Myoid hamartoma of the breast that proved difficult to diagnose: a case report.

Myoid hamartomas of the breast are extremely rare breast lesions, with a poorly understood pathogenesis. We describe the case of a 38-year-old premenopausal woman who presenting with a mass in the left breast. Mammography revealed an oval mass that was partly indistinct, and ultrasonography showed a hypoechoic mass with a slightly irregular margin. Bilateral breast dynamic magnetic resonance imaging was performed for a more detailed evaluation. The images showed rapid initial enhancement and a microlobulated margin. Because the suspicion of malignancy was strong at that time, core needle biopsy was performed. Histologically, the tumor was identified as fibroadenoma. A case of myoid hamartoma of the breast that proved difficult to diagnose is reported, and discussed with reference to the literature.

[A case of effective combination therapy with docetaxel, cyclophosphamide and trastuzumab as primary systemic therapy for locally advanced HER2-positive breast cancer].

We experienced a case of locally advanced breast cancer achieving a significant improvement by using a combination of docetaxel(DOC), cyclophosphamide(CPA)and trastuzumab as a primary systemic therapy.The patient was a 54-year-old woman suffering from a right breast mass, who was referred to our hospital and diagnosed with HER2-positive breast cancer with subclavicular lymph nodes metastases.The combination therapy of DOC(75 mg/m / 2), CPA(600 mg/m2)and trastuzumab(loading dose 8 mg/kg, then 6 mg/kg)for 6 courses at q3 week intervals, was started as the primary systemic therapy. After 6 courses of treatment, a right modified radical mastectomy was performed.There were a little breast cancer cells in the breast, and no axillary lymph node metastases.The combination chemotherapeutic regime with DOC, CPA and trastuzumab seems to be useful for treatment of HER2-positive breast cancer.

[Long-term complete response in a patient with breast cancer and bone and pleura metastases after treatment with a combination of S-1 and zoledronic acid].

We report a long-term complete response (CR) in a patient with postoperative recurrent breast cancer and bone and pleura metastases after treatment with a combination of S-1 and zoledronic acid. We administered 4 courses of tri-weekly CE (epirubicin 75 mg/m2, cyclophosphamide 600 mg/m2) and 12 courses of weekly paclitaxel (80 mg/m2) as adjuvant chemotherapy. However, combination therapy with S-1 and zoledronic acid was started because of the development of bone and pleura metastases. S-1 was administered orally at 100 mg/day everyday for 2 weeks, followed by a 1-week rest interval as 1 course; 4 mg of zoledronic acid was injected every 4 weeks. After 3 cycles of treatment, the patient's tumor marker levels had decreased to normal values, and both the bone and pleura metastases had disappeared. A long-term complete response was obtained as a result of this combination therapy.

Acute lung inflammation and ventilator-induced lung injury caused by ATP via the P2Y receptors: an experimental study.

BACKGROUND: Extracellular adenosine 5'-triphosphate (ATP) is an endogenous signaling molecule involved in multiple biological phenomena, including inflammation. The effects of extracellular ATP in the lung have not been fully clarified. This study examined 1) the biological roles of extracellular ATP in the pathogenesis of lung inflammation and 2) the possibility of involvement of extracellular ATP in mechanical ventilation-induced lung injury. METHODS: The effects of intratracheal ATP on lung permeability, edema or lung inflammation were assessed by measurements of the lung wet-to-dry weight ratio and lung permeability index, immunohistochemistry and expression of key cytokines by real-time polymerase chain reaction. The ATP concentration in broncho-alveolar lavage (BAL) fluid from mice mechanically ventilated was measured by luciferin-luciferase assay. The suppressive effects of a P2 receptor antagonist on ventilator-induced lung inflammation were also examined. RESULTS: ATP induced inflammatory reactions in the lung mainly via the ATP-P2Y receptor system. These reactions were alleviated by the co-administration of a specific P2 receptor antagonist. Mechanical ventilation with a large tidal volume caused lung inflammation and increased the ATP concentration in BAL fluid. P2 receptor antagonism partially mitigated the inflammatory effects of large tidal volume ventilation. CONCLUSION: Our observations suggest that the ATP-P2Y receptor system is partially involved in the pathogenesis of ventilator-induced lung injury.

Induction of mitochondria-dependent apoptosis through the inhibition of mevalonate pathway in human breast cancer cells by YM529, a new third generation bisphosphonate.

YM529, a new third generation bisphosphonate, induced apoptosis of a human breast cancer cell line, MX-1. Cytotoxic activity of YM529 was more potent than that of incadronate. YM529 activated caspase-9, but not caspase-8, and induced the release of cytochrome c into cytosol. YM529 increased Bax expression and decreased Bcl-2 expression, while it did not induce caspase-8-dependent Bid truncation. Farnesyl pyrophosphate prevented YM529-mediated cytotoxicity. These results suggest that YM529 is a potent therapeutic agent for human breast cancers, activating the mitochondria-dependent apoptotic pathway through the inhibition of protein farnesylation.

Aberrant expression of Fra-1 in estrogen receptor-negative breast cancers and suppression of their propagation in vivo by ascochlorin, an antibiotic that inhibits cellular activator protein-1 activity.

Estrogen receptor-negative breast cancers generally are highly malignant, resistant to chemotherapy and poorly prognostic. Here we demonstrate that estrogen receptor-negative human breast cancer cell lines highly express Fra-1, c-Fos and c-Jun, components of the transcription factor, activator protein-1 (AP-1). Retrospective observation of breast cancer tissues obtained by core needle biopsy before surgery from stages II and III patients demonstrates that Fra-1 expression is high in estrogen receptor-negative human breast cancers, and negatively correlated to paclitaxel sensitivity. Ascochlorin, which suppresses cellular AP-1 activity, selectively kills estrogen receptor-negative human and mouse breast cancer cell lines, and prolongs the survival time of mice implanted with an estrogen receptor-negative mammary carcinoma. These results suggest that chemotherapy targeting AP-1 activity is a potent strategy for estrogen receptor-negative human breast cancers.

[Local survey of practice patterns for barrier precautions during anesthesia practice].

BACKGROUND: Performing appropriate infection control procedures including barrier precautions with aseptic technique during anesthesia practice is extremely important in order to prevent nosocomial infection in surgical patients, as well as to avoid occupational exposure for anesthesiologists. METHODS: We conducted a survey to investigate current practice patterns of anesthesiologists with special emphasis on the application of barrier precautions during invasive procedure; intravascular catheter insertion or endotracheal intubation. RESULTS: In general, the compliance of hand hygiene practice was poor specifically immediately before or after performing invasive procedures; approximately two-thirds of the anesthesiologists were not performing hand washing. Despite most anesthesiologists have knowledge regarding the importance of maximal barrir precautions (MBP) during central venous catheter insertion, only a half of them did perform the MPB. Concerns for additional costs or time for anesthesia preparation, as well as poor arrangement for alcohol-based antiseptics handrubs in the operation room could be the factors affecting the poor compliance. CONCLUSIONS: Anesthesiologists should change their practice to adequately apply appropriate aseptic barrier precautions including hand hygiene. Improvement of the medical payment system to cover the costs for infection control in the operating room should also be considered.

[A case of multi-drug resistant recurrent breast cancer with multiple bone metastasis responding to TS-1 and trastuzumab].

We experienced a case of multi-drug resistant recurrent breast cancer with multiple bone metastases achieving a significant improvement by TS-1 and trastuzumab. The prior treatments including taxane or vinorelbine and trastuzumab were changed in the regimen to TS-1 and trastuzumab because of the progressive disease. TS-1 was administered orally at 100 mg/day everyday for 2 weeks, followed by a 1-week rest interval as 1 cycle, and trastuzumab was injected at 2 mg/kg/week for 4 weeks, followed by a 1-week rest interval as 1 cycle. After 3 cycles of the treatment, the level of tumor markers and tumor sizes of bone metastases became reduced. In conclusion, the combination treatment of TS-1 and trastuzumab is thought to be effective for multi-drug resistant recurrent breast cancer.

Fas ligand released by activated monocytes causes apoptosis of lung epithelial cells in human acute lung injury model in vitro.

Alveolar epithelial cell death plays a crucial role in the progression of acute lung injury. We have demonstrated up-regulation of Fas expression on alveolar epithelial cells, and soluble Fas ligand secretion from inflammatory cells upon acute lung injury. Here we show that the lipopolysaccharide-stimulated human monocyte cell line THP-1 releases Fas ligand, and that conditioned medium from lipopolysaccharide-stimulated THP-1 cells induces apoptosis of the human pulmonary adenocarcinoma cell line A549. Activation of caspase-3 and -8 is associated with the apoptosis. Gene targeting on Fas in A549 cells by specific small interfering RNA impairs apoptosis induced by conditioned medium from activated THP-1, while that on Fas ligand in THP-1 cells impairs the apoptosis-inducing activity of the conditioned medium produced by lipopolysaccharide-stimulated cells. These results suggest that Fas ligand released by monocytes causes alveolar epithelial cell death through a Fas-dependent apoptotic mechanism in the development of acute lung injury.

Apoptosis and inactivation of the PI3-kinase pathway by tetrocarcin A in breast cancers.

A survival kinase, Akt, is a downstream factor in the phosphatidylinositide-3'-kinase-dependent pathway, which mediates many biological responses including glucose uptake, protein synthesis and the regulation of proliferation and apoptosis, which is assumed to contribute to acquisition of malignant properties of human cancers. Here we find that an anti-tumor antibiotic, tetrocarcin A, directly induces apoptosis of human breast cancer cells. The apoptosis is accompanied by the activation of a proteolytic cascade of caspases including caspase-3 and -9, and concomitantly decreases phosphorylation of Akt, PDK1, and PTEN, a tumor suppressor that regulates the activity of Akt through the dephosphorylation of polyphosphoinositides. Tetrocarcin A affected neither expression of Akt, PDK1, or PTEN, nor did it affect the expression of Bcl family members including Bcl-2, Bcl-X(L), and Bax. These results suggest that tetrocarcin A could be a potent chemotherapeutic agent for human breast cancer targeting the phosphatidylinositide-3'-kinase/Akt signaling pathway.