人乳腺癌组织的显微拉曼光谱研究

研究了人类正常与癌变乳腺组织的显微拉曼光谱特性。与正常乳腺组织相比,癌变组织的核酸骨架磷酸离子vs(PO^-2)特征谱线由1082移到1097cm^-1、强度加强,位于817cm^-1的RNA主链vs(O-P-O)的谱线强度增加;蛋白质酰胺Ⅰ和酰胺Ⅲ两个特征谱带从1657,1273cm^-1分别位移到1662和1264cm^-1,其中1264cm^-1谱线的宽度和强度均增加,某些氨基酸残基的C—O谱线向高波数位移,色氨酸特征峰1368cm^-1在癌变组织中几乎观察不到;脂类特征谱线减少。上述谱线变化表明,癌变组织中核酸的相对含量增加、主链结构发生变化;蛋白质结构同时呈现α-螺旋、无规卷曲、卢．折叠以及β-回折4种构象特征,其分子间的氢键近乎断裂,蛋白质变得松散和无序,色氨酸残基的吲哚环呈现“暴露式”;脂类含量减少。研究表明,显微拉曼光谱可以为乳腺癌变的生化机理研究以及活体诊断提供有力的实验依据。     

Preliminary attempt on maximum likelihood tomosynthesis reconstruction of DEI data

Tomosynthesis is a three-dimension reconstruction method that can remove the effect of superim- position with limited angle projections. It is especially promising in mammography where radiation dose is concerned. In this paper, we propose a maximum likelihood tomosynthesis reconstruction algorithm （ML-TS） on the apparent absorption data of diffraction enhanced imaging （DEI）. The motivation of this contribution is to develop a tomosynthesis algorithm in low-dose or noisy circumstances and make DEI get closer to clinic application. The theoretical statistical models of DEI data in physics are analyzed and the proposed algorithm is validated with the experimental data at the Beijing Synchrotron Radiation Facility （BSRF）. The results of ML-TS have better contrast compared with the well known ＇shift-and-add＇ algorithm and FBP algorithm.     

Exact quantification of time signals from magnetic resonance spectroscopy by the fast Padé transform with applications to breast cancer diagnostics

Mathematical modeling via the fast Padé transform (FPT) is applied according to experimental NMR data encoded from (a) normal, non-infiltrated breast tissue, (b) benign pathology (fibroadenoma) and (c) malignant breast tissue. At a partial signal length N _P  = 1500, the FPT provided exact reconstruction of all the input spectral parameters for the time signals corresponding to the normal, benign as well as to the malignant lesions. The converged parametric results remained stable at longer signal lengths. The Padé absorption spectra yielded unequivocal resolution of all the extracted physical metabolites, even of those that were nearly completely overlapping (phosphocholine and phosphoethanolamine at 3.22 ppm). The capacity of the FPT to resolve and precisely quantify the physical resonances as encountered in normal versus benign versus malignant breast is demonstrated. In particular, the FPT unambiguously delineated and quantified diagnostically important metabolites such as lactate, as well as choline, phosphocholine and glycerophosphocholine that are very closely overlapping and may represent MR-retrievable molecular markers of breast cancer. This was achieved by the FPT without any fitting or numerical integration of peak areas. We conclude that these advantages of the FPT could be of definite benefit for breast cancer diagnostics via NMR and that this line of investigation should continue with encoded data from benign and malignant breast tissue, in vitro and in vivo. We anticipate that Padé-optimized MRS will reduce the false positive rates of MR-based modalities and further improve their sensitivity. Once this is achieved, and given that MR entails no ionizing radiation, new possibilities for screening/early detection open up, especially for risk groups, e.g. Padé-optimized MRS could be used with greater surveillance frequency among younger women with high breast cancer risk.     

Anti-epidermal growth factor receptor (anti-EGFR) antibody conjugated fluorescent nanoparticles probe for breast cancer imaging

Fluorescent nanoparticles (FNs) with unique optical properties may be useful as biosensors in living cancer cell imaging and cancer targeting. In this study, anti-EGFR antibody conjugated fluorescent nanoparticles (FNs) (anti-EGFR antibody conjugated FNs) probe was used to detect breast cancer cells. FNs with excellent character such as non-toxicity and photostability were first synthesized with a simple, cost-effective and environmentally friendly modified Stőber synthesis method, and then successfully modified with anti-EGFR antibody. This kind of fluorescence probe based on the anti-EGFR antibody conjugated FNs has been used to detect breast cancer cells with fluorescence microscopy imaging technology. The experimental results demonstrate that the anti-EGFR antibody conjugated FNs can effectively recognize breast cancer cells and exhibited good sensitivity and exceptional photostability, which would provide a novel way for the diagnosis and curative effect observation of breast cancer cells and offer a new method in detecting EGFR.     

Short communication for targeting natural compounds against HER2 kinase domain as potential anticancer drugs applying pharmacophore based molecular modelling approaches- part 2

Breast cancer is one of the common causes of death noticed in women globally. In order to find effective therapeutics, the current investigation has focussed on identifying candidate compounds for EGFR and HER2. Accordingly, the pharmacophore modelling approaches were adapted to identify two prospective compounds and were docked against the target 3RCD that is complexed with TAK-285 a known dual inhibitor. Focussing on the target 3RCD, our results have showed that the compounds have demonstrated a good binding affinity towards the target occupying the binding pocket. They have established key residue interactions with stable molecular dynamics simulation results. The Hit compounds have demonstrated a potential to penetrate the blood brain barrier thereby enriching their therapeutics towards breast cancer brain metastasis. Taken together, our findings propose two candidate compounds as EGFR/HER2 inhibitors that might serve as novel chemical spaces for designing and developing new inhibitors.     

Diagnostic performance of apparent diffusion coefficient and quantitative kinetic parameters for predicting additional malignancy in patients with newly diagnosed breast cancer

Purpose

To evaluate the diagnostic performance of an apparent diffusion coefficient (ADC) and quantitative kinetic parameters in patients with newly diagnosed breast cancer.

Materials and Methods

We enrolled 169 lesions in 89 patients with breast cancer who underwent dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI). Comparisons between benign and malignant lesions were performed for lesion type (mass or nonmass-like enhancement), size (≥ 1 cm or < 1 cm), ADC, kinetic parameters and the presence of a US correlate.

Results

There were 63 benign and 106 malignant lesions. The mean size and initial peak enhancement of the benign lesions were significantly lower than those of malignant lesions (P < 0.001 for both). The ADC of the benign lesions was significantly higher than that of malignant lesions (1.42 × 10^− 3 mm²/sec vs. 1.04 × 10^− 3 mm²/sec; P < 0.001). The area under the receiver operating characteristic curve (AUC) for predicting malignancy was 0.87 for the combined parameters of size, ADC, and initial peak enhancement, which was higher than those of each parameter.

Conclusions

Combination of quantitative kinetic parameters and ADC showed higher diagnostic performance for predicting malignancy than each parameter alone for the evaluation of patients with breast cancer.     

Research and progress in magnetic resonance imaging of triple-negative breast cancer

Triple-negative breast cancer (TNBC), which characterized by distinct biological and clinical pathological features, has a worse prognosis because the lack of effective therapeutic targets. Breast MR is the most accurate imaging modality for diagnosis of breast cancer currently. MR imaging recognition could assist in diagnosis, pretreatment planning and prognosis evaluation of TNBC. MR findings of a larger solitary lesion, mass with smooth mass margin, high signal intensity on T₂-weighted images and rim enhancement are typical MRI features associated with TNBC. Further work is necessary about the clinical application of dynamic contrast-enhanced MR imaging (DCE-MRI), DWI and MRS.     

Design,cytotoxic effects on breast cancer cell line (MDA-MB 231), and molecular docking of some maleimide-benzenesulfonamide derivatives

A group of novel maleimide-benzenesulfonamide derivatives 3a-d was designed and synthesized for their evaluation as a potential anti-breast cancer agent. The structures of these derivatives were confirmed by their ¹H, ¹³C NMR, Mass, FT-IR spectral data, and melting points. The cytotoxic activity (in vitro) of the selected molecules against MDA-MB231 ​cell line was evaluated by MTT method. Among them, compounds 3a and 3d exhibited a significant cytotoxicity with the IC₅₀ value of 1.61 and 1.26 ​μM, respectively, whereas compounds 3b and 3c showed a moderate cytotoxicity with IC₅₀ values of 0.45 and 1.12 ​μM, respectively against MDA-MB231 ​cells. Docking modeling of the synthesized compounds 3a-d into binding sites of human aromatase protein (PDB ID: 4GL7) was performed to investigate if these derivatives possess analogous binding mode to breast cancer proteins. Docking results showed these compounds have efficient interactions such as hydrogen bonding, Van der Waals interactions, and hydrophobic interactions with the active site residues of the aromatase protein (PDB ID: 4GL7). The low binding energies and a number of hydrogen bonding indicated that the maleimide-benzenesulfonamide derivatives might be considered as a promising anti-breast cancer agent with further developments in drug discovery.