Correlation of AIB1 overexpression with advanced clinical stage of human colorectal carcinoma

AIB1, a member of the steroid receptor coactivator 1 family, has been cloned on 20q12 and is a candidate oncogene in human breast cancer. It is commonly amplified and overexpressed in several types of human cancers. In this study, we examined the expression of AIB1, as related to clinicopathologic features, in 85 human colorectal cancers (CRCs). The status of the number of AIB1 copies, p53 expression, and DNA ploidy was also analyzed. The overexpression of AIB1 was detected in 35% of CRCs. Amplification of AIB1 was observed in 10% of CRCs. In addition, the overexpression of AIB1 was observed more frequently in CRCs in later clinical stages (T3 N1 M0/T3 N0 2M1), compared with that in T3 N0 M0 stage (P < .05). These results suggest that overexpression of AIB1 might provide a selective advantage for the developmental growth and/or progression of subsets of CRCs. In addition, a significant correlation (P < .05) of overexpression of AIB1 with p53 overexpression as well as with aneuploid DNA content was observed in these CRCs. The overexpression of p53 was also correlated significantly with CRC DNA ploidy (P < .05). Furthermore, there was a substantial population of CRCs showing overexpression of both AIB1 and p53 protein and all had aneuploid DNA content; most of these were in the later clinical stage. These findings suggest a possible convergence of AIB1 with a pathway involving p53, which might induce chromosomal instability and affect the clinical phenotype of a subset of CRCs.     

Myc基因家族在喉癌中的异常扩增及其意义

目的探讨Ｍｙｃ基因家族在喉癌中的异常扩增及其临床意义。方法应用ＰＣＲ非变性聚丙稀酰胺凝胶电泳激光扫描技术检测了３２例喉癌组织、１２例癌旁组织和６例正常组织。结果正常组织细胞Ｍｙｃ基因无扩增，３２例喉癌中４７％（１５／３２）有Ｃｍｙｃ和Ｌｍｙｃ扩增，４１％（１３／３２）有Ｎｍｙｃ基因扩增。Ｍｙｃ基因扩增率与年龄、性别、喉癌临床分期及分化程度无关（Ｐ＞０．０５），但有淋巴结转移的患者的Ｎｍｙｃ扩增率明显高于无淋巴结转移者（Ｐ＜０．０１）。结论Ｍｙｃ基因３个成员异常扩增是喉癌发生的原因之一，Ｎｍｙｃ扩增在喉癌淋巴结转移过程中可能起正性调控作用。     

乙型肝炎病毒前C区A83突变检测及临床研究

目的　应用扩增抗拒突变系统 (AmplificationrefractorymutationssystemARMS)检测乙型肝炎病毒前C区A83突变 ,同时应用基因测序法评价其可行性 ,并探讨乙型肝炎病毒前C区A83突变与患者临床病情及血清中HBeAg表达的关系。　方法　采用ARMS对 13 9例乙型肝炎病毒感染者血清中HBVDNA前C区nt1896位点进行检测 ,并对其中 62例标本采用巢式PCR扩增HBVDNA前C区基因片段后直接测序。　结果　 62例标本中 ,ARMS检测出A83突变3 5例 ,基因测序法检测出A83突变 41例 ,A83突变例数差异无显著性 ( χ2 =1.2 3 ,P >0 .0 5 ) ;在ARMS检测的 13 9例标本中 ,HBeAg阳性标本 5 7例 ,有 5例A83突变 ,占 8.8% ,HBeAg阴性的 82例标本中有 5 6例A83突变 ,占 68.3 % ( χ2 =48.4,P <0 .0 1) ;2 2例急性肝炎 (AH )患者未检测到A83位点突变 ,79例慢性肝炎患者 (CH )有 3 1例A83位点突变( 3 9.2 % ) ,2 9例肝硬化患者 (HLC)中有 2 1例A83位点突变 ( 72 .4% ) ,9例肝癌患者 (HCC)均有A83位点突变 ( 10 0 % )。　结论　HBeAg阴性患者病毒前C区A83突变率明显高于HBeAg阳性患者 ;前C区A83突变与患者感染乙型肝炎病毒后的慢性化有关 ;ARMS检测方法简单、快速、结果可靠 ,可以满足临床对乙肝病毒前C区A83突变分析的需要。     

Hearing aids as an adjunct to counseling: Tinnitus patients who choose amplification do better than those that don't

Abstract

Hearing aids are commonly used for tinnitus management () but there is limited evidence to support their use. The purpose of this study was to quantify the effectiveness of hearing aids and counseling as a tinnitus treatment option. This study is a retrospective analysis of tinnitus handicap questionnaire (THQ, ) results from 58 tinnitus patients with hearing loss who received counseling, and (1) chose to follow recommendations of hearing aid fitting, or (2) chose not to have hearing aids. The groups (N = 29 each) had similar audiometric configuration, tinnitus duration, and age. It was hypothesized that the use of hearing aids would provide greater reduction in THQ scores than counseling alone. THQ scores were reduced 12 months following counseling but improvement in THQ only reached statistical significance for the group that received hearing aids (p < 0.0001). The hearing aid group had reduced; psychosocial handicap (p < 0.0002); and tinnitus-hearing handicap (p < 0.0005). It is concluded that patients with hearing loss and tinnitus should trial amplification.

Sumario

Los auxiliares auditivos son usados comúnmente para el manejo del acúfeno () pero existe evidencia limitada para apoyar su uso. El propósito de este estudio fue cuantificar la efectividad de los auxiliares auditivos y de la consejería como una opción de tratamiento del acúfeno. Este estudio es un análisis retrospectivo del los resultados del cuestionario de desventaja por acúfeno (TQH, Luky col, 1990) de 58 pacientes con acúfeno y con hipoacusia, que recibieron orientación, y (1) escogieron seguir la recomendación de adaptación de un auxiliar auditivo, o (2) escogieron no utilizar auxiliares auditivos. Los grupos (N = 29 cada uno) tenían configuraciones audiométricas, duración del acúfeno y edades similares. Se estableció la hipótesis de que el uso de auxiliares auditivos proporcionaría una mayor reducción en los puntajes THQ que la orientación sola. Los puntajes THQ se redujeron 12 meses después de recibir consejería, pero la mejoría en THQ sólo alcanzó significancia estadística para el grupo que utilizó auxiliares auditivos (p < 0.0001). El grupo con auxiliares auditivos tuvo un impedimento psico-social reducido (p < 0.0002) y un impedimento acúfeno-audición reducido (p < 0.0005). Se concluye que los pacientes con hipoacusia y acúfeno deberían intentar la amplificación.     

Clinical research in small genomically stratified patient populations

The paradigm of early drug development in cancer is shifting from ‘histology-oriented’ to ‘molecularly oriented’ clinical trials. This change can be attributed to the vast amount of tumour biology knowledge generated by large international research initiatives such as The Cancer Genome Atlas (TCGA) and the use of next generation sequencing (NGS) techniques developed in recent years. However, targeting infrequent molecular alterations entails a series of special challenges. The optimal molecular profiling method, the lack of standardised biological thresholds, inter- and intra-tumor heterogeneity, availability of enough tumour material, correct clinical trials design, attrition rate, logistics or costs are only some of the issues that need to be taken into consideration in clinical research in small genomically stratified patient populations. This article examines the most relevant challenges inherent to clinical research in these populations. Moreover, perspectives from the Academia point of view are reviewed as well as initiatives to be taken in forthcoming years.     

Mutation Spectrum of β-Thalassemia and Other Hemoglobinopathies in Chittagong,Southeast Bangladesh

Abstract

Thalassemia is one of the most common autosomal recessive blood disorders in the world. It shows a variety of clinical expression, starting from asymptomatic to severe blood transfusion dependence. More than 500 alleles have been characterized in or around the β-globin region. Moreover, most geographical regions have their own characteristics, frequency and availability of these alleles, predominantly circulating within the communities present in that particular region. In this study, we explored the spectrum of β-thalassemia (β-thal) alleles present in Chittagong, Southeast Bangladesh. This study comprises β-thal and Hb E (HBB: c.79?G?>?A) patients from in and around the area of Chittagong. Not only exploring the complete β-globin mutation spectrum of the area, but we also tried to look at the origin of the mutated alleles. The β-thal mutations of Bangladesh show a relatively wide spectrum of alleles, which further demonstrates the heterogeneity of the disease in this country. Although our study showed that the majority of the mutations have their origin in neighboring countries such as India, countries of Southeast Asia, Pakistan, etc., some unusual alleles do not originate in neighboring countries and put a little more diversity in the overall spectrum of β-thal-specific alleles. Overall, this study demonstrates the mutation spectrum related to β-thal in Chittagong, Southeast Bangladesh.     

Amplification of chromosome 2:Lq22.3 harboring trefoil factor family genes in liver fluke related cholangiocarcinoma is associated with poor prognosis

AIM: To determine allelic imbalance on chromosomal region 21q22-qter including trefoil factor family genes (TFF) in cholangiocarcinoma (CCA) patients and analyze the correlation between allelic imbalances and clinicopathological parameters.METHODS: Quantitative PCR amplification was performed on four microsatellite markers and trefoil factor family genes (TFF1, TFF2, and TFF3) using a standard curve and SYBR Green Ⅰ dye method. The relative copy number was determined by DNA copy number of tested locus to reference locus. The relative copy number was interpreted as deletion or amplification by comparison with normal reference range. Associations between allelic imbalance and clinicopathological parameters of CCA patients were evaluated by x2-tests.Kaplan-Meier method was used to analyze survival.RESULTS: The frequencies of amplification at D21S1890,D21S1893, and TFF3 were 32.5%, 30.0%, and 28.7%,respectively. Patients who had amplification at regions covering D21S1893, D21S1890, and TFF showed poor prognosis, whereas patients who had deletion showed favorable prognosis (mean: 51.7 wk vs 124.82 wk,P = 0.012). Multivariate Cox regression analysis revealed that amplification of D21S1893, D21S1890 and TFF,blood vessel invasion, and staging were associated with poor prognosis.CONCLUSION: D21S1893-D21S1890 region may harbor candidate genes especially TFF and serine protease family, which might be involved in tumor invasion and metastasis contributing to poor survival. The amplification in this region may be used as a prognostic marker in the treatment of CCA patients.     

Molecular and clinicopathological analysis of dermatofibrosarcoma protuberans

Dermatofibrosarcoma protuberans (DFSP) is a dermal and subcutaneous tumor of intermediate malignancy. The most remarkable cytogenetic feature of DFSP is the chromosomal translocation t(17;22)(q22;q13), causing a fusion of the platelet-derived growth factor beta chain (PDGFB) gene at 22q13, and the collagen type 1 alpha 1 (COL1A1) at 17q22. The aim of the study was to analyze the molecular characteristic of DFSP in conjunction with histopathological and clinical features.     

Chlamydia trachomatis inhibits telomeric DNA damage signaling via transient hTERT upregulation

Epidemiological data exist to support a positive association between Chlamydia trachomatis (Ctr) infection and gynecological cancers; however, putative cellular mechanisms for this association are lacking. Here, we identified Ctr-induced perturbations to host cell phenotypes in vitro that persisted after clearance of infection and could directly contribute to host cell transformation. In particular, human telomerase catalytic subunit (hTERT) mRNA expression and catalytic subunit activity were increased in acute infected late passage IMR90E1A cells. hTERT upregulation was accompanied by recruitment of ceramide, a known regulator of hTERT, to the chlamydial inclusion and was abrogated following doxycycline-mediated infection clearance. In cells cleared of Ctr infection, average telomere length was slightly increased and immunofluorescence staining of the DNA damage marker γH2A.X was reduced after clearance of infection compared with cells that had not been infected. Reduced p53 binding to the promoter of the cell cycle checkpoint regulator p21 was also detected in cells cleared of infection and p21 levels were reduced; moreover, this cell population exhibited increased resistance to etoposide-induced DNA damage. Thus, Ctr infection altered cell aging and survival pathways, which persisted after infection clearance. Cells that survive infection are likely to exhibit altered physiology, as evidenced by an increased resistance to DNA damage-induced apoptosis, which may support cellular transformation.