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At least 19 recordsLinked to original sources

[Establishment and characterization of human inflammatory breast carcinoma neoplasm transplantation in nude mice].

OBJECTIVE: To establish and characterize human inflammatory breast cancer xenograft in nude mice. METHODS: Animal studies, Northern and Western blot, zymograms and immunohistochemistry were used in our studies. RESULTS: Human transplantable inflammatory carcinoma were established in nude mice. This xenograft as its human counterpart exhibited striking erythema of the overlying skin, lympho-vascular invasion and other similar biological characteristics. It also exhibited lung metastasis 4-6 weeks after growth. This xenograft was ER, PR, Her-2/neu negative and p53, EGFR positive. Comparative studies of inflammatory breast cancer xenograft with non-inflammatory xenograft indicated 10-20 fold overexpression of E-cadherin and MUC1. CONCLUSIONS: This human inflammatory breast carcinoma xenograft will provide an excellent animal model to allow us to further dissect out both the upstream regulatory machinery and downstream effector molecules responsible for the inflammatory carcinoma phenotype.

Animals↗

[A Case of Stage Ⅳ Lung Adenocarcinoma with Bilateral Breast Metastases Mimicking Inflammatory Breast Cancer].

Breast metastases from primary lung cancers with inflammatory breast cancer (IBC)-like features are rare. Here, we report a patient with bilateral breast metastases from an advanced lung adenocarcinoma that mimicked IBC. A 67-year-old woman was diagnosed with right middle lobe lung adenocarcinoma with pleural and peritoneal dissemination (cT2aN2M1c, cStage ⅣB) and received systemic therapy. Twenty-nine months later, skin erythema and edema appeared in both breasts, suggesting bilateral IBC. Core needle biopsies of both breasts revealed atypical carcinomas without intraductal or lobular in situ components. Immunohistochemistry showed thyroid transcription factor-1 and Napsin A positivity and GATA3 negativity, supporting the diagnosis of metastatic lung adenocarcinoma of the breasts. Comprehensive genomic profiling of the breast specimen revealed an EGFR exon 19 deletion, and osimertinib achieved disease control within 1 year. This report highlights a diagnostic pitfall in which lung adenocarcinoma metastasis to the breast mimics IBC and underscores the importance of biopsy, an appropriate immunohistochemical panel, and molecular testing to establish a correct diagnosis and guide optimal systemic therapy.

Humans↗

Normal and malignant breast tissue is a target organ for 1,25-(0H)2 vitamin D3.

Malignant and benign human breast tumours as well as rabbit breast tissue were examined for specific receptors for 1,25-dihydroxyvitamin D3 using competitive binding studies and sucrose density gradient analysis. Classical high affinity, low capacity receptors for 1,25-dihydroxyvitamin D3 were found in breast and node tissue in seven of ten patients with breast cancer and in all three patients with benign neoplasms. An inflammatory breast mass showed no binding. Similar receptors were found in breast tissue from pregnant and lactating rabbits. Taken with other recent data, these results suggest that 1,25-dihydroxyvitamin D3 may activate calcium transport in the malignant as well as in the normal lactating breast.

Animals↗

Dirofilariasis of breast: report of two cases diagnosed by fine-needle aspiration biopsy.

We report on 2 cases of dirofilariasis of the breast occurring in adult Chinese females residing in Hong Kong. The diagnosis was made by fine-needle aspiration biopsies. The direct smears contained numerous acute inflammatory cells, including eosinophils. A partially necrotic adult nematode of about 400-450 microm in diameter was identified in the cell-block sections of each case. The worm was characterized by a thick cuticle with longitudinal cuticular ridges and fine transverse surface striations, abundant somatic muscle, an intestine, and a reproductive tube or uterus. The morphologic features of this round worm were most compatible with those of Dirofilaria repens. While the clinical and radiologic findings of dirofilariasis of the breast are nonspecific and mimic those of breast neoplasms or inflammatory conditions, a definitive diagnosis is possible with fine-needle aspiration biopsy. A correct diagnosis of dirofilariasis may help to spare patients from unnecessary medical and surgical interventions.

Adult↗

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

Clinical and flow cytometry characteristics of malignant pleural effusions in patients after intracavitary administration of methylprednisolone acetate.

Ten patients with recurrent pleural effusions due to advanced cancer were treated by intracavitary methylprednisolone acetate (Depo-Medrol [DM], Upjohn, Kalamazoo, MI). They received one to six courses of DM (median, three courses per patient) with doses ranging from 80 to 160 mg per course. Effusion cells were cryopreserved before and during DM installation for subsequent determination of ploidy by flow cytometry. Pleural effusion in all three patients with advanced breast cancer resolved and did not reaccumulate throughout follow-up for 11+, 10+, and 8+ months. Pleural effusion in a patient with metastatic gastric cancer and in two of four patients with adenocarcinoma of unknown origin partially resolved. Altogether six of ten patients (60%) subjectively and objectively benefited from this therapy. All patients tolerated the treatment well with no local or systemic side effects. Flow cytometry showed a reduction in ploidy of effusion cells in all three patients with breast cancer, from a peak mean channel of 6C to nearly 2C after therapy. Transient reduction of ploidy was seen also in the effusion of a patient with unknown primary tumor associated with clinical improvement. The clinical and laboratory data reported offers initial evidence that DM when instilled into the pleural cavity after incomplete thoracentesis may act as effective palliative therapy either alone or in combination with other anticancer agents.

Adult↗

Three novel hormone-responsive cell lines derived from primary human breast carcinomas: functional characterization.

Human breast cancer primary cultures are useful tools for the study of several aspects of cancer biology, including the effects of chemotherapy and acute gene expression in response to different hormonal/chemotherapy treatments. The present study reports the conditions for primary culture of breast cancer samples from untreated patients and the most effective collagenization method to dissociate human samples consisting in an overnight incubation with 1 mg/ml types II or IV collagenase and further incubation in DMEM:F12 (1:1) medium supplemented with glutamine, bovine insulin, penicillin-streptomycin, HEPES, estradiol, cortisol (F), tri-iodothyronine (T(3)), transferrine (TR), and 10% fetal calf serum (FCS). These conditions proved to be appropriate for both primary culture and the development of stable cell lines. Of the seven cell lines obtained, three fast growing and estrogen receptor (ER)+/progesterone receptor (PgR)+/EGF receptor (EGFR)+ have been characterized. The cells are able to grow both in soft agar and in nude mice, and express cytokeratins, all parameters characteristic of malignant epithelial cell lines. The cells also exhibit an increased proliferation rate in the presence of estradiol, progesterone, and EGF, suggesting the presence of the corresponding receptors. The mRNA expression of type alpha- and beta-ER as well as EGFR, was confirmed by RT-PCR. In conclusion, the novel cell lines described, arose from primary tumors and are sensitive to estradiol, progesterone, and EGF. This not only expands the repertoire of breast cancer cells available as potentially useful tools for examining most parameters in breast cancer "in vitro", but also provides unique new models to explore the complex regulation by steroids as well as growth factors in such cells.

Adult↗

[Pyoderma gangrenosum: a rare cause of unexpected wound healing delay].

Pyoderma gangrenosum represents a rare but severe disturbance of wound healing following operative interventions. A case report of pyoderma gangrenosum after breast surgery is presented and the aetiology and the various options regarding investigations and treatment are discussed considering the current literature.

Anti-Inflammatory Agents↗

Decreased efficacy of bisphosphonates for recurrences of tumor-induced hypercalcemia.

Bisphosphonates are now the standard treatment for tumor-induced hypercalcemia (TIH), and pamidronate can normalize serum Ca in at least 90% of the patients treated for the first time. However, there are few data on the treatment of TIH when it recurs, and published results are contradictory. We studied 29 patients with solid tumors, 14 of whom had breast cancer and all of whom were naive to bisphosphonate therapy. They were retreated with pamidronate (median dose 1 mg/kg for both courses) for recurrence of TIH after a median interval of 78 (range 7-297) days. Fourteen of them, 7 of whom had breast cancer, were treated a third time 28 (range 5-79) days after the second course (median dose of pamidronate 1.5 mg/kg). Baseline Ca levels were not significantly different before each course, but the nadirs after each treatment progressively increased, 9.3 +/- 0.2 mg/dl, 10.5 +/- 0.3 mg/dl, and 12.3 +/- 0.4 mg/dl after the 1st, 2nd and 3rd administrations, respectively (P<0.05). The percentage of treatment failures also progressively increased: 10%, 31% and 85% (P< 0.05). This decreased hypocalcemic effect was essentially observed in patients without bone metastases or with tumors other than breast cancer. Thus, in patients without bone metastases, Ca levels did not decrease at all after the 3rd course, whereas the responses were not significantly different between the three courses in patients with bone metastases. Baseline urinary hydroxyproline, a marker of bone resorption, increased progressively from course to course, especially in patients with bone metastases or breast cancer, but this was not the case for parameters of bone formation. There was also a progressive increase in PTHrP levels accompanied by an increase in the number of patients with enhanced kidney reabsorption of Ca and a decrease in the threshold for Pi excretion, which was significant in patients without bone metastases. In conclusion, pamidronate was progressively less efficient when hypercalcemia recurred. This was observed mainly in patients with hypercalcemia of humoral origin. Tumor progression is accompanied by an enhanced release of osteolytic factors, notably PTHrP, that increase bone resorption and enhance kidney calcium reabsorption, especially in patients without bone metastases. When both phenomena occur, the response to bisphosphonates becomes minimal and the usefulness of therapy questionable.

Adult↗

Potent corticosteroid cream (mometasone furoate) significantly reduces acute radiation dermatitis: results from a double-blind, randomized study.

PURPOSE: Radiation-induced dermatitis is a very common side effect of radiation therapy, and may necessitate interruption of the therapy. There is a substantial lack of evidence-based treatments for this condition. The aim of this study was to investigate the effect of mometasone furoate cream (MMF) on radiation dermatitis in a prospective, double-blind, randomized study. MATERIAL AND METHODS: The study comprised 49 patients with node-negative breast cancer. They were operated on with sector resection and scheduled for postoperative radiotherapy using photons with identical radiation qualities and dosage to the breast parenchyma. The patients were randomized to receive either MMF or emollient cream. The cream was applied on the irradiated skin twice a week from the start of radiotherapy until the 12th fraction (24 Gy) and thereafter once daily until 3 weeks after completion of radiation. Both groups additionally received non-blinded emollient cream daily. The intensity of the acute radiation dermatitis was evaluated on a weekly basis regarding erythema and pigmentation, using a reflectance spectrophotometer together with visual scoring of the skin reactions. RESULTS: MMF in combination with emollient cream treatment significantly decreased acute radiation dermatitis (P=0.0033) compared with emollient cream alone. There was no significant difference in pigmentation between the two groups. CONCLUSIONS: Adding MMF, a potent topical corticosteroid, to an emollient cream is statistically significantly more effective than emollient cream alone in reducing acute radiation dermatitis.

Acute Disease↗

Bronchiolitis obliterans organizing pneumonia syndrome in breast-conserving therapy for early breast cancer: radiation-induced lung toxicity.

PURPOSE: Breast-conserving surgery and postoperative radiotherapy have played important roles in the treatment of early breast cancer. Bronchiolitis obliterans organizing pneumonia (BOOP) syndrome has recently been reported to be one of the complications of adjuvant radiotherapy. The purpose of this study was to determine the incidence of and risk factors for BOOP syndrome in breast cancer patients. METHODS AND MATERIALS: Between January 1996 and December 1998, 157 patients with breast cancer underwent radiotherapy after breast-conserving surgery. The criteria used for the diagnosis of BOOP syndrome were as follows: 1) radiation therapy to the breast within 12 months, 2) general and/or respiratory symptoms lasting for at least 2 weeks, 3) radiographic lung infiltrates outside the radiation port, and 4) no evidence of a specific cause. RESULTS: BOOP syndrome developed in 4 (2.5%) patients, who had fever and nonproductive cough, with patchy infiltrative shadows on chest roentgenograms which emerged between 5 and 6 months after radiotherapy. The symptoms and pulmonary infiltrates were rapidly improved by treatment with prednisone (40 mg/day), which was tapered over 2- to 5-month periods. However, BOOP syndrome relapsed in all cases during the tapering period or after withdrawal of prednisone. The eosinophil and neutrophil counts were increased and the ratios of CD4+ to CD8+ lymphocytes were elevated in bronchoalveolar lavage fluid in all four cases. There were no differences in proportions of patients by age, irradiated breast site, use of tamoxifen and/or chemotherapy, or radiation dose between those with and without BOOP syndrome. CONCLUSIONS: BOOP syndrome is considered an intractable form of lung toxicity after radiotherapy to the breast. An immunologic reaction mediated by eosinophils, neutrophils, and lymphocytes may be responsible for the development of this syndrome. Methods of prevention of BOOP syndrome should be established.

Adult↗

Beta-adrenoceptor signaling and its control of cell replication in MDA-MB-231 human breast cancer cells.

MDA-MB-231 human breast cancer cells express high beta-adrenoceptor levels, predominantly the beta2 subtype. Receptor stimulation by isoproterenol evoked immediate reductions in DNA synthesis which were blocked completely by propranolol and were of the same magnitude as effects elicited by high concentrations of 8-Br-cAMP. Isoproterenol-induced inhibition of DNA synthesis was maintained throughout several days of exposure, resulting in a decrement in total cell number, and the effects were augmented by cotreatment with dexamethasone; an even greater effect was seen when cAMP breakdown was inhibited by theophylline, with or without addition of isoproterenol. Despite the persistent effect of isoproterenol, receptor downregulation was evident with as little as 1 h of treatment, and over 90% of the receptors were lost within 24 h. Receptor downregulation was paralleled by homologous desensitization of the adenylyl cyclase response to beta-adrenoceptor stimulation. Dexamethasone augmented the effects of isoproterenol on DNA synthesis but did not prevent receptor downregulation or desensitization. These results indicate that beta-adrenoceptors are effectively linked, through cAMP, to the termination of cell replication in MDA-MB-231 human breast cancer cells, and that activation of only a small number of receptors is sufficient for a maximal effect. Novel pharmacologic strategies that focus on cell surface receptors operating through adenylyl cyclase may offer opportunities to combat cancers that are unresponsive to hormonal agents, or that have developed multidrug resistance.

Adenylyl Cyclases↗