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

Ellipticine and some derivatives are highly cytotoxic substances which kill L1210 cells at concentrations ranging form 10(-8) to 10(-6)M. Some compounds in this series bind with high affinity to DNA (affinity constant between 10(7) M-1 and 10(5) M-1) by intercalation between base pairs. The antitumoral properties of these derivatives are thought to be related to their DNA-binding ability. Both 9-hydroxylation of ellipticine and quaternarization of 2-pyridinic nitrogen tend to increase DNA binding and antitumor activity. 2-Methyl-9-hydroxyellipticine (NSC 264-137) was selected for a phase I and later for a phase II trial in human cancer. This drug does not affect blood cell counts in animals or in man. It is not mutagenic in the Ames' test nor teratogenic in mice, but is endowed with anti-inflammatory properties and induces a marked decrease of motoricity in mice. Transient bradycardia and decrease of blood pressure are the most noticeable cardiovascular effects in dogs. This compound administered at 80-100 mg/m2/week in 1-h intravenous (IV) infusion induces objective remissions in about 25% of patients suffering from advanced breast cancer refractory to all other treatment. These remissions, which occurred after 3-4 weeks, lasted for 1-18 months. This drug seems particularly to improve the condition of patients suffering from oesteolytic breast cancer metastasis. Activity against anaplastic thyroid carcinoma and ovarian carcinoma has also been observed in some cases. Toxic side effects are nausea and vomiting (one-third of the patients), hypertension (less than 10% of the patients), muscular cramp (one-third of the patients), fatigue which can be very pronounced (in most patients after 3 months of treatment), mouth dryness, and mycosis of the tongue and esophagus (less than 20% of the patients).
 ...
PMID:Antitumor activity, pharmacology, and toxicity of ellipticines, ellipticinium, and 9-hydroxy derivatives: preliminary clinical trials of 2-methyl-9-hydroxy ellipticinium (NSC 264-137). 700 58

The value of having estrogen receptor protein analysis is more widely appreciated, and the estrogen receptor determination at the time of biopsy or mastectomy is rapidly becoming a standard procedure. The patients with positive estrogen receptors (and progesterone receptors) are now identified as those who will respond to hormone ablation or manipulation. Some authors have stated that a positive estrogen receptor has a "protective" value against regional metastasis and early recurrence. At the time of biopsy, a portion of the tumor is frozen in liquid nitrogen and sent for estrogen receptor (and progesterone receptor) analysis. The 200 breast cancer patients had estrogen receptors performed with 118 estrogen receptors positive and 82 estrogen receptors negative. The following is an analysis of the 130 mastectomy patients. Negative nodes: ER+, 50; ER-, 20. One to three positive nodes: ER+, 23; ER-, 12. Four and more positive nodes: ER+, 15; ER-, 10. At the present time, the data is being correlated to the patient's age, the time of recurrence, and its relationship to estrogen receptors and progesterone receptors.
 ...
PMID:Estrogen receptor protein and its correlation to recurrent breast cancer. A study of 213 patients at the Pennsylvania Hospital. 721 59

14 samples of the Musculus pectoralis major from patients with early stages of breast cancer and 3 samples from patients with nonmalignant mammary diseases were stored in liquid nitrogen and investigated histologically, histochemically and histometrically. Main changes are lipomatosis, fibre necrosis, occasionally perifascicular atrophy, metabolic changes (e.g. accumulation of lipids), and alterations of the activity of oxidative enzymes. Histometrically we found an atrophy of type 2-fibres. There may be relations between the degree of the muscle changes and the severity of the tumour disease. The paraneoplastic muscle disease is a "concomitant myopathy" and may be regarded as a "functional myopathy". In its development we can differentiate a phase of compensation and a phase of decompensation.
 ...
PMID:Muscular changes in carcinomas of the breast. 726 27

Prenylcysteine methyl esters that represent the C-terminal structures of prenylated proteins demonstrate specific substrate-like interactions with P-glycoprotein (Zhang, L., Sachs, C. W., Fine, R. L., and Casey, P. J. (1994) J. Biol. Chem. 269, 15973-15976). The simplicity of these compounds provides a unique system for probing the structural specificity of P-glycoprotein substrates. We have further assessed the structural elements of prenylcysteines involved in the interaction with P-glycoprotein. Carboxyl group methylation, a modification in many prenylated proteins, plays an essential role of blocking the negative charge at the free carboxylate. Substitution of the methyl ester with a methyl amide or simple amide does not change the ability of the molecule to stimulate P-glycoprotein ATPase activity, but substitution with a glycine is not tolerated unless the carboxyl group of glycine is methylated. The presence of a nitrogen atom, which is found in many P-glycoprotein substrates and modifiers, is also essential for prenylcysteines to interact with P-glycoprotein. The structure at the nitrogen atom can, however, influence the type of interaction. Acetylation of the free amino group of prenylcysteine/results in a significant loss in the ability of prenylcysteines to stimulate P-glycoprotein ATPase activity. Instead, certain acetylated prenylcysteines behave as inhibitors of this activity. In studies using MDR1-transfected human breast cancer cells, the acetylated prenylcysteine analogs inhibit P-glycoprotein-mediated drug transport and enhance the steady-state accumulation of [3H]vinblastine, [3H]colchicine, and [3H]taxol. These inhibitors do not, however, affect drug accumulation in parental cells. These studies provide a novel approach for designing P-glycoprotein inhibitors that could prove effective in reversing the phenotype of multidrug resistance in tumor cells.
 ...
PMID:Characterization of prenylcysteines that interact with P-glycoprotein and inhibit drug transport in tumor cells. 755 20

In a retrospective study, liquid nitrogen preserved specimens from 50 women with primary breast cancer, who underwent surgery at the Beijing Institute for Cancer Research between June, 1986 and September, 1988, were investigated. All patients under this study were staged in TNM II or later, involved with axillary lymph node metastasis, and treated with systemic postoperative adjuvant chemotherapy. The median length of follow-up was 69 months. The expression of P-glycoprotein was investigated by means of immunohistochemistry, using a monoclonal antibody C219 specifically against P-glycoprotein and avidin-biotin peroxidase method. Positive staining for P-glycoprotein was found in 23 (46%) of the 50 patients. The P-glycoprotein expression negative group fared better than the group that was P-glycoprotein positive in overall survival curves (p = 0.0008, by the generalized Wilcoxon test). The prognostic effect of P-glycoprotein expression remained statistically significant (p = 0.0007) after adjustment by multivariate analysis (Cox's model) for other prognostic factors. It is demonstrated that P-glycoprotein expression is a significant and independent predictor of postoperative survival in breast cancer patients. The results of the present study suggest that P-glycoprotein expression might also influence the biological behavior of breast cancers.
 ...
PMID:P-glycoprotein expression in primary breast cancer. 778 Jan 10

Pilot retrospective studies have pointed to the prognostic value of thymidine kinase (TK) in breast cancer. We studied the Prolifigen TK-REA assay (Sangtec Medical, Sweden), usually applied to serum, for TK analysis in breast cancer cytosols. Reproducibility was good, provided that small volume pipetting was performed carefully. The TK assay was not influenced by the short-term storage of cytosols in liquid nitrogen or at -80 degrees C. However, some steps appeared critical for good laboratory practice. The TK level was affected by thawing the cytosols more than twice. Tumour storage in liquid nitrogen should be preferred over storage at -80 degrees C. The components of the homogenisation buffer, especially sodium molybdate and KCl can have a marked influence on results. Finally, linearity problems arose with some cytosols. Thus, although assay of TK in cytosols is apparently simple, care must be taken in practice. The TK-REA kit should be standardised before widespread use in breast cancer.
 ...
PMID:Technical evaluation of thymidine kinase assay in cytosols from breast cancers. EORTC Receptor Study Group Report. 785 17

Low-density lipoprotein (LDL) is a potential drug carrier in cancer chemotherapy. Two novel cytotoxic lipophilic steroid derivatives with two nitrogen carbamate groups on a C-17 side chain were successfully incorporated into LDL using a reassembly technique. The antineoplastic activity of the new agents against T-47D breast cancer cells in culture was approximately twice that of a previously characterized compound with only one such group.
 ...
PMID:Cytotoxic activity of two new lipophilic steroid nitrogen carbamates incorporated into low-density lipoprotein. 794 29

The detection of epidermal growth factor receptors (EGFR) has been proposed as a prognostic factor in different kinds of neoplastic diseases. In this study, we have compared different conditions of EGFR assay, in human placental membranes, in order to establish the best conditions for the routine use of EGFR assay in clinical laboratories. Three kinds of membrane treatment (non-treated, preincubated at 37 degrees C for 30 min, or acid treated at pH 3.0 for 3 min at 0 degrees C), two different separation conditions (hydroxylapatite and centrifugation), two different incubation times (30 min at 37 degrees C and overnight at 18 degrees C) and the effect of proteolytic enzyme inhibitors have been investigated. Preincubated or acid treated membranes showed a two- and three-fold increase of the number of receptors, respectively, as compared with non-treated membranes. In the case of acid pretreated membranes a second, low affinity, site became apparent. Both separation methods gave similar results. The addition of aprotinin had an effect only during long incubation conditions. Freezing of membranes in liquid nitrogen, followed by storage at -80 degrees C for 48 h, resulted in three different patterns. No change was observed in non-treated membranes. Preincubated samples showed a significant decrease both in the number and the affinity of detected EGFR. Acid treated membranes showed a decrease of the affinity of high affinity EGFR with no modification of their number. It is proposed that acid pretreatment, freshly prepared membranes, addition of aprotinin and the use of hydroxylapatite, for the separation of bound and free radiolabelled EGF, should be used in order to standardize the EGFR assay in clinical laboratories. Using these conditions, we were able to detect a significantly higher number of EGFR in 6/29 cases of human breast cancer specimens.
 ...
PMID:Acidification reveals a greater number of epidermal growth factor receptors in human placental and breast cancer membranes. 795 25

Manifestations of resistance to androgens vary within a wide range from an almost normal female phenotype to men whose only complaint is infertility. Insensitivity is caused by mutation of the gene for androgenic receptors, located on the X chromosome. Androgenic insensitivity is associated of all known hormonal resistances with the most varied mutational changes-some hundred of the latter were described. Mutations do not correlate with the clinical picture. Insensitivity to androgens is not necessarily associated with the inability of androgens to bind with the appropriate receptor, because mutations can affect any of the three receptor domains, i.e. not only the domain binding the ligand but also the domain by which the steroid receptor complex is linked to the DNA of the regulated gene or N-terminal, the so-called transactivation domain, responsible for the transfer of the hormone-borne signal to the initiation site of the controlled gene. Androgenic insensitivity can be associated with some tumourous diseases depending on steroid sex hormones such as prostate or breast cancer and also-as reported for the first time in this paper-e.g. with lymphogranuloma. Some neurodegerative diseases are also associated with a certain degree of androgenic insensitivity. For detection of androgenic resistance in addition to molecular genetic analysis dynamic tests were recommended which involve the follow-up of androgen-dependent indicators after androgen administration. These indicators are e.g. nitrogen retention or the SHBG level. The original modification of the SHBG test for androgen insensitivity is described.
 ...
PMID:[Androgen insensitivity]. 806 28

Alkylating agents which are activated by glutathion-S-transferases (GSTs) have been designed and synthesized. The model compound gamma-glutamyl-alpha-amino-beta-[(2-ethyl N,N,N',N'-tetraethylphosphorodiamidate) sulfonyl]propionylglycine (1) and the nitrogen mustards gamma-glutamyl-alpha- amino-beta-[[2-ethyl N,N,N',N'-tetrakis (2-chloroethyl)phosphorodiamidate] sulfonyl]propionylglycine (2) and gamma-glutamyl-alpha-amino-beta-[[2-ethyl-N,N,N',N'-tetrakis(2- chloroethyl)phosphorodiamidate]sulfonyl]-propionyl-(R)-(-)-phenylg lycine (3) were prepared via multistep chemical synthesis. The compounds were tested with recombinant human A1-1, M1a-1a and P1-1 GSTs. HPLC studies showed that the compounds were differentially and catalytically cleaved by biologically relevant concentrations of the GSTs. Mass spectral studies of the cleavage mixture of 2 showed that M1a-1a GST liberated the cytotoxic phosphate moiety needed for efficacy as an alkylating agent. Cell culture studies with MCF-7 breast cancer cells showed that 1 was not toxic at 200 microM, while 2 and 3 showed IC50S of 40.6 and 37.5 microM, respectively, for the same cell line. MCF-7 cells transfected to overexpress P1-1 GST showed enhanced sensitivity with 2 and 3, with IC50S of 20.9 and 9.5 microM, respectively. This result correlates well with the rates of cleavage of 2 and 3 by P1-1 GST observed in vitro and demonstrates that higher levels of cellular P1-1 GST will give increased sensitivity to these drugs.
 ...
PMID:Glutathione-S-transferase activates novel alkylating agents. 818 9


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>