Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone marrow transplantation (BMT) is now increasingly applied not only to hematologic disorders such as leukemias and aplastic anemia but also to some of solid tumors. We experienced ten cases of bone marrow harvest and six cases of autologous or allogeneic BMT during the period from June, 1986 to August, 1987. For autologous BMT cases, bone marrow cells were harvested and cryopreserved at -196 degrees C in liquid nitrogen tank and colony forming assays were examined to ascertain the colony forming ability of harvested bone marrow stem cells. Recovery of colony forming ability after cryopreservation in colony forming unit in culture and burst forming unit in erythrocyte is about 63 to 73% and well preserved. Among 6 cases undergone BMT, five cases are patients with advanced solid tumors including breast cancer, seminoma, lung cancer, malignant lymphoma and brain tumor and these 5 cases have undergone autologous BMT. Conditioning regimen for each cancer in autologous BMT differs based upon conventional chemotherapy regimen and two to four fold dose of conventionally used chemotherapy regimen were administered and after two or three days of high dose chemotherapy, cryopreserved bone marrow cells were thawed and infused. Peripheral white blood cells and platelets were recovered to more than 1000/microliters and 5 x 10(4)/microliters, respectively, within 21 days after bone marrow cell infusion. Disappearance or decrease in tumor size was observed in all cases except brain tumor even though those cases were advanced ones. After autologous BMT, recurrence occurred within three to five months in three cases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Basic and clinical studies on patients who have undergone autologous or allogeneic bone marrow transplantation]. 306 93

The structure/activity relationships for inhibition of aromatase and cholesterol side-chain cleavage enzyme (CSCC) by aminoglutethimide and some of its analogues are reviewed. Although more effective against aromatase than CSCC, aminoglutethimide markedly inhibits both enzymes. Optimal competitive antagonism of aromatase is obtained with a free amino or basic group at the 4' position of the phenyl ring substituent. This is important because two major metabolites of aminoglutethimide where the amino group is conjugated have low or no inhibitory effect on aromatase. Relocation of the free amino group to the nitrogen atom of the piperidinedione ring enhances CSCC inhibition. The piperidinedione ring is not essential for inhibitory activity, several 4'-aminophenyl pyrrolidinediones being as potent as aminoglutethimide for aromatase but less effective against CSCC. In this series 3-(4'-aminophenyl)-pyrrolidine-2,5-dione is a selective aromatase inhibitor. Inactivity of 4'-aminophenyl derivatives of imidazolidinedione and pyrimidinetrione indicate that the 4'-aminophenyl moiety alone is insufficient for antagonist activity against aromatase. Replacement of the aminophenyl group by the stronger basic 4-pyridyl moiety in aminoglutethimide yields a selective aromatase inhibitor. The structure/activity data suggest that there is a critical distance between the basic centre and the dione moiety for effective aromatase inhibition. Aminoglutethimide and its analogues possessing a free basic centre elicit a Type II difference spectrum with various cytochrome P-450 isozymes. The spectrally-determined binding affinity correlates with inhibitory activity of these compounds and indicates binding of the amino group to the iron centre of this haem enzyme. In reviewing the postulated mechanisms for the enzyme-mediated aromatisation of substrates it is seen that the initial oxidative attack is at the C-19 position of the steroid. It is proposed that two binding or association sites on the protohaem moiety of this P-450 enzyme (iron and propionic acid residues respectively) are required for the orientation of the substrate. Crystallographic evidence indicates there is a distance of about 6.3 A between the C-17 oxygen and the C-19 methyl of the aromatase substrates (these points interacting with the association sites). There is a similar distance between the basic function and the C-6 keto group for aminoglutethimide (and the C-5 keto group for the pyrrolidinediones). It is proposed that aminoglutethimide and its active analogues interact with aromatase at these binding sites competitively inhibiting the aromatisation of androstenedione and testosterone.
Breast Cancer Res Treat 1986
PMID:Pharmacology of aminoglutethimide: structure/activity relationships and receptor interactions. 375 30

Hydroxy-2-phenylindoles carrying substituted benzyl groups and similar substituents at the nitrogen were synthesized and tested for their ability to displace estradiol from its receptor. All of the derivatives tested exhibited high binding affinities for the calf uterine estrogen receptor, with RBA values ranging from 0.55 to 16 (estradiol 100). The mouse uterine weight tested revealed only low estrogenicity for this class of compounds. Several derivatives showed antiestrogenic activity with a maximum inhibition of estrone-stimulated uterine growth of 40%. Two of the compounds (6c, 21c) were tested for antitumor activity in dimethylbenanthracene- (DMBA-) induced estrogen-dependent rat mammary tumors. Only the 4-cyanobenzyl derivative 21c was active. After 4 weeks of treatment with 12 mg/kg (6 times/week), the average tumor area was decreased by 57% (control +204%). In vitro, an inhibitory effect of 21b was only observed with hormone-sensitive MCF-7 breast cancer cells but not with hormone-independent MDA-MB 231 cells. These results make a mode of action involving the estrogen receptor system likely.
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PMID:2-Phenylindoles. Effect of N-benzylation on estrogen receptor affinity, estrogenic properties, and mammary tumor inhibiting activity. 380 90

3-Deazaguanine (dezaguanine, USAN; CI-908) is a new antipurine antimetabolite which is entering Phase I studies in the USA. This compound differs from guanine only in the substitution of a carbon for the 3-nitrogen of guanine. Dezaguanine has an unusual spectrum of activity against experimental rodent tumors; its activity against transplantable rodent leukemias is only modest, but it has significant activity against transplantable rodent solid tumors, particularly mammary adenocarcinomas. Mammary adenocarcinoma models against which this compound is active include slow and fast-growing tumors, hormone sensitive and hormone insensitive tumors, and the subrenal capsule implanted human breast cancer xenograft, MX-1. Dezaguanine must be converted to its nucleotides to be active. Dezaguanine nucleotides inhibit synthesis of guanine nucleotides, and can be incorporated into nucleic acids in place of guanine nucleotides; incorporation into DNA may be particularly important in the cytotoxicity of this compound. Addition of certain purines or purine nucleosides can prevent dezaguanine cytotoxicity in vitro. Preclinical studies suggest that dezaguanine does not undergo deamination to 3-deazaxanthine, and is not metabolized by xanthine oxidase. Therefore, this compound may not be subject to metabolic inactivation in vivo, and active metabolites may have a prolonged half-life. This concept is supported by the prolonged half-life of radiolabelled dezaguanine in rats. Finally, dezaguanine can cross the blood-brain barrier. In summary, the novel biochemical and experimental antitumor properties of dezaguanine indicate that this compound could have better activity against some human solid tumors than currently used purine antimetabolites.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dezaguanine mesylate: a new antipurine antimetabolite. 406 18

The effect of inhalation of gaseous hypoxic mixture GHM-10 (oxygen--10 +/- 1.0 and nitrogen--90.0 +/- 1.0%) on radiation response of normal tissues was studied in 184 breast cancer patients. The mixture was administered to 120 patients while 74 controls received a standard course of radiotherapy. Administration of the mixture improved normal tissue resistance to radiotherapy for breast cancer and was followed by lower incidence of long-term radiation injury, lower frequency and shorter duration of general vegetative reactions to radiation.
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PMID:[The immediate and late results of protecting the patient's normal tissues by using the gas hypoxic mixture GHM-10 in the radiation therapy of breast cancer]. 408 5

The correlation between nutrition and immunological potentiation on patients with cancer of the esophagus was investigated in preoperative and postoperative periods. Preoperative immunological status: These patients were already suffering from malnutrition, because of the impossibility of peros intake. Natural killer (NK) cell activity and interleukin-II inducing activity of peripheral mononuclear cells in the above patients were clearly lower than such activities of cells in the patients with breast cancer whose nutritional condition was as normal as that of healthy people. These two immunological parameters in the majority of the patients were improved by active total parenteral and enteral nutrition. However, there were a few patients whose nutritional status could not be improved. Postoperative immunological status: The movement of peripheral lymphocyte subpopulation was successively checked with several kinds of monoclonal antibodies such as OKT-3 (anti-T cells), Leu-7 (anti-NK cells), OKIa-1 (anti-B cells), OKT-4 (anti-inducer and/or suppressor T cells) and OKT-8 (suppressor and/or cytotoxic T cells). In nutritionally controlled patients, the population of OKT-3, Leu-7 and OKIa-1 showed a pattern similar to the preoperative value, but in undernourished patients, that population was disturbed soon after the operation. Patterns of OKT-4 and OKT-8 showed a converse correlation. Nearly two weeks after operation, all these five kinds of population had changed. Moreover, nitrogen balance recovered from negative to positive. The time of is thought to be the turning point of surgical metabolism and the immunological status.
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PMID:[Significance of active nutritional support for maintenance of immunopotentiation on the surgical treatment of esophageal cancer]. 408 20

Estrogen receptor (ER) was measured in 275 samples from 170 patients with breast cancer by DCC assay. The results showed that the ER status and content of cytosol separated by ultracentrifuge (105,000 X G) or orthocentrifuge (1,200 X G) confirmed well (P greater than 0.5). Therefore, the ordinary centrifuge is suitable. But there was a poor correlation between the ER level measured by DCC method and that by Lee's cytochemical method (P greater than 0.05). The store time of the sample in liquid nitrogen did not seem to effect much on the ER positive rate (chi 2 = 0.7686). The ER status in samples obtained from the primary or metastatic lesion or at different intervals were generally similar in the same patient (P greater than 0.2). It is suggested that the ER status be an inherent property of patients with breast cancer. The authors propose that more samples be taken in order to render the determination more reliable.
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PMID:[The influence and significance of obtaining, storing and assay on estrogen receptor (ER) content in breast cancer tissue]. 409 77

The expression of a mouse mammary tumor virus is inducible by hormones, and the virus contains a hormone-responsive element. Viral particles and RNA-directed DNA polymerase (RDDP, EC 2.7.7.7; reverse transcriptase) are both detectable in human breast tumors but the frequency and significance of these findings are unknown. Breast tumor biopsy specimens (from either the primary site or a metastasis), frozen in liquid nitrogen at the time of surgery, were routinely obtained to determine estrogen receptor (ERP) concentration. A sample of the tissue was pulverized, homogenized and centrifuged at low speed to remove nuclei and mitochondria. The supernate was then centrifuged at 225,000 g to obtain the cytosol fraction for estrogen and progestin receptor (PgR) assays. Partially purified membranes for the RDDP assays were prepared from the high-speed pellet by discontinuous sucrose density gradient centrifugation. The RDDP assay involved measuring primer-dependent poly(dT) synthesis in the presence of poly(A) as template and oligo-(dT)12-18 as primer. To date, we have studied biopsy specimens from 46 patients with breast cancer. 27 (59%) had ERP and 23 (50%) were RDDP-positive. There was no significant correlation between ERP concentration and RDDP activity. PgR data were available on 36 of the patients; 17 (47%) were positive. No correlation between RDDP and PgR was apparent. Similarly, there was no correlation between RDDP and clinical stage of the disease.
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PMID:RNA-directed DNA polymerase activity in human breast cancer biopsy specimens. Relation to estrogen receptor protein. 620 38

The clinical effect of intralesional injection of interleukin-2 (IL-2)-cultured autologous lymphocytes was assessed in seven patients with cutaneous, recurrent tumor nodules (12 melanoma and 8 mammary cancer lesions). Each tumor nodule was injected 3-10 times, once weekly, with IL-2-cultured lymphoid cells (CLC), 40-400 million cells at each injection. Lymphoid cells obtained from buffy coats were separated on Ficoll-Paque, cryopreserved in liquid nitrogen, thawed, and cultured for 1-2 weeks in the presence of crude IL-2 (containing phytohemagglutinin) before injection. CLC were tested for sterility, percent E-rosette-forming cells, and cytotoxicity against K562, allogeneic melanoma, and breast cancer cell lines and autologous tumor cells. Enhanced cytotoxicity was expressed by IL-2 CLC, as compared with nonstimulated peripheral blood lymphocytes (PBL). Arrest of tumor growth (compared with untreated lesions) was observed in eight lesions and partial regression in three lesions. Moreover, complete regression was noted in one large melanoma lesion treated with low-dose irradiation prior to intralesional administration of CLC and in three small intracutaneous melanoma lesions treated with CLC only. Histopathological findings of responding lesions showed infiltration with lymphoid cells and macrophages, with the tumor cells sparsely dispersed. No untoward side effects of CLC injections were observed. The present study points to the feasibility of trials of adoptive immunotherapy in cancer patients as indicated by the following: (a) response of lymphoid cells to IL-2 adequate--although reduced--in patients with metastatic disease, including those after chemo- or radiotherapy; (b) possibility of cryopreservation of PBL and repeated culturing in IL-2 after thawing, with cytotoxic activity unimpaired; (c) demonstrably enhanced cytotoxicity in vitro of IL-2 CLC; (d) demonstrable--although limited--clinical response to in situ treatments with IL-2 CLC; (e) good tolerance of treatment with CLC.
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PMID:Intralesional injection of interleukin-2-expanded autologous lymphocytes in melanoma and breast cancer patients: a pilot study. 633 37

Free N-acetylsialic acid (NeuNAc) and CMP-N-acetylsialic acids (CMP-NeuNAc) are extracted from freeze-clamped or liquid nitrogen-frozen biological material by sequential extraction with cold acetone and acetone/water. [14C]NeuNAc and [14C]CMP-NeuNAc (20,000 dpm each) are added to the frozen material to correct for small losses occurring during the subsequent steps. NeuNAc and CMP-NeuNAc are separated by anion-exchange chromatography. CMP-NeuNAc is hydrolyzed with formic acid and again chromatographed on an ion-exchange column. The NeuNAc-containing fractions (representing free NeuNAc and CMP-NeuNAc) are converted to [14C]CMP-NeuNAc in the presence of [14C]CTP and CMP-NeuNAc synthetase. [14C]CMP-NeuNAc is separated by paper chromatography and the radioactivity measured by liquid scintillation counting. The amount of NeuNAc is calculated from a calibration curve obtained with NeuNAc standards. The small amounts of [14C]NeuNAc and [14C]CMP-NeuNAc added initially do not interfere with the final assay. The method gives reliable values down to 50 pmol/assay, but the sensitivity can be easily increased by a factor of 10. Recoveries, with NeuNAc and CMP-NeuNAc added to biological extracts, were 98.3 and 98.5% for NeuNAc and CMP-NeuNAc, respectively. With this method values of 61.2 +/- 12.8 and 24.4 +/- 5.2 nmol/g wet wt were found in rat liver for free NeuNAc and CMP-NeuNAc, respectively. Values for free NeuNAc found in human blood plasma were 600 +/- 476 and 373 +/- 180 pmol/g plasma for healthy persons and patients with breast cancer, respectively. Free CMP-NeuNAc could not be found in plasma.
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PMID:Radioenzymatic determination of CMP-N-acetylsialic acid and free N-acetylsialic acid in biological material. 686 23


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