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)

The case histories of 4 patients who developed bone marrow damage after therapy with melphalan are described. In 3 patients bone marrow damage manifested initially as a sideroblastic anaemia which was later followed by acute myeloid leukaemia. The last patient developed a dyserythropoietic anaemia with leucopenia, but thus far there has been no further progression. None of the 4 patients had any haematological abnormality prior to the melphalan therapy. Two were suffering from carcinoma of the breast and 2 had ovarian neoplasms. The fact that melphalan was given as adjuvant therapy in all 4 patients prior to the development of the haematological abnormalities supports the concept that it was of aetiological importance. These findings are in line with a number of reports in the literature in which acute leukaemia has developed in subjects treated for malignant tumours (especially multiple myeloma and ovarian cancer) with melphalan.
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PMID:Bone marrow damage due to melphalan and other cytostatic agents. 693 39

Therapeutic intervention in a course of illness, while producing the desired result, also may have some adverse long-term effects on the patient. Second malignancies are one of the known complications of therapy. The treatments of gynecologic cancers by surgery, irradiation and chemotherapy have been associated with subsequent neoplasms. Care must be exercised in associating previous therapy and a subsequent malignancy. "Naturally" occurring second cancers must be separated from those which are iatrogenic. Associations in the literature have been made involving malignancies as a sequelae of prior gynecologic therapy. The use of normal skin from the thigh to fabricate an artificial vagina has resulted in more squamous cell carcinomas than expected. Alkylating agents used in the treatment of ovarian cancer and other diseases have been shown to lead to an increased risk of leukemia. Irradiation therapy, however, has not yet been shown to be related to leukemia in cervical cancer patients. The incidence of lymphoma and uterine, urinary bladder and colon carcinomas has been associated with prior irradiation for gynecologic disease. The literature regarding the therapeutically induced risk factors in gynecologic therapy is reviewed and areas of our knowledge that require more investigation are identified.
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PMID:Gynecologic cancer treatment: risk factors for therapeutically induced neoplasia. 702 60

VP16-213 and VM26 are compounds with definite anticancer activity in specific tumor types. Despite 10 years of clinical development the full impact of these compounds in current cancer therapy requires further study. There is no conclusive evidence that one compound is superior to the other in any specific tumor type. The composite activities suggest possible differences in certain cancers such as small cell anaplastic lung cancer, lymphoma, leukemia, bladder and ovarian cancer, but sufficiently adequate studies to determine this have not been reported for any tumor. Understanding the basic pharmacology of these compounds should also be considered of high priority since it is obvious that there is much to learn in this area and further clarification should allow improved clinical utilization. It is hoped that the presentations and discussions of the First International Symposium will generate a new wave of interest in future podophyllotoxin research and development.
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PMID:The podophyllotoxin derivatives VP16-213 and VM26. 704 93

Late side effects of chemotherapy were studied in 51 women who had received at least 300 mg of melphalan for ovarian cancer and had survived for at least three years. Hematologic, statistical, and cytogenetic methods were employed. Six cases of iatrogenic leukemia were found. They appeared to represent a hematologic entity that is fairly difficult to recognize. The risk of iatrogenic leukemia in women who survived for three years or more after melphalan treatment was calculated to be 950 times greater than the leukemia risk in the total female population. The cytogenetic changes were studied with three methods focused on sister chromatid exchange, chromosome aberrations, and DNA damage. The sister chromatid exchange frequency showed a marked increase, but it was corrected within a few months. Chromosome aberrations expressed by chromosome rearrangements were increased in the peripheral lymphocytes and may persist for several years. The frequency of DNA stand breaks was decreased indicating the presence of DNA cross-links. Any of these types of genetic alteration could be the initiating event in carcinogenesis.
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PMID:Late side effects of chemotherapy in ovarian carcinoma: a cytogenetic, hematologic, and statistical study. 707 40

While radiotherapy and antineoplastic chemotherapy often control malignancies they may, paradoxically, cause new cancers to develop as long-term complications. Although almost any type of neoplasm can occur, radiation-induced malignancies are most likely to affect the myelopoietic tissues and the thyroid gland. The former tissues are also most frequently involved by chemotherapy. The combination of intensive radiotherapy and intensive chemotherapy is particularly leukemogenic. Acute myeloid leukemia has occurred with increased frequency following treatment of Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, ovarian cancer, polycythemia vera, carcinoma of the thyroid gland, and carcinoma of the breast. Radiation-induced malignancies usually occur in the field of irradiation. For example, radiotherapy for carcinoma of the cervix may be followed by the development of carcinomas of the endometrium, vagina, urinary bladder, colon , rectum, and anus, as well as mesotheliomas of the peritoneum and osteosarcomas of the pelvis. Tumors developing in an irradiated field include a substantial number of soft tissue sarcomas or osteosarcomas. There is a 20-fold increase of second cancers following treatment of childhood malignancies, mostly sarcomas of bone and soft tissues, but including leukemia, and carcinomas of the thyroid gland, skin, and breast. The latent period between radiotherapy and the appearance of a second cancer ranges from 2 years to several decades, often being 10-15 years. With chemotherapy the mean latent period is shorter, approximately 4 years. The mechanism of oncogenesis by radiotherapy or chemotherapy is poorly understood and probably involves a complex interplay of somatic mutation, co-oncogenic effects, depression of host immunity, stimulation of cellular proliferation, and genetic susceptibility. The danger of developing second malignancies following radiotherapy or chemotherapy emphasizes the need for lifelong follow-up of patients given these forms of treatment; particularly in those with a long life expectancy as are those treated for childhood neoplasms.
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PMID:Second neoplasms following radiotherapy or chemotherapy for cancer. 708 Nov 42

Human tumor stem cell assay is an in vitro colony-forming technique. Double soft agar layers are used for culture tumor cells and cell lethality is judged by the numbers of colony formation in this assay. Single-cell suspension made from various malignant materials in cancer patients is placed in culture after exposing to various anticancer agents for one hour and incubated for two weeks. Antitumor effects of various anticancer agents against individual patients are evaluated by % inhibition of colony formation. Of 57 tumor specimens 42 (74%) formed at least five colonies per plate (per 0.5 x 10(6) cells). The colony-forming rates of various malignancies are as follows: breast cancer 14/15 (93%), ovarian cancer 8/10 (80%), stomach cancer 5/13 (38%), sarcoma 4/5 (80%), lung cancer 1/4 (25%), colon cancer 3/3, each of pancreas cancer, leukemia and primary unknown adenocarcinoma 2/2, malignant lymphoma 1/1. The median plating efficiency (number of colonies/number of nucleated cells plated) is 0.02% (range: 0.001-0.3%). High correlation between human tumor stem cell assay results and response of an individual patient's tumor to chemotherapy is reported by Salmon and Von Hoff. Human tumor stem cell assay is useful tool for the high prediction of chemosensitivity response.
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PMID:[Human tumor stem cell assay]. 718 17

Acute non-lymphocytic leukemia occurred in eight women following long-term treatment with Treosulfan (= dihydroxybusulfan) for ovarian carcinoma. The leukemia developed from 21 to 58 months (median 50 months) after the institution of chemotherapy. At the time when the leukemia appeared seven of the patients were in complete, and one in partial, remission as regards the ovarian carcinoma. Seven of the eight cases of acute leukemia occurred in a series of 553 patients treated with Treosulfan for ovarian cancer in the period from 1970 to 1977 and followed closely for a total of 1159 patient-years up to February 1978. As compared with an expected number of 0.04 cases of acute myeloblastic leukemia based on patient-years, the observed seven cases correspond to a 175-times increased risk. Although the cumulative probability of acute non-lymphocytic leukemia among surviving patients at five years using life-table statistics was 7.6%, the survival curve for the 553 patients with ovarian carcinoma was only slightly affected by death from leukemia. The probability of developing acute leukemia in this study was not significantly correlated to the total cumulative dosage of Treosulfan. Cytogenetic studies of the bone marrow performed after the development of acute leukemia showed chromosome abnormalities in all five patients examined, with hypodiploidy and loss of B and C group chromosomes.
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PMID:Acute non-lymphocytic leukemia in patients with ovarian carcinoma following long-term treatment with Treosulfan (= dihydroxybusulfan). 735 Oct

Treosulfan and busulphan are similar molecules, the former used in the treatment of ovarian cancer and the latter in chronic myelogenous leukaemia. We have used both in the differential staining cytotoxicity (DiSC) assay for in vitro drug sensitivity testing to aid in the choice of chemotherapy for individual patients. It was observed that occasionally the viability of control cells in one assay box was reduced compared with control cells in other boxes from the same assay. Treosulfan was suspected as the cause because cells throughout the microtitre box containing treosulfan had reduced viability in 28/62 (45%) experiments and in 9 of these, total kill of all cells in the box was observed. We tested the hypothesis that a metabolite of treosulfan might be the cause of this airborne cytotoxicity, and found that whilst 10 mg ml-1 of either methane sulphonic acid or tetrahydrofuran had no airborne cytotoxic effect, 1 mg ml-1 diepoxybutane killed over 95% of cells in all tubes in the same box. Treosulfan is another chemical (cf. azide, mafosfamide and possibly other cytotoxic agents) that can cause airborne cytotoxicity.
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PMID:Airborne cytotoxicity in the DiSC assay caused by solutions of treosulfan but not busulphan. 753 65

Three new quassinoid glucosides, bruceosides D [1], E [2], and F [3], were isolated from Brucea javanica, and their structures were elucidated by spectral evidence and chemical transformation to known compounds. Compounds 1-3 show selective cytotoxicity in the leukemia and non-small cell lung, colon, CNS, melanoma, and ovarian cancer cell lines with log GI50 values in the range of -4.14 to -5.72.
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PMID:Bruceosides D, E, and F, three new cytotoxic quassinoid glucosides from Brucea javanica. 756 96

The Stockholm-Gotland Cancer Register was used to study the risk of developing second primary malignancies (SPM) in women diagnosed with cancer of the uterine cervix, uterine corpus and ovaries during the period 1958-1992. Among 5,325 patients with uterine cervix cancer, 619 developed SPM. Standardized incidence ratio (SIR) was 1.29 (95% confidence interval (CI) 1.19-1.39). Significantly increased risks were observed for cancer of the colon, rectum, lung, vulva, kidney and bladder. A total of 4,815 women with uterine corpus cancer were followed and 660 SPM were found. The overall SIR was 1.21 (95% CI 1.12-1.30) with significantly increased risk for cancer of the colon, ovary, vulva and bladder. The incidence of leukemia was also significantly elevated (SIR = 3.03; 95% CI 1.70-5.00). Among 5,060 patients with ovarian cancer, 379 SPM were found (SIR 1.49; 95% CI 1.34-1.64). Increased risks of cancer of the colon, rectum, breast, uterine corpus, bladder and leukemia were observed. All three primary sites showed elevated risks of cancer of the colon and bladder. For patients with a primary cancer of the corpus and ovary an elevated risk of leukemia was also noted. The conclusion from these findings is that SPM to some extent can be explained by previously known factors, i.e. treatment and common risk factors. However, further studies concerning the role of common etiology, for instance hereditary and hormonal factors, are needed to increase the knowledge on the etiology of second primary malignancies.
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PMID:Increased risk of second primary malignancies in patients with gynecological cancer. A Swedish record-linkage study. 757 44


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