Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The safety of administering the live attenuated Oka/Merck varicella vaccine to the well siblings of children with malignancy was evaluated as a strategy for reducing the risk of household exposure to varicella among immunocompromised children. Susceptible well children were eligible for vaccination if the child with malignancy had leukemia, lymphoma, or solid tumor in remission for 3 months or longer. No evidence of vaccine virus transmission was found among 30 children with malignancy whose 37 healthy susceptible siblings were immunized with varicella vaccine. Varicella-zoster virus was not isolated from the oropharyngeal secretions taken from 17 vaccinees or their 14 immunocompromised siblings. None of the 30 immunocompromised children had vaccine-related rashes or showed immunologic evidence of subclinical varicella-zoster virus infection based on testing for varicella-zoster virus IgG antibodies and T-lymphocyte proliferation to varicella-zoster virus. Four healthy vaccinees eventually had mild breakthrough cases of varicella, with transmission to the high-risk sibling in 3 cases. However, even in these families, the immunocompromised children had been protected from household exposure varicella for at least 20 months early in the course of their immunosuppressive treatment.
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PMID:Lack of transmission of the live attenuated varicella vaccine virus to immunocompromised children after immunization of their siblings. 184 36

Nuclear and membrane markers that have been related to proliferative activity were measured by flow cytometry. The markers studied were transferrin receptor (TR), Ki-67 antigen, and epidermal growth factor receptor (EGFR). Two-color analysis for DNA via propidium iodide binding and for antigen expression via either a direct or indirect immunofluorescence assay was performed on three different cell lines and a solid human tumor model. The three cell lines tested were MCF-7 (breast), K-562 (leukemia), and A431 (a squamous cell). The solid tumor was obtained by subcutaneous injection of A431 cells into an athymic nude mouse. Our results demonstrate that TR are cell-cycle specific and can be readily measured in the cell lines. Ki-67 antigen is also cell-cycle specific in the cell lines tested, but the mean channel specific fluorescence uptake varies in the cell types. Finally, the EGFR was observed only in the A431 cell line, with most cells equally expressing this receptor. A bimodal distribution of EGFR was observed in A431 cells obtained from a solid tumor grown in an athymic nude mouse system. This suggests that cell line analysis may not always represent what might be observed under in vivo conditions. There are advantages to flow cytometry measurements of these factors which might be useful in predicting how patients should be treated and possibly the prognosis of cancer patients.
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PMID:Measurement of proliferation nuclear and membrane markers in tumor cells by flow cytometry. 185 60

In this study, the influence of different stages and transplantation routes of the experimentally widely used solid tumor melanoma B16 on the pharmacokinetics of the antineoplastic agent mitoguazone was investigated in B6D2F1 mice. It could be shown that changes of the pharmacokinetic parameters as well as the distribution pattern of this drug were clearly influenced and dependent on the tumor stage but not by the tumor inoculation route. Advanced melanoma (d16) led to a sharp decrease in the terminal elimination half-life as well as to decreased spleen levels and increased initial liver concentrations of the drug. With respect to the results obtained in leukemia P388-bearing mice it can be concluded that the tumor stage as well as the tumor model are to be considered as important factors in which way and to which extent a tumor may alter the pharmacokinetics of antineoplastic agents.
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PMID:Influence of melanoma B16 on the pharmacokinetics of mitoguazone in mice. 185 30

Merocyanine 540 (MC 540) is a photosensitizing dye that has been used in a phase I clinical trial for the purging of leukemia and lymphoma cells from autologous bone marrow grafts. In this paper we examine the role of plasma membrane negative charge, plasma membrane fluidity, and plasma membrane hydrophobicity in the regulation of a cell's susceptibility to MC 540-sensitized photoirradiation. Among solid tumor cells, we found an inverse correlation between surface electronegativity, affinity for dye molecules, and susceptibility to MC 540-sensitized photoinactivation. That is, the least electronegative cells bound the highest amount of dye and were the most susceptible to dye-sensitized photoirradiation. By contrast, no such correlations were found among leukemia/lymphoma cells. This suggested that dye binding and susceptibility to MC 540-mediated photodynamic damages are regulated differently in hematopoietic/lymphopoietic and solid tumor cells.
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PMID:Plasma membrane properties regulating the sensitivity of leukemia, lymphoma, and solid tumor cells to merocyanine 540-sensitized photoirradiation. 186 93

3 cases of leukemia after solid tumor and 2 cases of solid tumors after leukemia were reported. The features of leukemia after solid tumor and the relationship between the solid tumor and leukemia, as well as the possible pathogenetic factors of the secondary malignancies were discussed.
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PMID:[Leukemia and solid tumor]. 187 91

A set of 30 mitomycin C and mitomycin A analogues, including five new compounds, was screened against three different solid human tumor cell lines using the MTT tetrazolium dye assay. A statistically significant correlation among antitumor activity, quinone reduction potential (E1/2), and the logarithm of the partition coefficient (log P) was obtained, with the most easily reduced and the most lipophilic compounds being the most potent. When these analogues were separated into mitomycin C and mitomycin A subsets, the former gave a correlation only with E1/2, whereas the latter (which differ little in their E1/2 values) gave a correlation only with log P. These correlations are in contrast to those made in the P388 leukemia assay in mice wherein the most active mitomycin C and mitomycin A analogues were the most hydrophilic ones. When the same compounds were tested against P388 leukemia cells in the MTT assay, the results were the same as those of the solid tumor assays. Thus, the substantial differences in relative potencies of mitomycins are related not to the kind of tumor cell, but to the type of assay performed, cell culture versus whole animal. No correlation was found between antitumor potency in the cell culture systems and calculated relative DNA binding strengths, probably because the limiting factors in antitumor potency of mitomycins appear to be tumor cell uptake (log P) and/or bioreductive activation (E1/2).
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PMID:Structure-activity relationships for mitomycin C and mitomycin A analogues. 190 9

Through the extensive investigation of new mitomycin C (MMC) derivatives, several compounds with disulfide at N-7 were found to show activities superior to MMC against murine Sarcoma 180 solid tumor. Among them, 7-N-[[2-[[2-(gamma-L-glutamylamino)ethyl]dithio]ethyl]]- mitomycin C (KW-2149) was selected for further evaluation of antitumor activity and toxicity in mice. KW-2149 exhibited activity superior to MMC in increasing survival of i.p. inoculated P388 leukemia-, M5076 sarcoma-, and B16 melanoma-bearing mice. KW-2149 administered i.v. also exhibited superior activity in inhibiting the growth of s.c. inoculated P388 leukemia, M5076 sarcoma, and colon 26 adenocarcinoma and in increasing survival of i.v. inoculated P388 leukemia- and M5076 sarcoma-bearing mice. Furthermore, KW-2149 remarkably increased the life span of MMC-resistant P388 leukemia- and L1210 leukemia-bearing mice. KW-2149 and MMC inhibited the growth of human tumors inoculated into nude mice. The activity of KW-2149 was prominent in human lung carcinoma Lu-65 and Lu-99, bladder carcinoma T24, and epidermoid carcinoma A431. KW-2149 was comparable to MMC in decreasing the number of WBC in the peripheral blood, and the thrombopenia induced by KW-2149 was mild and recovery was rapid. The in vitro anticellular spectrum of KW-2149 against 23 human tumor cell lines was similar to that of MMC. However, KW-2149 inhibited the growth of the cell lines at concentrations of 10- to 100-fold lower than MMC and showed efficient cytotoxicity against MMC-insensitive tumor cell lines. These included lung epidermoid carcinoma Calu-1, stomach carcinoma MKN-28, colon adenocarcinoma DLD-1, colon adenocarcinoma LoVo, bladder carcinoma HT-1197, sarcoma G-292, and melanoma SK-MEL-28 cells. These results indicate that KW-2149 bears interesting characteristics as a new anticancer drug and warrants further development.
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PMID:Antitumor activity of 7-N-[[2-[[2-(gamma-L-glutamylamino)ethyl]dithio]ethyl]]-mitomycin C. 198 76

The risk of second primary cancer (SPC) was evaluated in 947 patients treated for Hodgkin's disease (HD) during the period January 1969 to December 1979. The median follow-up of this series was 10.5 years (range, 9 to 19). Treatment categories included radiotherapy (RT) alone (115 patients, 12%), chemotherapy (CHT) alone (161 patients, 17%), combined RT plus CHT (381 patients, 40%), and salvage treatment for resistant or relapsing HD (290 patients, 30.6%). Fifty-six SPCs were observed, occurring between 1 and 17 years from initial treatment. Among these, secondary acute nonlymphoid leukemia (s-ANLL) was the most frequent SPC (23 cases). Secondary non-Hodgkin's lymphoma (s-NHL) occurred in 5 patients, whereas a secondary solid tumor (s-ST) was observed in 28 patients. The calculated actuarial risk (+/- SE) of developing SPC was 5.0% (+/- 0.9%) and 23.1% (+/- 5.8%) at 10 and 19 years, respectively. Concerning treatment modalities and s-ANLL risk, no cases were observed in the radiotherapy group, whereas CHT plus RT and salvage groups showed the highest actuarial risk. This was, in fact, at 10 and 19 years, 3.1% (+/- 0.9%) and 8.1% (+/- 4.0%) in the former group, and 1.8% (+/- 1.0%) and 16% (+/- 9.0%) in the latter. A statistically significant difference was observed when the CHT plus RT group was compared with CHT and RT groups (P = .04). Concerning the relationships with chemotherapeutic regimens, 12 s-ANLL cases occurred in the mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) plus RT group, and only one case in the group receiving doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus RT. A statistically significant difference of s-ANLL actuarial risk was found comparing patients receiving MOPP plus RT to all other treatment groups (P = .04). With respect to s-ST, the actuarial risk at 10 and 19 years was 2.0% (+/- 0.6%) and 13.0% (+/- 3.8%), respectively. No significant differences were found among groups treated with different modalities. These data were confirmed by a multivariate analysis, which indicated treatment modality and age as independent variables for s-ANLL and s-ST development, respectively. Based on the prolonged follow-up analysis, the actuarial SPC risk at 10 years hereby reported should reflect the real SPC incidence in our series.
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PMID:Second primary cancer following Hodgkin's disease: updated results of an Italian multicentric study. 199 12

Penclomedine is 3,5-dichloro-2,4-dimethoxy-6-(trichloromethyl)pyridine (NSC 338720), an alpha-picoline derivative with p.o. antitumor activity in preclinical leukemia and solid tumor models. Described here are an in vivo cross-resistance profile of penclomedine, treatment schedule dependence studies, and studies exploring the effects of p.o. drug on human tumors xenografted into mouse brain. The latter studies exploited the apparent facile distribution of penclomedine to the central nervous system. Tumor models used included murine leukemia lines selected in vivo for acquired resistance to various antitumor drugs and the human mammary and lung tumor xenografts MX-1 and H82, respectively. The therapeutic effects of p.o. penclomedine against s.c. MX-1 and H82 xenografts were shown to be independent of treatment schedule. Therapeutic activity was comparable when p.o. and parenteral treatments were compared. Lines of P388 leukemia resistant to melphalan, cyclophosphamide, and carmustine were cross-resistant to penclomedine in vivo. Leukemia lines resistant to antimetabolites, DNA binders/intercalators, and vincristine were not cross-resistant to penclomedine. Intracerebrally implanted MX-1 xenografts retained their sensitivity to p.o. penclomedine, and therapeutic activity was at least comparable to that of carmustine, a drug known for its ability to cross the blood-brain barrier. These results demonstrate attributes of penclomedine that are relatively uncommon among currently available antitumor drugs and that are of interest for the anticipated clinical development of this drug.
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PMID:Preclinical antitumor activity of penclomedine in mice: cross-resistance, schedule dependence, and oral activity against tumor xenografts in brain. 200 16

We analyzed the changes of frequency of bacterial positive cases on the basis of blood cultures, clinical background and administrated antibiotics for the patients with bacteremia in Nagoya University Hospital from January 1978 to December 1987. During the ten years, the number of samples increased from 330 in 1978 to 1231 in 1987. Moreover, bacterial positive cases increased from 27 (8.2%) in 1978 to 152 (12.3%) in 1987. Organisms isolated consisted of 138 strains of coagulase negative Staphylococci (CNS), 81 Staphylococcus aureus, 60 Candida sp., 58 Escherichia coli, 47 Pseudomonas aeruginosa, and other species. During the period of 1986-1987, of the 92 patients with bacteremia, 85 patients (92.4%) had underlying diseases including leukemia, solid tumor, cardiovascular disease, diabetes mellitus or other diseases. In addition, 67 patients (73.9%) underwent intravascular catheters, urethral catheters, postoperative drainages or other prosthetic insertions. Fourteen patients died of septicemia within a week after recovery of the organism in the blood culture. The recovery rate for gram positive cocci in blood culture increased in the 1980's. It may partly be due to the prevalent use of these prosthetic insertions, and the preferable use of second and third generation cephalosporin antibiotics.
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PMID:[Bacterial survey of patients with bacteremia during the ten years (1978-1987) in Nagoya University Hospital]. 206 98


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