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)

Integrating systemic chemotherapy into the treatment of patients with invasive bladder cancer, where the majority of deaths are from systemic relapse, is crucial if survival is to be improved. However, the global recommendation of a single treatment approach for all patients is becoming outdated as several groups have found that appropriately selected patients enjoy comparable survival whether treated by transurethral resection alone or by partial or radical cystectomy. Thus, refining case selection becomes a critical area of investigation. Patients with a high risk of systemic relapse should be considered for systemic therapy early in the course of the disease, ideally as part of a clinical trial. The availability of growth factors has reduced the toxicities of the regimens currently in use. Improvements in assessing biologic potential are required, so that treatment recommendations will allow patients the maximal chance of cure and maintenance of organ function, while minimizing toxicities in patients for whom systemic approaches are unwarranted. Of interest are recent reports that G-CSF may enhance tumor sensitivity to methotrexate in vitro and increase the sensitivity of implanted urothelial tumors to chemotherapy in nude mice. Such findings suggest an expanded role for these agents. Unfortunately, simple escalation of all components of a combination regimen does not appear to be a viable strategy, as it is unlikely to significantly increase CR proportions without prohibitive toxicities. However, as more is understood about drug resistance, and in particular its development in vivo, better sequencing of the available of options should be possible. The availability of effective salvage therapies suggests that this is an appropriate therapeutic approach. In addition, a number of strategies aimed at reversing the mdr phenotype are under study. These include calcium channel blockers such as verapamil, cyclosporin, and tamoxifen. Alternatively, some groups are investigating transfecting the mdr gene into bone marrow cells to reduce the sensitivity of these cells to cytotoxic agents. These novel designs can be tested both in patients with metastatic disease and in patients with locally advanced (T3b, T4, and N+) disease, who have a high risk of metastatic failure and low CR proportions to available regimens.
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PMID:Systemic chemotherapy in regionally advanced bladder cancer. Theoretical considerations and results. 144 Oct 29

The paraneoplastic syndrome (PNS) is an association of symptoms and signs not directly related to the site or local manifestations of a malignant tumor or its metastases. Hematologic abnormalities as PNS include erythrocytosis, anemia, neutrophilia, neutropenia, eosinophilia, thrombocytosis, thrombocytopenia, venous thromboembolism and disseminated intravascular coagulation (DIC). These abnormalities are, by and large, due to the production of biologically active growth factors, hormones or as yet unidentified "humors" by the tumor. As our understanding of growth factors controlling hematopoiesis has increased in recent years, the biologic basis of hematologic PNS are better understood. For instance, tumor-associated neutrophilia is now known to be caused by the production of G-CSF by the tumor. The mechanism by which tumor causes thromboembolism have also been extensively investigated. Cancer cells induce platelet aggregation both in vitro and in vivo. Platelet aggregating material has been isolated and partially characterized from tumor cells. The involvement of platelet glycoprotein II b/IIIa in the tumor-platelet interaction has also been shown. Malignant cells contain a unique procoagulant, cancer procoagulant A, that directly activates factor X. Together with tissue factor, this procoagulant appears to have been contribute to a high incidence of thromboembolism in cancer patients. Better understanding of hematologic PNS is important for clinical care of the patients with cancer.
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PMID:[Paraneoplastic syndrome hematologic abnormalities]. 200 36

Malignant prostatic carcinoma, a major cause of cancer mortality in males, most often metastasizes to secondary sites in bone. Frequently, the growth rate of the secondary tumor in bone marrow is considerably greater than that of the slowly growing primary prostatic tumor. We now report that two lines of human prostatic carcinoma cells proliferate in response to conditioned media from unstimulated human, rat, or bovine bone marrow. Nonprostatic tumor cell lines showed little or no growth response to the same medium. The proliferative activity found in bone marrow was not duplicated by any of a variety of purified growth factors including epidermal growth factor (EGF), acidic or basic fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF) alpha or beta, interleukins 1, 2, 3, 4 or 6, granulocyte (G), macrophage (M) or granulocyte-macrophage (GM) colony stimulating factor (CSF). Whereas a mixture of G-CSF, M-CSF, and IL 3 produced a mitogenic response in the prostatic carcinoma cells, these three factors were not present in our bone marrow samples in sufficient quantities to promote the observed proliferative response. To further identify the cellular source of the proliferative activity present in bone marrow-conditioned medium, we tested conditioned media made from human bone marrow stromal cells. The stromal cell conditioned medium stimulated increased growth of the prostatic carcinoma cells to levels equivalent to those observed with the bone marrow conditioned medium. These results suggest that novel mitogenic factors that are produced by bone marrow stromal cells and remain in the bone marrow cavity may account, in part, for the preferential growth of prostatic metastases in bone.
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PMID:Stimulation of human prostatic carcinoma cell growth by factors present in human bone marrow. 278 90

The aim of this study was to evaluate the feasibility of CMF 1.8-28 regimen, with all three drugs administered intravenously (IV), and to compare the hematologic toxicity of this regimen with or without G-CSF. Patients aged 18 to 65 years with histologically proven breast cancer treated by surgery and without distant metastases were eligible for the study. All patients had to have normal white blood cells (WBC) count (WBC > or = 3000/mm3 and/or neutrophils > or = 2000), and platelets (Plt) counts (> or = 100,000/mm3), and adequate renal and hepatic function. The toxicity was recorded according to World Health Organization Scale. CMF 1.8 regimen was: cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, 5-fluorouracil 600 mg/m2. The drugs were given IV on day 1 and 8, and cycles repeated every 28 days. G-CSF (5 micrograms/kg/day) was administered subcutaneously from day 9 to 20, starting from the second cycle of chemotherapy. A complete blood count with white-cell differential and platelet count was obtained twice a week. For each patient bone marrow toxicity variables recorded during the first cycle (without G-CSF) were compared with values during the second cycle (with G-CSF). One of 10 entered patients, 1 was not evaluated due to missing data on hematologic toxicity. All patients received chemotherapy with or without G-CSF at the scheduled 28th day. Treatment with G-CSF after CMF 1.8 regimen resulted in a significantly WBC's earlier nadir (average day of nadir 14 vs 17; p = 0.0005), while there was no difference in the average values of WBC at the nadir. Moreover, the average value of platelets recorded at the nadir was significantly lower with the use of G-CSF (average No. of platelets/mm3; 185,111 vs 116,000; p = 0.001). Complete hematologic recovery without and with G-CSF was reached on day 25 and 20 respectively (p = 0.001). CMF 1.8 with IV cyclophosphamide is a feasible regimen with and without G-CSF and can be used in adjuvant setting instead of "classic" CMF in order to improve the low compliance observed when cyclophosphamide is given by mouth. As reported by others, we observed that after standard chemotherapy G-CSF anticipated the nadir of WBC and hastened hematologic recovery (WBC > 3000 and Plt > or = 100,000).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Feasibility of a cyclophosphamide methotrexate and 5-fluorouracil regime intravenously administered with and without granulocyte-colony stimulating factor in surgically treated breast carcinoma]. 750 19

The delivery of high-dose epirubicin in patients with advanced breast cancer usually entails serious myelotoxicity and frequent treatment delays. Concurrent administration of G-CSF probably allows the administration of epirubicin on schedule with minimal morbidity. From August 1990 to February 1992, 42 women with advanced breast cancer were treated with six cycles of epirubicin 110 mg/m2 every 4 weeks. Filgrastim 5 micrograms/kg per day for 14 days was administered subcutaneously starting 24 hours after chemotherapy. All patients had multiple metastatic sites, and 39 had visceral metastases. All cases were evaluable for response, toxicity, and survival. Treatment was delayed in only two cases. The actually administered average dose per unit time per patient amounted to 99.6% of the dose prescribed by the protocol. Two (4.5%; 95% confidence interval [C.I.] 0-16%) patients demonstrated a complete response and 14 (33%; 95% C.I. 19-49%) a partial response. Median time to progression was 31 weeks and median survival was 60 weeks. Severe granulocytopenia was seen in six patients; stomatitis and diarrhea in one patient each. Myoskeletal pain was noticed in 23 (55%) patients, while cardiac problems were reported in 3 cases. The present study shows that the prophylactic use of r-met-hu G-CSF allows the administration of high-dose epirubicin every 4 weeks with minimal morbidity and an improved quality of life.
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PMID:High-dose epirubicin and r-met-hu G-CSF (filgrastim) in the treatment of patients with advanced breast cancer: A Hellenic Cooperative Oncology Group study. 752 43

Twenty patients with locally advanced or metastatic breast cancer were treated with four cycles of ifosfamide/mesna 5 g m-2 and epirubicin 60 mg m-2 every 14 days with granulocyte colony-stimulating factor (G-CSF, Filgrastim). Complete remission occurred in six out of the 20 patients (30%, 95% confidence interval 12-54%) and there were 12 partial responders (60%, 95% confidence interval 37-81%), thus giving an overall response rate of 90% (95% confidence interval 63-97%). Two patients had progressive disease. The median duration of response for those patients with metastatic disease was 7.3 (1.3-20.1+) months. The median survival time for these patients was 15 (5.3-27.9+) months. Of the four patients treated with locally advanced disease three achieved a complete clinical response and one a partial response. Three out of four of these patients subsequently underwent a mastectomy, and in one of these no viable tumour was seen. Our conclusion is that this regimen is excellent palliation for metastatic disease and possibly useful neoadjuvant treatment.
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PMID:The use of granulocyte colony-stimulating factor to deliver four cycles of ifosfamide and epirubicin every 14 days in women with advanced or metastatic breast cancer. 753 18

In order to study the clinical usefulness of biological response modifiers (BRMs) in eliminating malignant solid tumors, we have investigated the effect of various combination therapies on the murine Colon26 solid tumor model. When the tumor-bearing mice were treated with chemotherapeutics, G-CSF and OK-432 (streptococcal preparation), the tumors completely disappeared from all of the treated mice. When these survivors were rechallenged with Colon26 tumor cells on Day 120, all of them survived without showing any sign of recurrence or metastases. The results indicate that mice with malignant solid tumors, which can not be cured using chemotherapeutics alone, may be completely healed with a combination immuno-chemotherapy. During the course of this combination therapy, study, it was found that there was a clear positive correlation between immunosuppressive acidic protein (IAP) levels and tumor sizes. Suppressor macrophages (sM phi) which produce IAP were found to be decreased in bone marrow and spleen of treated mice. This suggests that the combination therapy may make the mice recover from a suppressed immune state caused by sM phi. In conclusion, the combination therapy with chemotherapeutics and BRMs could cure the solid tumor-bearing mice very effectively through not only synergistic direct tumor cell destruction but also indirect immunomodulation of the host.
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PMID:Curative treatments of murine Colon26 solid tumors by immunochemotherapy with G-CSF and OK-432. 754 45

The restoration of hematopoiesis after high-dose chemotherapy may be accelerated by the use of stem cells from the bone marrow (BM) or peripheral blood. Numerous reports utilizing mobilized peripheral blood progenitor cells (PBPC) for stem cell rescue have shown that PBPC are sufficient to restore hematopoiesis, but there are little data comparing the recovery among patients treated with various stem cell sources. We reviewed the clinical outcomes of 69 women at our institution who were treated for locally advanced or metastatic breast cancer with high-dose cyclophosphamide (CY) and thiotepa and autologous stem cell and growth factor support. Of the 43 patients with normal BM, 19 received BM alone and 24 received BM plus G-CSF mobilized PBPC. Of the 26 patients with evidence of metastatic disease in the BM, or evidence of fibrosis and hypocellularity, 15 received CY-mobilized PBPC and 11 received CY/G-CSF-mobilized PBPC. Of the marrow-negative patients, those receiving BM alone had significantly longer (P < 0.001) granulocyte recovery (absolute neutrophil count > 500 x 10(6)/l) and platelet recovery (platelets > 50 x 10(9)/l) compared with BM + G-CSF-mobilized PBPC. They also had significantly longer (P < 0.001) durations of antibiotic and amphotericin usage, increased transfusion requirements and longer hospitalizations. Of the marrow-positive patients, there was a slightly shortened granulocyte recovery, shortened hospital stays and lessened amphotericin usage in the patients who received CY/G-CSF-mobilized PBPC compared with the CY-mobilized patients. Although the number of harvested mononuclear cells differed significantly between the groups, this did not correlate with the time to hematopoietic recovery.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Source of stem cells impacts on hematopoietic recovery after high-dose chemotherapy. 758 Oct 92

A 53-year-old male with von Recklinghausen's disease, diagnosed to have metastatic large cell carcinoma in the left supraclavicular lymph node, was admitted for radiotherapy. No other primary lesions were found. Emphysematous bullae in both upper lung fields were seen on chest roentgenograph, and the leucocyte count and G-CSF level were extremely elevated. Later, when metastases appeared, systemic chemotherapy was supplemented, but in vain. An autopsy showed large cell carcinoma of the lung derived from the wall of emphysematous bullae in left lung along with multiple metastases. The presence of von Recklinghausen's disease, emphysematous bullae and lung cancer together are noteworthy.
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PMID:von Recklinghausen's disease with lung cancer derived from the wall of emphysematous bullae. 806 96

A 49-year-old woman who suffered from caecal cancer in 1988 underwent chemohyperthermic peritoneal perfusion for peritoneal and ovarian metastases in 1990, and high dose chemotherapy (HDC) with peripheral blood stem cell transplantation (PBSCT) for lung metastases in 1995. Heated saline containing anticancer drugs such as cisplatin, mitomycin C, etoposide (ETP), and pirarubicin, was intraperitoneally perfused at 43 degrees C for 60 minutes. The CD34 positive cells were mobilized by intravenous 500 micrograms G-CSF administration on five consecutive days. These cells were transplanted three days after the last day in the course of HDC, which included intravenous administration of 475 mg carboplatin, 2,020 mg cyclophosphamide, and 540 mg etoposide. The patient has survived with no sign of the disease.
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PMID:[Chemohyperthermic peritoneal perfusion and high-dose chemotherapy followed by peripheral blood stem cell transplantation in advanced colon cancer--a case report]. 885 10


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