The authors studied the radiosensitization of breast cancer stem‐like cells in vitro after treatment with the most commonly used statin, simvastatin, and examined the influence on local control after ...postmastectomy radiation among inflammatory breast cancer patients taking statins. This work provides new insight on combination regimens for breast cancer treatment and radiosensitization of this clinically radioresistant disease.
Reported rates of local failure after adjuvant radiation for women with inflammatory breast cancer (IBC) and triple‐negative non‐IBC are higher than those of women with receptor‐expressing non‐IBC. These high rates of locoregional recurrence are potentially influenced by the contribution of radioresistant cancer stem cells to these cancers. Statins have been shown to target stem cells and improve disease‐free survival among IBC patients. We examined simvastatin radiosensitization of multiple subtypes of breast cancer cell lines in vitro in monolayer and mammosphere‐based clonogenic assays and examined the therapeutic benefit of statin use on local control after postmastectomy radiation (PMRT) among IBC patients. We found that simvastatin radiosensitizes mammosphere‐initiating cells (MICs) of IBC cell lines (MDA‐IBC3, SUM149, SUM190) and of the metaplastic, non‐IBC triple‐negative receptor cell line (SUM159). However, simvastatin radioprotects MICs of non‐IBC cell lines MCF‐7 and SKBR3. In a retrospective clinical study of 519 IBC patients treated with PMRT, 53 patients used a statin. On univariate analysis, actuarial 3‐year local recurrence‐free survival (LRFS) was higher among statin users, and on multivariate analysis, triple negative breast cancer, absence of lymphatic invasion, neoadjuvant pathological tumor response to preoperative chemotherapy, and statin use were independently associated with higher LRFS. In conclusion, patients with IBC and triple‐negative non‐IBC breast cancer have the highest rates of local failure, and there are no available known radiosensitizers. We report significant improvement in local control after PMRT among statin users with IBC and significant radiosensitization across triple‐negative and IBC cell lines of multiple subtypes using simvastatin. These data suggest that simvastatin should be justified as a radiosensitizing agent by a prospective clinical trial.
This paper presents improvement of a novel levitation system in which soft magnetic material can be levitated by high-temperature superconductor (HTS). The levitation system consists of two permanent ...magnets, HTS samples of Dy/sub 1/Ba/sub 2/Cu/sub 3/Oy (DBCO), and movable yoke with cylindrical parts to which trapped flux in the HTS is gathered and produces an attractive force. The attractive force generally increases with decreasing air gap, but it decreases in a certain air gap called "positive stiffness air gap," which causes positive stiffness to achieve stable levitation of the movable yoke. In this work, we propose closed magnetic circuit using ferromagnetic yoke to enhance the magnetic force and investigate the relationship between attractive force and air gap with different thicknesses of the HTS and different diameters of cylindrical parts. By our proposing closed magnetic circuit, we obtain maximum levitation force of 85 N and stiffness of 4.5 N/mm. The tradeoff between the levitation force and positive stiffness air gap with the thickness of the HTS indicates that there is optimal thickness of HTS for the practical levitation system.
We investigate the dynamic response of a magnetic force control device composed of a laminate composite of magnetostrictive/piezoelectric material. The device exploits the inverse magnetostrictive ...effect of a magnetostrictive material so that the variation in the magnetization of the material, and hence the magnetic force in a magnetic circuit, can be controlled with a voltage to the piezoelectric material. Here, we compare the voltage-induced frequency responses of the admittance and flux (magnetic force) between the new device and a conventional electromagnet in order to identify the factors that degrade the response of the device. A finite-element calculation of the modal shape of the composite supports the observed correlation between the vibration of the composite and the flux in the gap in dynamic response.
a Department of Thoracic and Cardiovascular Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima City, Kagoshima 890-8520, Japan
b Department of ...Human Pathology Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima City, Kagoshima 890-8520, Japan
*Corresponding author. Tel.: +81-99-275-5368; fax: +81-99-265-8177. E-mail address : surgery2kadai{at}yahoo.co.jp (S. Iwamoto).
Prevention of paraplegia remains an important issue in repair of descending thoracic and thoracoabdominal aneurysms. Therefore, we investigated the protective effect of sivelestat sodium hydrate (ONO-5046) on ischemia-induced spinal cord damage in a rabbit model. Twenty New Zealand white rabbits were divided into two equal groups; ONO-5046 (1.6 mg/kg)+isotonic NaCl (30 ml) was administered selectively to the spinal cord via the lumbar arteries for the first 3 min during 30 min of infra-renal aorta clamping in the experimental group (group E), whereas NaCl was given alone in the control group (group C). Motor function of the lower limbs was assessed two days later by Tarlov criteria. The number of intact motor neurons in the anterior segment of the cord (L5 level) was counted after hematoxylin–eosin staining and the number of apoptotic motor neurons after TUNEL staining. Motor function of the lower limbs in group E was significantly better ( P =0.003) than that in group C. The number of intact motor neurons was greater and of apoptotic motor neurons was less in group E than C. Selective infusion of sivelestat sodium hydrate directly into the spinal cord via the lumbar arteries significantly attenuated functional and morphological ischemia-induced spinal cord injury.
Key Words: Ischemia/reperfusion; Spinal cord; Aortic operation
This study examined whether telmisartan, a unique angiotensin II type 1 receptor blocker (ARB) with peroxisome proliferator-activated receptor-γ (PPAR-γ)-modulating activity, improved insulin ...resistance in advanced glycation end-product (AGE)-exposed human hepatoma (Hep3B) cells. AGE increased phosphorylation of insulin receptor substrate-1 (IRS-1) at serine-307 residues in Hep3B cells. It also decreased tyrosine phosphorylation of IRS-1 and, subsequently, reduced the association of the p85 subunit of phosphatidylinositol 3-kinase with IRS-1 and glycogen synthesis in insulin-exposed Hep3B cells, all of which were inhibited by telmisartan. The insulin-sensitizing properties of telmisartan in AGE-exposed Hep3B cells were significantly blocked by GW9662, an inhibitor of PPAR-γ. Candesartan, another ARB, did not affect AGEs-induced serine phosphorylation of IRS-1 at serine-307 residues in Hep3B cells. Our study suggests that telmisartan could improve AGE-elicited insulin resistance in Hep3B cells by inhibiting serine phosphorylation of IRS-1, at least in part, via activation of PPAR-γ. Telmisartan may play a protective role against hepatic insulin resistance in diabetes.
Abstract Chronic inflammation, which is characterized by the proliferation of granulation tissues, is known to be regulated by angiogenesis. Recent results suggest that bone marrow-derived ...(BM-derived) hematopoietic cells regulate angiogenesis in vivo. We previously reported that the angiogenesis occurring during chronic inflammation is enhanced in response to the endogenous prostaglandins (PGs) derived from an inducible cyclooxygenase-2 (COX-2). In the present study, we examined the role of BM-derived cells expressing an E-type PG receptor subtype, EP3, in sponge-induced angiogenesis. The replacement of wild-type (WT) BM with BM cells (BMCs) from green fluorescent protein (GFP) transgenic mice revealed that the formation of granulation tissue around the sponge implants developed via the recruitment of BMCs. This recruitment was enhanced by topical injections of vascular endothelial growth factor (VEGF)-A, and a VEGF-dependent increase in the recruitment of BMCs was inhibited by a COX-2 inhibitor, celecoxib. FACS analysis of the granulation tissues after treatment with collagenase revealed that the Mac-1-positive macrophage fraction was enhanced by topical injections of VEGF-A, and that this increased recruitment of Mac-1-positive BMCs was inhibited by celecoxib. Selective knockdown of EP3 performed by BM transplantation with BMCs isolated from EP3 knockout (EP3) mice reduced sponge-induced angiogenesis, as estimated by mean vascular number and CD31 expression in the granulation tissues. This reduction in angiogenesis in EP3−/− BM chimeric mice was accompanied by reductions in the recruitment of BMCs, especially of Mac-1-positive cells and Gr-1-positive cells. These results indicate that the recruited bone marrow cells that express the EP3 receptor have a significant role in enhancing angiogenesis during chronic proliferative inflammation.
The pathogenesis of reduced postoperative ileus (POI) in laparoscopic gastrointestinal (GI) surgery still remains controversial. The aim of this study was to investigate the effect of surgical ...incision on postoperative ileus.
The effects of length, depth, and site of the incision on GI transit were compared using the geometric center of 51Cr in rats. The inhibitory mechanism of abdominal incision on GI transit also was studied.
The findings showed that 5 cm of abdominal skin and the 5-cm back muscle incision had no significant effect on GI transit. However, the 5-cm abdominal muscle-fascia incision and a 5-cm laparotomy significantly delayed GI transit. Gastrointestinal transit after a 5-cm laparotomy was significantly delayed, as compared with that of a 1-cm laparotomy regardless whether intestinal manipulation was performed or not. Guanethidine and yohimbine, but not propranolol, significantly improved the impaired GI transit after a 5-cm laparotomy.
The results suggest that the longer and deeper abdominal incision more profoundly inhibits GI transit. The inhibitory effect of abdominal incision is mediated via the activation of the somatosympathetic reflex and alpha-2 adrenoceptors.
Purpose.
Limited information is available about the optimal management and clinical outcome of bone‐only metastases in breast cancer patients. The objective of this study was to define prognostic ...factors for patients with bone‐only metastases. Our second objective was to compare progression‐free survival (PFS) and overall survival (OS) between patients with hormone receptor (HR)+ tumors and bone‐only metastases who received combinatory therapy (chemotherapy followed by endocrine therapy, or endocrine therapy combined with molecular targeted therapy) and those treated with endocrine or chemotherapy alone.
Patients and Methods.
We retrospectively identified 351 breast cancer patients diagnosed with bone‐only metastasis in 1997–2008 at our institution.
Results.
Patients with metastasis detected at the time of their primary breast cancer diagnosis (rather than at recurrence), a single metastasis, or asymptomatic bone disease had a longer PFS interval, and patients with a performance status of 0–1, a single metastasis, or asymptomatic bone disease had a longer OS time. Among patients with HR+ human epidermal growth factor receptor (HER)‐2− disease, combinatory therapy was associated with longer PFS and OS times than with endocrine therapy. In multivariate analyses, combinatory therapy was not associated with longer PFS or OS times than with endocrine therapy. Among patients with HER‐2+ disease, trastuzumab led to a longer PFS interval but no difference in the OS time.
Conclusion.
Our results indicate that, for HR+ disease, a prospective trial of chemotherapy followed by endocrine therapy is warranted to determine whether it prolongs survival more than endocrine therapy alone in patients with bone‐only metastases.
摘要
目的. 仅有骨转移的乳腺癌患者的适宜治疗和临床转归方面的信息有限。本研究主要目的是明确仅有骨转移的患者的预后因素。次要目的是在仅有骨转移的激素受体阳性（HR）+乳腺癌患者中，比较联合疗法（化疗继以内分泌疗法，或内分泌疗法+分子靶向治疗）与单纯内分泌疗法或单纯化疗的无进展生存（PFS）和总生存（OS）。
患者与方法. 对1997~2008年本院351例仅有骨转移的乳腺癌患者进行回顾性研究。
结果. 乳腺癌初次获诊时（而非复发时）即检出转移者、单发转移者或无症状骨病者，PFS间期更长，而体能状态评分0~1分者、单发转移者或无症状骨病者，OS时间更长。HR+人类表皮生长因子受体（HER）‐2‐患者中，联合疗法组的PFS和OS时间比内分泌疗法组更长。多因素分析显示，联合疗法组的PFS或OS时间并不比内分泌疗法组更长。HER‐2+患者中，曲妥珠单抗组PFS间期更长，但OS时间无差异。
结论. 本研究结果表明，在仅有骨转移的HR+患者中，前瞻性试验有助于明确化疗继以内分泌疗法组的生存期能否优于单纯内分泌疗法组。
The study defines prognostic factors for breast cancer patients with bone‐only metastases and examines progression‐free and overall survival times in patients with hormone receptor–positive disease and bone‐only metastases treated with different therapies.
A ferromagnetic material can be levitated by the pinning effect of a field-cooled superconductor. This paper presents two methods for modeling this effect: 1) an approximate calculation to determine ...the relationship between attractive force and air gap at both room temperature and superconductive temperature (77 K) and 2) a novel way of modeling the pinning effect by a finite-element method (FEM). A comparison of analytical and FEM results with experimental results verifies the validity of the methods. The methods can be used to estimate the system's behavior when the cylindrical yoke is replaced by a ring yoke. The stiffness of the system will increase by 70% (to 5.3 N/mm) when a ring yoke with the same surface area is used instead of a cylindrical yoke
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