Cytosine arabinoside-based chemotherapy coupled with anthracycline is currently the first-line treatment for acute myeloid leukaemia (AML), but diverse responses to the regimen constitute obstacles to successful treatment. Therefore, outcome prediction to chemotherapy at diagnosis is believed to be a critical consideration.
The mRNA expression of 12 genes closely involved in the actions of cytosine arabinoside and anthracycline was evaluated by real-time reverse transcriptase PCR (RT–PCR), in 54 diagnostic bone marrow specimens of M2-subtype AML.
Low expression levels of ribonucleotide reductase M2 (RRM2) and high expression levels of topoisomerase 2 beta (TOP2B) were correlated with longer survival in a univariate analysis. Another interesting finding is that high ratios of TOP2B/RRM2 and TOP2B/TOP2 alpha (TOP2A) in a combined analysis were also shown to have a prognostic impact for longer survival with improved accuracy. Among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the TOP2B/TOP2A ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (HR, 0.24; P=0.002) and overall survival (HR, 0.29; P=0.005).
Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype.
AML; standard chemotherapy; prognosis; topoisomerase 2
The aim of this study was to correlate the apparent diffusion coefficient (ADC) value of breast cancer with prognostic factors.
335 patients with invasive ductal carcinoma not otherwise specified (IDC NOS) and ductal carcinoma in situ (DCIS) who underwent breast MRI with diffusion-weighted imaging were included in this study. ADC of breast cancer was calculated using two b factors (0 and 1000 s mm–2). Mean ADCs of IDC NOS and DCIS were compared and evaluated. Among cases of IDC NOS, mean ADCs were compared with lymph node status, size and immunochemical prognostic factors using Student's t-test. ADC was also correlated with histological grade using the Kruskal–Wallis test.
Mean ADC of IDC NOS was significantly lower than that of DCIS (p<0.001). However, the mean ADC of histological grade of IDC NOS was not significantly different (p=0.564). Mean ADC of oestrogen receptor (ER)-positive or progesterone receptor (PR)-positive cancer was significantly lower than that of ER-negative or PR-negative cancer (p=0.003 vs
p=0.032). Mean ADC of Ki-67 index-positive cancer was significantly lower than that of Ki-67 index-negative cancer (p=0.028). Mean ADC values of cancers with increased microvascular density (MVD) were significantly lower than those of cancer with no MVD increase (p=0.009). No correlations were observed between mean ADC value and human growth factor receptor 2 expression, tumour size and lymph node metastasis.
Low ADC value was correlated with positive expression of ER, PR, increased Ki-67 index, and increased MVD of breast cancer.
The insulin-like growth factor-1 receptor (IGF-1R) signaling pathway is critical for both normal mammary gland development and malignant transformation. It has been reported that the IGF-1 stimulates breast cancer cell proliferation and is upregulated in tumors with BRCA1/2 mutations. We report here that IGF-1 is negatively regulated by BRCA1 at the transcriptional level in human breast cancer cells. BRCA1 knockdown (BRCA1-KD) induces the expression of IGF-1 mRNA in MCF7 cells in an estrogen receptor α (ERα)-dependent manner. We found that both BRCA1 and ERα bind to the endogenous IGF-1 promoter region containing an estrogen-responsive element-like (EREL) site. BRCA1-KD does not significantly affect ERα binding on the IGF-1 promoter. Reporter analysis demonstrates that BRCA1 could regulate IGF-1 transcripts via this EREL site. In addition, enzyme-linked immunosorbent assay revealed that de-repression of IGF-1 transcription by BRCA1-KD increases the level of extracellular IGF-1 protein, and secreted IGF-1 seems to increase the phospho-IGF-1Rβ and activate its downstream signaling pathway. Blocking the IGF-1/IGF-1R/phosphoinositide 3-kinase (PI3K)/AKT pathway either by a neutralizing antibody or by small-molecule inhibitors preferentially reduces the proliferation of BRCA1-KD cells. Furthermore, the IGF-1-EREL-Luc reporter assay demonstrates that various inhibitors, which can inhibit the IGF-1R pathway, can suppress this reporter activity. These findings suggest that BRCA1 defectiveness keeps turning on IGF-1/PI3K/AKT signaling, which significantly contributes to increase cell survival and proliferation.
BRCA1; IGF-1; negative regulation; ERα; positive-feedback activation
We underwent protein assay for Myc expression in 76 human gastric cancer tissues using immunohistochemistry. Expression of Myc protein was analyzed according to proliferative indices measured by flow cytometry. Levels of Myc protein expression was evaluated by correlating with biologic and clinical parameters. In 36 (47.4%) of 76 primary gastric cancers, overexpression of Myc was observed. We could observe expression of Myc protein in a significant portion of early gastric cancer (42.9%). Expression of Myc protein was demonstrated to be more frequent in poorly differentiated cancer cells (p=0.043). However, expression of Myc protein had little influence over progress or extent of the disease. Expression of Myc protein was significantly correlated with increased proliferative activity (p=0.032) and patients with high levels of Myc expression had poor disease-free survival. In a certain proportion of human gastric cancer, Myc protein may function as a regulator of cancer cell growth and expression of Myc may represent an aggressive phenotype of gastric cancer.
Coccidioidomycosis is an endemic disease found in the southwestern part of North America. Travellers who visit the endemic area may carry the infection. We report a case of pulmonary coccidioidomycosis in a 74-year-old woman. She was healthy before visiting Arizona, U.S.A twice. After returning home, she began to complain of intermittent dry coughing. The symptom was mild, however, and she was treated symptomatically. Later a chest radiograph, which was taken 4 years after the onset of the symptom, showed a solitary pulmonary nodule in the right upper lobe. By percutaneous needle aspiration, a few clusters of atypical cells were noted in the necrotic background. A right upper and middle lobectomy was done. A 1.5 x 1.5 x 1.2 cm sized tan nodule was present in otherwise normal lung parenchyma. Microscopically, the nodule consisted of aggregates of multiple solid granulomas inside of which was mostly necrotic. Neutrophils and nuclear debris were scattered along the periphery of the necrotic foci. Numerous multinucleated giant cells were associated with the granulomas. In the necrotic area, mature spherules of Coccidioides immitis, which were 30-100 microm in diameter, were present. They contained numerous endospores which ranged from 5 to 15 microm and were also noted in multinucleated giant cells. The diagnosis of coccidioidomycosis was made. She is doing well after the resection.
Hepatoblastoma is thought to originate from embryonal hepatic tissue, and most of these tumors occur in children under the age of 2 years. Hepatoblastoma in adults is extremely rare, and the prognosis is much worse than the mixed hepatoblastoma of childhood. We experienced a case of mixed hepatoblastoma in a 51 year old female patient. She had been suffering from a mild pain and a palpable lump in the epigastric area. Serum AFP was 43,850 ng/ml. Computerized tomography and selective abdominal angiography showed a large low-density mass. With a suspicion of hepatocellular carcinoma of the left lobe, a left lateral segmentectomy was performed. The external surface showed a huge protruding mass and the capsule was previously ruptured. On section, the tumor was a 11 x 7 cm sized expanding mass which had a variegated surface composed of yellow-white friable tissue with multifocal hemorrhagic areas. Microscopic examination revealed a tumor consisted of epithelial and mesenchymal elements. The mesenchymal cells were spindle in shape and proliferated over the whole tumor with focal osteosarcomatous differentiation. The epithelial components showed well-differentiated hepatocellular carcinoma-like areas, poorly differentiated acinar or tubular structures.
Spinal congenital dermal sinus (CDS) is a rare entity which supposedly results from the failure of the neuroectoderm to separate from the cutaneous ectoderm during the process of neurulation. The lesions are most frequent at the lumbosacral followed by the occipital region. CDS of the thoracic region is very rare. The patients with spinal CDS present with meningitis and/or mass effect from the associated inclusion tumor. They are usually dermoid or epidermoid cysts. Teratoma is rarely associated. The authors experienced 5 cases of spinal CDS over a 10 year period. Of the 5 cases, 2 were at thoracic and 3 were at lumbosacral levels. Dermoid cyst, epidermoid cyst and teratoma were associated in one case each. Two cases presented with neurological deficit and meningitis while an additional case presented with neurological deficit and a history of probable meningitis. Pain was present in 2 cases. Magnetic resonance imaging played an important role in the diagnosis of the lesion and planning of surgery. All the cases showed a good response to surgery even though one patient had persistent neurological deficit.
The purpose of this study was to identify genes that are differentially expressed in chemosensitive serous papillary ovarian carcinomas relative to those expressed in chemoresistant tumours.
To identify novel candidate biomarkers, differences in gene expression were analysed in 26 stage IIIC/IV serous ovarian adenocarcinomas (12 chemosensitive tumours and 14 chemoresistant tumours). We subsequently investigated the immunohistochemical expression of GRIA2 in 48 independent sets of advanced ovarian serous carcinomas.
Microarray analysis revealed a total of 57 genes that were differentially expressed in chemoresistant and chemosensitive tumours. Of the 57 genes, 39 genes were upregulated and 18 genes were downregulated in chemosensitive tumours. Five differentially expressed genes (CD36, LIFR, CHL1, GRIA2, and FCGBP) were validated by quantitative real-time PCR. The expression of GRIA2 was validated at the protein level by immunohistochemistry, and patients with GRIA2 expression showed a longer progression-free and overall survival (P=0.051 and P=0.031 respectively).
We found 57 differentially expressed genes to distinguish between chemosensitive and chemoresistant tumours. We also demonstrated that the expression of GRIA2 among the differentially expressed genes provides better prognosis of patients with advanced serous papillary ovarian adenocarcinoma.
gene expression profiling; microarray; ovarian serous adenocarcinoma; GRIA2; survival
The pancreas and hypothalamus are critical for maintaining nutrient and energy homeostasis, and combined disorders in these organs account for the onset of the metabolic syndrome. Activating transcription factor 3 (ATF3) is an adaptive response transcription factor. The physiological role of ATF3 in the pancreas has been controversial, and its role in the hypothalamus remains unknown. To elucidate the roles of ATF3 in these organs, we generated pancreas- and hypothalamus-specific Atf3 knockout (PHT-Atf3-KO) mice in this study.
We crossed mice bearing floxed Atf3 alleles with Pdx1-cre mice, in which cre is specifically expressed in the pancreas and hypothalamus, and analysed metabolic variables, pancreatic morphology, food intake, energy expenditure and sympathetic activity in adipose tissue. We also used a hypothalamic cell line to investigate the molecular mechanism by which ATF3 regulates transcription of the gene encoding agouti-related protein (Agrp).
Although PHT-Atf3-KO mice displayed better glucose tolerance, neither plasma glucagon nor insulin level was altered in these mice. However, these mice exhibited higher insulin sensitivity, which was accompanied by a leaner phenotype due to decreased food intake and increased energy expenditure. We also observed decreased hypothalamic Agrp expression in PHT-Atf3-KO mice. Importantly, an increase in ATF3 levels is induced by fasting or low glucose in the hypothalamus. We also showed that ATF3 interacts with forkhead box-containing protein, O subfamily 1 (FoxO1) on the Agrp promoter and activates Agrp transcription.
Our results suggest that ATF3 plays an important role in the control of glucose and energy metabolism by regulating Agrp.
Electronic supplementary material
The online version of this article (doi:10.1007/s00125-013-2879-z) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Agrp; ATF3; Energy expenditure; Food intake; FoxO1; Hypothalamus
Gintonin is a unique lysophosphatidic acid (LPA) receptor ligand
found in Panax ginseng. Gintonin induces transient
through G protein-coupled LPA receptors. Large-conductance Ca2+-activated
channels are expressed in blood vessels and neurons and
play important roles in blood vessel relaxation and attenuation of
neuronal excitability. BKCa channels are activated by transient
and are regulated by various Ca2+-dependent kinases. We
investigated the molecular mechanisms of BKCa channel activation
by gintonin. BKCa channels are heterologously expressed in
Xenopus oocytes. Gintonin treatment induced BKCa channel activation in
oocytes expressing the BKCa channel α subunit in a
concentration-dependent manner (EC50 = 0.71 ± 0.08 µg/mL).
Gintonin-mediated BKCa channel activation was blocked by a PKC
inhibitor, calphostin, and by the calmodulin inhibitor,
calmidazolium. Site-directed mutations in BKCa channels targeting
CaM kinase II or PKC phosphorylation sites but not PKA
phosphorylation sites attenuated gintonin action. Mutations in the
Ca2+ bowl and the regulator of K+ conductance (RCK) site also
blocked gintonin action. These results indicate that
gintonin-mediated BKCa channel activations are achieved through
LPA1 receptor-phospholipase C-IP3-Ca2+-PKC-calmodulin-CaM kinase
II pathways and calcium binding to the Ca2+ bowl and RCK domain.
Gintonin could be a novel contributor against blood vessel
constriction and over-excitation of neurons.
An important challenge in the biomaterials field is to mimic the structure of functional tissues via cell and extracellular matrix (ECM) alignment and anisotropy. Toward this goal, silk-based scaffolds resembling bone lamellar structure were developed using a freeze-drying technique. The structure could be controlled directly by solute concentration and freezing parameters, resulting in lamellar scaffolds with regular morphology. Different post-treatments were investigated to induce water stability, such as methanol, water annealing and steam sterilization. The resulting structures exhibited significant differences in terms of morphological integrity, structure and mechanical properties. the lamellar thicknesses were around ~2,6 μm for the methanol treated scaffolds and ~5,8 μm for water-annealed. These values are in the range of the reported for human lamellar bone. Human bone marrow-derived mesenchymal stem cells (hMSCs) were seeded on these silk fibroin lamellar scaffolds and grown under osteogenic conditions to assess the effect of the microstructure on cell behaviour. Collagen in the newly deposited ECM, was found aligned along the lamellar architectures. In the case of methanol treated lamellar structures the hMSCs were able to migrate into the interior of the scaffolds producing a multilamellar hybrid construct. The present morphology constitutes a useful pattern onto which hMSCs cells attach and proliferate for guided formation of a highly oriented extracellular matrix.
Silk fibroin; scaffold; freeze-drying; directional freezing; tissue engineering; lamellar morphology; cell alignment
c-Jun N-terminal kinase (JNK) is activated by dual phosphorylation of both threonine and tyrosine residues in the phosphorylation loop of the protein in response to several stress factors. However, the precise molecular mechanisms for activation after phosphorylation remain elusive. Here we show that Pin1, a peptidyl-prolyl isomerase, has a key role in the JNK1 activation process by modulating a phospho-Thr-Pro motif in the phosphorylation loop. Pin1 overexpression in human breast cancer cell lines correlates with increased JNK activity. In addition, small interfering RNA (siRNA) analyses showed that knockdown of Pin1 in a human breast cancer cell line decreased JNK1 activity. Pin1 associates with JNK1, and then catalyzes prolyl isomerization of the phospho-Thr-Pro motif in JNK1 from trans- to cis-conformation. Furthermore, Pin1 enhances the association of JNK1 with its substrates. As a result, Pin1−/− cells are defective in JNK activation and resistant to oxidative stress. These results provide novel insights that, following stress-induced phosphorylation of Thr in the Thr-Pro motif of JNK1, JNK1 associates with Pin1 and undergoes conformational changes to promote the binding of JNK1 to its substrates, resulting in cellular responses from extracellular signals.
c-Jun N-terminal kinase; peptidyl-prolyl cis/trans-isomerase; apoptosis
We report our experience with endovascular treatment of supra-aortic arteries and follow-up results in patients with Takayasu’s arteritis (TA) presenting with neurological symptoms. Of the 20 patients with TA who underwent cerebral angiography for neurological manifestations between May 2002 and May 2009, 12 (11 females, one male; mean age, 39 years; range 31-56 years) underwent endovascular treatment and evaluated outcome for 21 lesions, including nine common carotid arteries, four vertebral arteries, four subclavian arteries, two internal carotid arteries, and one brachiocephalic artery. Eight patients underwent multiple endovascular procedures for different lesions in single or multiple stages. Mean angiographic and clinical follow-up durations were 34 months (range, 11-79 months) and 39 months (range 11-91 months), respectively.
Technical success was achieved for 20 procedures in 11 patients. One procedure failed, with 50% residual stenosis after stenting due to dense calcification of vessel walls. There were no procedure-related complications. Restenosis occurred at two lesions in two patients were treated by re-stenting. Asymptomatic occlusion occurred at two lesions in one patient. Ten patients remained in 0-1 on the modified Rankin scale (mRs) during mean 39 months. One patient, however, had a score of 3 on mRs due to a traumatic contusion during follow-up. One patient died from cardiac failure 36 months after successful angioplasty.
Our data suggest that endovascular treatment of symptomatic supra-aortic lesions of TA is effective and durable in selected patients with neurologic symptoms.
Takayasu’s arteritis, angiography, stroke, stenosis, angioplasty
Detection of aquaporin-4–specific immunoglobulin G (IgG) has expanded the spectrum of neuromyelitis optica (NMO). Rare reports of familial aggregation have suggested a component of genetic susceptibility but these reports mostly antedated the discovery of the NMO-IgG biomarker and recently updated diagnostic criteria.
We report a case series describing the demographic, clinical, neuroimaging, and NMO-IgG serologic status of 12 multiplex NMO pedigrees with a total of 25 affected individuals.
Twenty-one patients (84%) were women. Families were Asian (n = 5), Latino (n = 4), white (n = 1), or African (n = 2). Apparent transmission was either maternal (n = 5) or paternal (n = 2). In 1 family, 3 individuals had NMO; in the others, 2 individuals were affected. Sibling pairs (n = 6), parent-child (n = 4), and aunt-niece (n = 3) pairs were observed. Nineteen patients (76%) were NMO-IgG positive. Twelve (48%) had clinical or serologic evidence of another autoimmune disease. Familial occurrence of NMO occurs in approximately 3% of patients with well-established diagnosis of NMO.
A small proportion of patients with NMO have relatives with this condition, but familial occurrence is more common than would be expected from its frequency in the general population. Familial NMO is indistinguishable from sporadic NMO based on clinical symptoms, age at onset, sex distribution, and frequency of NMO-IgG detection. One or 2 generations were affected and affected individuals represented a small fraction of family members. Taken together, these data suggest complex genetic susceptibility in NMO.
= confidence interval;
= human leukocyte antigen;
= immunoglobulin G;
= longitudinally extensive transverse myelitis;
= multiple sclerosis;
= neuromyelitis optica;
= optic neuritis;
= odds ratio.
We sought the long-term efficacy of traditionally used antidiabetic herbs in controlling blood glucose homeostasis and low-grade inflammation. Ninety-four subjects with either impaired glucose tolerance or mild T2D were randomized either to treatment arm or placebo arm and received 1 : 1 : 1 mixture of ginseng roots, mulberry leaf water extract, and banaba leaf water extract (6 g/d) for 24 weeks. Oral 75 g glucose tolerance test was performed to measure glucose and insulin responses. Blood biomarkers of low-grade inflammation were also determined. Results found no significant difference in glucose homeostasis control measure changes. However, plasma intracellular adhesion molecule-1 (ICAM-1) concentration was decreased showing a significant between-treatment changes (P = 0.037). The concentrations of vascular cell adhesion molecule-1 (VCAM-1) (P = 0.014) and ICAM-1 (P = 0.048) were decreased in the treatment group at week 24, and the oxidized low-density lipoprotein (ox-LDL) concentration was reduced at week 24 compared to the baseline value in the treatment group (P = 0.003). These results indicate a long-term supplementation of ginseng, mulberry leaf, and banaba leaf suppresses inflammatory responses in T2D.
The main determinant of muscle carnosine (M-Carn) content is undoubtedly species, with, for example, aerobically trained female vegetarian athletes [with circa 13 mmol/kg dry muscle (dm)] having just 1/10th of that found in trained thoroughbred horses. Muscle fibre type is another key determinant, as type II fibres have a higher M-Carn or muscle histidine containing dipeptide (M-HCD) content than type I fibres. In vegetarians, M-Carn is limited by hepatic synthesis of β-alanine, whereas in omnivores this is augmented by the hydrolysis of dietary supplied HCD’s resulting in muscle levels two or more times higher. β-alanine supplementation will increase M-Carn. The same increase in M-Carn occurs with administration of an equal molar quantity of carnosine as an alternative source of β-alanine. Following the cessation of supplementation, M-Carn returns to pre-supplementation levels, with an estimated t1/2 of 5–9 weeks. Higher than normal M-Carn contents have been noted in some chronically weight-trained subjects, but it is unclear if this is due to the training per se, or secondary to changes in muscle fibre composition, an increase in β-alanine intake or even anabolic steroid use. There is no measureable loss of M-Carn with acute exercise, although exercise-induced muscle damage may result in raised plasma concentrations in equines. Animal studies indicate effects of gender and age, but human studies lack sufficient control of the effects of diet and changes in muscle fibre composition.
Muscle carnosine; β-alanine; Species; Diet; Exercise and training; Age and gender
A uterus-like mass is a rare, benign extra-uterine tumour composed of smooth muscle and endometrium. The majority of uterus-like masses occur in the ovary. Rarely, uterus-like masses occur in the broad ligament, small bowel, small bowel mesentery or uterine cervix. Here, we report a case of a uterus-like mass in the sigmoid mesocolon. A well-defined, markedly enhanced soft-tissue mass with central cystic change and haemorrhage was observed on CT. The current report describes the CT characteristics of this sigmoid mesocolon uterus-like mass together with the differential diagnoses.
To study cross‐national inequalities in mortality of adults and of children aged <5 years using a novel approach, with clustering techniques to stratify countries into mortality groups (better‐off, worse‐off, mid‐level) and to examine risk factors associated with inequality.
Design, setting and participants
Analysis of data from the World Development Indicators 2003 database, compiled by the World Bank.
Main outcome measures
Adult and child mortality among countries placed into distinct mortality categories by cluster analysis.
29 countries had a high adult mortality (mean 584/1000; range 460/1000 to 725/1000) and 23 had a high child mortality (mean 207/1000, range 160/1000 to 316/1000). All these countries were in western and sub‐Saharan Africa and Afghanistan. Bivariate analyses showed that relative to countries with low child mortality, those with high child mortality had significantly higher rates of extreme poverty (p<0.001), populations living in rural areas (p<0.001) and female illiteracy (p<0.001), significantly lower per capita expenditure on healthcare (p<0.001), outpatient visits, hospital beds and doctors, and lower rates of access to improved water (p<0.001), sanitation (p<0.001) and immunisations. In multivariate analyses, countries with high adult mortality had a higher prevalence of HIV infection (odds ratio per 1% increase 18.6; 95% CI 0.3 to 1135.5). Between 1960 and 2000, adult male mortality in countries with high mortality increased at >4 times the rate in countries with low mortality. For child mortality, the worse‐off group made slower progress in reducing <5 mortality than the better‐off group.
Inequalities in child and adult mortality are large, are growing, and are related to several economic, social and health sector variables. Global efforts to deal with this problem require attention to the worse‐off countries, geographic concentrations, and adopt a multidimensional approaches to development.
To evaluate an improved quantitative lung fibrosis score based on a computer-aided diagnosis (CAD) system that classifies CT pixels with the visual semi-quantitative pulmonary fibrosis score in patients with sclero-derma-related interstitial lung disease (SSc-ILD).
High-resolution, thin-section CT images were obtained and analysed on 129 subjects with SSc-ILD (36 men, 93 women; mean age 48.8±12.1 years) who underwent baseline CT in the prone position at full inspiration. The CAD system segmented each lung of each patient into 3 zones. A quantitative lung fibrosis (QLF) score was established via 5 steps: 1) images were denoised; 2) images were grid sampled; 3) the characteristics of grid intensities were converted into texture features; 4) texture features classified pixels as fibrotic or non-fibrotic, with fibrosis defined by a reticular pattern with architectural distortion; and 5) fibrotic pixels were reported as percentages. Quantitative scores were obtained from 709 zones with complete data and then compared with ordinal scores from two independent expert radiologists. ROC curve analyses were used to measure performance.
When the two radiologists agreed that fibrosis affected more than 1% or 25% of a zone or zones, the areas under the ROC curves for QLF score were 0.86 and 0.96, respectively.
Our technique exhibited good accuracy for detecting fibrosis at a threshold of both 1% (i.e. presence or absence of pulmonary fibrosis) and a clinically meaningful threshold of 25% extent of fibrosis in patients with SSc-ILD.
texture feature; classification; scleroderma; interstitial lung disease; CAD
Management of symptomatic carotid near occlusion especially in high-risk patients is different from outcome analysis of NASCET. We evaluated outcome in high-risk patients with symptomatic near occlusion.
For 48 patients with near occlusion out of 166 symptomatic high-risk patients who underwent carotid stenting, we assessed the procedural success defined as residual stenosis <30%, modified Rankin Scale (mRS) at one and six months following stenting, and the 13 cerebrovascular factors related to the outcome. Initial National Institutes of Health Stroke Scale (NIHSS) ≥4,1-3 and 0 were 13,14 and 21 patients each. We compared the outcome with patients who underwent CAS (n=118) due to symptomatic stenosis without near occlusion during the same period.
Our procedural success rate was 98%. A good outcome (mRS ≥2) was achieved in 44 patients (92%) at six months. There were five events (10%) within six months, i.e. three minor strokes, one major stroke caused by hemorrhage, and one death excluding two deaths not related to stroke. Hyperperfusion (n=4) was the most common cause of events leading to two minor strokes and a major stroke. Although initial NIHSS (P = .012) was related to poor outcome (mRS >2) compared to the CAS group, there was no statistical significance between two groups in the event rate of stroke, death or restenosis.
The outcome of carotid stenting in high-risk patients with symptomatic near occlusion did not reveal any difference compared with CAS. Poor outcome was related to the initial NIHSS (>4). Hyperperfusion tended to be more commonly related to an event occurring after stenting.
carotid arteries, stenosis or obstruction, stenting, outcome
The aim of this study is to compare blinded with partially blinded detection of gastric cancer with multidetector (MD) CT by using surgery and endoscopic submucosal dissection (ESD) as reference standards. 44 patients with gastric cancer underwent MDCT with air as an oral contrast agent. Surgery was performed on 37 patients, ESD on six and surgery after ESD on one. To provide comparison cases of blinded evaluation, 38 MDCT examinations were added for cases where no focal gastric lesion was seen on endoscopy. Two radiologists, blinded to the presence, number and location of the tumours, evaluated axial and axial plus multiplanar reformation (MPR) images of 82 MDCT examinations with or without gastric cancer. For partially blinded evaluation, the same radiologists, blinded to the location and number of tumours, evaluated axial and axial plus MPR images of 44 MDCT examinations of gastric cancer. Differences in assessment were resolved by consensus. 45 gastric cancers were found in surgical and ESD specimens. Detection rates of gastric cancer from axial and axial plus MPR images during blinded evaluation and from axial and axial plus MPR images during partially blinded evaluation were 62% (28/45), 64% (29/45), 64% (29/45) and 71% (32/45), respectively. There was no statistical significance for the comparison between blinded and partially blinded detection rates of gastric cancer. The detection rate of gastric cancer with MDCT during blinded evaluation showed no specific difference compared with the detection rate of gastric cancer with MDCT during partially blinded evaluation.
An experimental study of picosecond pulse amplification in a gyrotron-traveling wave tube (gyro-TWT) has been carried out. The gyro-TWT operates with 30 dB of small signal gain near 140 GHz in the HE06 mode of a confocal waveguide. Picosecond pulses show broadening and transit time delay due to two distinct effects: the frequency dependence of the group velocity near cutoff and gain narrowing by the finite gain bandwidth of 1.2 GHz. Experimental results taken over a wide range of parameters show good agreement with a theoretical model in the small signal gain regime. These results show that in order to limit the pulse broadening effect in gyrotron amplifiers, it is crucial to both choose an operating frequency at least several percent above the cutoff of the waveguide circuit and operate at the center of the gain spectrum with sufficient gain bandwidth.
The purpose of this study was to evaluate intratumoral cystic lesions of pancreatic ductal adenocarcinoma (PDAC) depicted on MRI, and to correlate these cystic lesions with their histopathological findings. This study included 12 patients (7 males and 5 females; mean age, 59 years) with intratumoral cystic lesions of PDAC detected on a retrospective MRI review. We reviewed the histopathological findings of the cystic lesions within PDACs and analysed the MRI findings, focusing on the appearance of the intratumoral cystic lesions, i.e. the size, number, margin and intratumoral location, and on the ancillary findings of PDAC, i.e. peripancreatic infiltration, upstream pancreatic duct dilatation and distal parenchymal atrophy. Intratumoral cystic lesions were classified as neoplastic mucin cysts (n = 7, 58%) or cystic necrosis (n = 5, 42%) according to the histopathological findings; they ranged in greatest dimension from 0.5 cm to 3.4 cm (mean, 1.7 cm). Seven patients had only one cystic lesion each, while the remaining five had multiple cystic lesions. Most of the neoplastic mucin cysts had smooth margins (n = 6, 86%) and eccentric locations (n = 6), whereas most cystic necroses had irregular margins (n = 4, 80%) and centric locations (n = 4). The most common ancillary findings of PDAC were peripancreatic infiltration, distal pancreatic atrophy and upstream pancreatic duct dilatation (92%, 75% and 58%, respectively). The intratumoral cystic lesions of PDACs on MRI were classified as either neoplastic mucin cysts with smooth margins and eccentric locations or cystic necroses with irregular margins and centric locations.
Stathmin1 is a microtubule-regulating protein that has an important role in the assembly and disassembly of the mitotic spindle. The roles of stathmin1 in carcinogenesis of various cancers, including prostate and breast cancer, have been explored. However, its expression and roles in gastric cancer have not yet been described.
Stathmin1 expression in paraffin-embedded tissue sections from 226 patients was analysed by immunohistochemistry. Roles of stathmin1 were studied using a specific small interfering RNA (siRNA).
The expression of stathmin1 was positively correlated with lymph node metastasis, TNM stages and vascular invasion, and negatively with recurrence-free survival, in the diffuse type of gastric cancer. The median recurrence-free survival in patients with a negative and positive expression of stathmin1 was 17.0 and 7.0 months, respectively (P=0.009). When the expression of stathmin1 was knocked down using siRNA, the proliferation, migration and invasion of poorly differentiated gastric cancer cells in vitro were significantly inhibited. Moreover, stathmin1 siRNA transfection significantly slowed the growth of xenografts in nude mice.
These results suggest that stathmin1 can be a good prognostic factor for recurrence-free survival rate and is a therapeutic target in diffuse-type gastric cancer.
stathmin1; gastric cancer; proliferation; migration