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

By a plasma-concentration of hydroxy-urea (HU) higher than 0.5-2.2x10(-4)M the DNA-synthesis in leukemia cells was blocked reversibly in 9 patients. The plasma half-time of HU varied between 120 and 198 min. To synchronize leukemic cell populations the DNS-synthesis was blocked over a period of 36 hours by maintaining the HU-concentration above the critical lower level. In a second phase-specific therapeutic step cytosine-arabinoside (AraC) was given 4 times in a dose of 1 mg/kg each. A recruitment after the application of AarC made more cells available for the next following synchronization step. 4 acute myeloblastic leukemias with high peripheral cell counts were treated according to this schedule. One patient is still in complete remission for now 14 month. This synchronization/recruitment schedule seems to be successful in acute myeloblastic leukemias with high proliferation rates measured by biochemical and cytokinetic methods.
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PMID:[Pharmakokinetics of hydroxy-urea. Therapy of acute myeoblastic leukemias using synchronization and recruitment effects (author' transl)]. 106 36

Aliphatic triazenes, such as 1,3-dimethyltriazene, are potent biological alkylating agents because they form alkyldiazonium ions. They are also subject to very rapid proteolytic decomposition, even at physiological pH. The acylated analogues 1,3-dialkyl-3-acyltrizenes are much more stable in aqueous solution, but they also give rise to alkyldiazonium ions. Four acylated 1,3-dimethyltriazenes, where the acyl groups were diethylphosphoryl (DMP), carbethoxy (DMC), acetyl (DMA), and N-methylcarbamoyl (DMM), were studied kinetically. Rate-pH profiles indicated that the acyl group had a profound effect on the mechanism of decomposition. The cytotoxic potential of all four compounds was studied in vitro by using the MTT-tetrazolium assay. The compounds had fair-to-good activity against some cell lines, particularly those deficient in methylation repair. In vivo assays of DMC and DMM against several tumor xenografts in nude mice showed promising activity for some cancers, particularly in the case of DMM. In vitro assays were also carried out on three 1-(2-chloroethyl)-3-methyl-3-acyltriazenes. The acyl groups were carbethoxy (CMC), acetyl (CMA), and N-methylcarbamoyl (CMM). The activity of these compounds largely paralleled that of bis(2-chloroethyl)-N-nitrosourea (BCNU), except for those cell lines which exhibited the Rem phenotype; triazenes were more active in those lines than BCNU. The in vivo activity of CMC, CMA, and CMM was tested in the P388 leukemia assay. All three were active but CMC and CMA proved to be rather toxic. CMM was well tolerated and was examined in several tumor xenografts in nude mice. Significant activity was found against MX-1 mammary carcinoma, against LX-1 small cell lung carcinoma, and particularly against LOX amelanotic melanoma, where complete cures were effected. The antineoplastic activity of the acyltriazenes is well-correlated with their chemical behavior.
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PMID:1,3-Dialkyl-3-acyltriazenes, a novel class of antineoplastic alkylating agents. 239 96

Lower prevalence of non-reproductive system cancers among former college athletes. Med. Sci. Sports Exerc., Vol. 21, No. 3, pp. 250-253, 1989. The prevalence (lifetime occurrence) rates of cancers of nonreproductive organs and tissues were determined for 5,398 living alumnae, 2,622 of whom were former college athletes and 2,776 who had been nonathletes, from data on medical history, reproductive history, athletic training, and diet. The non-reproductive system cancers were divided into two classes: class I, which included cancers of the digestive system, thyroid, bladder, lung, and other sites and hematopoietic cancers (lymphoma, leukemia, myeloma, and Hodgkin's disease), and class II, which included skin cancers and cutaneous melanoma. The former college athletes had a significantly lower prevalence of class I cancers compared to the nonathletes; the age-adjusted relative risk (RR) equals 3.34, 95% confidence limits (1.35, 8.33), P = 0.009. In contrast, the prevalence rates of malignant melanomas and skin cancers did not differ significantly between the former athletes and nonathletes. The age-adjusted RR did not differ from 1.0. The lower prevalence rate of class I cancers among the former athletes is in accord with previous findings of a significantly lower prevalence rate of breast cancer and cancers of the reproductive system among former college athletes compared to nonathletes.
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PMID:Lower prevalence of non-reproductive system cancers among female former college athletes. 278 2

A simultaneous microcytometric analysis of nuclear DNA content and size was performed in 8 European peripheral T cell lymphomas (EPTL) and 8 adult T-cell leukemia/lymphomas (ATLL), comparing their patterns on the nuclear density scattergram (NDS) of DNA content versus nuclear size. The intermingling lymphocytes with or without irregular-shaped nuclei in EPTL and ATLL were interpreted as stimulated reactive. Medium-sized cell-dominated T-zone lymphomas and ATLL pleomorphic medium-sized cell type showed two distribution patterns in the diploid range. The first was oblique zonal cluster (OZC) with the second high concentration in the middle part of it, suggesting mixed proliferation with stimulated reactive lymphocytes, and the second was the high concentration in the lower region of the NDS with some cells corresponding to the growth fraction. In large cell-dominated T-zone lymphomas and ATLL pleomorphic large cell type, the third decreasing pattern in the cell density from the lower part of the OZC to its upper part was found upto the hypertetraploid range. The wide distribution on DNS and giant cells with aneuploid high DNA content were found only in the pleomorphic large cell type and the pleomorphic medium-sized and large cell type of ATLL. The T-immunoblastic type of EPTL showed the third pattern and the pleomorphic large cell type of EPTL, characteristic in the clear cytoplasm, showed the second pattern.
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PMID:Comparative microcytometric analysis of European peripheral T-cell malignant lymphomas (EPTL) and adult T-cell leukemia/lymphomas (ATLL) in Japan. 288 1

The segmental flexibility of mouse immunoglobulin E (IgE) bound to its high-affinity receptor on membrane vesicles from rat basophilic leukemia cells was compared to that of IgE in solution by measuring the steady-state anisotropy as a function of temperature and viscosity. A monoclonal IgE was used to bind the fluorescent probe N-[5-(dimethylamino)naphthalene-1-sulfonyl]-L-lysine (DNS-Lys) rigidly and specifically in the antigen combining site at the tip of the Fab region. The average rotational correlation time, phi, of 74-89 ns for the receptor-bound IgE is only slightly longer than that for IgE in solution where phi = 54 ns. Another mouse monoclonal IgE was covalently labeled in the Fab region with N-(1-pyrenyl)maleimide. Anisotropy measurements with this derivative yielded results that are very similar to those found with anti-DNS IgE and DNS-Lys. These findings are strikingly different from that expected for a rigid IgE bound to its receptor since in this case phi is likely to be very much larger. Evidently, the segmental flexibility of IgE is not greatly altered upon binding to its receptor.
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PMID:Segmental flexibility of receptor-bound immunoglobulin E. 293 92

Recently, the National Cancer Institute published a comprehensive monograph on multiple primary cancers in Connecticut and Denmark. This paper summarizes some of the observations made on the Connecticut population. Data compiled by the Connecticut Tumor Registry have extended our knowledge about the patterns of multiple primary cancers, especially among long-term survivors of cancer and among patients with relatively rare tumors about which little information currently exists. When compared with the general Connecticut population, cancer patients had a 31 percent (RR = 1.31) increased risk of developing a second cancer and a 23 percent (RR = 1.23) elevated risk of second cancer at a different site from the first. Common environmental exposures seemed responsible for the excess occurrence of many second cancers, particularly those related to cigarette smoking, alcohol consumption, or both. For example, persons with epithelial cancers of the lung, larynx, esophagus, buccal cavity, and pharynx were particularly prone to develop new cancers in the same or contiguous tissue throughout their lifetimes. Cancers of the colon, uterine corpus, breast, and ovary frequently occurred together, suggesting underlying hormonal or dietary influences. Only patients with prostate cancer were at significantly low risk for second cancer development; this might be an artifact of case finding, since advanced age at initial diagnosis was generally associated with an underascertainment of second cancers. Radiotherapy may have caused rectal and other cancer among patients with cancers of the female genital tract, and leukemia among patients with uterine corpus cancer. Chemotherapy with alkylating agents probably contributed to the excess of acute nonlymphocytic leukemia following multiple myeloma or cancers of the breast and ovary. Genetic susceptibility seemed to explain some tumor complexes, such as the multiple occurrences of cutaneous melanoma and the excess of bone cancer following retinoblastoma. Research into multiple cancer syndromes should enhance our understanding of carcinogenic factors and mechanisms and the development of strategies for cancer prevention and control.
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PMID:Multiple primary cancers in Connecticut, 1935-82. 354 9

Resonance energy-transfer methods have been used to investigate the structure of immunoglobulin E (IgE) bound to its high-affinity receptor on plasma membrane vesicles derived from rat basophilic leukemia cells. The structural mapping of receptor-bound IgE was initiated in an earlier study [Holowka, D., & Baird, B. (1983) Biochemistry 22, 3475], and it is based on measuring the minimal distance from IgE sites that are selectively labeled with donor probes to a plane of amphipathic acceptors at the membrane surface. This paper describes the use of monoclonal IgE specific for 5-(dimethylamino)naphthalene-1-sulfonyl (DNS) to place a donor probe, DNS-L-Lys, in the antibody combining sites. The distance from these sites to the membrane surface was determined to be greater than 100 A with two different amphipathic acceptor probes. Another site in the Fab segments of monoclonal IgE (anti-dinitrophenyl) could be labeled selectively with N-[4-[7-(diethylamino)-4-methylcoumarin-3-yl]phenyl]maleimide (CPM) in the absence of reducing agents [CPM(-)], and the reaction could not be blocked by prereaction with N-ethylmaleimide. The pattern of CPM(-)-labeled proteolytic fragments and the lack of fluorescence quenching by (trinitrophenyl)lysine in the antibody combining sites suggested the CPM(-)-labeled site to be in the C epsilon 1 domain of IgE. The distance between this site on receptor-bound IgE and the membrane surface was determined to be 75-87 A with two different amphipathic acceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Structural mapping of Fc receptor bound immunoglobulin E: proximity to the membrane surface of the antibody combining site and another site in the Fab segments. 408 17

The risk of developing a second primary cancer was evaluated in approximately 19,000 persons with initial cancers of the lymphatic and hematopoietic system in Connecticut between 1935 and 1982. Significant excesses for all second cancers were observed among patients with leukemia (34%), Hodgkin's disease (70%), non-Hodgkin's lymphoma (25%), and multiple myeloma (24%). In general, the risk of second cancers was greater in males than in females, even for cohorts not showing an excess of surveillance-related prostate cancer. Among patients with leukemia, significant excesses of cancers of the lung, kidney/ureter, and prostate were noted; cutaneous melanoma was elevated only in males. These excesses did not persist in the small number of long-term survivors. Possible etiologic factors included tobacco smoking for lung and kidney cancers, medical surveillance artifact for prostate cancer, and immunosuppression for malignant melanoma and lung cancer. The large number and good prognoses of patients with chronic lymphocytic leukemia strongly influenced the pattern of second cancers when all leukemias were analyzed together; no evidence was found for an increased risk of second cancer in patients with acute lymphocytic leukemia. A disproportionate number of subsequent cancers, particularly those of the kidney and ureter, were diagnosed incidentally at autopsy. Patients with Hodgkin's disease displayed significant excesses of cancers of the buccal cavity and pharynx, lung, female breast, and thyroid. The latter 3 sites remained significantly elevated in long-term survivors (10 yr or more postdiagnosis), so that radiation therapy may have contributed to their development. Among persons with non-Hodgkin's lymphoma, cancers of the stomach, lung, brain, and connective tissue occurred excessively. The first 3 sites, plus cancers of the urinary bladder, remained elevated among long-term survivors. The brain cancer excess, not previously reported, may represent misclassification of central nervous system lymphoma. The risk of gastric cancer is reminiscent of similar findings in patients with both acquired and genetically determined immunodeficiency disorders. The alkylating agent, cyclophosphamide, used extensively in the treatment of non-Hodgkin's lymphoma, is known to cause bladder cancer in man.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Second cancer following lymphatic and hematopoietic cancers in Connecticut, 1935-82. 408 98

Three adult patients with leukemia and a patient with cutaneous melanoma were treated with a variety of therapeutic agents administered systemically. Three of these patients received either cytosine arabinoside or thio-TEPA, by intrathecal injection and radiotherapy to the cranium or spine. Three patients developed progressive motor and sensory deficits and the fourth became confused and disoriented. These symptoms were chronologically related to the time when chemotherapy was begun. Death occurred 11/2, 2, 5 and 7 months, respectively, after the beginning of neurologic deficit. The spinal white matter showed vacuolation, myelin disintegration, axonal swelling, fibrillary gliosis, and infiltration by macrophages. Vesicular disintegration of the myelin lamellae seems to be the earliest lesion affecting both central and peripheral myelin. Gliosis and macrophages were visible only in the two patients who survived at least five months from the time of the neurologic deficit.
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PMID:Central and peripheral myelinopathy associated with systemic neoplasia and chemotherapy. 679 25

Risk of cancer mortality from 1973 to 1985 in persons born in the Indian subcontinent who migrated to England and Wales was analysed by ethnicity, and compared with cancer mortality in the England and Wales native population, using data from England and Wales death certificates. There were substantial highly significant raised risks in Indian ethnic migrants for cancers of the mouth and pharynx, gall bladder, and liver in each sex, larynx and thyroid in males, and oesophagus in females. There were also substantial raised risks in these migrants of each sex for non-Hodgkin's lymphoma and myeloma. For the mouth and pharynx, and liver in each sex, and gall bladder in females, there were also raised risks of lesser magnitude in British ethnic migrants. For colon and rectal cancer and cutaneous melanoma in each sex, ovarian cancer in women and bladder cancer in men, there were appreciable significantly reduced risks in the Indian ethnic migrants not shared by those of British ethnicity. Appreciable raised risks in British ethnic migrants not shared by those of Indian ethnicity occurred for nasopharyngeal cancer in males, soft tissue malignancy in both sexes and non-melanoma skin cancer in males. In migrants of both ethnicities there were appreciable significantly raised risks in each sex for leukaemia and decreased risks in each sex for gastric cancer, for lung cancer except in females of British ethnicity and in males for testicular cancer. The results suggest the need for public health measures to combat the high risks of oral and pharyngeal cancers and liver cancer in the Indian ethnic immigrant population of England and Wales, by prevention of betel quid chewing and hepatitis transmission respectively. The data also imply that early exposures or early acquired behaviours in India, or exposures during migration, may increase the risk of leukaemia and reduce the risks of gastric and testicular cancers in the migrants irrespective of their ethnicity. Aetiological studies would be worthwhile to investigate the reasons for the sizeable decreased risk of colon and rectal cancer and increased risk of gall bladder cancer in each sex and the increased risk of thyroid and laryngeal cancer in males and oesophageal cancer in females of Indian ethnicity but not of British ethnicity who have migrated from the Indian subcontinent.
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PMID:Cancer mortality in Indian and British ethnic immigrants from the Indian subcontinent to England and Wales. 757 89


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