Background
The 21-gene recurrence score (RS) predicts outcome and benefit from adjuvant chemotherapy benefit in breast cancer patients treated with adjuvant endocrine therapy. In the NSABP B-28 ...study, we evaluated the 21-gene RS for its prognostic impact and its ability to predict benefit from paclitaxel (P) in node-positive, estrogen receptor-positive (ER+) breast cancer patients treated with adjuvant chemotherapy plus tamoxifen.
Methods
The B-28 trial compared doxorubicin/cyclophosphamide (AC) with AC followed by P in 3060 patients. Tamoxifen for 5 years was also given to patients
>
50 years and those < 50 years with ER+ and/or progesterone receptor-positive (PR+) tumors. The present study includes 1065 ER-positive, tamoxifen-treated patients with RS assessment. Median follow-up time was 11.2 years.
Results
In univariate analyses, RS was a significant predictor of outcome. In multivariate analyses, RS remained a significant independent predictor of outcome beyond clinico-pathologic factors, age, and type of surgery (
p
< 0.001). In the study population (
n
= 1065), the disease-free survival (DFS) hazard ratio (HR) with adding P to AC was 0.87 (95% CI 0.72–1.05;
p
= 0.14). RS was not a significant predictor of P benefit: for DFS, HRs for adding P to AC in RS low, intermediate, and high subgroups were 1.01 (95% CI 0.69–1.47;
p
= 0.99), 0.84 (95% CI 0.62–1.14;
p
= 0.26), and 0.81 (95% CI 0.60–1.10;
p
= 0.21), respectively (interaction
p
= 0.64). Similar findings were observed for the other study endpoints.
Conclusions
RS maintains significant prognostic impact in ER-positive, node-positive patients treated with adjuvant chemotherapy plus tamoxifen. However, RS did not significantly predict benefit from adding paclitaxel to AC chemotherapy. (Trial Registration: PDQ: NSABP-B-28).
Novel series of stilbenylbenzoxazole (
SBO) and stilbenylbenzothiazole (
SBT) derivatives were synthesized and evaluated by competitive binding assay against β-amyloid 1–42 (Aβ42) aggregates using
...125ITZDM. All the derivatives displayed higher binding affinities with
K
i values in the subnanomolar range (0.10–0.74
nM) than PIB (0.77
nM). In conclusion, the preliminary results suggest that these compounds are implying a possibility as a probe for detection of Aβ fibrils in Alzheimer’s disease (AD) patients.
This paper describes a novel series of stilbenylbenzoxazole (
SBO) and stilbenylbenzothiazole (
SBT) derivatives for β-amyloid specific binding probes. These 24 compounds were synthesized and evaluated by competitive binding assay against β-amyloid 1–42 (Aβ42) aggregates using
125ITZDM. All the derivatives displayed higher binding affinities with
K
i value in the subnanomolar range (0.10–0.74
nM) than Pittsburgh Compound-B (PIB) (0.77
nM). Among these derivatives,
SBT-2, 5-fluoroethoxy-2-{4-2-(4-methylaminophenyl)vinylphenyl}benzothiazole, showed lowest
K
i value (0.10
nM). In conclusion, the preliminary results suggest that these compounds are implying a possibility as a probe for detection of Aβ fibrils in Alzheimer’s disease (AD) patients.
A 68-year-old woman with progressive paraparesis and altered sensation lasting approximately five days was admitted to our clinic. Magnetic resonance imaging (MRI) revealed an advanced stage T7-8 ...epidural mass ventral to the spinal cord, which was believed to be a metastatic tumor considering the patient's age. A highly enhanced epidural mass and pedicle appeared during the MR scan. However, the pathologic findings were compatible with the diagnosis of a primary meningeal melanocytic tumor. Primary epidural melanomas are extremely rare lesions. This case was finally diagnosed as a primary thoracic spinal epidural melanoma.
To investigate the association between headache outcomes and coil embolization and to identify potential factors associated with different headache outcomes in patients with unruptured intracranial ...aneurysms (UIAs) after treatment with coil embolization.
A prospective study of patients with planned coil embolization for UIAs was conducted. The changes in headache patterns, headache-related disability, and depression were assessed before coil embolization and at 3 days and 2 and 6 weeks after coil embolization. All variables were analyzed to identify factors associated with different headache outcomes.
Fifty-nine (72%) of 82 patients reported headaches before coil embolization. Of these, improvements in the severity of headaches were reported by 42 patients (71%). In addition to a significant reduction in headache severity, significant reductions in headache-related disability and depression scores also were observed. Demographic factors, aneurysmal characteristics, or procedural factors were not found to be significantly associated with improvement in the severity of headaches after coil embolization. In addition, the number of microemboli on diffusion-weighted imaging was not significantly associated with improvement of headaches after coil embolization.
Twenty-three patients reported no headaches before coil embolization, and 3 (13%) patients reported new-onset headaches after coil embolization. All new-onset headaches were mild and dull in nature without combined symptoms in the temporal area.
Our study suggested that regardless of headache characteristics, the aneurysm size (even those <5 mm in diameter), technique used (stent-assisted or not stent-assisted), and coil embolization of UIAs resulted in headache improvement in most patients with pretreatment headaches.
•Coil embolization of UIAs results in headache improvement in most patients (>70%) with pretreatment headaches.•No patients reported worsening of headaches after coil embolization.•Patients with migraine without aura or tension type headache are expected improvement of headache.•Only some patients (13%) without pretreatment headache reported new headache, which was mild and short-lived.
The purpose of this study was to identify the risk factors related to the hemorrhagic progression (HP) of brain contusion in patients after traumatic brain injury (TBI). Recently, many studies have ...reported abnormal lipid levels associated with hemorrhagic stroke. Unlike hemorrhage stroke, however, the lipid profiles in patients with TBI have not been examined. Therefore, we evaluated the risk factors of HP in patients with TBI and focused on lipid profiles. Fifty-six patients with TBI with mild to moderate injuries (Glasgow Coma Scale ≥9) who initially did not need surgical intervention were enrolled in this study. Patients underwent repeated computed tomography (CT) scans at 4 h and 24 h after injury. Magnetic resonance imaging (MRI) was performed 7 days after the initial injury. In each noncontrast CT scan, the hemorrhage volume was quantified using the ABC/2 technique. Clinical features, previous medical history, initial CT, and microbleeding on follow-up MRI were analyzed retrospectively. There were 31 (55%) patients in whom significant HP developed (volume >30%). Current smoking (p=0.034), higher initial systolic blood pressure (p=0.035), and lower triglyceride levels (p=0.039) were significantly associated with HP. Current smoking and a triglyceride (TG) level <150 mg/dL were the only statistically significant predictors of HP in the multivariate analysis (p=0.019, p=0.021, respectively). HP with TBI is common in patients who currently smoke and have lower TG levels (150 mg/dL). These patients should be monitored closely, and surgery may be considered before deterioration occurs.
Solid tumors contain normoxic and hypoxic regions depending on the distance from the capillary. Normal cells may also be exposed to hypoxia under certain physiological conditions. Tumor hypoxia has ...been shown to associate strongly with tumor propagation and malignant progression. Hypoxia-inducible factor (HIF)-1alpha is stable under hypoxia and induces transcription of target genes by binding to the hypoxia-response element (HRE). Here we investigated the oncolytic effects of a novel adenovirus mutant with a deleted E1B55 gene (Ad.Delta55.HRE), in which the expression of E1A, which is essential for adenoviral replication, is regulated under the control of an HRE-expression system. Ad.Delta55.HRE expressed E1A under normoxia and more E1A under hypoxia and exhibited oncolytic effects on various cultured tumor cells, but its cytotoxic effect is relatively attenuated in normal fibroblast cells under normoxic and hypoxic conditions. Ad.Delta55.HRE lysed Huh-7 hepatoma cells stably expressing HIF-1alpha more effectively compared to parental cells. Ad.Delta55.HRE treatment exhibited significant antitumor activity in PC-3 prostate- and MDA-MB-435 breast tumor-bearing nude mice in which HIF-1alpha protein was immunohistochemically detected. The E1A and hexon proteins of adenovirus were immunostained in MDA-MB-435 xenografts after Ad.Delta55.HRE treatment, suggestive of viral replication. Our results suggest that Ad.Delta55.HRE may be useful for the treatment of solid tumors.
Abstract We aimed to use array comparative genomic hybridization (CGH) to identify chromosomal loci that contribute to the pathogenesis of ruptured intracranial aneurysms (IAs) in a Korean population ...and to confirm the results using real-time polymerase chain reaction (PCR). Twenty-three patients with ruptured IAs were enrolled in this study. Array CGH revealed copy number aberrations in 19 chromosomal regions. Chromosomal gains were identified at a high frequency in regions 1p12, 4q24, 5p15.31, 5p15.33, 6p12.2, 6q22.33, 7p21.1, 9q22.1, 10q24.32, 10q26.3, 12q13.13, 17p12, 18q12.3, 18q23, 19p13.3, 20q13.33, 21q11.2, and 21q22.3, whereas chromosomal losses were identified at 15q11.2 and 22q11.21. Real-time PCR confirmed the results of the array CGH studies of the COL6A2 , GRIN3B , MUC17 , and PRODH genes. This is the first study to identify candidate regions by array CGH in patients with IAs. The identification of genes that may predispose an individual to the development of IAs may lead to a better understanding of the mechanism of IA formation. Multicenter studies comparing cohorts of patients of different ethnicities are needed to better understand the mechanism of IA formation.
Fibrous polyp of the gallbladder is a rare variant of benign gallbladder polyp. Differentiation between a benign polyp and polypoid carcinoma of the gallbladder is often difficult when the polyp is ...more than 1 cm in diameter. We report a rare case of a large fibrous polyp of the gallbladder mimicking a carcinoma. A 44-year-old Korean woman who presented with abdominal pain was diagnosed with a large gallbladder polyp, measuring 1.26 cm in diameter, by abdominal ultrasonography. The lesion was echogenic with a nodular surface on ultrasonography, and showed contrast enhancement on computed tomography. Neither evidence of infiltration into the gallbladder wall nor lymph node enlargement was shown. The resected gallbladder showed a 1.2 x 0.8-cm-sized polyp with a nodular surface. Histologically, it showed a leaf-like configuration and loose or cellular connective stroma containing scattered duct-like structures, varying-sized vessels, and patchy infiltration of chronic inflammatory cells. Stromal cells were immunoreactive for vimentin and smooth-muscle actin and negative for S-100 protein and desmin. Large fibrous polyps of the gallbladder should be considered in the differential diagnosis of benign and malignant polypoid lesions of the gallbladder.
To characterize largazole’s structural requirements for histone deacetylase (HDAC) inhibitory and antiproliferative activities, a series of analogues with modifications to the side chain or ...16-membered macrocycle were prepared and biologically evaluated. Structure−activity relationships suggested that the four-atom linker between the macrocycle and octanoyl group in the side chain and the (S)-configuration at the C17 position are critical to repression of HDAC activity. However, the valine residue in the macrocycle can be replaced with alanine without significant loss of activity.
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