Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elevation of transcobalamin I and serum vitamin B12 levels has usually been associated with increased granulocytic proliferation, such as occurs in chronic myelogenous leukemia. Two patients with metastatic cancer had extremely high serum vitamin B12 and transcobalamin I levels--greater than those seen in even the most intense granulocytic proliferation--that were not explainable by leukocytosis. The subjects' serum vitamin B12 levels were 18,750 and 21,221 pg per milliliter (normal, 471 plus or minus 174 pg per milliliter, mean plus or minus S.D.) and unsaturated vitamin B12 binding capacity 158,750 and 5,400 pg per milliliter (normal, 1153 plus or minus 313 pg per milliliter) respectively. The abnormally elevated serum binder was shown to be identical with transcobalamin balamin I in every respect. Levels of transcobalamin II and serum third binder were normal. The cause of the binder abnormality is unknown, but factors other than granulocyte proliferation may control or contribute to the production or accumulation of transcobalamin I.
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PMID:Extreme elevation of serum transcobalamin I in patients with metastatic cancer. 105 6

Forty-seven previously untreated patients with histologically or cytologically proven non-small cell lung cancer were treated with ICE (ifosfamide/cisplatin/etoposide). Patients received ifosfamide 4 g/m2 with mesna uroprotection on day 1, and cisplatin 25 mg/m2/d and etoposide 100 mg/m2/d on days 1, 2, and 3; courses were repeated every 28 days. Premedication with prochlorperazine, dexamethasone, and high-dose metoclopramide was given to prevent nausea; lorazepam was added on days 2 and 3 only. Thirty-four men and 13 women (median age, 60 years) received a total of 146 treatment cycles. One patient had stage IIIA disease, seven had IIIB disease, and 39 had hematogenous metastases. Forty-six patients were evaluable for response and toxicity. One patient suffered a myocardial infarction on day 7 that was judged unrelated to treatment. Two patients suffered early death from toxicity and have been classified as nonresponders. Three patients achieved complete response (median, 42+ weeks) and 14 patients achieved partial response (median, 29+ weeks; range, 10 to 82+), for an overall response rate of 37% (95% confidence limits, 23% to 51%). The median survival of the entire group is 26 weeks (1 to 82+). The median nadir granulocyte count was 0.275 x 10(9)/L (range, 0 to 2.3 x 10(9)/L), and there were 14 episodes (in 11 patients) or neutropenia-associated fever, one of which resulted in death. Seven of these patients had not had the required protocol dose reduction for nadir neutrophil count in the preceding cycle. The median nadir platelet count was 120 x 10(9)/L (range, 13 to 385 x 10(9)/L), and three patients required platelet transfusions. Eleven patients had RBC transfusions. Only ten patients had grade 2 gastrointestinal toxicity. Five patients had microscopic hematuria, and one patient had central nervous system toxicity.
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PMID:Ifosfamide, cisplatin, and etoposide (ICE) in the treatment of advanced non-small cell lung cancer. 132 13

Nine patients with progressive, metastatic disease from primary carcinoma of the colon were entered into a phase I/II study using continuous intravenous infusions of granulocyte-macrophage colony-stimulating factor (GM-CSF) and high dose melphalan (120 mg m-2). GM-CSF was given alone to six patients during the first part of the study to determine a dose that would produce a peripheral leucocyte count (WCC) greater than or equal to 50 X 10(9) 1(-1) and was initially given at 3 micrograms kg-1 day-1 and escalated to 10 micrograms kg-1 day-1 after 10 days. The infusion was discontinued when the WCC exceeded 50 X 10(9) 1(-1) and after a gap of one week, melphalan was given over 30 min. GM-CSF was recommenced 8 h later and was continued until the neutrophil count had exceeded 0.5 X 10(9) 1(-1) for greater than 1 week. One patient achieved a WCC greater than 50 X 10(9) 1(-1) with GM-CSF 3 micrograms kg-1 day-1, but the other five who entered this phase of the study required dose escalation to 10 micrograms kg-1. No toxicity attributed to GM-CSF was seen. After melphalan, the median times to severe neutropenia (less than 0.5 X 10(9) 1(-1] and thrombocytopenia (greater than 20 X 10(9) 1(-1] were 6 and 9 days respectively. The median durations of neutropenia and thrombocytopenia were 14 and 10 days respectively. All patients required intensive support with a median duration of inpatient stay of 24 days. There was one treatment related death due to renal failure. One complete and two partial remissions (33% response rate) were seen but these were of short duration (median of 10 weeks). This study demonstrates that GM-CSF given by continuous intravenous infusion produces significant increments of peripheral granulocyte counts at 3 and 10 micrograms kg-1 day-1 and is not associated with any toxicity. The duration of neutropenia and thrombocytopenia induced by high-dose melphalan appears to be reduced by the subsequent administration of GM-CSF to times which are at least as short as have been reported in historical series which have used autologous bone marrow rescue.
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PMID:Granulocyte-macrophage colony stimulating factor (GM-CSF) after high-dose melphalan in patients with advanced colon cancer. 169 72

Leukocytosis associated with malignant disease has been known as a paraneoplastic syndrome and occurs occasionally in patients with oral malignancies. In this study, mechanisms underlying leukocytosis associated with malignancy was investigated, using a squamous cell carcinoma of the maxilla from a patient who manifested marked leukocytosis. When the patient's tumor was inoculated into nude mice, it formed squamous cell carcinoma (MH85) and induced leukocytosis and splenomegaly. Leukocytosis and splenomegaly paralleled tumor growth. Surgical excision of MH85 tumor resulted in a dramatic reduction of leukocyte count and spleen weight, indicating an involvement of humoral mediators released by MH85. MH85 cells conditioned medium (MH85CM) were shown to contain granulocyte-colony stimulating factor (G-CSF) activity, which is a potent growth factor specific for granulocytes. These results suggest G-CSF or G-CSF like substance secreted by MH85 cells is responsible for leukocytosis in MH85 bearing nude mice (MH85 mice) and in the patient. MH85 cell growth was stimulated by G-CSF and inhibited by anti-G-CSF antibody, thus suggesting that G-CSF like substance is a autocrine growth factor for MH85 cells. Splenectomized MH85 mice developed less severe leukocytosis than did non-splenectomized mice. This finding indicated that not only G-CSF like substance secreted by MH85 cells but other humoral factors released by the hyperplastic spleen contribute to the development of leukocytosis. Splenic monocytes derived from MH85 mice and MH85CM-stimulated splenic monocytes showed increased secretion of tumor necrosis factor (TNF) and interleukin-1 (IL-1), both of which have been reported to induce neutrophilia in animals. Moreover, injection of anti-TNF-antibody into neutrophilic MH85 mice significantly, although not completely, decreased leukocyte count. Thus, it seemed likely that increased secretion of TNF and IL-1 by spleen cells that are stimulated by humoral factors released from MH85 also contributes to the progression of leukocytosis. In splenectomized mice, enlargement of MH85 tumor was retarded and metastases were impaired compared these in nonsplenectomized mice. Coculture of splenocytes from MH85 mice with normal spleen cells, inhibited blastogenesis in response to mitogen. The result suggests that splenocytes from MH85 mice played as immune suppressive cells. MH85CM conferred immune suppressive activity on normal spleen cells. This suppressor cell-inducing factor (SCIF) in MH85CM was found to have an apparent molecular weight of approximately 25kd, and its biological activity was neutralized by anti-G-CSF antibody. Therefore, SCIF secreted by MH85 cells was likely to be G-CSF like substance.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Studies on the pathophysiology of paraneoplastic syndromes: both cancer cells and host immune cells are responsible for the pathophysiology of leukocytosis associated with oral cancer]. 172 87

The monoclonal antibody LICR-LON-M8 was used in a series of experiments to determine how an immunohistochemical technique could be used as a diagnostic test for micrometastatic disease in patients with operable, primary breast carcinoma. Optimal tissue and antigen preservation was obtained with fixatives containing either picric acid or a heavy metal such as mercury to allow staining with the monoclonal antibody diluted to 1:12,000 to 1:16,000 from unpurified mouse ascites. Tissue affected by primary and metastatic disease stains in a characteristic fashion, which is distinct from benign breast tissue. All the ductal tumours stained positively for malignant cells with the monoclonal antibody preparation. Within the bone marrow, occasional granulocytes and granulocyte precursors stained positively if the endogenous peroxidase activity was incompletely blocked. These cells were readily differentiated from tumour cells on cytologic examination. With these monoclonal antibody and immunohistochemical staining techniques it may now be possible to detect early micrometastatic disease in the bone marrow of patients with primary breast cancer.
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PMID:Detection of micrometastases from primary breast cancer. 184 53

Twenty previously untreated patients with histologically or cytologically proven non-small cell lung cancer (NSCLC) were treated with ifosfamide in combination with cisplatin and etoposide. Patients received ifosfamide 4 g/m2 with mesna uroprotection on day 1 and cisplatin 25 mg/m2 and etoposide 100 mg/m2 on days 1 through 3. Courses were repeated every 28 days. Premedication with prochlorperazine, dexamethasone, and high-dose metoclopramide was given to prevent nausea, and lorazepam was added on days 2 and 3 only. Seventeen male and three female patients (median age, 57 years) have been treated. Two patients had stage IIIb disease, and 18 had hematogenous metastases. Eighteen patients are evaluable for response and toxicity, and it is too early to evaluate two patients. Early in the study, two patients died of toxicity and have been classified as nonresponders. One patient achieved complete response (21+ weeks), and seven patients achieved partial response (median, 30+ weeks; range, 5 to 38+), for an overall response rate of 44.5%. The median survival of the group has not been reached, and 14 patients are alive 5 to 38+ weeks from the start of treatment. The median nadir granulocyte count was 0.275 x 10(9)/L (range, 0 to 2.283 x 10(9)/L), and there were six episodes (involving 5 patients) of neutropenia-associated fever, one of which resulted in death. The median nadir platelet count was 120 x 10(9)/L (range, 13 to 385 x 10(9)/L), but no patient experienced bleeding or required platelet transfusions. Five patients required RBC transfusions. Only eight patients had grade 2 gastrointestinal toxicity, and one patient had microscopic hematuria; there was no CNS toxicity.
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PMID:A phase II study of ifosfamide, cisplatin, etoposide in patients with advanced non-small cell lung cancer: a preliminary report. 215 85

At present, no sufficient therapy for metastatic renal cell carcinoma is available. Several immunotherapeutical protocols have been studied, success rates, however, were inconsistent. The purpose of this study was to assess the pretherapeutic immunological status of 13 patients with metastatic and 16 patients with nonmetastatic renal cell carcinoma and of 15 healthy volunteers. Determined were differential blood counts, lymphocyte subpopulations, beta 2-microglobulin, tumor necrosis factor (TNF), neopterin, immunoglobulin, fibronectin and ferritin. Additionally, these parameters were recorded for monitoring an immunotherapeutical approach with the xenogeneic biological response modifier Keyhole limpet hemocyanine (KLH) in 10 patients with metastatic and in 5 patients with nonmetastatic disease. The pretherapeutic immunological status of patients with metastatic disease was characterized by significantly reduced T4-, T8- and B-cell counts. Significantly increased were granulocyte counts, beta 2-microglobulin, neopterin and TNF. In patients who did not suffer from metastases, only beta 2-microglobulin and neopterin were increased significantly. During immunotherapy, in patients with metastases, there was a decline of lymphocyte subsets and of the T4/T8-ratio, which correlated with progress of the disease. Humoral immune parameters showed no changes compared to pretherapeutic values. In patients who did not suffer from metastases, cellular immune parameters showed stable values during immunotherapy; neopterin, beta 2-microglobulin and TNF increased considerably. These findings indicate immunosuppression in patients with metastatic renal cell carcinoma, increasing with progression of the disease and possibly impairing the immunostimulating effects of biological response modifiers during immunotherapy. In conclusion, the clinical response of metastatic renal cell carcinoma to immunotherapy might be improved if the immunostimulant is combined with agents suitable to overcome immunosuppression, i.e. low doses of cyclophosphamide or inhibitors of prostaglandin synthesis. In addition, assessment of immune parameters for monitoring the actual immune status of a patient and the immunological effects of therapy was found to be a necessary part of immunotherapy.
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PMID:Immune status and immune therapy of renal cell carcinoma. 221 64

Twenty-eight evaluable patients with metastatic cancer refractory to standard therapy received escalating doses of muramyl tripeptide phosphatidylethanolamine (MTP-PE) (.05 to 12 mg/m2) in phosphatidylserine (PC):phosphatidylcholine (PS) liposomes (lipid:MTP-PE) ratio 250:1). Liposomal MTP-PE (L-MTP-PE) was infused over 1 hour twice weekly; doses were escalated within individual patients every 3 weeks as tolerated for a total treatment duration of 9 weeks. Routine clinical laboratory parameters, acute phase reactants and various immunologic tests were monitored at various time points during treatment. Toxicity was moderate (less than or equal to grade II) in 24 patients with chief side effects being chills (80% of patients), fever (70%), malaise (60%), and nausea (55%). In four patients L-MTP-PE treatment was deescalated due to severe malaise and recurrent fever higher than 38.8 degrees C. The maximum-tolerated dose (MTD) was 6 mg/m2. Significant (P less than .05) increases in WBC count, absolute granulocyte count, ceruloplasmin, beta 2-microglobulin, c-reactive protein, monocyte tumoricidal activity, and serum IL-1 beta were found. Significant decreases in serum cholesterol were also observed. Clearance of intravenously (iv)-infused technetium-99 (99mTc)-labeled liposomes containing MTP-PE in four patients was biphasic; gamma camera scans revealed uptake of radiolabel in liver, spleen, lung, nasopharynx, thyroid gland, and tumor (two patients). No objective tumor regression was seen. In view of its definite immunobiologic activity and lack of major toxicity, additional phase II and adjuvant trials of L-MTP-PE are warranted.
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PMID:Phase I trial of liposomal muramyl tripeptide phosphatidylethanolamine in cancer patients. 247 21

Combinations of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) demonstrate synergistic antiproliferative activity in vitro. Therefore, we initiated a clinical study of recombinant TNF-alpha (rTNF-alpha) and rIFN-gamma combination therapy in humans. Twenty-five patients with metastatic cancer received both rTNF-alpha and rIFN-gamma by intramuscular injection for 5 consecutive days every 2 weeks for a total of 4 weeks. The dose levels were 5/5, 10/5, 10/10, 25/10, 25/25, 50/25, 50/50, 75/50, and 75/75 micrograms/m2 per day of rTNF-alpha/rIFN-gamma. A minimum of 2 patients were entered sequentially at each dose level. If the first 2-week cycle of therapy was well tolerated, the dose was increased to the next highest dose level during the second 2-week cycle. Fever, chills, and fatigue were observed at all doses. Severity of symptoms corresponded to increasing dose levels. Although TNF is identical to a molecule known as "cachectin," the vast majority of our patients did not lose weight while on study. However, alterations in lipid metabolism occurred and were manifested by a median change in triglyceride values of +40 mg/dl (range, -130 to +318 mg/dl), and in cholesterol values of -30 mg/dl (range, -103 to +2 mg/dl). The maximum tolerated dose was 75 micrograms/m2 of rTNF-alpha combined with 50 micrograms/m2 of rIFN-gamma, with dose-limiting side effects being mainly constitutional symptoms. A dose-related suppression in granulocyte and platelet counts was observed. Hematologic parameters returned to baseline within 72 h after therapy was discontinued, and neither infection nor bleeding occurred. Ten of 22 evaluable patients had stable disease for a median of 8 weeks (range, 4-21 weeks); 12 patients showed progressive disease. This study will form the framework for phase II trials of rTNF-alpha and rIFN-gamma combination therapy.
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PMID:Phase I study of a combination of recombinant tumor necrosis factor-alpha and recombinant interferon-gamma in cancer patients. 250 84

Mature blood cells of all lineages are derived from a single class of cell, the haemopoietic stem cell. Stem cells are pluripotent and capable of almost limitless self-renewal. In the bone marrow they form part of a hierarchy that includes progenitor cells, which are more restricted in the lineages their progeny can adopt, and precursor cells, which are committed to differentiation. The mechanisms that regulate progression through this hierarchy are not fully understood, but evidence suggests that both bone marrow stromal cells and soluble growth factors have a role in controlling haemopoiesis. Four growth factors act on progenitor cells to promote their survival, proliferation, differentiation, and maturation: interleukin-3 (IL-3), granulocyte/macrophage-colony stimulating factor (GM-CSF), granulocyte-CSF (G-CSF), and macrophage-CSF (M-CSF). They can also activate the function of mature cells. Considerable overlap is found in the target cells for these four growth factors. We have found that growth factors acting in synergy can recruit more primitive cells than had previously been appreciated. These factors can also determine the lineage that the progeny of multipotential progenitors will adopt. Thus, colony-stimulating factors (CSFs) have the potential to regulate the development of primitive haemopoietic cells in vivo. The properties of CSFs have made them useful in treating malignant disease: G-CSF, in particular, has been used to reduce the period of neutropaenia that follows cytotoxic therapy for various malignancies. The success of these early trials gives ground for cautious optimism about the clinical use of these compounds.
Cancer Metastasis Rev 1989 Dec
PMID:The role of growth factors in haemopoietic development: clinical and biological implications. 269 73


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