Outcomes of embolization procedures for type II endoleaks following endovascular abdominal aortic repair.

OBJECTIVE: The objective of this study was to investigate the mid-term outcomes of embolization procedures for type II endoleak after endovascular abdominal aortic repair, and clarify the risk factors for aneurysm enlargement after embolization procedures. METHODS: This was a retrospective multicenter registry study enrolling patients who underwent embolization procedures for type II endoleaks after EVAR from January 2012 to December 2018 at 19 Japanese centers. The primary end point was the rate of freedom from aneurysm enlargement, more than 5 mm in the aortic maximum diameter, after an embolization procedure. Demographic, procedural, follow-up, and laboratory data were collected. Continuous variables were summarized descriptively, and Kaplan-Meier analyses and a Cox regression model were used for statistical analyses. RESULTS: A total of 315 patients (248 men and 67 women) were enrolled. The average duration from the initial embolization procedure to the last follow-up was 31.6 ± 24.6 months. The rates of freedom from aneurysm enlargement at 3 and 5 years were 55.4 ± 3.8% and 37.0 ± 5.2%, respectively. A multivariate analysis revealed that a larger aortic diameter at the initial embolization procedure and the presence of a Moyamoya endoleak, defined as heterogeneous contrast opacity with an indistinct faint border, were associated with aneurysm enlargement after embolization management. CONCLUSIONS: The embolization procedures were generally ineffective in preventing further expansion of abdominal aortic aneurysms in patients with type II endoleaks after EVAR, especially in patients with a large abdominal aortic aneurysm and/or a presence of a Moyamoya endoleak.

A Comparison of Retrospective ECG-Gated CT and Surgical or Angiographical Findings in Acute Aortic Syndrome.

The best cardiac phases in retrospective ECG-gated CT for detecting an intimal tear (IT) in aortic dissection (AD) and an ulcer-like projection (ULP) in an intramural hematoma (IMH) have not been established. This study aimed to compare the detection accuracy of diastolic-phase and systolic-phase ECG-gated CT for IT in AD and ULP in IMH, with subsequent surgical or angiographical confirmation as the reference standard.In total, 81 patients (67.6 ± 11.8 years; 41 men) who underwent emergency ECG-gated CT and subsequent open surgery or thoracic endovascular aortic repair for AD (n = 52) or IMH (n = 29) were included. The accuracies of detecting IT and ULP were compared among only diastolic-phase, only systolic-phase, and both diastolic-phase and systolic-phase methods of retrospective ECG-gated CT; surgical or angiographical findings were used as the reference standard. The detection accuracy for IT and ULP using only diastolic-phase, only systolic-phase, and both diastolic-phase and systolic-phase methods of ECG-gated CT was 93% [95% CI: 87-97], 94% [95% CI: 88-97], and 95% [95% CI: 90-97], respectively. There were no significant differences in detection accuracy among the 3 acquisition methods (P = 0.55). Similarly, there were no significant differences in the accuracy of detecting IT in AD (P = 0.55) and ULP in IMH (P > 0.99) among only diastolic-phase, only systolic-phase, and both diastolic- and systolic-phase ECG-gated CT.Retrospective ECG-gated CT for detecting IT in AD and ULP in IMH yields highly accurate findings. There were no significant differences seen among only diastolic-phase, only systolic-phase, and both diastolic-phase and systolic-phase ECG-gated CT.

Optimal Phosphate Control Related to Coronary Artery Calcification in Dialysis Patients.

BACKGROUND: In patients on maintenance dialysis, cardiovascular mortality risk is remarkably high, which can be partly explained by severe coronary artery calcification (CAC). Hyperphosphatemia has been reported to be associated with the severity of CAC. However, the optimal phosphate range in patients on dialysis remains unknown. This study was planned to compare the effects on CAC progression of two types of noncalcium-based phosphate binders and of two different phosphate target ranges. METHODS: We conducted a randomized, open-label, multicenter, interventional trial with a two by two factorial design. A total of 160 adults on dialysis were enrolled and randomized to the sucroferric oxyhydroxide or lanthanum carbonate group, with the aim of reducing serum phosphate to two target levels (3.5-4.5 mg/dl in the strict group and 5.0-6.0 mg/dl in the standard group). The primary end point was percentage change in CAC scores during the 12-month treatment. RESULTS: The full analysis set included 115 patients. We observed no significant difference in percentage change in CAC scores between the lanthanum carbonate group and the sucroferric oxyhydroxide group. On the other hand, percentage change in CAC scores in the strict group (median of 8.52; interquartile range, -1.0-23.9) was significantly lower than that in the standard group (median of 21.8; interquartile range, 10.0-36.1; P=0.006). This effect was pronounced in older (aged 65-74 years) versus younger (aged 20-64 years) participants (P value for interaction =0.003). We observed a similar finding for the absolute change in CAC scores. CONCLUSIONS: Further study with a larger sample size is needed, but strict phosphate control shows promise for delaying progression of CAC in patients undergoing maintenance hemodialysis. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Evaluate the New Phosphate Iron-Based Binder Sucroferric Oxyhydroxide in Dialysis Patients with the Goal of Advancing the Practice of EBM (EPISODE), jRCTs051180048.

Aortic Elongation in Bicuspid Aortic Valve with Aortic Stenosis Assessed by Thin-Slice Electrocardiogram-Gated Computed Tomography.

Bicuspid aortic valve (BAV) patients with aortic stenosis (AS) are known to develop dilatation of the ascending aorta at a younger age, but the morphology of the aorta in these patients is yet to be investigated. Thus, in this study, we aim to evaluate the aortic morphology of BAV patients with severe AS using thin-slice electrocardiogram (ECG) -gated computed tomography (CT) and identify the possible contributing effect of age.In this retrospective study, 122 BAV and 154 tricuspid aortic valve (TAV) patients who received aortic valve replacement for severe AS were assessed by thin-slice ECG-gated CT and three-dimensional reconstruction. The morphology of the ascending aorta was also evaluated among BAV patients aged < 70 (n = 72) and ≥ 70 (n = 50) years old. As per our findings, BAV patients with severe AS had significantly greater diameter (P < 0.01), elongation (P < 0.01), and tortuosity (P = 0.03) of the ascending aorta; minimum aortic arch angle (P < 0.01); and significantly lower calcified plaque (P < 0.01) compared with those of TAV patients even after adjusting for background. Multiple regression analysis showed that standardized partial regression coefficients (ß) of dilatation (0.5) and elongation (0.35) were higher among other measurements of aortic morphology for BAV patients. BAV patients with severe AS aged ≥ 70 years had significantly greater diameter (42.0 [37.2-46.1] mm versus 40.4 [35.2-44.2] mm, P = 0.049) and elongation (133.8 [123.5-147.3] mm versus 127.0 [111.0-140.0] mm, P = 0.01) of the ascending aorta than those aged < 70 years.BAV patients with severe AS were determined to have greater dilatation and elongation of the ascending aorta. Moreover, BAV patients older than 70 years had greater diameter and elongation of the ascending aorta.

Management of Renal Arteries in Conjunction with Thoracic Endovascular Aortic Repair for Complicated Stanford Type B Aortic Dissection: The Japanese Multicenter Study (J-Predictive Study).

Background Management of abdominal branches associated with Stanford type B aortic dissection is controversial without definite criteria for therapy after thoracic endovascular aortic repair (TEVAR). This is in part due to lack of data on natural history related to branch vessels and their relationship with the dissection flap, true lumen, and false lumen. Purpose To investigate the natural history of abdominal branches after TEVAR for type B aortic dissection and the relationship between renal artery anatomy and renal volume as a surrogate measure of perfusion. Materials and Methods This study included patients who underwent TEVAR for complicated type B dissection from January 2012 to March 2017 at 20 centers. Abdominal aortic branches were classified with following features: patency, branch vessel origin, and presence of extension of the aortic dissection into a branch (pattern 1, supplied by the true lumen without branch dissection; pattern 2, supplied by the true lumen with branch dissection, etc). The branch artery patterns before TEVAR were compared with those of the last follow-up CT (mean interval, 19.7 months) for spontaneous healing. Patients with one kidney supplied by pattern 1 and the other kidney by a different pattern were identified, and kidney volumes over the course were compared by using a simple linear regression model. Results Two hundred nine patients (mean age ± standard deviation, 66 years ± 13; 165 men and 44 women; median follow-up, 18 months) were included. Four hundred fifty-nine abdominal branches at the last follow-up were evaluable. Spontaneous healing of the dissected branch occurred in 63% (64 of 102) of pattern 2 branches. Regarding the other patterns, 6.5% (six of 93) of branches achieved spontaneous healing. In 79 patients, renal volumes decreased in kidneys with pattern 2 branches with more than 50% stenosis and branches supplied by the aortic false lumen (patterns 3 and 4) compared with contralateral kidneys supplied by pattern 1 (pattern 2 vs pattern 1: -16% ± 16 vs 0.10% ± 11, P = .002; patterns 3 and 4 vs pattern 1: -13% ± 14 vs 8.5% ± 14, P = .004). Conclusion Spontaneous healing occurs more frequently in dissected branches arising from the true lumen than in other branch patterns. Renal artery branches supplied by the aortic false lumen or a persistently dissected artery with greater than 50% stenosis are associated with significantly greater kidney volume loss. © RSNA, 2019 Online supplemental material is available for this article.

Stable Accumulation of Photosystem II Requires ONE-HELIX PROTEIN1 (OHP1) of the Light Harvesting-Like Family.

The cellular functions of two Arabidopsis (Arabidopsis thaliana) one-helix proteins, OHP1 and OHP2 (also named LIGHT-HARVESTING-LIKE2 [LIL2] and LIL6, respectively, because they have sequence similarity to light-harvesting chlorophyll a/b-binding proteins), remain unclear. Tagged null mutants of OHP1 and OHP2 (ohp1 and ohp2) showed stunted growth with pale-green leaves on agar plates, and these mutants were unable to grow on soil. Leaf chlorophyll fluorescence and the composition of thylakoid membrane proteins revealed that ohp1 deletion substantially affected photosystem II (PSII) core protein function and led to reduced levels of photosystem I core proteins; however, it did not affect LHC accumulation. Transgenic ohp1 plants rescued with OHP1-HA or OHP1-Myc proteins developed a normal phenotype. Using these tagged OHP1 proteins in transgenic plants, we localized OHP1 to thylakoid membranes, where it formed protein complexes with both OHP2 and High Chlorophyll Fluorescence244 (HCF244). We also found PSII core proteins D1/D2, HCF136, and HCF173 and a few other plant-specific proteins associated with the OHP1/OHP2-HCF244 complex, suggesting that these complexes are early intermediates in PSII assembly. OHP1 interacted directly with HCF244 in the complex. Therefore, OHP1 and HCF244 play important roles in the stable accumulation of PSII.

Ultra-high-resolution CT angiography of the artery of Adamkiewicz: a feasibility study.

PURPOSE: Preoperative identification of the artery of Adamkiewicz can help prevent postoperative spinal cord injury following thoracic and thoracoabdominal aortic repair. Several studies have demonstrated the feasibility of evaluating the artery of Adamkiewicz using multi-detector row computed tomography (CT), but precise visualization remains a challenge. The present study was conducted to evaluate the usefulness of ultra-high-resolution CT for visualizing the artery of Adamkiewicz with a slice thickness of 0.25 versus 0.5 mm in patients with aortic aneurysms. METHODS: Our institutional review board approved this study. Twenty-four patients with thoracic and thoracoabdominal aneurysms were scanned with beam collimation of 0.25 mm × 128. Images were reconstructed with slice thicknesses of 0.25 and 0.5 mm. The signal-to-noise ratio (SNR) of the aorta and contrast-to-noise ratio (CNR) between the anterior spinal artery and spinal cord were measured. Two independent observers evaluated visualization of the artery of Adamkiewicz and its continuity between the anterior spinal artery and the aorta using a four-point scale. RESULTS: No significant differences in the SNR of the aorta or CNR of the anterior spinal artery were observed between 0.25- and 0.5-mm slices. The average visualization score was significantly higher for 0.25-mm slices (3.58 ± 0.78) than for 0.5-mm slices (3.13 ± 0.99) (p = 0.01). The percentage of patients with nondiagnostic image quality was significantly lower for 0.25-mm slices (8.3%) than for 0.5-mm slices (33.3%) (p = 0.03). CONCLUSION: In patients with aortic aneurysms, ultra-high-resolution CT with 0.25-mm slices significantly improves visualization of the artery of Adamkiewicz compared to 0.5-mm slices.

3D-computed tomography to compare the dimensions of the left atrial appendage in patients with normal sinus rhythm and those with paroxysmal atrial fibrillation.

Although paroxysmal atrial fibrillation (PAF) is an important cause of cardioembolic stroke, in contrast to chronic AF patients, the anatomical features of the left atrial appendage (LAA) in PAF patients remain unknown. Here, we investigated differences in LAA structures in patients with PAF and those with normal sinus rhythms (NSR) using 3D-computed tomography (3D-CT), which allows us to visualize complicated LAA structures at high spatial resolution. Study subjects were 30 consecutive PAF and 30 NSR patients with complete enhanced cardiac 3D-CT images available. After reconstruction of 3D LAA images, anatomical parameters of the LAA were measured and compared according to three proposed definitions of the LAA orifice plane determined by the following anatomical landmarks: DEF#1, center of warfarin ridge and centerline of proximal left circumflex artery; DEF#2, slope of warfarin ridge and mitral valve annulus; DEF#3, observers' discretion by progressive rotation using the observers' best estimate without the use of landmarks. The LAA volumes of the PAF groups were significantly greater than the NSR group according to all 3 definitions (DEF#1: 1.43 times, DEF#2: 1.44 times, and DEF#3: 1.36 times greater). The LAA orifice area was significantly larger in PAF than in NSR according to DEF#2, but was similar by DEF#1 and DEF#3. Intra-observer and inter-observer variations for any LAA measurements were very low. In conclusion, 3D-CT-based quantitative assessment of the LAA provides highly reproducible and detailed measurements, which can successfully discriminate differences of LAA volume between patients with NSR and those with PAF, suggesting significantly greater volumes in the latter.

Endovascular Embolization of Coronary Artery-Pulmonary Artery Fistulas with Double Coronary Aneurysms.

A 75-year-old woman with chest discomfort and a continuous murmur was admitted to our hospital. During noninvasive examination, computed tomography angiography showed a coronary artery-pulmonary artery fistula with double giant coronary aneurysms (one was 42 mm× 32 mm× 32 mm, and the other was 25 mm× 20 mm× 17 mm) arising from the proximal part of the left anterior descending (LAD) artery. Stress myocardial scintigraphy showed ischemia at the LAD area. Given her frailty, the heart team, including cardiac surgeons, judged that surgical treatment would be difficult. Thus, endovascular embolization for the abnormal vessels was selected. After coronary angiography, two coronary aneurysms were embolized by 53 coils, and the feeding artery was embolized by two coils and one Amplatzer Vascular Plug 4™. A small pulmonary artery fistula remained after the procedures; thus, additional embolization was performed 3 months after the index procedure. Thereafter, angiography showed no flow into the aneurysms, and her symptoms improved.Endovascular embolization might be an effective treatment to achieve aneurysm occlusion in patients at high risk for surgical treatment. Although the present case had double coronary aneurysms with a large feeder vessel, the combination procedure of coils and vascular plug was able to embolize this abnormal vessel.

Rap1GAP inhibits tumor progression in endometrial cancer.

OBJECTIVE: Endometrioid adenocarcinoma (EAC) is a common endometrial cancer with recent dramatic increases in incidence. Previous findings indicate that Rap1GAP acts as a tumor suppressor inhibiting Ras superfamily protein Rap1 in multiple aggressive carcinomas; however, Rap1GAP expression in EAC has not been investigated. In this study, the tumor suppressing activity of Rap1GAP in EAC was explored. METHODS: EAC cell lines were used to examine Rap1GAP levels by real-time RT-PCR and western blotting and the effects of Rap1GAP on cancer cell invasion and migration. Rap1GAP expression was analyzed by immunohistochemical staining for Rap1GAP, E-cadherin in surgically resected tumors of 114 EAC patients scored according to EAC differentiation grade. Prognostic variables such as age, stage, grade, tumor size, and immunostaining for Rap1GAP, E-cadherin were evaluated using Cox regression multivariate analysis. RESULTS: Low Rap1GAP expression was detected in poorly differentiated EAC cells. Rap1GAP deficiency significantly accelerated while Rap1 deficiency decreased cancer cell migration and invasion. Patients with higher Rap1GAP, E-cadherin, and especially combined Rap1GAP/E-cadherin levels had better overall survival than EAC patients with no or weak expression. In addition, Rap1GAP expression was an independent prognostic factor in EAC. CONCLUSIONS: Inhibition of Rap1GAP expression increases EAC cell migration and invasion through upregulation of Rap1. Low expression of Rap1GAP correlates with poor EAC differentiation. Our findings suggest that Rap1GAP is an important tumor suppressor with high prognostic value in EAC.

[A Case of Recurrent Rectal Cancer with Adrenal and Lung Metastasis with More than Ten-Year Survival after Surgery].

A 60-year-old man underwent low anterior resection for rectal cancer. Histological findings indicated well-differentiated adenocarcinoma(T3[SS]N1M0, ly3, v2, Stage III a). Two years and 1 month later, right adrenalectomy was performed for solitary adrenal metastasis. Three months thereafter, left partial pulmonary resection was performed for a metastatic lung tumor. All resected specimens showed metastatic adenocarcinoma derived from the rectal cancer. The patient is alive and well without recurrence for more than 10years after lung resection. Given that adrenal metastasis is usually found as widespread metastasis, aggressive resection of well-controlled metastatic lesions including those in the adrenal glands is recommended.

Radiation-Dose-Lowering Effects of Landiolol Hydrochloride in Coronary Angiography Using Computed Tomography (DELIGHT)　- A Prospective Multicenter Study.

BACKGROUND: Controlling and decreasing the heart rate (HR) of patients during coronary computed tomography angiography (CCTA) is necessary to reduce radiation exposure and improve image quality. This prospective multicenter study aimed to investigate whether HR control with landiolol hydrochloride is useful for reducing radiation exposure during CCTA. METHODS AND RESULTS: We investigated 219 patients with suspected ischemic heart disease whose pretest HRs were 50-80 beats/min. We measured the HR before and after administration of landiolol hydrochloride and compared the estimated exposure inferred from the HR before administration of landiolol hydrochloride with the actual dose. After administration of landiolol hydrochloride, the mean HR (59.9±6.4 beats/min) at the time of CCTA was significantly lower than before administration (69.3±7.3 beats/min; P<0.001); 80% of the patients had controlled HRs at ≤65 beats/min. HR and blood pressure of all the patients recovered after the scan. The mean radiation dose in all patients was approximately 50% derived from the inferred dose before use of landiolol hydrochloride (4.5±3.2 vs. 9.0±3.7 mSv; P<0.001). There were no adverse events during this study. CONCLUSIONS: The use of landiolol hydrochloride during CCTA was safe and resulted in approximately 50% decrease in radiation exposure dose, suggesting the clinical usefulness of this drug. (Circ J 2016; 80: 1225-1231).

Strategy for thoracic endovascular aortic repair based on collateral circulation to the artery of Adamkiewicz.

PURPOSE: Spinal cord ischemia (SCI) is a serious complication of thoracic endovascular aortic repair (TEVAR). The purpose of this study was to establish if preoperative identification of the artery of Adamkiewicz (AKA) can help prevent post-TEVAR SCI. METHODS: Of 74 post-TEVAR patients, 51 had the critical segmental artery (CSA) to the AKA pre-identified to help the surgeon deploy stent grafts. RESULTS: None of these 51 patients suffered permanent paraplegia postoperatively, but 5 (23.8 %) of the remaining 23 patients (2 of whom had pre-existing paraplegia) did suffer permanent SCI. The CSA/AKA was preserved in 43 patients with pre-identification of the CSA/AKA; however, in 8 patients, the CSA was completely or partially occluded by a stent graft. Transient SCI developed in one patient from each group, but both of these patients recovered fully before discharge. No change in the anatomical route was identified in 29 of the patients who had postoperative evaluation of the CSA/AKA. Five of eight patients whose CSA was completely occluded had new collateral circulation to the AKA. CONCLUSIONS: None of the 51 patients with the CSA/AKA identified before TEVAR suffered permanent paraplegia, whereas 5 of the 23 without pre-identification did suffer permanent SCI. Thus, careful identification of the CSA/AKA may prove useful for preventing postoperative SCI. Preservation of potential collateral circulation may also reduce the risk of postoperative SCI.

Alendronate attenuates eosinophilic airway inflammation associated with suppression of Th2 cytokines, Th17 cytokines, and eotaxin-2.

Bisphosphonates (BPs) have been widely used to treat osteoporosis. They act by inhibiting farnesyl diphosphate synthase in the mevalonate pathway. This resembles the action of statins, whose immune-modulating effect has recently been highlighted. In contrast, the effect of BPs on immune responses has not been elucidated well. In this study, we examined the effect of alendronate (ALN), a nitrogen-containing BP, on allergic airway inflammation in a mouse model. BALB/c mice were sensitized twice with OVA and challenged three times with nebulized OVA to induce eosinophilic airway inflammation. ALN was administered by an intragastric tube before each inhalation. ALN strongly suppressed airway eosinophilia and Th2, as well as Th17 cytokine production in the lung. ALN also attenuated eotaxin-2 production in the lung. Immunohistochemistry demonstrated that the major cell source of eotaxin-2 was peribronchial/perivascular macrophages, and flow cytometrical studies confirmed that ALN decreased eotaxin-2 expression in these macrophages. Furthermore, ALN attenuated eotaxin-2 production from mouse pleural macrophages and human monocyte/macrophage-like THP-1 cells in vitro. These results suggest that ALN suppressed Ag-induced airway responses in the mouse model. The suppression of eotaxin-2 production from macrophages appears to be one of ALN's immunomodulatory effects, whereas the mechanism by which ALN suppressed Th2 and Th17 responses could not be fully elucidated in this study. Although a clinical study should be conducted, ALN could be a novel therapeutic option for asthma.

Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following paclitaxel and carboplatin in patients with gynecologic cancers: A randomized, multicenter, phase-II trial.

AIM: Chemotherapy-induced nausea and vomiting (CINV) can affect a patient's quality of life, leading to poor compliance with further treatments. Previous studies have provided minimal data about carboplatin-based regimens. Female sex is a known risk factor for CINV. The purpose of this study was to evaluate palonosetron plus single-dose dexamethasone (DEX) for preventing CINV caused by carboplatin plus paclitaxel combination therapy (TC regimen) in patients with gynecologic cancers. MATERIAL AND METHODS: Patients were recruited for this phase-II, multicenter, randomized trial from 12 hospitals in Hokkaido, Japan. Eligible patients were women with uterine cervical, endometrial or ovarian cancer scheduled to receive conventional TC regimen or dose-dense TC regimen; 116 patients were randomly assigned to receive palonosetron in combination with 1-day DEX or 3-day DEX. RESULTS: During the overall period, complete response (CR) was observed in 67.9% (95% confidence interval, 53.7-80.1) of patients in the 3-day DEX arm, and 60.7% (95% confidence interval, 46.8-73.5) of patients in the 1-day DEX arm; CR was significantly lower in the 1-day DEX arm if motion sickness was already present (P = 0.0370). In the severe hyperemesis gravidarum cohort, CR in the 1-day DEX arm tended to be lower than in the 3-day DEX arm. CONCLUSION: Combination therapy of palonosetron and 1-day DEX was effective for subjects undergoing a TC regimen for gynecologic cancers. However, the possibility of reduced efficacy of 1-day only DEX therapy in women undergoing a TC regimen could not be refuted and requires further investigation.

Perillyl alcohol suppresses antigen-induced immune responses in the lung.

Perillyl alcohol (POH) is an isoprenoid which inhibits farnesyl transferase and geranylgeranyl transferase, key enzymes that induce conformational and functional changes in small G proteins to conduct signal production for cell proliferation. Thus, it has been tried for the treatment of cancers. However, although it affects the proliferation of immunocytes, its influence on immune responses has been examined in only a few studies. Notably, its effect on antigen-induced immune responses has not been studied. In this study, we examined whether POH suppresses Ag-induced immune responses with a mouse model of allergic airway inflammation. POH treatment of sensitized mice suppressed proliferation and cytokine production in Ag-stimulated spleen cells or CD4(+) T cells. Further, sensitized mice received aerosolized OVA to induce allergic airway inflammation, and some mice received POH treatment. POH significantly suppressed indicators of allergic airway inflammation such as airway eosinophilia. Cytokine production in thoracic lymph nodes was also significantly suppressed. These results demonstrate that POH suppresses antigen-induced immune responses in the lung. Considering that it exists naturally, POH could be a novel preventive or therapeutic option for immunologic lung disorders such as asthma with minimal side effects.

BAG3 upregulates Mcl-1 through downregulation of miR-29b to induce anticancer drug resistance in ovarian cancer.

OBJECTIVE: Ovarian cancer is the leading cause of death from gynecologic cancer, reflecting its often late diagnosis and its chemoresistance. We identified a set of microRNAs whose expression is altered upon BAG3 knockdown. Our primary objective was to examine the relationships between BAG3, miR-29b and Mcl-1, an antiapoptotic Bcl-2 family protein, in ovarian cancer cells. METHODS: Ovarian cancer cells were cultured and their responsiveness to paclitaxel was tested. Microarray analysis was performed to identify microRNAs differentially expressed in ES2 BAG3 knockdown ovarian cancer cells and their control cells. Primary ovarian cancer tissues were obtained from 56 patients operated on for ovarian cancer. The patients' clinical and pathological data were obtained from their medical records. RESULTS: BAG3 knockdown increased the chemosensitivity to paclitaxel of ES2 ovarian clear cell carcinoma cells to a greater degree than AMOC2 serous adenocarcinoma cells. qRT-PCR analysis showed that miR-29b expression was significantly upregulated in primary cancer tissue expressing low levels of BAG3, as compared to tissue expressing high levels. Moreover, levels of miR-29b correlated significantly with progression-free survival. Upregulation of miR-29b also reduced levels of Mcl-1 and sensitized ES2 cells to low-dose paclitaxel. CONCLUSIONS: BAG3 knockdown appears to downregulate expression of Mcl-1 through upregulation of miR-29b, thereby increasing the chemosensitivity of ovarian clear cell carcinoma cells. This suggests that BAG3 is a key determinant of the responsiveness of ovarian cancer cells, especially clear cell carcinoma, to paclitaxel and that BAG3 may be a useful therapeutic target for the treatment of ovarian cancer.

Prediction of the therapeutic effect of dienogest in ovarian endometrial cysts using the apparent diffusion coefficient.

The purpose of this study was to investigate whether apparent diffusion coefficient (ADC) mean values can be used for predicting the treatment response in ovarian endometrial cyst patients with dienogest (DNG) administration. Eighteen patients received DNG (2 mg/day, orally) for 60 days, among whom 26 ovarian endometrial cysts were retrospectively identified. Mean ADC values of individual ovarian endometrial cysts were obtained by ADC maps inside the tumor. There was a significant correlation between ADC values and reduction ratio. When calculating the mean ADC values for three groups; more than 50%, 50-25% and less than 25%, ADC values significantly increased with increasing reduction ratio; 2.05 × 10(-3)mm(2)/s, 1.28 × 10(-3)mm(2)/s and 0.94 × 10(-3)mm(2)/s, respectively (p = 0.0180). Multiple regression analysis by reduction ratio (%), ADC mean values (× 10(-3)mm(2)/s), tumor longest diameter (cm) and CA125 (U/ml) revealed that tumor reduction ratio by DNG administration could be predicted by the following equation; R = 19.3 + 24.0x - 0.4y + 0.1z (R: Reduction ratio, x: ADC mean, y: Longest diameter, z: CA125). In conclusion, the ADC mean value is useful for the prediction of the treatment response in ovarian endometrial cyst patients with DNG administration.

Low-dose SN-38 with paclitaxel induces lethality in human uterine cervical adenocarcinoma cells by increasing caspase activity.

Combination of anticancer drugs may provide a rational molecular basis for novel chemotherapeutic strategies. Paclitaxel and SN-38 (an active metabolite of CPT-11) are effective for many kinds of cancer. Therefore, we investigated the possibility that combination of these drugs could be effective against cervical adenocarcinoma cells. In this study, we examined cell growth inhibition after 96 h using the MTT assay and examined the release of fragmented DNA into the cytoplasm during apoptotic cell death by PI staining. Single and combined use of paclitaxel and SN-38 produced significant cytolethality against the cervical adenocarcinoma cell line CAC-1. Addition of a low concentration of SN-38 reduced the IC50 value of paclitaxel compared to that without SN-38, although the low concentration of paclitaxel did not enhance the cytotoxicity of SN-38. FACS scan analysis suggested that these drugs induced apoptosis and cell cycle arrest, and that caspase-3 and -7 were activated in the process. MTT assay and the IC50 demonstrated that paclitaxel had strong cytotoxicity against CAC-1 as well as other cancer cells. In this study, though only a single cell line was used for the experiment and the data are limited, our results suggest that paclitaxel together with low-dose CPT-11 is a promising basis for a new combination cancer chemotherapy.