Possible monitoring of mesophotic scleractinian corals using an underwater mini-ROV to sample coral eDNA.

Mesophotic coral ecosystems (MCEs) are light-dependent tropical or subtropical communities occurring at depths of 30-150 m. Broader surveys of MCEs are needed to better understand stony corals, the keystone species of coral-reef ecosystems. While MCEs have been studied by professional SCUBA divers and with deep-sea robots, comprehensive surveys of MCEs are required. An eDNA metabarcoding method has recently been used to survey scleractinian corals in shallow reefs. We tested whether MCEs might be more comprehensively surveyed by collecting seawater samples using an underwater mini-remote operated vehicle (mini-ROV). Seawater was collected 1-2 m above reef tops at depths of 20-80 m at 24 sites in six locations around the Zamami Islands (Okinawa, Japan). Water samples were then subjected to coral-specific eDNA amplification. Metabarcoding analyses of amplicons showed that except for one site, coral-specific eDNA from approximately 0.5 l seawater samples was sufficient to identify genera. The proportion of Acropora eDNA was higher at shallow reefs and upper ridges of slopes, while the proportion of Porites increased at mesophotic sites. Although further technical improvements are required, this study suggests that it may be possible to monitor mesophotic corals to the generic level using eDNA collected using mini-ROVs.

Role of HER2-Related Biomarkers (HER2, p95HER2, HER3, PTEN, and PIK3CA) in the Efficacy of Lapatinib plus Capecitabine in HER2-Positive Advanced Breast Cancer Refractory to Trastuzumab.

OBJECTIVE: The aim of this study was to investigate the correlation between human epidermal growth factor receptor 2 (HER2)-related biomarkers and the treatment outcomes using lapatinib plus capecitabine (LC) and to evaluate the influence of the estrogen receptor (ER) status in trastuzumab-refractory HER2-positive advanced breast cancer. METHOD: Eighty patients were enrolled in this study. Total HER2, p95HER2, and total HER3 expression were quantified using the VeraTag assays. PTEN (phosphatase and tensin homolog) and p95 expression was evaluated using immunohistochemistry and PIK3CA mutation using direct sequencing. RESULTS: The response rate to LC was 30%, clinical benefit rate was 51.3%, and the median progression-free survival (PFS) was 174.5 days. ER negativity significantly correlated with higher HER2 and p95HER2. The lower HER2 and PIK3CA mutations were often observed in the nonresponders. A high p95HER2 expression correlated with longer PFS especially in the high HER2- and ER-positive cases. Patients without the PIK3CA mutation showed longer PFS in the same subset. Overall survival after LC significantly correlated with the number of recurrence organs. CONCLUSION: LC therapy is effective in trastuzumab-refractory HER2-positive breast cancer. Moreover, the biomarker expression differed depending on ER status, and a high p95HER2 expression and wild-type PIK3CA gene correlated with longer PFS especially in the ER-positive cases.

Inhibition of the proliferation of acquired aromatase inhibitor-resistant breast cancer cells by histone deacetylase inhibitor LBH589 (panobinostat).

Aromatase inhibitors (AIs) are important drugs for treating postmenopausal patients with hormone receptor-positive breast cancer. However, acquired resistance to AI therapies is a significant problem. Our study has revealed that the histone deacetylase inhibitor LBH589 treatment abrogated growth of AI-resistant cells in vitro and in vivo, causing cell cycle G2/M arrest and induced apoptosis. LBH589 treatment also reduced the level of NF-κB1 which is overexpressed when AI resistance develops. Analyzing paired tumor specimens from 12 patients, we found that NF-κB1 expression was increased in recurrent AI-resistant tumors as compared to the paired primary tumors before AI treatment. This finding was consistent with up-regulated NF-κB1 expression seen in a collection of well-established AI-resistant cell lines. Furthermore, knockdown of NF-κB1 expression significantly suppressed the proliferation of AI-resistant cells. Treatment of AI-resistant cell lines with LBH589 suppressed NF-κB1 mRNA and protein expression. In addition, LBH589 treatment abrogated growth of AI-resistant tumors in mice, and was associated with significantly decreased levels of NF-κB1 in tumors. In all, our findings strongly support further investigation of LBH589 as a novel therapeutic strategy for patients with AI-resistant breast cancer, in part by suppressing the NF-κB1 pathway.

Clinical features and prognostic factors of bone metastases from colorectal cancer.

PURPOSE: To investigate the clinical features and prognoses of patients with diagnosed bone metastases from colorectal cancer (CRC). METHODS: This was a 16-year retrospective study of 32 patients with bone metastases secondary to CRC, who were seen at National Kokura Hospital between 1993 and 2008. The influence of clinical and pathologic variables on survival was assessed by univariate and multivariate analyses. RESULTS: The bone most commonly involved was the spinal column. The mean disease-free interval was 17.6 months and mean survival from the diagnosis of bone metastases was 9.3 months. On univariate analysis, the serum CEA level at the time of diagnosis of bone metastases (p = 0.020) and history of pulmonary metastases (p = 0.013) were significant. On multivariate analysis, a history of bone metastases in the ribs (hazard ratio 3.669, p = 0.025) and a history of pulmonary metastases (hazard ratio 3.854, p = 0.022) significantly affected survival. CONCLUSIONS: It is important to investigate for bone metastases in patients who complain of back pain and lumbago after CRC surgery.

Information-seeking experiences and decision-making roles of Japanese women with breast cancer.

PURPOSE: To investigate the information-seeking experiences and decision-making roles of Japanese women with breast cancer, to examine the relationship between information-seeking experiences and decision-making roles, and to explore the factors that influenced taking a more active role than the preferred role during the treatment decision-making process. METHODS: In a cross-sectional study, women with breast cancer were retrospectively administered the Control Preferences Scale and the Information-Seeking Experience Scale. The Chi-Square test was used to compare differences among individual variables in decision-making roles and information-seeking experiences. Logistic regression analysis was used to explore the factors that influenced taking a more active role than the preferred role. RESULTS: One hundred and four patients with breast cancer participated in the investigation. Eighty-five patients (78%) perceived themselves as having knowledge of breast cancer and most patients (92%) sought information on breast cancer. The preferred roles in decision-making that they reported having before treatment were 18% active, 69% collaborative and 13% passive. The actual roles they perceived having experienced were 27% active, 43% collaborative and 30% passive. Although there was concordance of preferred and actual role for only 59% of the women, most patients reported that they were satisfied with their decision-making. Many women with breast cancer reported negative experiences with information seeking, including wanting more information (49%), expending a lot of effort to obtain the information needed (53%), not having enough time to obtain needed information (55%), frustration during the search for information (44%), concerns about the quality of the information (45%) and difficulty understanding the information received (49%). This study revealed that having a more active actual role than the initial preferred role was associated with emotional expression to the physician, having undergone mastectomy, and the desire for more information. CONCLUSION: Most women with breast cancer sought information on breast cancer and expressed a preference for a collaborative relationship with physicians in treatment decision-making. Patients who expressed emotion to their physician, wanted more information, and underwent mastectomy were most likely to change their actual decision-making role toward a more active choice.

[Docetaxel in combination with epirubicin as the first-line chemotherapy for advanced and recurrent breast cancer: a multicenter phase II study].

This study examined the efficacy and tolerability of docetaxel(DOC)in combination with epirubicin(EPI)as the first-line treatment for patients with advanced and recurrent breast cancer. A total of 56 female patients with metastatic breast cancer not previously treated for metastatic disease received DOC(60mg/m²)and EPI(60mg/m2)on day 1 every 3 weeks. The patient characteristics included a median age of 53 years. Advanced disease was present in 86% of patients, and recurrent disease was found in 14%; 3 or more metastatic sites had been diagnosed in 38% of patients, and 59% patients were ER+. The median number of courses administered was 6. The median dose intensity was 18. 7mg/m²week for DOC and EPI, and the relative dose intensities were 93. 5%and 93. 3%, respectively. The clinical responses included a complete response in 5%, a partial response in 54%, and stable disease in 33% of patients, with a disease control rate of 92%. The progression-free survival was 78. 3%, and the overall survival was 91. 9% at 1 year. Grade 3/4 toxicities included neutropenia in 82%, leukopenia in 71%, febrile neutropenia in 16%, anorexia in 9%, and anemia in 7%of the patients. Neither congestive heart failure nor toxic death occurred. The D and E combination with doses of 60mg/m2 is an active and generally well-tolerated regimen that can be used as first-line chemotherapy for patients with metastatic breast cancer.

Short-term and low-dose prednisolone administration reduces aromatase inhibitor-induced arthralgia in patients with breast cancer.

Aromatase inhibitors (AIs) are important therapeutic drugs for postmenopausal women with hormone receptor-positive breast cancer. However, adverse effects of AIs such as arthralgia have been extensively reported. We performed a joint prospective, multi-institutional investigation to find out whether a low-dose and short-term prednisolone is effective against AI-induced arthralgia in 27 patients with breast cancer. Patients were administered 5 mg of oral prednisolone once a day in the morning for only one week. Patients were then asked to answer a questionnaire about joint pain symptoms at one week, one month and two months after the beginning of prednisolone use. Joint pain symptoms improved in 67% of patients immediately after prednisolone use, with 63% still reporting analgesic effect at one month, and 52% at two months after beginning internal use of prednisolone. At one week, one month and two months after the use of prednisolone, 30%, 30% and 26% of patients reported improved daily life, respectively. Our results suggest that prednisolone could substitute non-steroidal anti-inflammatory drugs, acetoaminophen or cyclooxygenase-2 inhibitors in patients with AI-induced arthralgia.

[Adjuvant epirubicin and cyclophosphamide followed by weekly paclitaxel for Japanese women with node-positive breast cancer: a multi-institutional feasibility study].

We evaluated the feasibility of epirubicin plus cyclophosphamide(EC)followed by weekly paclitaxel (wPTX) as an adjuvant therapy for node-positive breast cancer in a variety of practice settings. Thirty-two patients received EC (twenty-two: 75, 600 mg/m(2), ten: 90, 600 mg/m(2))every 3 weeks for 4 cycles. Twenty-eight of them received wPTX for 4 cycles subsequently, which were 3 consecutive weekly administrations with a following week pause per cycle. Grade 3 or 4 hematologic toxicity included leukopenia(5 for E75C600, 6 for E90C600, 2 for wPTX), neutropenia(6 for E75C600, 8 for E90C600, 4 for wPTX), febrile neutropenia (1 for E90C600), anemia (1 for wPTX), and GOT/GPT elevation (1 for wPTX). Non-hematologic toxicity of more than grade 3 was not seen. There were seven treatment discontinuations, including four patients' refusal, two allergic reactions to paclitaxel, and one liver dysfunction. EC followed by wPTX can be safely performed with a little toxicity at doses of 75/90 mg/m(2), 600 mg/m(2) and 80 mg/m(2), respectively.

Corneal and conjunctival toxicity of disinfectants--assessing safety for use with ophthalmic surgical instruments.

We investigated the corneal toxicity of ortho-phthalaldehyde (Cidex OPA, Johnson and Johnson K.K.) and its predecessor glutaraldehyde (Cidex, Johnson and Johnson K.K.). We made primary cultures of porcine and human corneal endothelial cells. Commercially available cell lines were also used including human, bovine, and rabbit corneal epithelium and human conjunctival cells. Following incubation for two days, cell survival was measured using a WST-1 assay for endothelia and a MTT assay for the other cells. Test solutions included 2.25% and 3.5% glutaraldehyde and 0.55% ortho-phthalaldehyde. Cell survival was presented as a percentage of the control value. ortho-phthalaldehyde displayed less toxicity than glutaraldehyde for all cell types tested. As expected 3.5% glutaraldehyde was slightly more toxic than 2.25% glutaraldehyde. When primary human corneal endothelial cultures were exposed to ortho-phthalaldehyde, the survival rates were 88% for 100-fold dilutions and 95% for 500-fold dilutions. The survival rates for all cells tested were greater than 90% when dilutions of 1000-fold or more were used. In conclusion, the corneal toxicity of glutaraldehyde and ortho-phthalaldehyde appears to be within safe levels following washing procedures and therefore the use of these disinfectants may be suitable for selected ophthalmic surgical instruments in urgent or under-equipped circumstances.

Inhibition of inducible nitric oxide synthase prevents hepatic, but not pulmonary, injury following ischemia-reperfusion of rat liver.

The aim of this study was to investigate the contribution of inducible nitric oxide synthase (iNOS)-derived nitric oxide on the liver and lung injury following hepatic ischemia-reperfusion (I/R) using a novel and potent iNOS inhibitor, ONO-1714. Rats were subjected to 90 min of partial hepatic ischemia followed by 3, 6, 12, and 24 hr of reperfusion. Expression of iNOS mRNA peaked at 3 hr of reperfusion in the liver and lung. Plasma nitric oxide levels were increased fourfold at 24 hr of reperfusion and plasma ALT was increased, reaching a peak at 12 hr of reperfusion; both were significantly inhibited by ONO-1714. Histological examination revealed extensive liver damage, whereas this was not seen in the ONO-1714 group. Lung injury was not significantly changed in groups with versus without ONO-1714. Nitrotyrosine expression was seen in regions similar to those of the histological injuries of the liver, while this staining was absent in the ONO-1714 group. These data show that generation of peroxynitrite could be involved in the pathogenesis of liver injury but not lung injury after hepatic I/R. Inhibition of iNOS could be applied for attenuation of liver injury following hepatic I/R.

A case of breast cholesterol granuloma accompanied by cancer.

Cholesterol granuloma of the breast is a very rare benign disease with clinical and imaging features that are often indistinguishable from cancer preoperatively. We report a case of breast cholesterol granuloma accompanied by cancer. The patient was a 78-year-old woman who complained of a lump in her right breast. Mammography and ultrasonography showed a well-circumscribed mass. Fine needle aspiration cytology showed many cholesterol crystals and inflammatory cells without malignancy. With a diagnosis of cholesterol granuloma, tumor extirpation was performed. Histopathologic examination revealed cholesterol granuloma together with breast cancer, and additional partial mastectomy was subsequently performed. It is noted that breast cholesterol granuloma could be accompanied by cancer.

Role of leukotrienes on hepatic ischemia/reperfusion injury in rats.

BACKGROUND: Leukotrienes (LT), composed of cysteinyl LT (cLT; LTC(4), LTD(4), and LTE(4)) and LTB(4), are potent lipid mediators enhancing the vascular permeability and recruitment of neutrophils, which are common features of hepatic ischemia/reperfusion (I/R) injury. The aim of this study was to investigate whether LT can mediate the liver and lung injuries following hepatic I/R. MATERIALS AND METHODS: Sprague-Dawley rats were subjected to 90 min of partial hepatic ischemia followed by 3, 12, and 24 h of reperfusion. In the hepatic and pulmonary tissues, LT content and the mRNA expression of LT-synthesis enzymes, 5-lypoxygenase (5-LO), LTC(4) synthase (LTC(4)-S), and LTA(4) hydrolase (LTA(4)-H) were measured. Tissue injuries were assessed by plasma ALT, histological examination, and wet-to-dry tissue weight ratios. RESULTS: The cLT content in the hepatic tissue after 12 and 24 h reperfusion was increased 4- to 5-fold compared to controls and this was accompanied by the enhancement of hepatic edema and plasma ALT elevation. There were no significant changes in the mRNA expression of LT-synthesis enzymes in both tissues. LTB(4) levels were not increased despite a significant neutrophil infiltration in both tissues. CONCLUSIONS: These data suggest that cLT are generated in the liver during the reperfusion period and may contribute to the development of hepatic edema and exert cytotoxicity. Factors other than LTB(4) may contribute to neutrophil infiltration.

Endoscopic neck surgery: current status for thyroid and parathyroid diseases.

During the last 3 years, 59 patients underwent endoscopic neck surgery. We started the video-assisted neck surgery with the gasless skin-lifting method for benign thyroid and parathyroid diseases to avoid complications of carbon dioxide (CO2) insufflation. Hemithyroidectomy was performed for benign thyroid tumors and subtotal thyroidectomy was selected for Graves' disease. Parathyroid adenomas were extirpated for primary hyperparathyroidism with precise preoperative localization by imaging modalities. In order to obtain a better visual field and to improve the cosmetic results, we have adopted the complete endoscopic method via breast approach with low CO2 insufflation pressure since August 2001. An intraoperative parathormone assay was introduced recently to confirm the complete removal of parathyroid adenomas. Both gasless and insufflation methods are feasible for endoscopic neck surgery with excellent cosmetic results.