Prognostic and predictive value of HER2/neu oncogene in breast cancer

Assessment of HER2/neu oncogene has been used as both a prognostic and predictive marker for breast cancer. However, the choice of the best method to assess the status of HER2/neu oncogene in breast cancer tissue remains controversial. A variety of techniques are available to detect HER2/neu gene amplification and overexpression. Tissue-based detection methods by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) offers a clear advantage over other approaches. FISH is a costly and relatively difficult assay and yet appears to be a better predictor of response to Herceptin (Trastuzumab) therapy and patient outcome. IHC is less expensive and is easier to perform; however, it suffers from a high rate of false negativity and positivity as well as inter-observer variability among pathologists. Suggestions have been made to use IHC as a screening procedure followed by confirmation by FISH in selected cases. Considering the importance of an accurate assessment of HER2/neu oncogene in selecting therapy, a better alternative may be to use FISH as the primary testing for HER2/neu oncogene. Herceptin therapy is associated with several side effects and is expensive. Thus, in the long term, it may be more cost-effective to use the FISH procedure and reduce the possibility of under-treatment or over-treatment of breast cancer patients. In addition, assessment of HER2/neu oncogene on every newly diagnosed early breast carcinoma may not be necessary. Metastatic lesions, when they occur, can be sampled by fine needle aspiration biopsy or core needle biopsy for assessment of HER2/Neu status.     

Immunohistochemical Evaluation of Adaptor Protein FAM159B Expression in Normal and Neoplastic Human Tissues

FAM159B is a so-called adaptor protein. These proteins are essential components in numerous cell signalling pathways. However, little is known regarding FAM159B expression in normal and neoplastic human tissues. The commercially available rabbit polyclonal anti-human FAM159B antibody HPA011778 was initially characterised for its specificity using Western blot analyses and immunocytochemistry and then applied to a large series of formalin-fixed, paraffin-embedded normal and neoplastic human tissue samples. Confirmation of FAM159B’s predicted size and antibody specificity was achieved in BON-1 cells, a neuroendocrine tumour cell line endogenously expressing FAM159B, using targeted siRNA. Immunocytochemical experiments additionally revealed cytoplasmic expression of the adaptor protein. Immunohistochemical staining detected FAM159B expression in neuronal and neuroendocrine tissues such as the cortex, the trigeminal ganglia, dorsal root and intestinal ganglia, the pancreatic islets and the neuroendocrine cells of the bronchopulmonary and gastrointestinal tract, but also in the syncytiotrophoblasts of the placenta. FAM159B was also expressed in many of the 28 tumour entities investigated, with high levels in medullary and anaplastic thyroid carcinomas, parathyroid adenomas, lung and ovarian carcinomas, lymphomas and neuroendocrine tumours of different origins. The antibody HPA011778 can act as a useful tool for basic research and identifying FAM159B expression in tissue samples.     

山楂酸对腹泻型肠易激综合征的作用研究

本文探究了山楂酸是否对腹泻型肠易激综合征有治疗作用,实验分空白组,模型组,阳性对照组和山楂酸高、低剂量共5组,运用乙酸-束缚联合刺激法建立了大鼠腹泻型肠易激综合征模型,检测分析了粪便含水量、腹腔回缩反射、离体肠肌动力、结肠组织病理染色、5-羟色胺免疫组化等多项体内体外指标。实验结果显示在体实验中,山楂酸高剂量组可明显改善大鼠稀便状况,且可使腹腔回缩反射恢复至正常范围,作用效果与阳性药相当,低剂量的山楂酸也表现出一定作用,但效果较弱;离体实验中,五组均无病理变化;高剂量山楂酸可恢复结肠对乙酰胆碱、5-羟色胺的正常敏感度,且使5-羟色胺免疫组化反应阳性的肠嗜铬细胞减少。本研究得出,山楂酸对腹泻型肠易激综合征有一定的治疗效果,且高剂量优于低剂量。     

Trace Amine-Associated Receptor 1 (TAAR1) Is a Positive Prognosticator for Epithelial Ovarian Cancer

Trace amine-associated receptor 1 (TAAR1) is a G_αs- protein coupled receptor that plays an important role in the regulation of the immune system and neurotransmission in the CNS. In ovarian cancer cell lines, stimulation of TAAR1 via 3-iodothyronamine (T₁AM) reduces cell viability and induces cell death and DNA damage. Aim of this study was to evaluate the prognostic value of TAAR1 on overall survival of ovarian carcinoma patients and the correlation of TAAR1 expression with clinical parameters. Ovarian cancer tissue of n = 156 patients who were diagnosed with epithelial ovarian cancer (serous, n = 110 (high-grade, n = 80; low-grade, n = 24; unknown, n = 6); clear cell, n = 12; endometrioid, n = 21; mucinous, n = 13), and who underwent surgery at the Department of Obstetrics and Gynecology, University Hospital of the Ludwig-Maximilians University Munich, Germany between 1990 and 2002, were analyzed. The tissue was stained immunohistochemically with anti-TAAR1 and evaluated with the semiquantitative immunoreactive score (IRS). TAAR1 expression was correlated with grading, FIGO and TNM-classification, and analyzed via the Spearman’s rank correlation coefficient. Further statistical analysis was obtained using nonparametric Kruskal-Wallis rank-sum test and Mann-Whitney-U-test. This study shows that high TAAR1 expression is a positive prognosticator for overall survival in ovarian cancer patients and is significantly enhanced in low-grade serous carcinomas compared to high-grade serous carcinomas. The influence of TAAR1 as a positive prognosticator on overall survival indicates a potential prognostic relevance of signal transduction of thyroid hormone derivatives in epithelial ovarian cancer. Further studies are required to evaluate TAAR1 and its role in the development of ovarian cancer.     

In Vivo Examination of an Injectable Hydrogel System Crosslinked by Peptide–Oligosaccharide Interaction in Immunocompetent Nude Mice

Hydrogels can serve as matrices to mimic natural tissue function and be used for wide‐ranging applications such as tissue regeneration and drug delivery. Injectable hydrogels are particularly favorable because their uses are minimally invasive. However, creating moldable substance for injection often results in compromised function and stability. This study reports an injectable hydrogel system crosslinked by peptide–oligosaccharide noncovalent interaction. The dynamic network shows fast self‐healing, a property essential for injectability. Injected hydrogels in immunocompetent mice and release of encapsulated compound are monitored up to 9 months by magnetic resonance imaging (MRI) and optical imaging. This surprisingly stable hydrogel does not cause adverse inflammatory response, as analyzed by measuring cytokine levels, immunohistochemistry, and MRI. Hydrogel degradation is associated with invasion of macrophages and vascular formation. The facile synthesis, high biocompatibility, and stability of this injectable hydrogel can lead to various experimental and clinical applications in regenerative medicine and drug delivery.     

小鼠睾丸发育过程中Caspase-3蛋白的表达规律

为探讨Caspase-3蛋白在小鼠睾丸生后发育全过程中的表达规律,以17组出生后不同发育阶段的昆明种正常小鼠睾丸组织为材料,在其石蜡组织切片上进行Caspase-3蛋白的免疫组化检测;同时部分时段实施Caspase-3基因的DNA-mRNA原位杂交检测.结果发现Caspase-3蛋白在生后1 d直至57 d的小鼠睾丸组织中均有表达,在细胞核中的表达主要涉及精原细胞,而在细胞质中的表达则涉及初级精母细胞、次级精母细胞、精子细胞等多种细胞类型.上述结果表明小鼠睾丸生后发育过程中各级生精细胞内均有Caspase-3蛋白存在,但并不意味着这些细胞均会发生凋亡,Caspase-3蛋白的活性表达可能仅主要涉及精原细胞.     

Differential Expression of Peroxisomal Proteins in Distinct Types of Parotid Gland Tumors

Salivary gland cancers are rare but aggressive tumors that have poor prognosis and lack effective cure. Of those, parotid tumors constitute the majority. Functioning as metabolic machinery contributing to cellular redox balance, peroxisomes have emerged as crucial players in tumorigenesis. Studies on murine and human cells have examined the role of peroxisomes in carcinogenesis with conflicting results. These studies either examined the consequences of altered peroxisomal proliferators or compared their expression in healthy and neoplastic tissues. None, however, examined such differences exclusively in human parotid tissue or extended comparison to peroxisomal proteins and their associated gene expressions. Therefore, we examined differences in peroxisomal dynamics in parotid tumors of different morphologies. Using immunofluorescence and quantitative PCR, we compared the expression levels of key peroxisomal enzymes and proliferators in healthy and neoplastic parotid tissue samples. Three parotid tumor subtypes were examined: pleomorphic adenoma, mucoepidermoid carcinoma and acinic cell carcinoma. We observed higher expression of peroxisomal matrix proteins in neoplastic samples with exceptional down regulation of certain enzymes; however, the degree of expression varied between tumor subtypes. Our findings confirm previous experimental results on other organ tissues and suggest peroxisomes as possible therapeutic targets or markers in all or certain subtypes of parotid neoplasms.     

Periostin Expression and Its Prognostic Value for Colorectal Cancer

Integrin is important for cell growth, invasion and metastasis, which are frequently observed in malignant tumors. The periostin (POSTN) gene encodes the ligand for integrin, one of the key focal adhesion proteins contributing to the formation of a structural link between the extracellular matrix and integrins. High expression levels of the POSTN gene are correlated with numerous human malignancies. We examined POSTN protein in colorectal cancer specimens from 115 patients by strictly following up using immunohistochemistry. Cytoplasm immunohistochemical staining showed POSTN protein expression in colorectal cancers. The positive expression rate of POSTN protein (59.13%, 68/115) in colorectal cancers was significantly higher than that in adjacent normal colon mucosa (0.47%, 11/109). POSTN over-expression in colorectal cancers was positively correlated with tumor size, differentiation, lymph node metastasis, serosal invasion, clinical stage and five-year survival rates. Further analysis showed that patients with advanced stage colorectal cancer and high POSTN expression levels had lower survival rates than those with early stage colorectal cancer and low POSTN expression levels. Overall, our results showed that POSTN played an important role in the progression of colorectal cancers.     

Androgen Receptor Signaling Induces Cisplatin Resistance via Down-Regulating GULP1 Expression in Bladder Cancer

The underlying molecular mechanisms of resistance to cisplatin-based systemic chemotherapy in bladder cancer patients remain to be elucidated, while the link between androgen receptor (AR) activity and chemosensitivity in urothelial cancer has been implicated. Our DNA microarray analysis in control vs. AR knockdown bladder cancer lines identified GULP1 as a potential target of AR signaling. We herein determined the relationship between AR activity and GULP1 expression in bladder cancer cells and then assessed the functional role of GULP1 in cisplatin sensitivity. Androgen treatment in AR-positive cells or AR overexpression in AR-negative cells considerably reduced the levels of GULP1 expression. Chromatin immunoprecipitation further showed direct interaction of AR with the promoter region of GULP1. Meanwhile, GULP1 knockdown sublines were significantly more resistant to cisplatin treatment compared with respective controls. GULP1 knockdown also resulted in a significant decrease in apoptosis, as well as a significant increase in G2/M phases, when treated with cisplatin. In addition, GULP1 was immunoreactive in 74% of muscle-invasive bladder cancers from patients who had subsequently undergone neoadjuvant chemotherapy, including 53% of responders showing moderate (2+)/strong (3+) expression vs. 23% of non-responders showing 2+/3+ expression (P = 0.044). These findings indicate that GULP1 represents a key downstream effector of AR signaling in enhancing sensitivity to cisplatin treatment.