Multiple toll-like receptors (TLRs) display differential bacterial and ligand specificity in the earthworm, Eisenia andrei.

Toll-like receptors (TLRs), an ancient and well-conserved group of pattern recognition receptors (PRRs), recognize conserved pathogen-associated molecular patterns. TLRs consist of three domains: the extracellular N-terminal domain, containing one or more leucine-rich repeats (LRRs), responsible for the recognizing and binding of antigens; the type-I transmembrane domain; and the intracellular domain known as the Toll/Interleukin-1 receptor (TIR) domain required for the downstream signaling pathway. We identified six new full-length complementary DNA (cDNA) sequences, Ean-TLR1/2/3/4/5/6. The deduced amino acid sequences indicate that Ean-TLRs consist of one signal peptide, one LRR N-terminal domain (Ean-TLR4/5), varying numbers of LRRs, one (Ean-TLR1/2/3/4/5) or two (Ean-TLR6) LRR C-terminal domains, one type-I transmembrane domain, and a TIR domain. In addition, a TIR domain alignment revealed that three conserved motifs, designated as Box 1, Box 2, and Box 3, contain essential amino acid residues for downstream signaling activity. Phylogenetic analysis of earthworm TLRs generated two separate evolutionary branches representing single (sccTLR) and multiple (mccTLR) cysteine cluster TLRs. Ean-TLR1/2/3/4 (sccTLR type) and Ean-TLR6 (mccTLR type) were clustered with corresponding types of previously reported earthworm TLRs as well as TLRs from Clitellata and Polychaete. As PRRs, earthworm TLRs should be capable of sensing a diverse range of pathogens. Except for Ean-TLR3, which was not responsive to any bacteria, earthworm TLR expression was significantly induced by Gram-positive but not Gram-negative bacteria. Moreover, it is likely that earthworms can differentiate between different species of Gram-positive bacteria via their TLR responses. The ligand specificity of earthworm TLRs suggests that their pathogenic ligand recognition is likely to be as specific and diverse as the mammalian TLR pathogen-sensing system.

Development of Korea Neuroethics Guidelines.

BACKGROUND: Advances in neuroscience and neurotechnology provide great benefits to humans though unknown challenges may arise. We should address these challenges using new standards as well as existing ones. Novel standards should include ethical, legal, and social aspects which would be appropriate for advancing neuroscience and technology. Therefore, the Korea Neuroethics Guidelines were developed by stakeholders related to neuroscience and neurotechnology, including experts, policy makers, and the public in the Republic of Korea. METHOD: The guidelines were drafted by neuroethics experts, were disclosed at a public hearing, and were subsequently revised by opinions of various stakeholders. RESULTS: The guidelines are composed of twelve issues; humanity or human dignity, individual personality and identity, social justice, safety, sociocultural prejudice and public communication, misuse of technology, responsibility for the use of neuroscience and technology, specificity according to the purpose of using neurotechnology, autonomy, privacy and personal information, research, and enhancement. CONCLUSION: Although the guidelines may require a more detailed discussion after future advances in neuroscience and technology or changes in socio-cultural milieu, the development of the Korea Neuroethics Guidelines is a milestone for the scientific community and society in general for the ongoing development in neuroscience and neurotechnology.

Immediate postoperative inflammation is an important prognostic factor in breast cancer.

OBJECTIVE: Inflammation is associated with worse outcomes in cancer. Operations induce an acute inflammatory response and could impact the clinical outcomes in breast cancer. The neutrophil-lymphocyte ratio (NLR) is a well-known indicator of inflammation. We investigated the prognostic significance of perioperative inflammation with the NLR in breast cancer. METHODS: We reviewed the clinical and pathological records of women diagnosed with invasive breast carcinoma at the Samsung Medical Center between 2000 and 2010. The NLR levels in the immediate preoperative period and the postoperative periods (1 week and 1 month) were assessed. RESULTS: The NLRs of a total of 3,116 breast cancer patients were examined. In the univariate analysis, the NLR in postoperative week 1, total mastectomy, the presence of lymphovascular invasion, a higher nuclear grade and pathologic TNM stage, and negative hormone receptor and subtypes were factors associated with poor disease-specific survival. The NLR in postoperative week 1 remained a significant prognostic factor in the multivariate analysis. A cutoff level of 5.2, determined by the minimum p value approach, was found to be a significant level for discriminating the impact on breast cancer-specific mortality (p = 0.0116 adjusted by the Bonferroni correction). CONCLUSIONS: Immediate postoperative inflammation is an important prognostic marker in breast cancer patients.

Effects of water-saving irrigation on emissions of greenhouse gases and prokaryotic communities in rice paddy soil.

The effects of water-saving irrigation on emissions of greenhouse gases and soil prokaryotic communities were investigated in an experimental rice field. The water layer was kept at 1-2 cm in the water-saving (WS) irrigation treatment and at 6 cm in the continuous flooding (CF) irrigation treatment. WS irrigation decreased CH(4) emissions by 78 % and increased N(2)O emissions by 533 %, resulting in 78 % reduction of global warming potential compared to the CF irrigation. WS irrigation did not affect the abundance or phylogenetic distribution of bacterial/archaeal 16S rRNA genes and the abundance of bacterial/archaeal 16S rRNAs. The transcript abundance of CH(4) emission-related genes generally followed CH(4) emission patterns, but the difference in abundance between mcrA transcripts and amoA/pmoA transcripts best described the differences in CH(4) emissions between the two irrigation practices. WS irrigation increased the relative abundance of 16S rRNAs and functional gene transcripts associated with Anaeromyxobacter and Methylocystis spp., suggesting that their activities might be important in emissions of the greenhouse gases. The N(2)O emission patterns were not reflected in the abundance of N(2)O emission-related genes and transcripts. We showed that the alternative irrigation practice was effective for mitigating greenhouse gas emissions from rice fields and that it did not affect the overall size and structure of the soil prokaryotic community but did affect the activity of some groups.

HER3 status by immunohistochemistry is correlated with poor prognosis in hormone receptor-negative breast cancer patients.

Breast cancer is a highly heterogeneous malignancy. The triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2) breast cancer subtypes are highly aggressive and are associated with a poor prognosis. The therapeutic targets for TNBC remain undefined, and many patients with the HER2 subtype acquire resistance to therapy after prolonged treatment. The objective of this study was to evaluate the prognostic significance of HER3 expression in invasive breast carcinoma. We established matched tissue microarray (TMA) blocks and clinical data from 950 cases of invasive breast carcinoma with long-term clinical follow-up data (median 109.7 months). Using the TMAs, we characterized the expression of ER, PR, HER2, EGFR, and HER3 by immunohistochemistry. Each case was classified as one of four IHC-based subtypes based on the expression of hormonal receptor (HR) and HER2. The clinicopathological characteristics and survival of 950 patients were analyzed by subtype. In the TNBC subtype, the HER3(+) group showed poorer disease-free survival (DFS, P = 0.010) and overall survival (OS, P = 0.015) than the HER3(-) group. In the HER2 subtype, the HER3(+) group also showed poorer DFS (P = 0.022) and OS (P = 0.077) than the HER3(-) group. However, there was no difference in patients with HR-positive breast cancer. HER3 expression was associated with poor DFS in both the TNBC and HER2 subtypes and poor OS in the TNBC subtype. HER3 overexpression is an important prognostic marker in hormone receptor-negative breast cancer, and further study is needed to clarify the role of HER-3 targeted treatment.

Round block technique without cerclage in breast-conserving surgery.

BACKGROUND: Round block technique is a unique breast resection through periareolar doughnut incision. However, it is more technically challenging and time consuming. We simplified the procedure by exclusion of round block cerclage. The purpose of this study was to introduce our round block technique without cerclage and to evaluate the results of oncological and cosmetic outcomes. METHODS: A total of 92 patients with centrally located breast cancer were treated with breast-conserving surgery using round block technique at Samsung Medical Center from July 2009 to May 2012. All patients had a small breast defect with excised breast volume less than 20 % compared to the total breast volume. We minimized the extent of skin removal and used simple interrupted inverted intradermal sutures without cerclage in doughnut closure. Patient's cosmetic satisfaction was assessed by subjective questionnaires at least 6 months after the operation. RESULTS: The median size of tumors was 1.7 cm (range 0.5-5.0 cm). The average distance of the tumors from the nipple was 2.0 cm (range 0.0-4.0 cm) on sonogram and most of the tumors were located upper breast (82.6 %). The median operative time was 101.5 min (range 55-180), including axillary surgeries. Median follow-up was 12.0 months (range 2-36), and none of patients have developed local recurrence. Up to the longest 3 years of follow-up, favorable cosmetic results have been found in patients treated with round block technique. CONCLUSIONS: Round block without cerclage is technically easy and feasible for centrally located breast tumors with favorable cosmetic results.

A new subfascial approach in open thyroidectomy: efficacy for postoperative voice, sensory, and swallowing symptoms. A randomized controlled study.

BACKGROUND: After open thyroidectomy, patients usually complain of voice, sensory, and swallowing symptoms. We approached the thyroid via the subfascial method to reduce these symptoms and compared postthyroidectomy symptoms with the conventional subplatysmal method. METHODS: Eighty-six patients undergoing thyroidectomy were recruited and randomized into either a conventional subplatysmal approach group (subplatysmal, 42 patients) group or a subanterior fascia of strap muscle approach group (subfascial, 44 patients). Voice symptoms were assessed using the Voice Handicap Index questionnaire and acoustic voice analysis. Sensory alterations were evaluated by the light touch and pain touch methods. Swallowing symptoms were assessed using the Swallowing Impairment Score (SIS) questionnaire, barium swallowing time, and hyoid bone movement range. Each variable was measured preoperatively, and at 2 weeks and 3 months after thyroidectomy. RESULTS: In both groups, the subjective symptoms of voice, sensation, and swallowing were significantly worsened at 2 weeks after operation, but improved 3 months after operation. Patients in the subplatysmal group had worse SIS scores than patients in the subfascial group (p = 0.016) and delayed barium swallowing time 2 weeks after operation (p = 0.008 compared to preoperative level). In the cohort over 50 years of age, SIS score did not recover to preoperative levels in the subplatysmal group 3 months after operation (p = 0.005 compared to preoperative level). CONCLUSIONS: The subfascial approach may be an effective method for reducing postthyroidectomy swallowing symptoms based on swallowing impairment score, especially in patients over 50 years of age.

The clinical meaning of intramammary lymph nodes.

OBJECTIVE: The clinical meaning of intramammary lymph nodes (iMLNs) is uncertain. We wanted to describe the clinical characteristics and understand the implications of iMLNs detected by sentinel LN biopsy (SLNB). METHODS: We reviewed the clinical, radiological and pathological records of women diagnosed with invasive carcinoma of the breast at the Samsung Medical Center between January 2001 and January 2011. A total of 69 patients were identified, and SLNB was performed in 31 patients. RESULTS: Of the 69 patients included in the study, 22 (31.9%) had metastases in iMLNs. The presence of lymphovascular invasion and the number of axillary LN metastases were associated with iMLN metastasis. Of the 31 patients who underwent SLNB, there were no cases with axillary LN metastasis when axillary SLNB was negative, even in cases of iMLN-positive patients. Of the 10 patients in whom intramammary SLNs (iMSLNs) were detected during SLNB, 8 patients without iMLN metastases were also negative for axillary LNs. CONCLUSION: Patients with metastatic iMLNs had more aggressive cancers with lymphovascular invasion and increased axillary LN metastases. When iMSLN was detected by SLNB, performing of axillary dissection could be determined by the status of the iMSLN itself.

Comparison between screen-detected and symptomatic breast cancers according to molecular subtypes.

Breast cancer screening programs make it possible to detect early cancer, thus reducing breast cancer mortality. We studied the clinicopathologic characteristics and prognosis of screen-detected invasive breast cancer compared with symptomatic breast cancer. And we compared the result according to molecular subtypes (luminal A, luminal B, Her2, and triple negative), with the goal of identifying the role of screening in each subtypes. From January 2002 to June 2008, 3,141 patients who underwent surgery for the treatment of invasive ductal carcinoma at Samsung Medical Center were included. Among them, 1,025 patients were screen-detected, and 2,116 patients who were screened over 2 years or never were symptomatic. We retrospectively reviewed the clinical and pathologic data. Screen-detected breast cancer was associated with older age, smaller tumor size, more hormone-receptor positive, less lymph node involvement, earlier stage, and reduced mortality compared with symptomatic breast cancer (P < 0.001). According to the molecular subtype, luminal A was most common (63.6%) and showed the most obvious survival benefit in screen-detected tumors in comparison with symptomatic tumors (5-year OS: 99.7 vs. 96.5%, 5-year DFS: 96.4 vs. 90.7%). Screen detection was independently associated with improved overall and disease-free survival outcomes after adjustment for covariates (HR 0.32, P = 0.035; HR 0.58, P = 0.020, respectively) only in the luminal A subtype. Differences in pathological features such as tumor size, nodal status, grade, and age at diagnosis with different molecular subtype distributions may explain the survival advantage of patients with screen-detected breast cancer. Screening programs seem to have a different efficacy depending on the molecular subtype of the breast cancer, especially in the luminal A subtype, for which screen detection acts as an independent prognostic factor itself.

Right paraesophageal lymph node dissection in papillary thyroid carcinoma.

BACKGROUND: This study was designed to identify the patients with papillary thyroid carcinoma (PTC) who would benefit from RPELN dissection. SUMMARY BACKGROUND DATA: The value of the right paraesophageal lymph nodes (RPELNs), which are located posterior to the right recurrent laryngeal nerve, may be underestimated. Although the RPELNs are common sites of nodal recurrence, few related studies have been reported. METHODS: We retrospectively reviewed the medical records of 369 patients (286 female, 83 male) who underwent total thyroidectomy (327 patients) or right lobectomy (42 patients) with therapeutic or prophylactic central lymph node dissection for primary PTC between August 2008 and January 2010 at the Department of Surgery, Samsung Medical Center. RESULTS: Central lymph node (CLN) metastases were present in 51.2% (189 of 369) of the patients, and RPELN metastases were present in 12.2% (45 of 369) of the patients. The rate of RPELN metastasis was 19.6% (37 of 189) in patients with CLN metastases, but only 4.4% (8 of 180) in patients with no CLN metastases (P < .001). A univariate analysis revealed that RPELN metastasis was significantly correlated with the size of the tumor, the perithyroidal extent (capsular invasion), CLN metastasis, and lateral lymph node metastases. There were no significant differences in terms of gender, mean age, or number of tumors between groups. A multivariate analysis revealed that tumor size (>1 cm) and number of CLN metastases (≥ 3) were significantly correlated with RPELN metastasis. CONCLUSIONS: RPELN dissection should be considered in patients with right thyroid cancer, tumors larger than 1 cm, or multiple CLN metastases.

Clinicopathologic risk factors for the local recurrence of phyllodes tumors of the breast.

BACKGROUND: Phyllodes tumors (PTs) are rare breast tumors that usually occur in middle-aged women. Here we discuss our recent experiences in the diagnosis, surgical management, and clinical follow-up of this disease. METHODS: We retrospectively reviewed 164 patients with PTs who underwent surgical treatment at the Department of Surgery, Samsung Medical Center, Seoul, Korea, from January 1995 to July 2009. Clinical and histopathological data were analyzed. RESULTS: The median follow-up period was 33.6 months (range 2-179 months), and the median patient age was 43 years (range of 11-72 years). Tumor size ranged from 1 to 30 cm, with a median of 6.1 cm. A total of 148 patients (90.2 %) received local or wide excisions. Mastectomies were performed in 16 patients (9.8 %). The pathologic diagnoses included 82 benign (50.0 %), 42 borderline (25.6 %), and 40 malignant PTs (24.4 %). The tumor border was infiltrating in 43 patients (26.2 %) and pushing in 116 patients (70.7 %). The resection margin was divided by based on the width. Local recurrence was observed in 31 patients (18.9 %), and distant metastasis developed in four patients with malignant PTs. Risk factors for the local recurrence of a PT were a positive resection margin (P = .029) and tumor size (P = .001). CONCLUSIONS: The presence of tumor cells on the resection margin was a strong prognostic factor for local recurrence of PTs. However, a 1 cm negative margin thickness did not confer any local control advantage over a thinner negative margin width.

Lymph node metastasis in patients with frozen section analyses that are negative for tumors.

OBJECTIVES: This study was designed to assess the necessity of delayed complete axillary lymph node dissection (cALND) for patients whose sentinel lymph nodes (SLNs) were negative for tumors on intraoperative frozen section analysis, but later proven positive on hematoxylin and eosin staining or immunohistochemistry. METHODS: We identified 341 patients who underwent sentinel lymph node biopsy (SLNB) with cALND at the Samsung Medical Center between 1998 and 2008, and reviewed the clinicopathological records of women diagnosed with invasive carcinoma of the breast. RESULTS: Of the 341 patients, 59 underwent delayed cALND due to negative results on frozen section. Only 1 patient had a non-SLNs metastasis in the group of delayed cALND. Delayed cALND was associated with higher rates of breast-conserving surgery, smaller primary tumor and metastasis size in SLNs, fewer metastatic lymph nodes and SLNs and a lower TNM stage. The detection of metastases of SLNs on frozen section and the number of metastatic SLNs were related to the detection of additional metastases of nonsentinel lymph nodes (NSLNs) in cALND. CONCLUSION: Our findings suggest that the lack of detection of metastases on frozen sections may be a predictive factor for nonmetastasis in NSLNs. cALND could therefore be omitted in such cases.

Berberine suppresses the TPA-induced MMP-1 and MMP-9 expressions through the inhibition of PKC-α in breast cancer cells.

BACKGROUND: Berberine (BBR) is one of the major alkaloids, and it has been reported to have a variety of pharmacologic effects, including inhibition of cell cycle progression. Here, we investigated the effect of BBR on the MMP-1 and MMP-9 expressions, which are predictors of metastasis and invasion in breast cancer cells. METHODS: MMP-1 and MMP-9 mRNA expressions were analyzed by real-time PCR. The levels of MMP-1 protein and PKC-α phosphorylation were detected by Western blotting. MMP-9 protein expression was detected by gelatin zymography. Cell cycle was analyzed by FACS analysis. PKC-α knock-down was examined by PKC-α siRNA transfection. RESULTS: The basal levels of both the MMP-1 and MMP-9 mRNA expressions were decreased by BBR treatment in a dose-dependent manner. In contrast, TPA, which is a tumor promoter, significantly increased the levels of the MMP-1 and MMP-9 mRNA and protein expressions in the MCF-7 breast cancer cells. We also observed that the TPA-induced MMP-1 and MMP-9 mRNA and protein expressions were prevented by BBR treatment. In addition, the TPA-induced MMP-1 and MMP-9 expressions were completely decreased by Go6983 and PKC-α siRNA, respectively. TPA-induced PKC-α phosphorylation was dose-dependently decreased by BBR treatment. CONCLUSION: The TPA-induced PKC-α phosphorylation is suppressed and then the MMP-1 and MMP-9 expressions are also inhibited by berberine. Therefore, we suggest that berberine may be used as a candidate drug for the inhibition of metastasis of human breast cancer.

Fabrication of copper nanoparticles in a thick polyimide film cured by rapid thermal annealing.

We investigated the imidization of a polyimide (PI) and the formation of Cu nanoparticles in a PI film by curinga precursor of PI (polyamic acid (PAA) dissolved in n-methyl-2-pyrrolidinone) in a reducing atmosphere in the rapid thermal annealing (RTA) system. A Cu film was deposited onto the SiO2/Si substrate, and the PAA was spin-coated onto the Cu film. After the PAA reacted with the Cu film, soft-baking was performed to evaporate the solvent. Finally, the PAA was imidized to PI at 450 degrees C by curing in a reducing atmosphere with the RTA. Fourier transform infrared spectroscopy showed that the PAA was successfully imidized by the RTA. X-ray diffraction patterns revealed that Cu nanoparticles formed by RTA curing at 450 degrees C for 5 minutes in a reducing atmosphere, and transmission electron microscopy showed that Cu nanoparticles about 6.5 nm in size were uniformly dispersed in the PI film. Curing by RTA is an attractive method because it takes only a few minutes.

Lung injury induced by the pulmonary instillation of povidone-iodine in rats.

PURPOSE: Povidone-iodine (polyvinylpyrrolidone iodine, PI), which is commonly used as a pre- and postoperative oral antiseptic, has been reported to cause pneumonia secondary to its pulmonary aspiration. Because no studies have yet investigated the underlying mechanisms of PI-induced pneumonia, we conducted an animal study to analyze the effect of PI on the lung following its pulmonary instillation. METHODS: The lungs of 61 male Sprague-Dawley rats (150-250 g) were instilled with varying volumes of either phosphate-buffered saline or PI solutions varying in strength from 0.01% to 10%. The lungs were harvested from the rats 1 h or 1, 3, 5, 7, 14, or 21 days after instillation for radiologic examination, macroscopic and light and scanning electron microscopic assessment, and an assessment of pulmonary toxicity using an MTT-based cytotoxicity assay. RESULTS: Macroscopically, atelectasis was the primary pulmonary lesion after PI instillation. The primary light and scanning electron microscopic findings were an initial inflammatory phase with edema, alveolar rupture, and leukocyte infiltration into the pulmonary interstitium, which progressed into a phase of lung parenchyma loss, and then resolved itself with scar tissue formation. Lung tissue viability following 1-day exposure to 0.01%, 0.1%, 1%, or 5% PI progressively decreased in a significant dose-dependent manner. CONCLUSIONS: PI aspiration can cause lung injury, including pulmonary fibrosis.

Estrogen-dependent transcription of the NEL-like 2 (NELL2) gene and its role in protection from cell death.

NELL2 (neural tissue-specific epidermal growth factor-like repeat domain-containing protein) is a secreted glycoprotein that is predominantly expressed in neural tissues. We reported previously that NELL2 mRNA abundance in brain is increased by estrogen (E2) treatment and that NELL2 is involved in the E2-dependent organization of a sexually dimorphic nucleus in the preoptic area. In this study we cloned the mouse NELL2 promoter and found it to contain two half-E2 response elements. Electrophoretic mobility shift assays and promoter assays showed that E2 and its receptors (ERalpha and ERbeta) stimulated NELL2 transcription by binding to the two half-E2 response elements. Hippocampal neuroprogenitor HiB5 cells expressing recombinant NELL2 showed increased cell survival under cell death-inducing conditions. Blockade of endogenous synthesis of NELL2 in HiB5 cells abolished the cell survival effect of E2 and resulted in a decrease in phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2). These data suggest that the NELL2 gene is trans-activated by E2 and contributes to mediating the survival promoting effects of E2 via intracellular signaling pathway of ERK.

The prognoses of metaplastic breast cancer patients compared to those of triple-negative breast cancer patients.

Metaplastic breast carcinoma (MBC) is a rare, heterogeneous breast cancer characterized by admixture of adenocarcinoma with metaplastic elements, low hormone receptor expression, and poor outcomes. The authors retrospectively reviewed the medical records of 47 MBC patients and 1,346 invasive ductal carcinoma (IDC) patients. Two hundred eighteen of the IDC patients were triple-negative (TN-IDC) for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 (ER-/PR-/HER2-). Patients were surgically treated at the Samsung Medical Center between 2005 and 2009. The MBC patients presented with a larger tumor size, lower lymph node involvement, higher histological and nuclear grades, higher triple negativity (ER-/PR-/HER2-) and higher p53, CK5/6, and EGFR expressions compared with those of the IDC group. However, there were no significant differences in clinicopathological characteristics between MBC and TN-IDC. During the follow-up period (median duration of 30.3 months, range 2.6-56.3 months), seven (14.9%) MBC patients, and 98 (7.1%) IDC patients had disease recurrence. The three-year disease-free survival (DFS) rate was 78.1% in the MBC group and 91.1% in IDC group (P < 0.001). The three-year DFS rate was not significantly different between the MBC and TN-IDC groups (78.1 vs. 84.9%, P = 0.114). However, in patients with lymph node metastasis who underwent adjuvant chemotherapy, the three-year DFS rate was 44.4% in the MBC group and 72.5% in the TN-IDC group (P = 0.025). The authors found that MBC had a poorer clinical outcome than did IDC. In breast cancer patients with nodal metastasis, MBC had a poorer prognosis than did TN-IDC, despite adjuvant chemotherapy.

Large clinical experience of primary angiosarcoma of the breast in a single Korean medical institute.

BACKGROUND: Angiosarcoma of the breast is rare. The purpose of the present study was to evaluate the clinicopathologic characteristics and the clinical outcomes of patients with primary breast angiosarcoma. METHODS: We analyzed the clinicopathologic factors of patients with angiosarcoma of the breast treated between 1997 and 2010 at the Samsung Medical Center. We reviewed the related demographic data, preoperative imaging studies, method of histologic confirmation, tumor size, histologic grades, status of hormonal receptors, treatment modality, and survival data. RESULTS: Nine women with angiosarcoma of the breast were identified. The median age of patients with primary angiosarcoma of the breast at diagnosis was 31 years (range: 19-63 years), and the median tumor size was 9.0 cm (range: 3.5-10.7 cm). Seven patients (77.7%) died within a median follow-up of 46.7 months (range: 3.9-63.3 months), and all deaths were directly attributed to angiosarcoma. Overall, the median time from diagnosis of angiosarcoma to death was 46.8 months (range: 8.21-63.3 months). The 5 year overall survival with angiosarcoma was 42.9%. CONCLUSIONS: Primary angiosarcoma of the breast is a rare malignancy with a poor prognosis, even with complete resection. Chemotherapy and radiation therapy have limited value as treatments to date. Total mastectomy appears to be the most appropriate and beneficial treatment. More aggressive surgical management should be considered, and future clinical research should explore the most appropriate adjuvant therapy in the treatment of angiosarcoma.

Ileal metastasis of breast cancer in a patient with a BRCA2 gene mutation: report of a case.

Breast cancer is the most common malignancy in females. Common sites of metastases include the liver, lung, bone, and brain, while metastases to the extrahepatic digestive system are very rare. This report presents a patient diagnosed with breast carcinoma metastasis in the terminal ileum. The patient underwent breast-conserving surgery on both breasts because of breast cancer at the age of 46 years. Both breast cancers were consistent with stage I invasive ductal carcinomas. Colonoscopy during an investigation for hematochezia revealed a 2-cm ulceration in the terminal ileum 22 months later, and microscopic examination of a biopsy specimen of the ulceration revealed a poorly differentiated mass that was strongly suggestive of metastatic adenocarcinoma with endolymphatic tumor emboli. She underwent hand-assisted laparoscopic ileocecectomy because of ileal metastasis. She had a family history of breast cancer (sister) and colon cancer (brother). She exhibited HER2/neu discordance and carried the BRCA2 gene mutation. Surgeons should remain aware that breast cancer can metastasize to the gastrointestinal tract.

Ex vivo organ culture of adipose tissue for in situ mobilization of adipose-derived stem cells and defining the stem cell niche.

In spite of the advances in the knowledge of adipose-derived stem cells (ASCs), in situ location of ASCs and the niche component of adipose tissue (AT) remain controversial due to the lack of an appropriate culture system. Here we describe a fibrin matrix-supported three-dimensional (3D) organ culture system for AT which sustains the ASC niche and allows for in situ mobilization and expansion of ASCs in vitro. AT fragments were completely encapsulated within the fibrin matrix and cultured under dynamic condition. The use of organ culture of AT resulted in a robust outgrowth and proliferation in the fibrin matrix. The outgrown cells were successfully recovered from fibrin by urokinase treatment. These outgrown cells fulfilled the criteria of mesenchymal stem cells, adherence to plastic, multilineage differentiation, and cell surface molecule expression. In vitro label retaining assay revealed that newly divided cells during the culture resided in interstitium between adipocytes and capillary endothelial cells. These interstitial stromal cells proliferated and outgrew into the fibrin matrix. Both in situ mobilized and outgrown cells expressed CD146 and alpha-smooth muscle actin (SMA), but no endothelial cell markers (CD31 and CD34). The structural integrity and spatial approximation of CD31(-)/CD34(-)/CD146(+)/SMA(+) interstitial stromal cells, adipocytes, and capillary endothelial cells were well preserved during in vitro culture. Our results suggest that ASCs are natively associated with the capillary wall and more specifically, belong to a subset of pericytes. Furthermore, organ culture of AT within a fibrin matrix-supported 3D environment can recapitulate the ASC niche in vitro.