Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred thirty-four pre- and perimenopausal patients presenting with metastatic breast cancer (median age, 42 years; range, 25 to 55) were treated with goserelin (Zoladex [ICI 118 630]; ICI Pharma, Plankstadt, Germany) a long-acting gonadotrophin-releasing hormone (GnRH)-analogue depot formulation, injected subcutaneously every 4 weeks, as a first-line therapy. One hundred eighteen patients were evaluable for response. Serum concentrations of estradiol, luteinizing hormones (LH), and follicle-stimulating hormones were significantly suppressed by Zoladex. Mean serum estradiol values fell into the range of castrated or postmenopausal women within 2 to 3 weeks of therapy. This suppression was maintained for the duration of therapy. Overall objective response was: 12 (10.2%) complete remission; 41 (34.7%) partial remission; 33 (28.0%) no change; and 32 (27.1%) progression. In responders, the median time to response was 4 months (range, 2 to 11 months), median duration of response was 8 + months (range 2 to 24 months), and median time to progression was 11 + months (range, 5 to 30 months). Objective responses were seen for different sites of metastases: loco-regional (62.5%), bone (46.7%), visceral (45.0%), and multiple (35.1%). Tumor remission was more common in patients in which the primary tumor was estrogen receptor (ER)-positive (49.3%) or ER-unknown (44.0%), but appreciable response rates were also observed in ER-poor patients (33.3%). Zoladex depot was well tolerated both locally and systemically. It produced effective castration and the objective response rates and duration of remission are at least comparable to those seen following oophorectomy; however, the side effects are less. The use of depot Zoladex avoids the psychological trauma and operative morbidity of the irreversible operative castration.
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PMID:Goserelin, a depot gonadotrophin-releasing hormone agonist in the treatment of premenopausal patients with metastatic breast cancer. German Zoladex Trial Group. 252 63

The identification of metastatic carcinoma of the breast may be difficult in the absence of a previous history of breast cancer. Various immunophenotypic markers have been introduced to aid in this process. A monoclonal antibody directed at a 15-kilodalton (kd) gross cystic disease fluid protein (GCDFP-15) was applied immunohistochemically to paraffin sections of 105 breast cancers and 585 nonmammary malignancies in order to assess its value in this context. In addition, GCDFP-15 was compared with another putative mammary epithelial marker, alpha-lactalbumin (ALA), with respect to sensitivity and specificity for a diagnosis of breast carcinoma. Overall, the rates of specificity and sensitivity and the predictive value of a positive result for GCDFP-15 were 95%, 74%, and 74%, respectively. Corresponding statistical parameters for ALA were 50%, 50%, and 23%. A consistent congruency between the reactivity patterns of primary and metastatic breast cancers was noted for GCDFP-15 but not for ALA. Besides mammary carcinomas, the major tumor types that expressed GCDFP-15 were carcinomas of the salivary glands, sweat glands, and prostate. Since the latter three types of lesions are unlikely to be diagnosed as metastatic breast cancer, statistical indices were recalculated after exclusion of these three tumor types. Following this exclusion, the adjusted rate of specificity of GCDFP-15 and the predictive value of a positive result for a diagnosis of metastatic carcinoma of the breast were each 99%. In contrast, predictive parameters for ALA were not altered. These results show that GCDFP-15 is a specific marker for breast cancer and is superior to ALA in this respect.
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PMID:Gross cystic disease fluid protein-15 as a marker for breast cancer: immunohistochemical analysis of 690 human neoplasms and comparison with alpha-lactalbumin. 254 51

Prior studies have shown that the P-glycoprotein is a cell membrane efflux pump that is quantitatively increased in expression in multidrug-resistant tumor cell lines. In this study, fresh tumor tissues from patients with multiple myeloma, malignant lymphoma, or metastatic breast cancer were studied immunohistochemically for P-glycoprotein expression and for in vitro sensitivity to doxorubicin. Twenty-six patients who were either previously untreated or in relapse after chemotherapy had tumor specimens submitted that could be evaluated in both assays. The testing was done independently and blindly in separate laboratories instead of our being provided relevant clinical data on the patients. Tumor cells from 12 of the 26 patients (46%) stained positively for P-glycoprotein. Fifteen of the 26 specimens (58%) exhibited drug resistance in vitro. Although only three (21%) of the 14 P-glycoprotein-negative tumors exhibited in vitro resistance to doxorubicin, all 12 fresh tumors that stained positively for P-glycoprotein were resistant to doxorubicin. The difference in frequency of intrinsic doxorubicin resistance between P-glycoprotein-negative and -positive tumors was highly significant (P less than .001). Similar trends were observed in each of the individual tumor categories and were statistically significant in myeloma and breast cancer. Four of the biopsy specimens that stained positively for P-glycoprotein and exhibited doxorubicin resistance were from patients who had not received prior cytotoxic chemotherapy. Similar conclusions were reached when results of drug sensitivity tests were ranked in relation to the median infective dose rather than by criteria based on correlations with clinical drug resistance. Our findings indicate that positive staining for P-glycoprotein associated with multidrug resistance predicts intrinsic cellular resistance of human cancers to doxorubicin. We anticipate that immunohistochemical staining for P-glycoprotein will prove useful in clinical oncology.
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PMID:Prediction of doxorubicin resistance in vitro in myeloma, lymphoma, and breast cancer by P-glycoprotein staining. 256 3

We determined the effect of long-term freezer storage and repeated thawing and freezing of serum on concentrations of electrolytes (sodium, potassium, calcium, and phosphate), enzymes (aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, and creatine kinase), total protein, tumor markers (carcinoembryonic antigen and alpha-fetoprotein), and other substances. Vials (1 ml) of frozen serum from a single blood drawing from 40 women with no breast disease and 70 with benign breast disease were analyzed annually from 1983 to 1987. Blood had been obtained from 40 subjects in 1978, 40 in 1980, and 30 in 1983. Thawing and refreezing studies were done in two ways: (1) serum samples from 30 subjects with benign breast disease were thawed at weekly intervals for 6 weeks and (2) serum samples from 30 patients with stage IV breast cancer were analyzed for alpha-fetoprotein and carcinoembryonic antigen, and serum specimens from 23 patients with benign breast disease and 7 control subjects were analyzed for lactate dehydrogenase and creatine kinase after thawing and keeping the samples at room temperature for up to 4 hours and then refreezing them. For measuring laboratory variability, duplicate samples were processed. Long-term storage (up to 10 years) and repeated thawing and refreezing did not affect the results of any tested constituents of serum. Although most measurements showed statistically significant variability over test cycles, these differences were thought to be due to laboratory variability.
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PMID:Effect of long-term freezer storage, thawing, and refreezing on selected constituents of serum. 259 13

Samples of tumor tissue obtained from 47 patients with primary and metastatic breast cancer were implanted under the renal capsule of mice (SRCA-test) to assess individual sensitivity of these malignancies to cytostatics, recombinant interferon (rIFN) and--in some cases--to tumor necrosis factor (TNF). Primary tumor was shown to respond to cytostatics and rIFN in as few as 33.3 and 26.7% of cases, respectively. Xenografts of metastases displayed higher rates of response to all the drugs studied, viz. 64.2, 86.7 and 90% for cytostatics, rIFN and TNF, respectively.
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PMID:[The cellular sensitivity of the primary tumor and its metastases in breast cancer patients to cytostatics, interferon and tumor necrosis factor]. 260 20

A patient with metastatic breast cancer treated with epirubicin (Pharmorubicin) developed a severe urticarial reaction which progressed to ulceration following possible sensitisation to the drug by preceding extravasation.
Med Oncol Tumor Pharmacother 1989
PMID:Hypersensitivity reaction to epirubicin. 261 33

In an attempt to clarify appropriate treatment options for women with stage IV breast cancer, we studied the survival experience of a large dataset of patients treated on Cancer and Leukemia Group B (CALGB) protocols. The study, restricted to women who had had no prior chemotherapy for metastatic disease, demonstrated a surprisingly poor prognosis, with an estimated median survival of 1.6 years and only 26% alive at 3 years. Analysis of prognostic factors permitted the identification of subsets with even shorter survival, such as women with estrogen receptor negative tumor in more than one metastatic site and prior adjuvant chemotherapy. We feel that an evaluation of intensive investigational treatment approaches, such as trials using autologous bone marrow transplantation, is justified for most stage IV breast cancer patients, in view of their poor prognosis.
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PMID:Diverse prognosis in metastatic breast cancer: who should be offered alternative initial therapies? 265 Jul 58

The efficacy and toxicity of leucovorin 500 mg/m2 administered intravenously (IV) over 30 minutes daily for five days followed in one hour by fluorouracil (5-FU) 375 mg/m2 administered IV daily for five days, each given every 3 weeks, was assessed in 54 previously treated patients with metastatic breast cancer. An overall objective response rate of 24% was achieved (95% confidence interval, 13% to 38%), with an additional 56% of patients maintaining stable disease. Eleven of 12 patients who responded had received previous 5-FU therapy. Toxicity of this regimen included grade 3 diarrhea in 13%, grade 3 or 4 mucositis in 33%, grade 3 or 4 granulocytopenia in 65%, and grade 3 or 4 thrombocytopenia in 19%. Delay of treatment was required for hematologic toxicity in 44 patients. Thirty-eight patients required dose reductions due to toxicity. Biochemical evaluation of tumor biopsy specimens obtained from 17 patients used as their own controls with and without leucovorin was performed. These studies reveal an increased stabilization of the 5-fluorodeoxyuridylate (FdUMP)-thymidylate synthase (TS) folate ternary complex with the addition of leucovorin. There was a 71% +/- 14% occupancy or inhibition of the enzyme with the use of both 5-FU and leucovorin, v 30% +/- 13% for 5-FU alone (P2 less than .037). The percent TS bound in responding patients was substantially higher than in those patients with progressive disease. Finally, the mean total tumor TS pre-therapy in seven patients was 31 fmol/mg compared with a mean of 81 fmol/mg in these same seven patients 24 hours after therapy. This 2.6-fold increase suggests that there is an induction of the enzyme, TS, with 5-FU treatment.
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PMID:Fluorouracil and high-dose leucovorin in previously treated patients with metastatic breast cancer. 266 35

A list of tumor markers evaluated in breast cancer patients is included as well as their relative value for a patient with metastatic breast cancer. Variations in the levels of circulating markers correlated well with disease course; however, the accuracy of these variations is not total.
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PMID:Circulating tumor markers in breast cancer. 269 93

Between October 1977 and December 1983, 379 consecutive patients have been treated for unilateral, non metastatic breast cancer, either with conservative (n = 205) or radical surgery (n = 174), with axillary dissection in all the cases. None of them had histologically proved lymph node involvement. Adjuvant radiotherapy was given in 268 cases. Estrogen receptor (ER) and progesterone receptor (PR) levels were measured on each tumor. Levels greater than 5 fmoles/mg cytosolic protein were considered as positive for both ER and PR. At 5 years, overall survival (OS) and disease-free survival (DFS) are respectively 88% and 79%. Unifactorial analysis using KAPLAN and MEIER estimates and Logrank test revealed that OS was significantly related to age, tumor size, histopathological grading, ER and PR. DFS was significantly related to the same factors. Menopausal status, number of intra mammary tumor foci, previous familial history of breast cancer were not significant. Multifactorial analysis revealed that DFS was significantly related to age (bad prognosis [bp]: less than or equal to 37 years old), tumor size, histopathological grading (bp: SBR = 3) and that OS was significantly related to tumor size and PR (bp: PR less than or equal to 5 fmoles/mg protein). A prognostic score was obtained which sampled our patients into 3 significantly different (P less than 0.0001) groups with high, intermediate and low risk of relapse. These results suggest that tumor size, histopathological grading and PR have their own prognostic weight in histologically node negative breast cancer. Grouping these factors together allows to define a high risk relapse group that could benefit from adjuvant treatment.
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PMID:[What are the prognostic factors in operable breast cancer without histologic axillary lymph node invasiveness. Results of an uni- and multifactorial analysis]. 271 15


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