Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chlorozotocin was given to 37 patients with advanced malignant tumors in a daily X 5 schedule at 6-week intervals. Total iv doses for each course ranged from 75 to 200 mg/m2. Myelosuppression was dose-limiting, with a platelet count depression regularly observed at doses of greater or equal to 150 mg/m2; leukopenia occurred only at the highest dose level. Nausea and vomiting were mild and uncommon. No hyperglycemia or adverse drug-related effects on renal or hepatic function were observed. No major antitumor activity occurred; however, three patients with renal cell carcinoma and one patient each with lung cancer, ovarian carcinoma, and Hodgkin's disease had minor objective decreases in tumor size. A dose range of 150--200 mg/m2 iv for each 5-day course is recommended for phase II studies.
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PMID:Phase I trial of chlorozotocin. 15 63

Streptozotocin (STZ) has shown antitumor activity against various tumors in man, but the clinical usefulness of this drug has been limited, mainly because of renal and gastrointestinal toxicity. Nineteen patients with advanced cancer of various types were given a mean dose of 3.4 g/m2 of STZ by continuous iv infusion over 5-6 days each month for one or two monthly cycles. Basic serum and urine studies were performed immediately before and after each treatment cycle. Following STZ treatment, no significant changes in BUN or creatinine were seen. Four patients in whom initial tests for proteinuria were negative developed grade 1 or 2+ proteinuria after completion of the treatment cycle. No myelosuppression or renal failure was observed. Six patients had no nausea or vomiting, seven patients had nausea only, three patients had nausea and vomiting which were well-controlled with antiemetics, and three patients had uncontrollable nausea and vomiting. Confusion, lethargy, and depression were noted in five patients who had no prior central nervous system abnormalities; these effects appeared during treatment or in the immediate posttreatment period. Two patients with diffuse non-Hodgkin's lymphoma had complete remission, while several other patients had documented improvement. Although central nervous system toxicity may be a limiting factor, prolonged STZ infusions may have significant clinical promise.
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PMID:Continuous streptozotocin infusion: a phase I study. 16 Aug 36

The effects of adriamycin were compared to a combination program of methyl-CCNU and imidozole carboxamide (DTIC) in 44 patients with disseminated malignant melanoma. There were objective clinical responses in 6 of 21 patients with the combination of DTIC and methyl-CCNU who received this program as primary treatment and none in 23 patients receiving adriamycin as primary treatment. Secondary responses were not observed with either treatment regimen. Toxicity with the combination program included leukocyte depression (less than 3,000/cu mm) in 25% and platelet depression (less than 100,000/cu mm) in 40% compared to 52% leukocyte depression and 16% platelet depression after adriamycin. There were no responses after the combination treatment program in the absence of myelosuppression. There was nausea and vomiting in virtually all patients, which was moderately severe in one third of the patients receiving the combination and in only 10% of those receiving adriamycin. Alopecia developed in all who received adriamycin but in only 15% of the combination treatment group. The combination treatment response of 28% was of the same order as most response rates previously reported in this disease. This randomized controlled clinical trail found adriamycin without clinical benefit and not worthy of further trial in patients with disseminated malignant melanoma.
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PMID:Clinical comparison of adriamycin and a combination of methyl-CCNU and imidazole carboxamide in disseminated malignant melanoma. 77 89

In order to determine whether piperazinedione used in low doses in combination with cyclophosphamide plus dimethyl-triazeno-imidazole carboxamide (DTIC) produced variable or severe myelosuppression, a Phase I Study was performed in 10 patients who received 16 courses of the three-drug combination. Although mild myelosuppression was consistently observed at doses of 4 mg piperazinedione, 400 mg cyclophosphamide, plus 400 mg DTIC, variable, severe, and prolonged myelosuppression was seen in three of six patients who received a dose of each of the drugs only 25% higher. The only other abnormality observed was nausea and vomiting. This study indicates that low doses of piperazinedione can produce variable and severe myelosuppression when used in combination with other myelosuppressive agents, and that only small increments in dosage may produce marked increases in the degree of myelosuppression. Future combination chemotherapy regimens employing piperazinedione should undergo cautious Phase I toxicity testing to avoid severe depression of blood counts.
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PMID:Severe myelosuppression from piperazinedione, (NSC No. 135758), cyclophosphamide plus dimethyl-triazeno-imidazole carboxamide (DTIC). 90 59

The present investigations have assessed the effects of prolonged cyclophosphamide (CY) and Corynebacterium (CP) treatment on the production of bone marrow macrophage precursors [colony-forming cells (CFC)] and on the cytotoxicity of macrophages comprising colonies produced by the CFC. The findings have been correlated with tumor growth in animals receiving the immunochemotherapy. In addition, studies have been directed toward ascertaining whether the administration of CP with CY might lessen the myelosuppressive effects of the latter. Following each consecutive weekly dose of CY (even after as many as 11), there was a significant depression in the number of bone marrow cells (BMC's) but, by the next injection, marrow cellularity had returned to normal. When the number of BMC's was reduced, the proportion of the remaining cells, which consisted of CFC, was increased. Upon reconstitution of the marrow, the proportion of CFC returned to the level of the controls. The total number of CFC in marrow was at no time following CY therapy significantly less than the number in marrow of untreated mice. The addition of CP to the treatment regimen with CY resulted in an absolute as well as relative increase in CFC at all times during administration of the combined therapy, i.e., when there was a depression in total numbers of marrow cells, as well as when marrow restoration had occurred. Although CP stimulated the number of cells entering into differentiation, it failed to affect the total numbers of marrow cells, as well as when marrow restoration had occurred. Although CP stimulated the number of cells entering into differentiation, it failed to affect the total BMC's had been neither increased nor prevented from decreasing, by CP administration, indicating that the use of total cellularity as an index of the CP marrow-sparing effect is without merit. The present results relative to cytotoxicity of macrophages derived from the CFC concur with and extend our previous findings indicating that the cytotoxic property of macrophages originates in its ancestral stem cell or CFC and that factors responsible for increasing the CFC population do not selectively stimulate precursor cells responsible for production of the cytotoxic macrophage. Although the proportion of cytotoxic macrophages was not altered by CP when administered with CY, the absolute number of such cells was increased. Since the increase in macrophage colony production and, consequently, in cytotoxic macrophages correlates with increased inhibition of tumor growth when CP was used with CY, it is suggested that macrophage precursors are the cells of primacy in CP immunopotentiation. Their stimulation, resulting in enhanced cytotoxic macrophage formation, could be responsible for the inhibition of tumor growth observed in our model system. The findings also suggest that when myelosuppression is a limiting factor in the use of a chemotherapeutic agent, the concomitant use of CP may be advantageous.
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PMID:Correlation of antitumor chemoimmunotherapy with bone marrow macrophage precursor cell stimulation and macrophage cytotoxicity. 127 29

Relapse continues to be a problem after bone marrow transplantation (BMT) for hematologic malignancies, particularly in recipients of autologous or T-cell-depleted allogeneic grafts and in patients with advanced disease. Interferon (IFN) has shown antiproliferative activity in several malignant hematologic diseases and potentially may be of benefit when administered early after BMT when the number of residual cells is minimal. We tested in a phase I study the maximum tolerated daily dose of recombinant IFN alpha-2b in patients who had received a transplant for a disease at high risk for relapse (acute myeloid leukemia or non-Hodgkin's lymphoma beyond first remission, advanced myelodysplastic syndrome, acute lymphoblastic leukemia at any stage, chronic myeloid leukemia in accelerated or blast phase. Recombinant IFN alpha-2b was started at a dose of 0.5 x 10(6) IU/m2 and escalated by 0.5 x 10(6) IU/m2 in groups of three or four patients. The intention was to administer IFN as soon as stable engraftment after BMT was achieved (defined as an absolute neutrophil count of greater than 2.0 x 10(9)/L and platelet count greater than 100 x 10(9)/L for 5 consecutive days) and continued for 2 months. A total of 14 patients were enrolled after autologous (n = 3) or allogeneic (n = 11) BMT. Dose-limiting toxicity was myelosuppression. Significant (grade 2 to 4) neutropenia and thrombocytopenia led to discontinuation or dose reduction in five of eight patients receiving 1.5 x 10(6) or 2 x 10(6) IU/m2 IFN. Mild to moderate (grade 1 or 2) anorexia, weight loss, and fatigue occurred in the majority of patients independent of the IFN dose. De novo acute GVHD responsive to steroid treatment developed in 3 of 11 allograft recipients. Natural killer (NK) cell function was low before IFN treatment and was not improved with the cytokine. Conversely, interleukin-2-activated NK cells showed normal function even before starting IFN and no change was seen during IFN treatment. Clonogenic hematopoietic progenitor studies showed depression of all progenitor lines (colony-forming unit [CFU]-granulocyte, erythroid, monocyte, megakaryocyte, CFU granulocyte-macrophage, burst-forming unit-erythroid) by IFN at all dose levels except at 0.5 x 10(6) IU/m2. Considering this result and the incidence and severity of marrow depression seen at doses greater than 1.0 x 10(6) IU/m2, we would consider this the maximum dose safely tolerated if IFN alpha-2b is administered in this setting for a prolonged course on a daily basis.
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PMID:Treatment with recombinant interferon (alpha-2b) early after bone marrow transplantation in patients at high risk for relapse [corrected]. 174 91

Myelosuppression in patients with cancer is usually the result of tumor invasion of the bone marrow, cytotoxic chemotherapy, or radiation therapy, all of which suppress bone marrow function. Anemia, thrombocytopenia, and neutropenia are the three most clinically significant complications that result from bone marrow depression. Although anemia and thrombocytopenia can produce serious clinical problems, blood-component transfusions--despite having inherent problems of their own--usually are successful in correcting or minimizing these complications. Although neutropenia is manageable in most situations, it remains a serious problem that, at its worst, can progress to life-threatening septicemia. The longer neutrophil counts remain low, the more susceptible patients become to infection by endogenous and exogenous microbial flora. Accordingly, the oncology nurse increases the frequency of patient assessment and monitoring for infection. Control measures are introduced to minimize environmental contaminants. These measures attempt to reduce the incidence of opportunistic infections that frequently occur in patients with severe or prolonged neutropenia and for which antimicrobial therapy is indicated. Implementing specific infection-control interventions and thoroughly educating the patient and his/her family help to limit the clinical problems associated with myelosuppression for most patients.
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PMID:Current strategies for managing myelosuppression in patients with cancer. 190 77

Hematopoietic depression and subsequent susceptibility to potentially lethal opportunistic infections are well-documented phenomena following radiotherapy. Methods to therapeutically mitigate radiation-induced myelosuppression could offer great clinical value. In vivo studies in our laboratory have demonstrated that interleukin-6 (IL-6) stimulates pluripotent hematopoietic stem cell (CFU-s), granulocyte-macrophage progenitor cell (GM-CFC), and erythroid progenitor cell (CFU-e) proliferation in normal mice. Based on these results, the ability of IL-6 to stimulate hematopoietic regeneration following radiation-induced hematopoietic injury was also evaluated. C3H/HeN female mice were exposed to 6.5 Gy 60Co radiation and subcutaneously administered either saline or IL-6 (1,000 micrograms/kg) on days 1 through 3 or 1 through 6 postexposure. On days 7, 10, 14, 17, and 22, femoral and splenic CFU-s, GM-CFC, and CFU-e contents and peripheral blood white cell, red cell, and platelet counts were determined. Compared with saline treatment, both 3-day and 6-day IL-6 treatments accelerated hematopoietic recovery; 6-day treatment produced the greater effects. For example, compared with normal control values (N), femoral and splenic CFU-s numbers in IL-6-treated mice 17 days postirradiation were 27% N and 136% N versus 2% N and 10% N in saline-treated mice. At the same time, bone marrow and splenic GM-CFC values were 58% N and 473% N versus 6% N and 196% N in saline-treated mice; bone marrow and splenic CFU-e numbers were 91% N and 250% N versus 31% N and 130% N in saline-treated mice; and peripheral blood white cell, red cell, and platelet values were 210% N, 60% N, and 24% N versus 18% N, 39% N, and 7% N in saline-treated mice. These studies demonstrate that therapeutically administered IL-6 can effectively accelerate multilineage hematopoietic recovery following radiation-induced hematopoietic injury.
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PMID:Administration of interleukin-6 stimulates multilineage hematopoiesis and accelerates recovery from radiation-induced hematopoietic depression. 199 Nov 64

Bone marrow depression (myelosuppression) in the patient with cancer may result from the disease itself or from its treatment. The consequences of myelosuppression are numerous; the most critical problem that results from leukopenia is infection. Serious clinical consequences follow depression of normal leukocyte function. A clear understanding of the functioning of each type of leukocyte is essential for managing the various complications associated with leukopenia. The three components of myelosuppression management are: prevention of infection, frequent patient assessment for the early detection of infection, and aggressive management when such infection arises. The oncology nurse minimizes patient- and environment-related sources of infection and is aware that detection is complicated by the lack or diminution of signs and symptoms in a leukopenic patient. Infections that arise are managed in different ways, depending on the pathogen and on available therapy. In addition to conventional antimicrobial therapy, newer therapeutic modalities, such as colony-stimulating factors, may hold promise for the treatment of leukopenic patients. The nurse is responsible for many aspects of the care for these patients.
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PMID:Management of myelosuppression in the patient with cancer. 210 82

We have investigated the effects of interleukin 1 (IL-1) administration on the ability of neutropenic mice to resist Pseudomonas aeruginosa challenge in vivo. Cyclophosphamide-treated mice received human rIL-1 beta at 7.0, 0.7, or 00.7 micrograms/kg, according to different regimens, to be challenged with a lethal ip inoculum of pseudomonas cells 5 days after myelosuppression. The repeated exposure of the neutropenic mice to an overall cytokine dosage of 7.0 or 0.7 micrograms/kg during the 4 days after myelosuppression was found to optimally restore the animals' antibacterial resistance. However, when administered as a single injection 24 hr before challenge, the same dosages of IL-1 had lower or no effect in enhancing survival, primarily leading only to a reduction in the amount of antipseudomonal chemotherapy required for cure. The regimen of IL-1 administration conferring optimal protection also resulted in a decrease in the number of pseudomonas cells recovered from the peritoneal cavity of infected mice. This regimen accelerated hematopoietic recovery in cyclophosphamide-treated mice. Assay of serum colony-stimulating activity (CSA) revealed that (a) cyclophosphamide treatment alone significantly increased the level of circulating CSA, (b) administration of a single dose of IL-1 to neutropenic mice induced an early, further increase in serum CSA, followed by depression, (c) a biphasic pattern of CSA response was also evident in mice repeatedly treated with IL-1. These results suggest that regulation of hematopoiesis may have an important role in the induction of antibacterial resistance in myelosuppressed hosts repeatedly treated with low dosages of IL-1.
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PMID:Antibacterial resistance induced by recombinant interleukin 1 in myelosuppressed mice: effect of treatment schedule and correlation with colony-stimulating activity in the bloodstream. 211 38


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