were removed from study due to neurotoxicity (depression and hallucinations). The strict response criteria used in this trial were not those that have been used in testing other active agents such as carmustine (BCNU). We conclude that AT-125 has objective antitumor activity in malignant astrocytomas and warrants further study.
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PMID:Objective antitumor activity of acivicin in patients with recurrent CNS malignancies: a Southwest Oncology Group trial. 164 69

Seventeen patients with small cell lung cancer were entered into a dose ranging phase I-II study using rhGM-CSF (Glaxo). In the phase I study patients received 50, 150, 300 or 500 micrograms/m2 GM-CSF for 10 days by daily subcutaneous injection. Full blood counts were performed thrice weekly. After 4 days off all therapy patients then received chemotherapy with doxorubicin 50 mg/m2 i.v. bolus, day 1, ifosfamide 5 g/m2 with mesna 5 g/m2 over 24 h by continuous infusion followed by mesna 3 g/m2, and etoposide 120 mg/m2 i.v. on days 1-3. A total of six courses of chemotherapy were given. In the phase II study patients received the same dose of GM-CSF as in the phase I. GM-CSF was given 24 h after the last dose of chemotherapy for 14 days. Full blood counts were checked thrice weekly and the incidence of infections noted. Patients were randomised to receive GM-CSF with either odd or even courses of chemotherapy. The leucocyte count rose from a mean of 8.7 to 21.6 x 10(9)/l at the 50 micrograms/m2 GM-CSF dosage and from 11.4 to 39.4 x 10(9)/l at the 500 micrograms/m2 dosage during the phase I study. Phase I toxicity was: bone pain in 65% of patients, rash in 47%, fever in 24%, lethargy in 12% and diarrhoea in 12%. In the phase II study the duration of neutropenia was less during the chemotherapy courses with GM-CSF (p = 0.04) but the number of infections was similar.(ABSTRACT TRUNCATED AT 250 WORDS)
Recent Results Cancer Res 1991
PMID:Recombinant human GM-CSF in small cell lung cancer: a phase I/II study. 165 15

In order to develop a more dose-intensive induction regimen for the treatment of far-advanced testicular tumours, the German Cooperative Group for Testicular Tumours started a dose-escalation trial of cisplatin, etoposide and ifosfamide. At the first dose level 18 patients with advanced testicular cancer (Indiana University classification) received cisplatin 25 mg/m2, etoposide 120-150 mg/m2 and ifosfamide 1.2 g/m2 for 5 days every 3 weeks. Of these, 13 patients (72%) became tumour-free, 2 achieved a stable, marker-negative partial remission, 2 had progressive disease and 1 patient died of Clostridium sepsis. The main toxicity was myelosuppression with a white blood cell nadir of 900/microliters and a thrombocyte nadir of 47,000/microliters. Granulocytopenic fever occurred in 43% of all cycles. At the second dose level 15 patients received cisplatin 30 mg/m2, etoposide 150 mg/m2 and ifosfamide 1.6 g/m2 five times every 3 weeks together with s.c. recombinant granulocyte/macrophage-colony-stimulating factor (GM-CSF) 10 micrograms/kg on days 6-15. Acute toxicity was severe with a white blood cell nadir of 300/microliters and thrombocyte nadir of 11,000/microliters. The duration of the thrombocytopenia increased with cycle number; 63% of all cycles were associated with granulocytopenic fever and in 83% platelet transfusions were required. One patient died from acute renal failure and Aspergillus sepsis; 3 patients experienced adverse reactions to GM-CSF, requiring omission of this drugs in 2; 33% had grade 3 or 4 mucositis. At this dose level 8 patients (53%) became tumour-free, 4 patients (26%) had marker normalization with irresectable residual disease and 2 patients were treatment failures. Though acute toxicity was severe at this dose level, there was no unexpected or unmanageable organ toxicity and thus patients are now entered at dose level 3, which consists of cisplatin 30 mg/m2, etoposide 200 mg/m2 and ifosfamide 1.6 g/m2 for 5 days and GM-CSF 10 micrograms kg-1 day-1 on days 6-15 s.c.
J Cancer Res Clin Oncol 1991
PMID:Cisplatin/etoposide/ifosfamide stepwise dose escalation with concomitant granulocyte/macrophage-colony-stimulating factor for patients with far-advanced testicular carcinoma. 166 92

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)
J Cancer Res Clin Oncol 1991
PMID:Effect of rhGM-CSF on haematopoietic reconstitution after chemotherapy in small-cell lung cancer. 166 93

Progressive growth of metastatic Lewis lung carcinoma (LLC) tumors results in a concurrent stimulation of myelopoiesis and the appearance of immune-suppressive bone marrow cells. The present study has shown that normal bone marrow cells could be induced to become immune-suppressive by 3 days of culture with supernatants of cloned metastatic LLC-LN7 variant cells. The capacity of the LLC-LN7 supernatants to stimulate the appearance of suppressor cells was directly proportional to the concentration of supernatant used in the bone marrow culture. When adoptively transferred with a LLC-LN7 tumor inoculum, the supernatant-induced suppressor bone marrow cells increased the rate of appearance of palpable tumors and the frequency of tumor establishment. The LLC-LN7 supernatants containing suppressor-cell-inducing activity also had colony-stimulating factor (CSF) activity. The CSF activity produced by the LLC-LN7 cells could be diminished with neutralizing antibodies to either granulocyte/monocyte(GM-) CSF or to interleukin-3 (IL-3). Likewise, the suppressor-inducing activity in the LLC-LN7 supernatants was diminished by pretreatment with anti-GM-CSF or anti-IL-3. The combination of anti-GM-CSF and anti-IL-3 completely neutralized all suppressor-inducing activity produced by the LLC-LN7 cells. These results suggest that the secretion of IL-3 and GM-CSF by LLC-LN7 tumor cells is a mechanism by which the tumors stimulate myelopoiesis and induce normal bone marrow cells to become immune-suppressive. Bone marrow cells that are induced to become immune-suppressive by culture with LLC-LN7 supernatants can, in turn, facilitate the establishment of tumor in vivo.
Cancer Immunol Immunother 1991
PMID:Antibodies to colony-stimulating factors block Lewis lung carcinoma cell stimulation of immune-suppressive bone marrow cells. 167 53

Substantial intensification of chemotherapy doses is a promising approach to the treatment of refractory malignancy currently receiving increasing attention. For the past 4 years we have used 3 repeated cycles of a combination of cyclophosphamide (5 g/m2), etoposide (1500 mg/m2), and cisplatin (150 mg/m2) without replacement of progenitor cells and with and without colony-stimulating factor support. The duration of threatening levels of granulocytopenia with this regimen averages 10.2 days, although an occasional patient has prolonged recovery (range, 5-20 days) and most patients require antibiotic therapy for cytopenic fever. We have not yet identified the optimal dose of GM-CSF, but 500 micrograms/m2 significantly shortens the duration of cytopenia (ANC less than 300/mm3) to 5.9 days with a resultant decrease in incidence and duration of cytopenic fever (from 10.8 to 1.7 days), use of antibiotics (from 10.8 to 7.6 days), and duration of hospitalization (from 22.2 to 16.3 days). Seventeen patients with metastatic breast cancer have received this regimen to date with a 35% complete response (CR) rate and a 53% partial response (PR) rate. Most of these patients were refractory to standard therapy. Four of six (67%) not refractory to standard therapy have achieved complete responses that are ongoing at 3.5 to 10.4 months. We conclude that dose-intensive therapy is an option that needs more careful exploration early in the treatment of advanced breast cancer and that GM-CSF decreases morbidity and risk of dose-intensive regimens.
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PMID:Dose-intensive treatment of breast cancer supported by granulocyte-macrophage colony-stimulating factor (GM-CSF). 168 3


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