Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human glandular kallikrein 2 (hK2) is a serine protease expressed by the prostate gland with 80% identity in primary structure to prostate-specific antigen (PSA). Recently, hK2 was shown to activate the zymogen form of PSA (proPSA) in vitro and is likely to be the physiological activator of PSA in the prostate. hK2 is also able to activate urokinase and effectively cleave fibronectin. We studied the substrate specificity of hK2 and regulation of its activity by zinc and extracellular protease inhibitors present in the prostate and seminal plasma. The enzymatic activity and substrate specificity was studied by determining hK2 cleavage sites in the major gel proteins in semen, semenogelin I and II, and by measuring hydrolysis of various tripeptide aminomethylcoumarin substrates. HK2 cleaves substrates C-terminal of single or double arginines. Basic amino acids were also occasionally found at several other positions N-terminal of the cleavage site. Therefore, the substrate specificity of hK2 fits in well with that of a processor of protein precursors. Possible regulation mechanisms were studied by testing the ability of Zn2+ and different protease inhibitors to inhibit hK2 by kinetic measurements. Inhibitory constants were determined for the most effective inhibitors PCI and Zn2+. The high affinity of PCI for hK2 (kass = 2.0 x 10(5) M-1 x s-1) and the high concentrations of PCI (4 microM) and hK2 (0.2 microM) in seminal plasma make hK2 a very likely physiological target protease for PCI. hK2 is inhibited by Zn2+ at micromolar concentrations well below the 9 mM zinc concentration found in the prostate. The enzymatic activity of hK2 is likely to be reversibly regulated by Zn2+ in prostatic fluid. This regulation may be impaired in CAP and advanced metastatic cancer resulting in lack of control of the hK2 activity and a need for other means of control.
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PMID:Enzymatic action of human glandular kallikrein 2 (hK2). Substrate specificity and regulation by Zn2+ and extracellular protease inhibitors. 1041 40

A 43-year-old female underwent muscle preserving mastectomy with 6 cycles of adjuvant CMF chemotherapy for breast cancer. She developed multiple lung metastases 16 months later. The metastases were refractory to 3 cycles of CAF administration, and worsened (PD). We therefore added high-dose toremifene to her treatment. This combination therapy brought a marked decrease in the lung metastases. After 9 cycles of CAF with high-dose toremifene therapy, lung metastatic findings had almost disappeared from her chest X-ray. Following this treatment, UFT and toremifene were orally administered for maintenance therapy. Thirty-two months later at present, no increase in these lesions has been observed. High-dose antiestrogen drugs have the potential to inhibit P-glycoprotein. The combination of high-dose toremifene with CAF is potentially effective against ADM-resistant breast cancer.
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PMID:[A case of breast cancer patient of CAF (cyclophosphamide, adriamycin, 5-fluorouracil) resistant lung metastasis with remarkable response to reverse drug-resistance by toremifene]. 1043 84

In spite of major advances in early detection and adjuvant therapy, metastatic breast cancer remains a major clinical problem affecting a significant number of patients. Metastatic disease is generally considered incurable and conventional therapy is used mainly with palliative intent. Therefore, the choice of appropriate therapeutic approach requires a reasoned evaluation of the likelihood of benefit from therapy balanced with the impact of therapy on the patient's quality of life. The estimated aggressiveness of the tumour and indicators of response to therapy (e.g. the status of hormonal receptors) are useful parameters to take into account before selecting a given treatment. Endocrine therapy is an important option in the management of stage IV disease, with tamoxifen the most widely used first-line drug in postmenopausal women. For progressing patients, the third generation of aromatase inhibitors (letrozole, anastrazole) are considered good second-line endocrine agents. The LH-RH agonists represent the initial choice in premenopausal patients candidate to receive hormonal therapy, with the use of tamoxifen as a valuable alternative. Combination chemotherapy regimens (e.g. CMF or CAF) are usually used for first-line treatment of patients with aggressive, steroid receptor-negative disease. Recently, several relatively new agents have shown significant activity in metastatic breast cancer. In particular, the taxanes (paclitaxel and docetaxel) are particularly promising as single agents but also in combination with other drugs, especially anthracyclines. Finally, another class of agents, the d mention because they represent an important new treatment modality in the management of metastatic.
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PMID:[Treatment of metastatic breast carcinoma]. 1046 41

A 49-year-old woman was diagnosed with local recurrence and cervical lymph node and bone metastases 55 months after surgery for breast cancer. She was treated with goserelin acetate and tamoxifen but the disease was assessed as progressive after 8 months. Five courses of CMF therapy were performed but lung, pleural and mediastinal lymph node metastases were detected. Then, five courses of CAF therapy were carried out, but a contralateral breast metastasis was detected and the patient complained of shortness of breath. The CAF therapy was assessed as PD. We attempted administration of doxifluridine (5'-DFUR) and mitomycin C (MMC) on an outpatient basis. After 6 months, no progressive disease was detected and she was relieved of her shortness of breath. The combination therapy was assessed as long NC. Combination therapy with 5'-DFUR and MMC is thus a useful treatment for adriamycin- and methotrexate-resistant breast cancer, especially in terms of quality of life.
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PMID:[A case of adriamycin and methotrexate-resistant recurrent breast cancer treated with doxifluridine and mitomycin C]. 1047 88

The frequency of c-erb-B2 expression, clinical correlates and treatment outcome was investigated in 92 patients with metastatic breast cancer. Positive c-erb-B2 immunostaining was found in 24/92 (26%) of tumours. There was a statistically significant inverse correlation between c-erb-B2 expression and ER status. There was also a significant inverse correlation between c-erb-B2 expression and tumour free interval. c-erb-B2 expression had no influence on response to treatment with tamoxifen among patients co-expressing both c-erb-B2 and estrogen receptor (ER). Following chemotherapy (CAF) treatment there was a trend to a lower response rate among c-erb-B2+ as compared to c-erb-B2- patients. However, more c-erb-B2+ patients had received prior adjuvant chemotherapy, and when this factor was included in a multivariate analysis only prior adjuvant chemotherapy treatment predicted for response to CAF chemotherapy for metastatic disease. Time to treatment failure (TTF) was significantly shorter among cerb B2+ as compared to c-erb-B2- patients. The current study suggests that the c-erb-B2 expression is found at similar frequency in metastatic as in primary breast cancer. Although c-erb-B2 expression did not predict for response to either hormonal therapy or to chemotherapy for metastatic disease, patients with c-erb-B2+ metastatic lesions appear to have a more aggressive clinical course.
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PMID:c-erb-B2 expression and response to treatment in metastatic breast cancer. 1071 56

Two cases of recurrent breast cancer are reported in which chemotherapy with mitoxantrone proved remarkably effective. Case 1 was a 61-year-old postmenopausal female. At 32 postoperative months, multiple metastases of lung and bone were found. Following unsuccessful treatment with anthracyclin and an antiestrogenic agent, we used MVP modified therapy (mitoxantrone (MIT) 16 mg and vincristine (VCR) 1.6 mg once per 4 weeks and medroxyprogesterone acetate (MPA) 1,200 mg/day) and 5'-deoxy-5-fluorouridine (5'-DFUR) 800 mg/daily. After 12 cycles were performed, the patient showed a partial response (PR) (nearly complete response (CR)) on a chest X-ray and bone scintigram. Case 2 was a 49-year-old premenopausal female. At 42 postoperative months, a local recurrence was found and resection was performed. However, after endocrine therapy with goserelin acetate (ZOL) and chemotherapy with CAF (cyclophosphamide, adriamycin and 5-FU) and UFT, local recurrence and pleural effusion were found 6 months after surgical operation. We then used MVP modified chemotherapy and endocrine therapy with ZOL. The patient showed a PR at 9 cycles after therapy. MVP modified chemotherapy is considered an effective treatment for recurrent breast cancer, especially for adriamycin or epirubicin resistant breast cancer.
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PMID:[Chemotherapy with mitoxantrone for the treatment of recurrent breast cancer]. 1092 94

A huge mass measuring 13 x 12 cm and wide cutaneous edema were detected in the right breast of a 51-year-old woman. Under a diagnosis of locally advanced breast cancer (T4bN2M1, stage IV) with liver metastases, we attempted sequential neoadjuvant chemotherapy. After three courses of CAF therapy (cyclophosphamide, doxorubicin (DXR), 5-FU), the primary tumor was decreased by 56% and the liver metastases had disappeared. A minor pathologic response was observed. Subsequently, three courses of docetaxel (TXT) administration were carried out. The primary tumor was then decreased by 75% and the axillary metastases had disappeared. Histopathological examination showed gross viable tumor cells in the residual tumor and positive axillary lymph nodes. The only toxic effect was nausea (grade 1) and no major adverse effects were observed. Neoadjuvant chemotherapy with sequential DXR followed by TXT is a useful treatment for locally advanced breast cancer.
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PMID:[A case of effective chemotherapy using CAF followed by docetaxel for advanced breast cancer]. 1101 5

A 52-year-old Japanese woman developed dermatomyositis. She had undergone a standard radical mastectomy for left breast cancer 21 years earlier. Though no physical sign of recurrent breast cancer appeared clinically, levels of tumor markers were abnormally elevated. Therefore, tamoxifen and CAF therapy were given. Further, the clinical course of dermatomyositis almost paralleled the level of serum tumor markers and the clinical course of her recurrent breast cancer. These markers were useful for detecting the recurrence, following the metastatic disease, and monitoring her response to therapy.
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PMID:Recurrent Breast Cancer at 21 years after Resection Detected by Serum Tumor Markers and Manifested as Dermatomyositis. 1109 10

The cases of 3 female patients with metastatic breast cancer treated with oral UFT and cyclophosphamide (CPA) are reported. Patient 1 had lymph node and bone metastases. Patient 2 had bone metastasis. Patient 3 had skin, lymph node, and peritoneal metastases. All had a history of mastectomy and chemo- and/or endocrine therapy for metastatic lesions. Patients 2 and 3 had also undergone CAF combination chemotherapy. However, the lesions did not change. UFT 400 mg and CPA 100 mg, everyday, were administered to patient 1. UFT 400 mg and CPA 100 mg, 2 weeks, and UFT 400 mg, 2 weeks, were given every 4 weeks to patient 2. UFT 300 mg and CPA 150 mg, 6 weeks per 8 weeks were given to patient 3. Improvements in the metastatic lesions were seen 4 weeks after the beginning of UFT and CPA therapy. Therapy is now continuing, and no patients had a progression of the disease. All had leukopenia 2 or 4 weeks after the beginning of this therapy, and two temporarily stopped the therapy. No other side-effect was observed. Oral UFT and CPA combination therapy was considered useful for metastatic breast cancer. To prevent leukopenia and prolong the term of treatment efficacy, a treatment regimen will need to be established.
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PMID:[Three cases of metastatic breast cancer, resistant to pre-chemo and/or endocrine therapy, markedly improved with UFT and cyclophosphamide oral combination therapy]. 1110 46

Recently initiated is a phase III randomized trial (MA.21 trial) of adjuvant chemotherapy for node-positive and high-risk node-negative, premenopausal and postmenopausal (< or = 60 years) women with breast cancer who have no distant metastases. Conducted by the National Cancer Institute of Canada-Clinical Trials Group, the trial will compare two standard therapies, CEF (cyclophosphamide [Cytoxan, Neosar], epirubicin [Ellence], fluorouracil) and AC-->T (doxorubicin [Adriamycin], cyclophosphamide, followed by paclitaxel [Taxol]), and includes a third arm consisting of a dose-dense, dose-intense EC-->T regimen (epirubicin, cyclophosphamide, followed by paclitaxel). These regimens were chosen for study based on results of previous clinical assessments of adjuvant therapies, which, taken together, suggest that CEF, FEC 100 (where 100 represents the dose in mg/m2 of epirubicin in FEC [fluorouracil, epirubicin, cyclophosphamide]), CAF (cyclophosphamide, doxorubicin, fluorouracil), and AC-->T may all be superior to standard AC or CMF (cyclophosphamide, methotrexate, fluorouracil) regimens. This article reviews trial results that support the testing of the regimens chosen for the MA.21 trial. The intent of the MA.21 study is to advance our ability to provide optimal adjuvant therapy for patients with breast cancer.
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PMID:Optimizing adjuvant breast cancer chemotherapy: rationale for the MA.21 study. 1139 66


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