Negative genic switch of HER-2 in the primary tumor instead of the synchronous metastatic nodal lesions after neoadjuvant chemotherapy in a patient with primary HER2-positive breast cancer.

BACKGROUND: A few retrospective studies have indicated that neoadjuvant chemotherapy (NAC) in breast cancer may change biomarker profiles of the primary tumor. Little is known about the status of HER-2 gene of the synchronous nodal metastases when that of the residual tumor undergoes negative conversion in a neoadjuvant setting. CASE PRESENTATION: We describe a female patient with left breast cancer (T2N2M0) who underwent negative conversion of HER-2 in the primary tumor instead of the synchronous nodal lesions after NAC. Core needle biopsy showed invasive ductal carcinoma with HER2 immunohistochemistry (IHC) (2+) and amplified HER-2 gene determined by fluorescence in situ hybridization (FISH). Then, the patient underwent 4 cycles of anthracycline- and taxane-based NAC and subsequent left modified radical mastectomy. Postoperative pathology showed invasive ductal carcinoma involving 4 of 12 surgically excised axillary lymph nodes with HER2 IHC (1+) and FISH negative (HER2 gene not amplified) in the residual tumor of the breast specimen. Due to the negative genic switch of HER2 after NAC, the patient rejected to accept trastuzumab. Under the patient's consent, the synchronous nodal lesions were further investigated and showed HER2 IHC(-) but FISH positive (HER-2 gene amplified). Therefore, the patient agreed to accept adjuvant trastuzumab treatment every 3 weeks for 1 year. CONCLUSIONS: We propose further assessment of HER2 gene in the synchronous nodal metastases, especially when negative genic switch of HER-2 occurs in the primary tumor after NAC in order to tailor the systemic regimens for breast cancer patients.

Influence of selective photon shield combined with sinogram-affirmed iterative reconstruction on image quality and radiation dose during dual-energy CT angiography-mediated diagnosis of intracranial aneurysms.

OBJECTIVE: To investigate the influence of a selective photon shield (SPS) combined with sinogram-affirmed iterative reconstruction (SAFIRE) on image quality and radiation dose during application of dual-energy CT angiography (CTA) for diagnosis of intracranial aneurysms. METHODS: We retrospectively reviewed clinical data for 80 patients with diagnoses of spontaneous subarachnoid hemorrhage. All patients underwent three-dimensional digital subtraction angiography scans within 1 week after CTA. Data for patients in the conventional method group were subjected to filtered-back-projection reconstruction, while data for patients in the experimental method group were subjected to SAFIRE reconstruction. Image quality and scanning radiation dose were evaluated. RESULTS: Background noise was significantly lower in the experimental method group than in the conventional method group, while the mean CT value did not differ between the groups. Signal-to-noise ratios were significantly higher in the experimental method group than in the conventional method group. However, the average CT value, contrast-to-noise ratio, and image quality scores did not differ between groups. All scores indicated acceptability for clinical diagnosis. The dose index of volume and effective dose were significantly lower in the experimental method group than in the conventional method group. Surgical verification showed that the detection rates in the experimental and conventional method groups were 100% (29/29) and 96% (25/26), respectively. CONCLUSIONS: SPS combined with SAFIRE applied for analysis of dual-energy CTA data improved the quality of CT images, reduced the radiation dosage, and increased diagnostic accuracy. ADVANCES IN KNOWLEDGE: SPS combined with SAFIRE may improve the accuracy of diagnosis of intracranial aneurysms.

Application Value of Selective Photon Shield in Dual-Energy Computed Tomography Angiography for Diagnosis of Intracranial Aneurysms.

PURPOSE: The aim of the study was to investigate the image quality of dual-energy computed tomography angiography (DECTA) using the selective photon shield (SPS) technique to diagnose intracranial aneurysms. MATERIALS AND METHODS: Eighty patients with a suspected intracranial aneurysm were randomly assigned to undergo DECTA with SPS (ie, SPS-DECTA) or DECTA without SPS (ie, DECTA). The objective image quality of these 2 groups was compared with digital subtraction angiography and surgical results as the reference. The location, number, and morphology of the aneurysms were evaluated between the 2 groups. The display degree and the size of aneurysmal neck and the diameters (ie, long and short axis) of the aneurysm were compared between the 2 groups. RESULTS: The signal-to-noise ratio and contrast-to-noise ratio of SPS-DECTA were significantly higher than those of DECTA (P < 0.05). The difference between the 2 groups in intracranial vascular subjective scoring was not statistically significant (P > 0.05). In 30 of the 40 patients in the SPS-DECTA group, an aneurysm was detected without misdiagnosis or missed diagnosis. The aneurysm location, aneurysm number, and measurements by the 2 methods were closely correlated without significant statistical differences (the R values were 0.953, 0.982, and 0.974, respectively; P = 0.000). The detection rate was 93% (26/28 patients). In the DECTA group, 2 patients were misdiagnosed. Mean long and short diameter and neck size by three-dimensional digital subtraction angiography were 5.82 ±â€Š3.27, 4.67 ±â€Š3.31, and 3.29 ±â€Š1.38 mm, respectively. Aneurysm locations, number, and neck size by the 2 methods were closely correlated without a significant statistical difference (R values were 0.964, 0.968, and 0.856, respectively; P = 0.000). CONCLUSIONS: The SPS-DECTA is very accurate for diagnosing intracranial aneurysms and could be a routine noninvasive screening method.

Synthesis of 6-alkyluridines from 6-cyanouridine via zinc(II) chloride-catalyzed nucleophilic substitution with alkyl Grignard reagents.

6-Cyanouracil derivatives underwent a direct nucleophilic substitution reaction with alkyl Grignard reagents in the presence of zinc(II) chloride as a catalyst to form the corresponding 6-alkyluracils. This methodology is applicable to sugar-protected 6-cyanouridine and 6-cyano-2'-deoxyuridine without the protection at the N(3)-imide and provides a facile and general access to versatile 6-alkyluracil and 6-alkyluridine derivatives.

BMP-2 suppresses renal interstitial fibrosis by regulating epithelial-mesenchymal transition.

Dysregulation of epithelial-to-mesenchymal transition (EMT) may contribute to renal fibrogenesis. Our previous study indicated that bone morphogenetic protein-2 (BMP-2) significantly reversed transforming growth factor (TGF)-ß1-induced renal interstitial fibrosis. In this study, we examined the underlying mechanism and elucidate the regulation of EMT process under BMP-2 treatment. Cultured renal interstitial fibroblast (NRK-49F) was treated with TGF-ß1 (10 ng/ml) with or without BMP-2 (10-250 ng/ml) for 24 h. The expression of α-smooth muscle actin (α-SMA), E-cadherin, fibronectin, or Snail transcriptional factors was analyzed by immunofluorescence staining or Western blotting. Cell migration was analyzed by wound-healing assay. NRK-49F treated with TGF-ß1 induced significant EMT including upregulatioin of α-SMA, fibronectin, and snail proteins and down-regulation of E-cadherin. Interestingly, co-treatment with BMP-2 dose-dependently reversed TGF-ß1-induced cellular fibrosis, cell migration, and above EMT change. The above effect was closely correlated with Snail since BMP-2 dose- and time-course dependently induced a significant decrease in the level of Snail. Moreover, Snail siRNA significantly reversed TGF-ß1-induced increases in the level of α-SMA and fibronectin (intracellular and extracellular). We suppose that BMP-2 have the potential to attenuate TGF-ß1-induced renal interstitial fibrosis by attenuating Snail expression and reversing EMT process.

Hyperosmolarity enhanced susceptibility to renal tubular fibrosis by modulating catabolism of type I transforming growth factor-beta receptors.

Hyperosmolarity plays an essential role in the pathogenesis of diabetic tubular fibrosis. However, the mechanism of the involvement of hyperosmolarity remains unclear. In this study, mannitol was used to evaluate the effects of hyperosmolarity on a renal distal tubule cell line (MDCK). We investigated transforming growth factor-beta receptors and their downstream fibrogenic signal proteins. We show that hyperosmolarity significantly enhances the susceptibility to exogenous transforming growth factor (TGF)-beta1, as mannitol (27.5 mM) significantly enhanced the TGF-beta1-induced increase in fibronectin levels compared with control experiments (5.5 mM). Specifically, hyperosmolarity induced tyrosine phosphorylation on TGF-beta RII at 336 residues in a time (0-24 h) and dose (5.5-38.5 mM) dependent manner. In addition, hyperosmolarity increased the level of TGF-beta RI in a dose- and time-course dependent manner. These observations may be closely related to decreased catabolism of TGF-beta RI. Hyperosmolarity significantly downregulated the expression of an inhibitory Smad (Smad7), decreased the level of Smurf 1, and reduced ubiquitination of TGF-beta RI. In addition, through the use of cycloheximide and the proteasome inhibitor MG132, we showed that hyperosmolarity significantly increased the half-life and inhibited the protein level of TGF-beta RI by polyubiquitination and proteasomal degradation. Taken together, our data suggest that hyperosmolarity enhances cellular susceptibility to renal tubular fibrosis by activating the Smad7 pathway and increasing the stability of type I TGF-beta receptors by retarding proteasomal degradation of TGF-beta RI. This study clarifies the mechanism underlying hyperosmotic-induced renal fibrosis in renal distal tubule cells.

Image quality evaluation for CARE kV technique combined with iterative reconstruction for chest computed tomography scanning.

BACKGROUND: To investigate the radiation dose and image quality for iterative reconstruction combined with the CARE kV technique in chest computed tomography (CT) scanning for physical examination. METHODS: A total of 130 patients who underwent chest CT scanning were randomly chosen and the quality reference value was set as 80 mAs. The scanning scheme was set and the patients were randomly divided into groups according to the scanning scheme. Sixty patients underwent a chest scan with 100 kV using the CARE kV technique and SAFIRE reconstruction (value=3) (experimental group) and the other 70 patients underwent chest scanning with 120 kV (control group). The mean CT value, image noise (SD), and signal-to-noise ratio (SNR) of the apex of the lung, the level of the descending aorta bifurcation of the trachea, and the middle area of the left atrium were measured. The image quality was assessed on a 5-point scale by two radiologists and results of the two groups were compared. The CT dose index of the volume (CTDIvol), dose length product (DLP), and effective dose (ED) were compared. RESULTS: All the images for both groups satisfied the diagnosis requirement. There was no statistical difference in the image quality between the two methods (P > 0.05). The mean CT value of the apex of the lung, the level of the descending aorta bifurcation of the trachea, and the middle area of the left atrium were not significantly different for both groups (P > 0.05), while the image noise (SD) and the signal-to-noise ratio (SNR) of the apex of the lung, the level of the descending aorta bifurcation of the trachea, and the middle area of the left atrium were statistically different for both groups (P < 0.05). The CTDIvol was 3.29 ±â€Š1.17 mGy for the experimental group and 5.30 ±â€Š1.53 mGy for the control group. The DLP was 114.9 ±â€Š43.73 mGy cm for the low-dose group and 167.6 ±â€Š44.59 mGy cm for the control group. The ED was 1.61 ±â€Š0.61 mSv for the low-dose group and 2.35 ±â€Š0.62 mSv for the control group (P  < 0.05). CONCLUSION: The CARE kV technique combined with iterative reconstruction for chest CT scanning for physical examination could reduce the radiation dosage and improve CT image quality, which has a potential clinical value for imaging the thorax.

[Imaging features of duplication of the internal auditory canal].

OBJECTIVE: To explore multiple slices computed tomography (MSCT) and magnetic resonance imaging (MRI) features of duplication of the internal auditory canal (DIAC) in order to improve the accuracy of diagnosis. METHODS: Four cases (5 ears) were analyzed and the related documents were reviewed retrospectively. MSCT was performed on all cases, and two cases had MRI scanning at the same time. RESULTS: MSCT has shown that the internal auditory canal were divided into two canals by a bony septum in 5 ears. The superior canal ended in a very narrow connection to the facial canal, the inferior portion ended in connection to the cochlea and vestibule. The bony septums from the 2 ears were found no longer intact. The sum of diameter of the two canals was greater than 2 mm. In addition, 5 ears were found to have an enlarged vestibules and the hypoplasia lateral semicircular canals, and meanwhile, 2 ears of them were combined with ipsilateral microtia. Also 1 case of them was combined with microtia, outer acoustic atresia as well as abnormal middle ear. Multiplanar reconstruction and volume rendering images can entirely show the bony septum and two canals. In this study, the vestibular nerve, cochlear nerve and facial nerve were total hypoplastic in one ear, in the other ear, the vestibular and cochlear nerve were hypoplastic, and however, the facial nerve was intact. CONCLUSIONS: MSCT can clearly depict duplication of the internal auditory canals and concomitant anomalies. MRI can clearly show the neural components and their associated malformation.