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11.
Chromosomes and causation of human cancer and leukemia. LIV. Near-tetraploidy in acute leukemia 总被引:2,自引:0,他引:2
R Abe A Raza H D Preisler C K Tebbi A A Sandberg 《Cancer Genetics and Cytogenetics》1985,14(1-2):45-59
Near-tetraploid cell populations were observed in a case of T-cell acute lymphoblastic leukemia (T-ALL) and in one of acute myeloblastic leukemia (AML). In the ALL case, hyperdiploid chromosomal changes, characterized by an isochromosome 17q [i(17q)], as well as other changes, were seen at the onset of the disease. At the first relapse, hypertetraploid cells appeared in about 10% of the mitoses in the bone marrow (BM), and by the second and third relapses, the hypertetraploidy was present in more than 90% of the mitoses in the BM. Even though karyotypic instability was evident, all abnormal karyotypes contained one or two i(17q) at every sampling. In spite of karyotypic instability at each relapse, karyotypic evolution was observed whenever relapse occurred. A normal female karyotype was confirmed in the BM of each period. Immunologic examinations performed at each sampling revealed no recognizable changes before and after the appearance of tetraploidy. In the AML case, which was classified as FAB M2, cytogenetic examination was performed at diagnosis and relapse. In both, hypotetraploid cells were observed in over 60% of the BM cells; the modal chromosome number was 90. Banding analysis was successful at relapse, and a pseudodiploid clone characterized by t(8;21) and a hypotetraploid clone with two t(8;21) and a loss of two Y chromosomes were observed in the same BM sample. A normal male karyotype was also observed in BM cells. In both cases, giant and bizarre blasts were seen in the BM. A close correlation between near-tetraploid mitoses and giant and bizarre blast cells in BM smears of the same samples was observed. Previously published tetraploid acute leukemia cases analyzed with banding methods were accumulated and compared with our two cases. 相似文献
12.
Preben Jakobsen Bente Søresen Lars Bastholt Mansoor Raza Mirza Susanne B. Gjedde Henning T. Mouridsen Carsten Rose 《Cancer chemotherapy and pharmacology》1994,35(1):45-52
A high-pressure liquid chromatographic method for determination of the bisdioxopiperazine derivative ADR-529 (ICRF-187), a compound proven effective in protection against anthracycline-induced cardiotoxicity, has been developed. The limit of quantitation was 5 ng/ml using a narrow-bore 5-m silica column and UV detection. The method was used for determination of pharmacokinetic profiles of ADR-529 after a 3-weekly i.v. administration of different doses of ADR-529 (600–1000 mg/m2) together with different doses of epirubicin (E, 60–100 mg/m2), fixed-dose cyclophosphamide (C, 600 mg/m2), fixed-dose 5-fluorouracil (F, 600 mg/m2), and daily administration of tamoxifen (T, 30 mg; CEF-T) in the treatment of patients with metastatic breast cancer. Pharmacokinetic parameters for epirubicin were also determined. The aim of the study was to determine (1) whether the pharmacokinetics of ADR-529 as part of a combination with CEF-T changes with increasing doses of ADR-529 and increasing doses of epirubicin and (2) whether the pharmacokinetics of epirubicin in the same combinations is altered with the administration of increasing doses of ADR-529. A total of 82 patients were included. A crossover study including 16 of the patients showed no significant difference in epirubicin pharmacokinetic parameters when epirubicin was given with or without concomitant administration of ADR-529. Apart from minor changes in the distributional half-lives, the pharmacokinetic parameters of epirubicin were not altered with increasing doses of ADR-529, nor were the pharmacokinetic parameters of ADR-529 itself. Escalating doses of epirubicin did not significantly alter the pharmacokinetic parameters of ADR-529 with the exception of a 30% increase in the terminal half-life and a decrease in total body clearance when the epirubicin dose was raised from 60 to 100 mg/m2. We conclude that concomitant administration of ADR-529 does not alter the distribution and elimination of epirubicin in doses suitable for preventing the anthracycline-induced cardiotoxicity. 相似文献
13.
Boyd Swinburn M.D. FRACP Garry Egger Ph.D. M.P.H. Fezeela Raza M.A. 《Preventive medicine》1999,29(6):563
Background. The “obesogenicity” of modern environments is fueling the obesity pandemic. We describe a framework, known as ANGELO (analysis grid for environments linked to obesity), which is a conceptual model for understanding the obesogenicity of environments and a practical tool for prioritizing environmental elements for research and intervention.Methods: Development of the ANGELO framework. The basic framework is a 2 × 4 grid which dissects the environment into environmental size (micro and macro) by type: physical (what is available), economic (what are the costs), political (what are the “rules”), and sociocultural (what are the attitudes and beliefs). Within this grid, the elements which influence food intake and physical activity are characterized as obe sogenic or “leptogenic” (promoting leanness).Results: Application of the ANGELO framework. The ANGELO framework has been piloted at the population level (island communities) to prioritize the settings/sectors for intervention and at the setting level (fast food outlets) to prioritize research needs and interventions. Environmental elements were prioritized by rating their validity (evidence of impact), relevance (to the local context), and potential changeability.Conclusions. The ANGELO framework appears to be a flexible and robust instrument for the needs analysis and problem identification stages of reducing the obe sogenicity of modern environments. 相似文献
14.
C. C. Blackwell A. T. Saadi M. W. Raza D. M. Weir A. Busuttil 《International journal of legal medicine》1993,105(6):333-338
Summary Toxigenic bacteria have been implicated in some cases of Sudden Infant Death Syndrome (SIDS). Although there is not much evidence thatClostridia spp. are associated with SIDS in Britain, strains ofStaphylococcus aureus producing pyrogenic toxins have been isolated from significant numbers of these infants at autopsy. The pyrogenic toxins, produced by some strains of group AStreptococcus pyogenes as well as staphylococci, are powerful superantigens that have significant physiological effects including induction of fever > 38°C. In this article, interactions between genetic and environmental factors that might enhance colonization of epithelial surfaces by toxigenic staphylococci are analyzed: infant's expression of Lewisa antigen which acts as a receptor for some microorganisms; viral infections; the effect of mother's smoking on susceptibility to respiratory infection. Based on epidemiological findings and laboratory investigations, a hypothesis is proposed to explain how bacteria producing pyrogenic toxins might contribute to some cot deaths. 相似文献
15.
H Preisler A Raza R Larson J Goldberg G Tricot M Carey C Kukla 《Leukemia research》1991,15(9):773-780
The failure of three consecutive treatment protocols to significantly increase the complete remission rate for poor prognosis newly diagnosed patients with acute myelocytic leukemia led to a detailed investigation of the causes of treatment failure. In the majority of cases treatment failure was attributable to "clinical resistance" to therapy. Upon close examination two types of "clinical resistance" were discernible: the failure of chemotherapy to produce adequate cytotoxic effects ("classical" drug resistance), and treatment failure attributed to the rapid regrowth of leukemia cells subsequent to the substantial killing of leukemia cells by cytotoxic therapy ("biological" resistance). Each form of resistance accounted for one-half of the treatment failures. 相似文献
16.
AlShaibani KM AlMeshari KA Raza SM AlFurayh O Mourad WA 《American journal of nephrology》2000,20(2):142-144
We describe a female patient who received double pediatric (en bloc) kidney transplants. She presented initially with fever of unknown origin 3 months after transplantation; 5 months after surgery, she presented with obstruction of one ureter followed by obstruction of the other. After 9 months she developed posttransplant lymphoproliferative disorder in both kidneys. To our knowledge, this is the first case report of this disorder occurring in en bloc kidneys and presenting with bilateral ureteric obstruction. 相似文献
17.
Azra Raza MD 《Medical oncology (Northwood, London, England)》1998,15(3):165-173
Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders which begin in a pluripotential bone marrow (BM) stem cell.
This early stem cell is believed to acquire a growth advantage over its neighbors as a result of an initial transforming event,
the nature of which has remained obscure. In this paper, we propose that pathogens such as those belonging to the herpesvirus
family of DNA viruses may play a role in the initial transformation of the stem cell. The case for cytomegalovirus (CMV) as
a representative of this family of viruses is discussed at length and a molecular mechanism which may be involved in the oncogenic
activity of CMV is proposed. No proof has been presented to implicate CMV directly in MDS, but circumstantial evidence which
supports such a possibility is provided. 相似文献
18.
Patterns of resistance and incomplete response to docetaxel by gene expression profiling in breast cancer patients. 总被引:8,自引:0,他引:8
Jenny C Chang Eric C Wooten Anna Tsimelzon Susan G Hilsenbeck M Carolina Gutierrez Yee-Lu Tham Mamta Kalidas Richard Elledge Syed Mohsin C Kent Osborne Gary C Chamness D Craig Allred Michael T Lewis Helen Wong Peter O'Connell 《Journal of clinical oncology》2005,23(6):1169-1177
PURPOSE: Chemotherapy for operable breast cancer decreases the risk of death. Docetaxel is one of the most active agents in breast cancer, but resistance or incomplete response is frequent. PATIENTS AND METHODS: Core biopsies from 24 patients were obtained before treatment with neoadjuvant docetaxel (four cycles, 100 mg/m(2) every 3 weeks), and response was assessed after chemotherapy. After 3 months of neoadjuvant chemotherapy, surgical specimens (n = 13) were obtained, and laser capture microdissection (LCM; n = 8) was performed to enrich for tumor cells. From each core, surgical, and LCM specimen, sufficient total RNA (3 to 6 microg) was extracted for cDNA array analysis using the Affymetrix HgU95-Av2 GeneChip (Affymetrix, Santa Clara, CA). RESULTS: From the initial core biopsies, differential patterns of expression of 92 genes correlated with docetaxel response (P = .001). However, the molecular patterns of the residual cancers after 3 months of docetaxel treatment were strikingly similar, independent of initial sensitivity or resistance. This relative genetic homogeneity after treatment was observed in both LCM and non-LCM surgical specimens. The residual tumor after treatment in tumors that were initially sensitive indicates selection of a residual and resistant subpopulation of cells. The gene expression pattern was populated by genes involved in cell cycle arrest at G(2)M (eg, mitotic cyclins and cdc2) and survival pathways involving the mammalian target of rapamycin. CONCLUSION: A specific and consistent gene expression pattern was found in residual tumors after docetaxel treatment. These profiles provide therapeutic targets that could lead to improved treatment. 相似文献
19.
20.
Raza M 《Journal of ethnopharmacology》2006,104(3):297-301
Ethnopharmacology investigations classically involved traditional healers, botanists, anthropologists, chemists and pharmacologists. The role of some groups of researchers but not of physician has been highlighted and well defined in ethnopharmacological investigations. Historical data shows that discovery of several important modern drugs of herbal origin owe to the medical knowledge and clinical expertise of physicians. Current trends indicate negligible role of physicians in ethnopharmacological studies. Rising cost of modern drug development is attributed to the lack of classical ethnopharmacological approach. Physicians can play multiple roles in the ethnopharmacological studies to facilitate drug discovery as well as to rescue authentic traditional knowledge of use of medicinal plants. These include: (1) Ethnopharmacological field work which involves interviewing healers, interpreting traditional terminologies into their modern counterparts, examining patients consuming herbal remedies and identifying the disease for which an herbal remedy is used. (2) Interpretation of signs and symptoms mentioned in ancient texts and suggesting proper use of old traditional remedies in the light of modern medicine. (3) Clinical studies on herbs and their interaction with modern medicines. (4) Advising pharmacologists to carryout laboratory studies on herbs observed during field studies. (5) Work in collaboration with local healers to strengthen traditional system of medicine in a community. In conclusion, physician's involvement in ethnopharmacological studies will lead to more reliable information on traditional use of medicinal plants both from field and ancient texts, more focused and cheaper natural product based drug discovery, as well as bridge the gap between traditional and modern medicine. 相似文献