Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RU-486 or mifepristone is best known as an antiprogestin and an abortifacient, but it has broad medical applicability. The drug is also a potent blocker of corticosteroid receptors, and it has shown promise in the treatment of breast cancer, inoperable meningioma, and cushing's disease. Cushing's is a model for the symptomatology of aging which may involve enhanced response to corticosteroid. RU-486 has reversed the osteoporosis, thinning of skin, muscle atrophy, obesity, adult onset diabetes, depression, hypertension, and immunosuppression associated with this disease. RU-486 may be of value in aiding cervical dilation, lactation, and the treatment of endometriosis. In addition, breast, bowel, kidney tumors, hepatomas, endometrial cancer, and fibrosarcomas can show corticosteroid dependency, suggesting that RU-486 may have clinical value against inoperable tumors. In a preliminary 1987 phase I study, in estrogen-positive, chemotherapy-refractory breast cancer patients in Montpelier, France, Ru-486 produced objective tumor regression (6 of 22) that was prolonged (3 months) in 4 patients. Clinical relief of bone pain was observed in 7 of 23 patients with a decline in carcinoembryonic antigen (CEA) tumor makers in 8 patients. Growing in vitro data also show that RU-486 can directly inhibit breast cancer cell proliferation. RU-486 has application for HIV infection, based on data that there is a serum factor in AIDS patients that enhances corticosteroid lympholysis. IN addition, the immune restorative action of RU-486 suggests that it could counteract the immunosuppression seen in aging, in cancer, or in viral or stress-related disease, which has recently focused clinical attention on its potential in the treatment of senile dementia and depression. Scientific conferences and workshops are needed to alert scientists, physicians, and the public to the potential medical benefits of this drug.
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PMID:RU 486: how abortion politics have impacted on a potentially useful drug of broad medical application. 150 96

To clarify the clinicopathological features of an atypical cystic duct (ACD) as defined by Tsuchiya's criteria as a precancerous lesion of the breast, we used 200 whole mammary gland serial sections of breast cancer. Forty-four (22%) of the 200 breast cancer patients had ACD breast lesions. The frequency of patients with ACD increased in premenopausal women (P = 0.001). There was no correlation between the ACD-present group and the ACD-absent group for immunohistochemical status of the estrogen receptor (ER), progesterone receptor (PgR), p53, or c-erbB2; Ki-67 labeling index of cancer tissues; size of tumor, or lymph node metastases. A number of ACD lesions displayed continuity to cancer lesions. In 500 serial sections of a paraffin-embedded tissue of a ACD case at 3 microm intervals, an apparent transition from ACD into ductal carcinoma in situ was observed. Immunohistochemical analysis using alpha-smooth muscle actin showed that myoepithelial cells of ACD stained strongly, and their nuclei and cytoplasm were thinning. In 16 of the 44 (36%) ACD-present patients, carcinoma cells stained positive for p53. Within those 16 cases, 12 cases (75%) were positive for p53 in ACD lesions. There was a significant correlation between the expression of p53 protein in malignant cells and ACD (P = 0.001). All 44 ACD lesions had no staining of c-erbB2, regardless of staining in malignant lesions. The mean Ki-67 labeling index of ACD lesions was low (0.3%), suggesting that ACD had a low proliferative rate. We suggest that ACD is the precancerous breast lesion because of a histologic continuum between ACD and malignancy, and because of p53 protein expression in ACD.
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PMID:Clinicopathological characteristics of atypical cystic duct (ACD) of the breast: assessment of ACD as a precancerous lesion. 1110 51

Amplification of the gene encoding the ErbB2 (Her2/neu) receptor tyrosine kinase is critical for the progression of several forms of breast cancer. In a large-scale clinical trial, treatment with Herceptin (trastuzumab), a humanized blocking antibody against ErbB2, led to marked improvement in survival. However, cardiomyopathy was uncovered as a mitigating side effect, thereby suggesting an important role for ErbB2 signaling as a modifier of human heart failure. To investigate the physiological role of ErbB2 signaling in the adult heart, we generated mice with a ventricular-restricted deletion of Erbb2. These ErbB2-deficient conditional mutant mice were viable and displayed no overt phenotype. However, physiological analysis revealed the onset of multiple independent parameters of dilated cardiomyopathy, including chamber dilation, wall thinning and decreased contractility. Additionally, cardiomyocytes isolated from these conditional mutants were more susceptible to anthracycline toxicity. ErbB2 signaling in cardiomyocytes is therefore essential for the prevention of dilated cardiomyopathy.
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PMID:ErbB2 is essential in the prevention of dilated cardiomyopathy. 1198 89

Bone is one of the most common sites of breast cancer metastasis. Metastases are often associated with bone destruction and are a major cause of morbidity. We examined structural bone changes induced by metastatic tumor in bone biopsies from 33 patients with metastatic breast carcinoma (20 from patients with pathological femoral fracture and 13 with no fracture) and 20 normal controls. In all metastatic biopsies bone remodeling was shown to be tumor volume-dependent. Bone resorption and bone formation were biphasic with both increasing at earlier stages of metastatic bone disease and decreasing later on. A comparison of patients with fracture and no fracture did not reveal statistically significant differences in the extent of bone destruction or trabecular thinning. Bone histomorphometry showed limited ability to explain the higher bone volume loss in fracture patients (decreases of 42% and 25%, respectively, in fracture and nonfracture patients compared with controls). However, changes in bone quality, including increased disconnectivity and decreased connectivity, as evaluated by node-strut analysis, suggested that there were more structural changes in the fracture compared with the nonfracture group. The nonfracture group included six patients with no radiological evidence of bone metastasis (occult metastasis). They showed a higher tumor volume and a twofold lower eroded surface compared with the rest of the group. The decrease in bone volume (14% lower than controls) was below the limit of X-ray detection. Because we observed no increase in osteoclast-related parameters and no correlation between osteoclast surface and eroded surface, we believe that, in occult metastasis, osteoclastic bone resorption is not an important factor in overall bone resorption. Quantitatively, the eroded surface in direct contact with tumor cells was threefold higher than the osteoclast surface in occult metastasis, whereas the rest of the metastatic group (27 of 33) showed predominantly osteoclast-mediated eroded surface. Node-strut analysis on occult metastasis revealed a significant increase in disconnectivity without a concomitant significant decrease in bone volume and trabecular thinning. We conclude that, in occult metastasis, bone resorption may be more osteoclast-independent and other mechanisms involving the tumor cells may be more prevalent.
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PMID:Morphological, histomorphometric, and microstructural alterations in human bone metastasis from breast carcinoma. 1239 51

Letrozole (Femara), a nonsteroidal, third-generation aromatase inhibitor administered orally once daily, has shown efficacy in the treatment of postmenopausal women with early-stage or advanced, hormone-sensitive breast cancer. In early-stage disease, extending adjuvant endocrine therapy with letrozole (beyond the standard 5-year period of tamoxifen) improved disease-free survival; compared with placebo there was a 43% relative reduction in disease recurrences or new contralateral breast tumours at a median follow-up of 2.4 years. The results of 4 months' neoadjuvant treatment with letrozole or tamoxifen in postmenopausal women with untreated primary disease favour letrozole. In advanced breast cancer, letrozole was superior to tamoxifen as first-line treatment; time to disease progression was significantly longer (9.4 vs 6.0 months, p < 0.0001) and objective response rate was significantly greater with letrozole, but median overall survival was similar between groups. For second-line therapy of advanced breast cancer that had progressed on antiestrogen therapy, letrozole showed efficacy equivalent to that of anastrozole and similar to or better than that of megestrol acetate. Letrozole is generally well tolerated and has a similar tolerability profile to tamoxifen; the most common treatment-related adverse events were hot flushes, nausea and hair thinning. In patients with tumours that had progressed on antiestrogen therapy, letrozole was tolerated as least as well as, or better than, anastrozole or megestrol acetate. In the trial of extended adjuvant therapy, adverse events reported more frequently with letrozole than placebo were hot flushes, arthralgia, myalgia and arthritis. The long-term effects of letrozole on bone mineral density or lipid profile have not been determined and these parameters may require monitoring. In several pharmacoeconomic modelling studies from various public healthcare system perspectives, letrozole was considered a cost effective choice for first-line (vs tamoxifen) or second-line (vs megestrol acetate) treatment for advanced breast cancer in postmenopausal women. In conclusion, letrozole 2.5 mg/day is effective in the treatment of postmenopausal women with early-stage or advanced breast cancer. The efficacy, cost effectiveness and favourable tolerability profile of letrozole are reflected in current treatment guidelines recommending the drug as first-line therapy for advanced breast cancer. Letrozole is superior to tamoxifen for first-line treatment and is at least as effective as standard second-line treatments in disease that has progressed on antiestrogen therapy. For early-stage disease, letrozole is superior to tamoxifen in the neoadjuvant setting, and prolongs disease-free survival when administered after the standard 5-year period of adjuvant tamoxifen therapy.
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PMID:Letrozole: a review of its use in postmenopausal women with breast cancer. 1516 28

Recent evidence has demonstrated that long-term estrogen deprivation using aromatase inhibitor therapy in postmenopausal women with breast cancer results in bone loss and increased fracture risk. Bisphosphonates are potent inhibitors of bone resorption and have demonstrated efficacy in preventing bone loss in postmenopausal women with low bone mineral density (BMD) and in patients with breast cancer receiving estrogen deprivation therapy. Therefore, this study investigated the effects of the bisphosphonate zoledronic acid on BMD and bone strength in rats treated with the aromatase inhibitor, letrozole. Peripheral quantitative computed tomography demonstrated that treatment of rats with daily oral letrozole (1 mg/kg) induced significant bone loss and cortical thinning compared with control animals (P < 0.01). A single prior intravenous dose of zoledronic acid dose dependently protected against letrozole-induced bone loss and cortical thinning, with the highest evaluated dose (20 microg/kg) resulting in BMD values that were not significantly different from controls over the 24 weeks of letrozole treatment. Furthermore, biomechanical testing of the distal femoral metaphysis demonstrated that zoledronic acid (20 microg/kg) significantly prevented the decrease in stiffness and elastic modulus induced by letrozole treatment. Taken together, these data support the use of zoledronic acid for the prevention of bone loss in women with breast cancer receiving aromatase inhibitor therapy.
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PMID:A single intravenous administration of zoledronic acid prevents the bone loss and mechanical compromise induced by aromatase inhibition in rats. 1684 41

Tumor vascularity is an important factor that has been shown to correlate with tumor malignancy and was demonstrated as a prognostic indicator for a wide range of cancers. Three-dimensional (3-D) power Doppler ultrasound (PDUS) offers a convenient tool for investigators to inspect the signals of blood flow and vascular structures in breast cancer. In this paper, a new computer-aided diagnosis (CAD) system for quantifying Doppler ultrasound images based on 3-D thinning algorithm and neural network is proposed. We extracted the skeleton of blood vessels from 3-D PDUS data to facilitate the capturing of morphological changes. Nine features including vessel-to-volume ratio, number of vascular trees, length of vessels, number of branching, mean of radius, number of cycles, and three tortuosity measures, were extracted from the thinning result. Benign and malignant tumors can therefore be differentiated by a score computed by a multilayered perceptron (MLP) neural network using these features as parameters. The proposed system was tested on 221 breast tumors, including 110 benign and 111 malignant lesions. The accuracy, sensitivity, specificity, and positive and negative predictive values were 88.69% (196/221), 91.89% (102/111), 85.45% (94/110), 86.44% (102/118), and 91.26% (94/103), respectively. The Az value of the ROC curve was 0.94. The results demonstrate a correlation between the morphology of blood vessels and tumor malignancy, indicating that the newly proposed method can retrieves a high accuracy in the classification of benign and malignant breast tumors.
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PMID:Analysis of tumor vascularity using three-dimensional power Doppler ultrasound images. 1833 28

The effects of a series of low molecular weight water-soluble cationic linear peptide analogs (LPAs, <1000 MW) with increasing hydrophobic/hydrophilic balance on lipid bilayer phase behavior and permeability were examined using liposomes composed of zwitterionic dipalmitoylphosphatidylcholine (DPPC) and mixed zwitterionic/anionic DPPC/dipalmitoylphosphatidylglycerol (DPPG) lipid bilayers. LPAs were synthesized using a previously reported alkyl linkage strategy as Arg-C(n)-Arg-C(n)-Lys, where C(n) represents the saturated alkyl linkage separating the cationic residues (n=4, 7, or 11) (Ye et al., 2007 [1]). Differential scanning calorimetry results show that the cationic LPAs bound to and disrupted DPPC and, to a greater extent, DPPC/DPPG phase behavior. When added to preformed unilamellar liposomes, the LPAs led to significant structural changes based on cryogenic transmission electron microscopy (cryo-TEM). Coupling cryo-TEM with carboxyfluorescein leakage studies indicate that the LPAs induced permeabilization through bilayer expansion, which caused membrane thinning. The effects were inconsistent with increasing LPA hydrophobicity, which suggests that a cooperative effect between electrostatic binding and hydrophobic insertion determined the location of LPAs within the bilayer and their membrane activity. Our results for LPA-induced membrane disruption correlate with previous breast cancer cell uptake studies that showed minimal LPA-C(4) uptake, but high LPA-C(11) uptake through a non-endocytic mechanism.
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PMID:Bilayer disruption and liposome restructuring by a homologous series of small Arg-rich synthetic peptides. 1991 94

Pathogenic macula determined by techniques including 3-dimensional optical coherence tomography OCT (3D-OCT), in six breast cancer patients who had received low cumulative doses (4.2 to 9.6 g) of tamoxifen is described. Fluorescein angiography showed varying amounts of foveolar hyperfluorescence. 3-dimensional OCT revealed one or several foveal cystoid spaces in 10 of 12 eyes with or without focal disruption of the photoreceptor transition zones. Time-domain OCT did not indicate cystoid spaces in two of the eyes that clearly showed intraretinal cysts on 3D-OCT. Tiny disruptions of photoreceptor transition zones were also more clearly visible on 3D-OCT. Previous studies have clearly shown retinopathy following long-term or high dosages of tamoxifen. Our results indicate that patients with low cumulative doses of tamoxifen can also suffer visual symptom-related foveal cystoid spaces and/or macular thinning. 3D-OCT is very effective in detecting early subtle changes in tamoxifen-induced maculopathy that can occur in asymptomatic patients.
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PMID:Early Detection of Tamoxifen-induced Maculopathy in Patients With Low Cumulative Doses of Tamoxifen. 2033 63

Anagen effluvium due to chemotherapy is usually reversible with complete hair regrowth. However, there is increased evidence that certain chemotherapy regimens can cause dose-dependent permanent alopecia. The histological features of this type of alopecia and the mechanisms of its origin are not known yet. We discuss the histological features of 10 cases of permanent alopecia after systematic chemotherapy with taxanes (docetaxel) for breast cancer (6 patients), busulfan for acute myelogenous leukemia (3 patients), and cisplatin and etoposide for lung cancer (1 patient). All patients had moderate to very severe hair thinning, which in 4 cases was more accentuated on androgen-dependent scalp regions. Patients complained that scalp hair did not grow longer than 10 cm and showed altered texture. Paired scalp biopsies from the affected scalp areas were obtained and evaluated in serial horizontal and vertical sections. The histology of all specimens was characterized by a nonscarring pattern with a preserved number of follicular units and lack of fibrosis. The hair count revealed decreased number of terminal hairs, increased telogen hairs, and increased miniaturized vellus-like hairs with a terminal to vellus and anagen to telogen ratios of 1:1 and 3.6:1, respectively. There was increased number of fibrous streamers (stelae) in both reticular dermis and subcutis. Arao-Perkins bodies were found in the subcutaneous portions of the streamers. The histological findings of permanent alopecia after chemotherapy are those of a nonscarring alopecia similar to androgenetic alopecia. Dermatopathologists should be aware of this condition as the absence of fibrosis and the presence of miniaturized hairs may be considered as features consistent with a diagnosis of androgenetic alopecia. Hence, these cases could easily be misdiagnosed in the absence of a good clinicopathological correlation.
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PMID:Permanent alopecia after systemic chemotherapy: a clinicopathological study of 10 cases. 2143 May 4


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