Topical delivery of paclitaxel for treatment of skin cancer

Context: Skin cancer represents the most growing types of cancer in human and ultraviolet radiation can be cited as one of the prime factor for its occurrence. Current therapy of skin cancer suffers from numerous side effects; for effective therapy, topical application of formulation of paclitaxel (PTX) can be considered as a novel approach.

Objective: The present study is an attempt to prepare formulation of solid lipid nanoparticles (SLN) of PTX for the effective treatment of various form of skin carcinoma.

Methods: The SLN were prepared by high-speed homogenization and ultrasonication method. The prepared SLN were characterized. The optimized PTX SLN were loaded in carbopol gel. The prepared gels were evaluated for its gelling properties and finally studied for in vivo anti-cancer efficacy and histopathological study.

Results: The particle size distribution was found to be in the range of 78.82–587.8?nm. The product yield (%) was found between 60% and 66% and showed a highest entrapment efficiency of 68.3%. The in vitro release of the drug from SLN dispersion was found to be biphasic with the initial burst effect, followed by slow release. SLN-loaded gel were subjected to permeability study and the results show steady-state flux (J_ss), permeability coefficient (K_p), and enhancement ratio were significantly increased in SLN-loaded gel formulation as compared with PTX-loaded gel. The histopathological study clearly reveals the efficacy of the SLN-F3 3G in the treatment of skin cancer.

Conclusion: The experimental formulations show controlled release of PTX and thus expected to show reduce dose-related side effects.     

Retrospective analysis for evaluation of the value of contrast-enhanced MRI in patients treated with breast conservative therapy

Purpose The aim of this study was to assess the value of contrast-enhanced (c.-e.) MRI in the follow-up of patients with conservatively treated breast cancer since detection and exclusion of malignancy may interfere significantly with posttherapeutic changes within the treated breast. Material and methods A total of 207 patients with a history of limited surgery and radiation therapy underwent MR imaging, 40 patients were examined 0–12 months and 167 patients were examined later than 12 months after radiotherapy. Suspicious or indeterminate findings were suggested by clinical examination or conventional imaging in 80 studies. In 127 women, MRI was performed within breast tissue that was difficult to assess due to scarring or dense breast tissue. Results Recurrent carcinoma was confirmed in 27 patients by surgical biopsy. All 27 carcinomas, except for one with a slow signal increase, demonstrated early rise of signal intensity on dynamic T1-weighted contrast enhanced images. During the first year after therapy, the diagnostic accuracy could not be improved by additional use of c.-e. MRI. Differentiation between posttherapeutic changes and recurrent carcinoma was frequently not possible because of strong and sometimes early and ill-circumscribed enhancement. Later than 12 months after therapy enhancement decreased significantly, thus the false positive calls could be reduced from 49 (conventional imaging) to 12 (conventional imaging plus MRI). A total of 12 of 26 recurrences and multifocality in 4/5 cases were diagnosed by MR imaging alone at this time interval. Conclusion In the first year after therapy, c.-e. MRI is only indicated in selected cases. The results later than 12 months emphasize that c.-e. MRI may contribute significant additional information. It allows better distinction of posttherapeutic fibrosis from recurrent carcinoma and proved to be able to detect recurrent disease more sensitive and at an earlier stage.     

Overexpression and elevated plasma level of tumor-associated antigen 90K/Mac-2 binding protein in colorectal carcinoma

The cancer cell secretome may contain potentially useful biomarkers. Previously, we have analyzed the colorectal carcinoma (CRC) cell secretome. In this study, tumor‐associated antigen 90K (TAA90K)/Mac‐2 binding protein (Mac‐2BP), one of the CRC cell secreted proteins, was chosen for evaluation as a potential CRC biomarker because its mRNA level was also found to be significantly elevated in CRC tissues and in a more metastatic CRC cell line from the analysis of two public domain array‐based datasets. Immunohistochemical analysis of 241 CRC specimens showed that TAA90K/Mac‐2BP was positively detected in 52.7% of the tumors, but weakly or not detected in over 95% of the adjacent nontumor epithelial cells. The plasma TAA90K/Mac‐2BP levels were significantly higher in CRC patients (N = 280) versus healthy controls (N = 147) (7.77 ± 3.49 vs. 5.72 ± 2.67 μg/mL, p<0.001). Moreover, combination of TAA90K/Mac‐2BP and carcinoembryonic antigen (CEA) could outperform CEA alone in discriminating CRC patients from healthy persons in this case‐control study. Our results collectively indicate that analysis of cancer cell secretome is a feasible strategy for identifying cancer biomarker candidates, and the TAA90K/Mac‐2BP may be a potential CRC biomarker.     

Identification of nasopharyngeal carcinoma antigens that induce humoral immune response by proteomic analysis

A proteomics-based approach has been used to identify proteins that commonly elicit a humoral immune response in nasopharyngeal carcinoma (NPC). Sera from 19 newly diagnosed NPC patients and 19 healthy individuals were analyzed for IgG autoantibodies against NPC proteins resolved by 2-DE. Protein spots that exhibited selective reactivity with sera from NPC patients were identified by MS. Among nine identified proteins, cytokeratin 19 (CK19), Erb3 binding protein (EBP1), and Rho GDP dissociation inhibitor-beta (Rho-GDI-2) induced autoantibodies in more than 36.8% of NPC patients but not in healthy individuals. Furthermore, Western blot analysis and immunohistochemical staining were performed to determine the expression and localization of CK19, EBP1, and Rho-GDI-2 in NPC and normal nasopharyngeal mucosal tissues. Up-regulated CK19 and EBP1, but not Rho-GDI-2, were observed in NPC vs. normal tissue. Subcellular localization of the three proteins in NPC tissue was same as that in the normal tissue. Thus, overexpression of CK19 and EBP1 may be one of the mechanisms for their autoantibody development in NPC. To validate the findings of a proteomic analysis, occurrence of autoantibodies against these three proteins was detected by immunoprecipitation and Western blot analysis in additional 30 NPC patients, 23 other types of cancer patients and 20 healthy individuals. Results showed that frequency of autoantibodies against CK19, EBP1 and Rho-GDI-2 in NPC patients was significantly higher than that in other types of cancer patients and healthy individuals. We conclude that CK19, EBP1 and Rho-GDI-2 may have utility in NPC screening and diagnosis.     

Contribution of laser microdissection-based technology to proteomic analysis in hepatocellular carcinoma developing on cirrhosis

Hepatocellular carcinoma (HCC) is a major cause of cancer worldwide. Proteomic studies provide opportunities to uncover targets for the diagnosis and treatment of this disease. However, in HCC developing in a setting of cirrhosis, the detection of proteome alterations may be hampered by the increased cellular heterogeneity of tissue when analysing global liver homogenates. The aim of this study was to evaluate whether the identification of proteome alterations in these HCC cases was improved when the differential protein profile between tumour and non-tumour areas of liver was determined using hepatocytes isolated by laser microdissection (LM). Differential profiles established with LM-hepatocytes and liver section homogenates using 2-DE and MS exhibited noticeable differences: 30% of the protein spots with deregulated expression in tumorous LM-samples did not display any modification in homogenates; conversely 15% of proteins altered in tumorous homogenates were not impaired in LM-hepatocytes. These alterations resulted from the presence in cirrhotic liver of fibrotic stroma which displayed a protein pattern different from that determined in LM-hepatocytes. In conclusion, our data demonstrate the interest of LM in distinguishing between fibrotic and hepatocyte proteome alterations and thus the benefit of LM to proteome studies of HCC developing in a context of cirrhosis.     

99Tcm(V)-DMSA与99Tcm-MIBI亲肿瘤显像在诊断甲状腺髓样癌中的对比

对62例甲状腺髓样癌(MTC)患者手术前行SPECT亲肿瘤显像,其中99Tcm(V)-DMSA显像组32例,99Tcm-MIBI显像组30例;并对两组患者早期和延迟影像的定性和半定量分析结果进行比较.结果显示两种显像方法对MTC原发灶诊断的阳性率无显著性差异(P＞0.05),但半定量分析结果显示99Tcm(V)-DMSA对原发灶显像的早期摄取比、延迟摄取比、滞留指数明显高于99Tcm-MIBI显像,差异有显著性(P＜0.001),提示99Tcm(V)-DMSA显像更具有优越性.     

HSP70基因在人胃癌、宫颈癌中高表达和癌变关系的研究

采用人的HSP70基因探针P17与人的胃癌、宫颈癌的癌组织中提取的RNA进行northern杂交，结果均出现了比正常组织较强的杂交信号。表明HSP70基因在癌变组织中呈现高表达，与组织的癌变程度表现出了很强的相关性，为进一步了解细胞的癌变机理和对癌症的预防及基因治疗提供了可靠的实验依据。     

DISCRETE WAVELET TRANSFORM FOR DENOISING RAMAN SPECTRA OF HUMAN SKIN TISSUES USED IN A DISCRIMINANT DIAGNOSTIC ALGORITHM

In this work, we applied the discrete wavelet transform (DWT) method as a denoising tool for dispersive Raman spectra of skin samples, and we compared the results obtained with the low-order polynomial fitting in a discriminating model based on principal components analysis (PCA). We used a set of 50 Raman spectra of skin tissue fragments diagnosed as normal (N) (25 spectra) and basocellular cell carcinoma (BCC) (25 spectra). A denoising procedure using DWT and its inverse was employed, and the resulting spectra were compared to denoising using low-order polynomial fitting and adjacent averaging smoothing. The tissue spectral profile showed changes in the intensity of bands below 1400 cm^?1 for DWT compared to the denoising by polynomial and smoothing. By applying PCA and Mahalanobis distance in both groups processed, we verified that the filtering method does not alter significantly the discrimination of N and BCC tissues. However, the DWT denoising presented an interesting result, which showed the main components after decomposition of the Raman signal used in the reconstruction.     

A nano- and micro- integrated protein chip based on quantum dot probes and a microfluidic network

A novel nano- and micro-integrated protein chip (NMIPC) that can detect proteins with ultrahigh sensitivity has been fabricated. A microfluidic network (μFN) was used to construct the protein chips, which allowed facile patterning of proteins and subsequent biomolecular recognition. Aqueous phase-synthesized, water-soluble fluorescent CdTe/CdS core-shell quantum dots (aqQDs), having high quantum yield and high photostability, were used as the signaling probe. Importantly, it was found that aqQDs were compatible with microfluidic format assays, which afforded highly sensitive protein chips for cancer biomarker assays. Electronic Supplementary Material  Supplementary material is available for this article at and is accessible for authorized users.     

miR-22-3p and miR-30e-5p Are Associated with Prognosis in Cervical Squamous Cell Carcinoma

Alteration in expression of miRNAs can cause various malignant changes and the metastatic process. Our aim was to identify the miRNAs involved in cervical squamous cell carcinoma (SqCC) and metastasis, and to test their utility as indicators of metastasis and survival. Using microarray technology, we performed miRNA expression profiling on primary cervical SqCC tissue (n = 6) compared with normal control (NC) tissue and compared SqCC that had (SqC-M; n = 3) and had not (SqC-NM; n = 3) metastasized. Four miRNAs were selected for validation by qRT-PCR on 29 SqC-NM and 27 SqC-M samples, and nine metastatic lesions (ML-SqC), from a total of 56 patients. Correlation of miRNA expression and clinicopathological parameters was analyzed to evaluate the clinical impact of candidate miRNAs. We found 40 miRNAs differentially altered in cervical SqCC tissue: 21 miRNAs were upregulated and 19 were downregulated (≥2-fold, p < 0.05). Eight were differentially altered in SqC-M compared with SqC-NM samples: four were upregulated (miR-494, miR-92a-3p, miR-205-5p, and miR-221-3p), and four were downregulated (miR-574-3p, miR-4769-3p, miR-1281, and miR-1825) (≥1.5-fold, p < 0.05). MiR-22-3p might be a metastamiR, which was gradually further downregulated in SqC-NM > SqC-M > ML-SqC. Downregulation of miR-30e-5p significantly correlated with high stage, lymph node metastasis, and low survival rate, suggesting an independent poor prognostic factor.