[p16INK4a protein is a specific molecular biomarker of breast cancer].

OBJECTIVE: To investigate the expression of p16INK4a protein in breast cancer and analyze its clinical significance. METHODS: A total of 132 surgical specimens of primary breast cancer obtained between 2014 and 2015 were examined for expressions of ER, PR, CK5/6, Her-2 and p16INK4a proteins using immunohistochemistry. RESULTS: The breast cancer samples were classified into 5 molecular subtypes, namely Luminal A (58 cases), Luminal B (32 cases), Her-2-positive (21 cases), basal-like (12 cases) and normal-like (9 cases) types. p16INK4a expression was negative in 7/132 (5.30%) cases, weakly positive in 15/132 (11.36%) cases, positive in 40/132 (30.30%) cases, and strongly positive in 70/132 (53.03%) cases. When categorizing negative and weakly positive cases into negative group and the positive and strongly positive cases into positive group, the total negative and positive expression rates of p16INK4a were 16.67% (22/132) and 83.33% (110/132) in the carcinoma tissues. Statistical analysis showed the expression intensity of p16INK4a differed significantly between the age groups (P<0.05) but was not significantly correlated with ER, PR, Her-2, molecular subtypes or metastasis of the tumors. CONCLUSION: The compensatory high expression of p16INK4a is the main mechanism of cell cycle deregulation in invasive breast cancer and can be an important specific molecular marker for invasive breast cancer.

Protective effect of intestinal ischemic preconditioning on ischemia reperfusion-caused lung injury in rats.

Intestinal ischemia reperfusion (IR) causes injury of distant critical organs. Remote intestinal ischemic preconditioning (IP) may confer the cytoprotection in critical organs including lung. The authors hypothesized that intestinal IP would be a prophylactic factor in the prevention of distant lung injury induced by IR. Rats were randomly divided into IR, IP, and Sham (S) group. Compared with IR group in the serum and lung tissue, MPO, MDA, TNF-α, and IL-1 levels were significantly decreased in the IP group. Following the same pattern, NO level in the serum and lung tissue was significantly increased in the IP group. And intestinal IP markedly abolished lung injury scores in contrast to IR group. Moreover, intestinal IP significantly attenuated caspase-3 expression, leading to the low expression of Bax and the high expression of Bcl-2. The present study showed that intestinal IP ameliorates the capacity of anti-oxygen free radical, inhibits the release of pro-inflammatory cytokines and alleviates apoptosis in IR-induced lung injury in rats. Intestinal IP may provide a novel prophylactic strategy for treatment of IR-induced lung injury.

Association between MDM2 rs 2279744 polymorphism and breast cancer susceptibility: a meta-analysis based on 9,788 cases and 11,195 controls.

PURPOSE: Previous studies have suggested associations between MDM2 (mouse double minute 2 homolog) polymorphisms and cancer risk. The aim of this study was to evaluate the relationship between the MDM2 rs 2279744 polymorphism and the susceptibility of breast cancer. METHODS: We searched PubMed, Web of Knowledge, Embase, and the Chinese National Knowledge Infrastructure (CNKI) database for case-control studies published up to October 2013 that investigated MDM2 rs 2279744 polymorphism and breast cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of these associations. RESULTS: A total of 19 studies were identified for the meta-analysis, including 9,788 cases and 11,195 controls. The variant heterozygote (TG) was associated with breast cancer risk in the overall population (TG vs TT: OR =1.10, 95% CI =1.04-1.17, P=0.001, P=0.23 for heterogeneity test). In the subgroup analyses by ethnicity, a significantly increased risk was observed among Asians (G vs T: OR =1.12, 95% CI =1.02-1.23, P=0.02, P het=0.04; GG vs TT: OR =1.29, 95% CI =1.06-1.56, P=0.01, P het=0.04; TG vs TT: OR =1.36, 95% CI =1.15-1.60, P=0.0004, P het=0.45; dominant model TG+GG vs TT: OR =1.21, 95% CI =1.03-1.41, P=0.02, P het=0.07). However, among Caucasians, rs 2279744 was associated with breast cancer risk in only one genotype (TG vs TT: OR =1.09, 95% CI =1.00-1.18, P=0.04, P het=0.37). No publication bias was found in the present study. CONCLUSION: This meta-analysis provides evidence for the association between the MDM2 rs 2279744 polymorphism and breast cancer susceptibility. The results suggest that the MDM2 rs 2279744 polymorphism plays an important role in breast cancer, especially in Asians.

[A novel histological typing and grading-scale system of colorectal cancer].

OBJECTIVE: To formulate a novel histological typing and grading-rated system for colorectal cancer (CRC) for evaluating the biological behavior of CRC and prognosis. METHODS: According to the highly heterogeneous histological features, WHO classification and histological differentiation criteria, and other biological behavior parameters of CRC, a novel histological typing and grading-scale system for CRC was designed. The histological typing and corresponding grading-scale of CRC was defined as the following: (1) No mucin-producing adenocarcinoma, including tubular adenocarcinoma, sieve-like acne adenocarcinoma, medullary carcinoma, serrated adenocarcinoma and micropapillary carcinoma, etc. (1-3 points); (2) Mucin-producing adenocarcinoma, including mucinous adenocarcinoma and signet ring cell carcinoma (3-4 points); (3) Squamous cell carcinoma (1-3 points); (4) Neuroendocrine tumors, including neuroendocrine tumors, neuroendocrine carcinoma (1-4 points); (5) The special type of CRC, including clear cell carcinoma, spindle cell carcinoma, etc. (4-points); (6) Undifferentiated carcinoma (5 points). The pathology report form was formatted based on the major histological type with the secondary histological type. The final total score of CRC was defined as the sum of the corresponding grading scores for different histological types. The total score of a single-structure CRC was defined as the corresponding grading score multiplied by 2. A total of 666 patients with advanced CRC were pathologically reviewed and analyzed to assess the correlation of the histological typing and grading scores with TNM staging and lymph node metastasis. RESULTS: The results showed a significant correlation of the histological grading-scale and TNM staging and lymph node metastasis (P<0.05). The scores of CRC histological grading-scale increased synchronously with the TNM staging and lymph node metastasis rate. CONCLUSION: The novel histological grading system allows objective evaluation of the biological behaviors and prognosis of CRC for determining individualized postoperative treatment. This system still needs further revision and updates based on evidence from prospective, multi-centered, large-scale trials.

Association between APE1 Single Nucleotide Polymorphism (rs1760944) and Cancer Risk: a Meta-Analysis Based on 6,419 Cancer Cases and 6,781 Case-free Controls.

Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential enzyme in the base excision repair pathway. Epidemiological studies have suggested associations between APE1 rs1760944 polymorphism and cancer risk. This study was aimed to evaluate the relationship between APE1 rs1760944 polymorphism and cancer risk. We searched Pubmed, ISI Web of Knowledge, Embase, Chinese National Knowledge Infrastructure (CNKI) databases until September 2013 to identify eligible studies. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to estimate the strength of the associations. 12 studies from 11 articles on APE1 rs1760944 genotypes and cancer risk were identified, including a total of 6,419 cancer cases and 6,781 case-free controls. Overall, APE1 rs1760944 polymorphism was significantly associated with the decreased risk of cancer in any genetic models (G vs. T: OR = 0.86, 95% CI = 0.82-0.90; homozygote comparison: OR = 0.74, 95% CI = 0.67-0.82; heterozygote comparison: OR =0.88, 95%CI = 0.81-0.95; dominant model TG+GG vs. TT: OR = 0.82, 95% CI = 0.76-0.89; recessive model GG vs. TT+TG: OR = 0.81, 95%CI = 0.75-0.88). In the stratified analysis by populations, the effect was remain in studies of Asian population (homozygote comparison: OR = 0.71, 95%CI = 0.63-0.79; heterozygote comparison: OR = 0.86, 95 %CI = 0.79- 0.94; dominant model: OR = 0.80, 95% CI = 0.74 -0.87 and recessive model: OR = 0.78, 95%CI = 0.71-0.86). Moreover, a significantly decreased risk was found in lung cancer studies (homozygote comparison: OR = 0.68, 95% CI = 0.59-0.79; heterozygote comparison: OR = 0.86, 95%CI = 0.77- 0.98; dominant model: OR = 0.80, 95%CI = 0.72-0.90 and recessive model: OR= 0.77, 95% CI= 0.68-0.87). These findings support that APE1 rs1760944 polymorphism has a possible protective effect on cancer susceptibility particularly among Asians. Further studies based on different ethnicity and various cancer types are warranted to verify our findings.

[Prediction and identification of B-cell linear epitopes of hepatitis B e antigen].

OBJECTIVE: To predict and identify B-cell linear epitopes of hepatitis B e antigen (HBeAg). METHODS: The B-cell linear epitopes of HBeAg were predicted using the software provided by NCBI Database and Immune Epitope Database (IEDB) and synthesized by a solid-phase method followed by conjugation with keyhole limpet hemocyanin (KLH). The KLH conjugates were used for immunization of New Zealand white rabbits, and the immune response of the rabbits was monitored by direct ELISA using a bovine serum albumin conjugate of the predicted epitopes. RESULTS Four new B-cell linear epitopes of HBeAg were identified, namely (1)MDIDPYKEFG(10), (37)LYREALESPEHCSP(50), (74)SNLEDPAS(81) and (127)RTPPAYRPPNAPIL(140). The rabbits immunized with the KLH conjugate showed an antibody titer over 1:512 000. The antisera of B-cell linear epitopes collected could specifically react with HBeAg as shown by ELISA. CONCLUSION: Four B-cell linear epitopes of HBeAg have been confirmed using bioinformatics methods, which provides new evidence for further functional studies of HBeAg in hepatitis B.

A novel tissue microarray instrumentation: the HT-1 tissue microarrayer.

BACKGROUND: Tissue microarray (TMA) is a novel and useful tool to efficiently analyze gene expression in histological tissues. AIM: Cost-efficient and easy to use automated tissue arrayers will provide a better instrumentation to generate TMAs. Thus, we designed and produced our tissue microarrayer to meet these needs. MATERIALS AND METHODS: The HT-1 tissue microarrayer we designed and manufactured consists primarily of four parts, including an instrument to make array pores for the recipient paraffin blocks, a punch needle, an instrument for negative-pressure embedding, and a special manipulator. By using the HT-1, 14 different TMAs were made to accommodate 312 cases of tissues and TMA sections were tested by hematoxylin-eosin (H&E) staining, in situ hybridization, and immunohistochemistry. RESULTS: Expand: Hematoxylin and eosin staining showed that the tissue cylinders were similar, even, and in order on the slides. Most importantly, the HT-1 microarrayer can make array pores in the recipient paraffin block with a single application in seconds. The HT-1 also contains a unique negative pressure system for embedding TMA blocks. In addition, HT-1 can make tissue cylinders with the same levels and depth for equally embedded and sectioning. CONCLUSIONS: The HT-1 tissue microarrayer is a device that is simple, economical and easy to use.

[Expression of TMEM16A in gastric carcinoma and its clinical implications].

OBJECTIVE: To investigate the expression of TMEM16A in gastric carcinoma and its clinical implications. METHODS: A total of 72 surgical specimens of gastric carcinoma were collected for examination of TMEM16A expression with immunohistochemical staining. RESULTS: TMEM16A expression was detected in the cytoplasm and cell membrane of the tumor cells. Of the 72 specimens of the tumor tissues, the total positivity rate of TMEM16A expression was 80.56% (58/72), significantly higher than the rate in the adjacent tissues (4.17%, 3/72, P<0.005). CONCLUSION: Aberrant expression of TMEM16A occurs in the majority of gastric carcinoma cases. TMEM16A can be used as a new candidate target for diagnosis and treatment of gastric carcinoma.

A giant intrathoracic osteolipoma: A case report and review of the literature.

INTRODUCTION: Lipomas are ubiquitous and can occur anywhere in the body. Intrathoracic lipomata are rare benign lesions. However, a complete removal giant intrathoracic osteolipoma is achieved with only 18 cases previous cases described in medical literature from 1960 to 2008. PRESENTATION OF CASE: A 66-year-old female presented to our hospital suffered from mild chest pain and mild shortness of breath for more than 10 days. A subsequent chest X-ray and CT scans revealed a large homogeneous, low-attenuation fat density mass containing an oval calcification area in the center of the mass. Following surgical resection was performed successfully to remove the entire mass, which weighed a total of 1568g and measured 26cm×19cm×12cm in size. The histological analysis confirmed a giant intrathoracic osteolipoma without evidence of malignancy. DISCUSSION: Intrathoracic lipomas are rare, slow-growing benign tumors without any symptom, which originate from the adipose tissue in submesothelial layers of the pleura parietalis, diaphragm, mediastinal and extrapericardial. They may extend into the chest cavity and fully encapsulate in most cases. Chest X-ray and CT and MRI scans are the most helpful tests in the diagnosis of intrathoracic lipomas. Complete enbloc removal of lipoma whenever possible, is the only definitive treatment option and the only way to prevent future recurrences. CONCLUSION: This case is the largest intrathoracic osteolipoma documented in the modern literature. Complete enbloc removal of lipoma whenever possible, is the only definitive treatment option.

[Investigation of clinical pathology and treatments on the auricle pseudocyst].

OBJECTIVE: To study the clinical pathology and treatments on the pseudocyst of auricle. METHODS: Sixty cases of auricular pseudocyst were treated by surgery from 1993 to 2008 in our hospital. Their operation effects and the clinic pathological features were analyzed. RESULTS: The clinic pathological data showed that the source of serous effusion of auricular pseudocyst origin from cartilage membrane in the top wall. In the early stage of the cyst, the top wall of auricular pseudocyst was the cartilage membrane. With the course progresses, the cartilage membrane in the top wall of auricular pseudocyst was proliferating, thickened and generated new cartilage. The new cartilage was formed from small piece to the big one, and eventually became an entire new cartilage on the top wall of auricular pseudocyst. Serous effusion at this time was terminated, and this cyst became intra-cartilaginous effusion of auricle. Finally the fluid between cartilages was absorbed and organized. In the cyst, the new cartilage and auricle cartilage were organized and adhered together each other. The auricle became thickened and deformed. The observation of capsule wall under light microscope showed that there were a few fibrous desmoplasia, anapetia and lymphocyte infiltrating in the fibrous tissue, as well as that there were cartilage cell layers from firmness to thicker. The cartilage cells and their lacunes were small, and the cartilage capsule and the basilaris substantia was showed as eosin. This data indicated that the cartilage was neogenesis but not degenerating. Sixty patients were followed up from 3 months to 1 year. The effect of surgical treatment for the auricular pseudocyst was satisfactory. There was no auricular deformation in these patients with the operation. CONCLUSIONS: Auricular pseudocyst can be divided into the early period (acute exudative period), the medium period (cartilage formation period) and the late period (proliferative and organized period). The treatment should be based on the pathological findings of auricular pseudocyst. The operation is easy, safe and reliable. The key of the operation is the complete removal of perichondrium and cartilage at the top of auricular pseudocyst.

Increased expression of collagens, transforming growth factor-beta1, and -beta3 in gluteal muscle contracture.

BACKGROUND: Gluteal muscle contracture (GMC) is a multi-factor human chronic fibrotic disease of the gluteal muscle. Fibrotic tissue is characterized by excessive accumulation of collagen in the muscle's extracellular matrix. Transforming growth factor (TGF)-beta1 and -beta2 are thought to play an important role in fibrogenesis, while TGF-beta3 is believed to have an anti-fibrotic function. We hypothesize that the expression of collagen and TGF-betas would be up-regulated in GMC patients. METHODS: The expression of collagen type I, type III and TGF-betas were studied in 23 fibrotic samples and 23 normal/control samples in GMC patients using immunohistochemistry, reverse transcription and polymerase chain reaction (RT-PCR) and western bolt analysis. RESULTS: Compared to the unaffected adjacent muscle, increased expression of TGF-beta1 and -beta3 was associated with deposition of collagen type I and type III in the fibrotic muscle of the GMC patients at the mRNA level. Strong up-regulation of these proteins in fibrotic muscle was confirmed by immunohistochemical staining and western blot analysis. TGF-beta2 was not up-regulated in relation to GMC. CONCLUSION: This study confirmed our hypothesis that collagen types I, III, TGF-beta1 and TGF-beta3 were up-regulated in biopsy specimens obtained from patients with GMC. Complex interaction of TGF-beta1 with profibrotic function and TGF-beta3 with antifibrotic function may increase synthesis of collagens and thereby significantly contribute to the process of gluteal muscle scarring in patients with GMC.

In situ expression and significance of B7 costimulatory molecules within tissues of human gastric carcinoma.

AIM: To explore the role and significance of costimulatory molecules B7H1,B7H2 and ICOS within tissues of human gastric carcinoma and the possible mechanisms in tumor escape. METHODS: mRNA expressions of costimulatory molecules including B7H1,B7H2,ICOS and B7-1 in tissues of human gastric carcinoma were investigated by in situ hybridization using digoxigenin-labeled oligonucleotide-probes. The tissue of chronic gastric ulcer was used as a control. All data were analyzed by SPSS statistic software. RESULTS: At the site of gastric carcinoma, mRNA expression levels of B7H1, B7H2 and ICOS were much higher than that of B7-1. Their mRNA positive expression indexes were 0.512+/-0.333, 0.812+/-0.454, 0.702+/-0.359 and 0.293+/-0.253, respectively. The positively stained cells were mainly tumor infiltrating lymphocytes (TILs), and some tumor cells. The difference between them was greatly significant P<0.005. The mRNA expression levels of four molecules were not correlated to the pathological grade and matastasis of gastric carcinoma. CONCLUSION: ICOS-B7H costimulatory pathway may be predominant at the site of gastric carcinoma. B7-1mRNA might be the basis of ICOS-B7H interaction. ICOS-B7H interaction induces the production of IL-10 which inhibits the antitumor immune responses. Therefore, it is supposed that ICOS-B7H costimulatory pathway may be involved in the negative regulation of cell-mediated immune responses.