Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autologous bone marrow transplantation (ABMT) is the treatment of choice for selected patients with acute myelogenous leukemia, non-Hodgkin's lymphoma, and poor prognosis breast cancer. A possible limitation of this approach is that clonogenic tumor cells could be collected and infused back into the patient along with the normal bone marrow. The major emphasis in our laboratory has been the development of marrow purging regimens for breast cancer patients. This paper describes two investigative approaches hematopoietic progenitor cell protection and selection. We describe how the use of G-CSF in the patients who receive positively selected marrow shortens the rate of engraftment.
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PMID:Purging of autologous bone marrow for transplantation: the protection and selection of the hematopoietic progenitor cell. 136 17

A 40-year-old female was admitted to our hospital with a large right breast tumor that was over 15 cm in diameter. We treated this locally advanced breast cancer by intra-arterial infusion chemotherapy. Through a catheter placed in the right subclavian artery, doses of 20-30 mg of ADM were injected intermittently with MMC and 5-FU. When a total of 120 mg of ADM had been infused, leukopenia developed, but this was immediately improved by G-CSF. With this treatment, her breast tumor and lung metastases were almost completely disappeared. Thus, an intra-arterial infusion chemotherapy was considered to be an effective treatment for locally advanced breast cancer.
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PMID:[Successfully treated locally advanced breast cancer by intra-arterial infusion chemotherapy: a case report]. 137 51

Expression of granulocyte (G) and granulocyte-macrophage (GM) colony stimulating factor (CSF) genes in human cells of astroglial lineage was studied. Primers for CSFs were used to analyze RNA transcripts in 5 cultured human astrocytoma cell lines and 8 fresh brain specimens by polymerase chain reaction. Constitutive expression of mRNA transcripts of GM-CSF could be detected in all astrocytoma and one neuroblastoma cell lines, and two out of 5 unstimulated astrocytomas, U87MG and U138 MG, expressed G-CSF genes. After stimulation with interleukin (IL)-1 beta + tumor necrosis factor (TNF)-alpha, all cell lines expressed G-CSF. In addition to the cultured cells, we examined gene expression within human malignant astrocytoma, peritumoral brain and autopsied normal brains. The results show that some of the tumor and its surrounding reactive lesions express G- and GM-CSF genes but normal brains do not. The concentration of G- and GM-CSF in supernatants of cultured cells was assessed at the protein level by ELISA. A low level of GM-CSF activity was constitutively present in all astrocytomas. G-CSF was detected in unstimulated U87MG and U138MG and other cell lines could synthesize G-CSF after the stimulation of IL-1 beta and TNF-alpha at the level of mRNA. Furthermore, the concentration of CSFs increased markedly upon stimulation with IL-1 beta and/or TNF-alpha in both a time- and dose-dependent fashion. From these results, it is suspected that astroglial cell-derived CSFs may participate in local immune reactions accompanying infection, degeneration and malignancies in the brain.
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PMID:Expression of granulocyte colony stimulating factor and granulocyte-macrophage colony stimulating factor genes in human astrocytoma cell lines and in glioma specimens. 137 84

The present study was designed to evaluate the effects of a recombinant human G-CSF (rhG-CSF) and a mutein G-CSF (KW-2228) on leucopenia and tumor growth in mice treated with 5-fluorouracil (5-FU). In normal mice, the number of leucocytes (white blood cell, WBC) reached the peak 12 hours after a single injection of either type of G-CSF and decreased to the normal level after 24 hours. Daily administration induced a continuous increase in the WBC count, however, administrations at intervals did not. Meth-A fibrosarcoma was subcutaneously inoculated into the backs of syngeneic BALB/c mice. The mice were treated with 5-FU alone or with G-CSFs. Chemotherapy with 5-FU alone resulted in leucopenia and an insignificant inhibition of tumor growth. The conjunctive administration of G-CSFs with 5-FU resulted in a significantly augmented inhibition of tumour growth, and leukopenia was not seen. This augmenting effect was more prominent with KW-2228. These results suggest that in 5-FU chemotherapy G-CSFs may be beneficial in restoring the number of leucocytes from leucopenic state and in augmenting the tumor inhibitory effect. Furthermore, KW-2228 may be more beneficial than the natural type rhG-CSF.
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PMID:Comparative effects of a recombinant and a mutein type of granulocyte colony stimulating factor on the growth of Meth-A fibrosarcoma with 5-fluorouracil chemotherapy. 137 28

Ru 41.740 (Biostim) is an immunostimulating drug of microbial origin which may stimulate human mononuclear blood cells (mainly monocytes) to release soluble factors which inhibit replication of several tumor cell lines in vitro. Since this effect may be of clinical importance in the treatment of cancer a number of tests have been conducted in order to find methods to augment this secretion. In vitro tests suggested that this non-specific antitumor activity of Biostim may not be enhanced by concomitant treatment of patients with inhibitors of cyclo-oxygenase and lipoxygenases or by interferons alpha, beta, gamma or the hemopoietic growth factors GM-CSF and G-CSF.
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PMID:Ru 41.740 triggers human mononuclear blood cells to release tumor growth inhibitory factors in vitro. 137 44

A modified recombinant human granulocyte colony-stimulating factor (rhG-CSF), KW-2228, has some excellent properties such as high specific activity in stimulating granulocyte colony-formation in vitro, great biological stability in plasma, good pharmacokinetic profile and high potency in granulopoiesis in normal mice in vivo. Recently, the application of G-CSF against infectious diseases has been considered, and some animal experiments have been carried out to support its in clinical applications. Patients with underlying diseases such as leukemia or cancer often have recurrent infections because of reduced number and functions of neutrophils, which mediate an early stage of host defense. We investigated the prophylactic effect of KW-2228 against an experimental systemic infection with Pseudomonas aeruginosa in tumor-bearing mice (colon 26: BALB/c) treated with cyclophosphamide. KW-2228 (0.25-2.0 micrograms/mouse) was administered (s.c.) once a day for 4 days before the experimental bacterial infection. As a result of KW-2228 administration, the reduction in peripheral blood neutrophils usually caused by the injection with cyclophosphamide was prevented markedly. KW-2228 displayed excellent protective potency dose-dependently against the infection with P. aeruginosa in tumor-bearing mice. These data show the possibility that prophylactic therapy with KW-2228 may augment the host defense of immunocompromised patients to infections. It present, clinical efficacy studies on KW-2228 are under way.
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PMID:[Protective effect of KW-2228 in a systemic infection model of CPA-treated tumor-bearing mice]. 137 51

A modified recombinant human granulocyte colony-stimulating factor (rhG-CSF), KW-2228, has some excellent properties such as high specific activity in stimulating granulocyte colony-formation in vitro, great biological stability in plasma, good pharmacokinetic profile and high potency in granulopoiesis in normal mice in vivo. Recently, the application of G-CSF against infectious diseases has been considered, and some animal experiments have been carried out to support its clinical applications. Patients with underlying diseases such as leukemia and cancer often have recurrent infections because of reduced numbers or functions of neutrophils, which mediate an early stage of host defense. In out present study, we established a new method to evaluate in vivo potency of G-CSF in colon 26 tumor-bearing mice. By using the method, we examined combination effects of KW-2228 with aminoglycoside antibiotics against a systemic infection caused by Pseudomonas aeruginosa. KW-2228 (1 microgram/mouse/day) was administered (s.c.) once a day for 4 days before the bacterial infection was introduced in colon 26 tumor-bearing mice receiving cyclophosphamide 3 days after the transplantation of tumor. Antibiotics were administered (s.c.) 2 hours after the introduction of the bacterial infection. ED50 of gentamicin (GM) alone and that of the combination with KW-2228 were 40.7 mg/kg and 3.6 mg/kg, respectively. ED50 of astromicin (ASTM) alone and that of the combination with KW-2228 were 386 mg/kg and 17.8 mg/kg, respectively. Thus the combination therapy of KW-2228 with GM or ASTM exhibited excellent protective effects in comparison to the treatment with antibiotic alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Combination effect of KW-2228 and aminoglycoside antibiotics on systemic infection in cyclophosphamide-treated tumor-bearing mice]. 137 53

Recent advances in our understanding of the hemolymphopoietic growth factors has revolutionized knowledge of blood cell development, the immune system, and of tumor cell biology. However, the rapid translation of these insights from basic research to the clinic has been perhaps the most dramatic part of the story. Commercially available erythropoietin has become established for the treatment of the anemia of end-stage renal disease, and promises to be of value in the supportive care of patients with cancer and perhaps other chronic diseases. It likely will be increasingly utilized for enhancing autologous blood donation and for perioperative management. Both GM-CSF and G-CSF only recently released by the FDA for specific clinical indications, though there are a variety of potential applications (Table 12). It is clear that G-CSF is the therapy of choice for most neutropenias and that both agents have effects in diminishing the myelotoxicity and mucositis seen after aggressive chemoradiotherapy. However, it is important to note that as yet there is no evidence that the use of either G-CSF or GM-CSF has resulted in increased cure rates or, in fact, increased survival in patients with various malignancies. It would appear that both G-CSF and GM-CSF will, in fact, allow dose escalation and/or diminished toxicity of various chemotherapeutic regimens. However, there are important considerations in the overall place of these cytokines with regard to treatment of human disease. A major goal in the therapy of patients with malignancy is obviously prolongation of life and cure. If, in fact, escalation of doses of chemotherapeutic agents does not result in increased tumor responses or cures then the use of these growth factors will have a relatively trivial impact on the care of cancer patients. In addition, the disturbing observations of receptors for these growth factors on various tumor cell lines and of varying degrees of in vitro tumor cell proliferative responses raises the possibility that in some situations they may actually stimulate tumor growth. This is an unknown which has not been adequately evaluated in any clinical study to date and which may vary from tumor to tumor. For example, if these cytokines increase tumor growth rate by 20-30% (an effect which would probably not be detected in the clinical studies to date) while allowing an escalation of chemotherapy doses it is possible that there would be no significant beneficial effect.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hematopoietic growth factors. 142 40

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 complex histological pattern in Hodgkin's disease and in part in large cell anaplastic lymphomas (ALCL) suggests that close interactions exist between the tumor cells and reactive bystander cells. These interactions are most likely mediated by short ranged cytokines. The production of cytokines was analyzed in primary tissues and cell lines from Hodgkin's disease and ALCL by enzyme linked immunosorbent tests (ELISA), Northern blotting, immunohistological staining and in situ hybridization experiments. Our results indicate that Hodgkin's disease derived cell lines produce a variety of cytokines, such as IL1 alpha, IL4, IL5, IL6, IL8, IL9, TNF alpha and TNF beta but not IL1 beta, IL2, IL3 and G-CSF. In addition, the receptors for IL6 were detected in some of the cell lines. The expression of IL6 and IL6 receptors and IL9 has been confirmed for some primary tissues of Hodgkin's disease. From our data, we conclude that IL6, IL9 and additional cytokines are involved in the biology of Hodgkin's disease and ALCL.
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PMID:Activation of cytokines in Hodgkin's disease. 145 74


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