染色体脆性位点抑癌基因与肿瘤关系的研究进展

近年来,对多种肿瘤组织和正常组织的对比研究发现,染色体脆性位点抑癌基因的减少和缺失与肿瘤的发生密切相关,其具体的作用机制尚待进一步研究明确.但其对肿瘤生物学行为的影响具有一定的临床应用价值.笔者就染色体脆性位点抑癌基因的结构和功能,可能的作用机制以及与肿瘤的发生、发展的相关研究进展进行综述,并对未来的研究前景进行展望.     

RNAi与肿瘤相关基因及在肿瘤治疗中的研究

RNA干扰（RNA interfcrence,RNAi）,是一种在动植物中广泛存在的通过双链RNA分子在mRNA水平上诱导特异性序列基因沉默的过程,随着对RNAi研究的不断深入,其作用机制正在逐步被阐明;同时作为阻断基因表达的新手段,RNAi技术也日趋完善和成熟。而恶性肿瘤基因学说也越来越得到重视,肿瘤相关基因的研究更加细致深入。本文就RNAi技术的基本原理、肿瘤相关基因的概念以及RNAi技术在肿瘤尤其是泌尿系肿瘤相关基因研究中的应用作一综述。     

膀胱癌相关蛋白基因(BLCAP)研究进展

恶性肿瘤一直是引起医学界极其关注,严重危害人类的主要疾病.近年来基因靶向治疗成为一种崭新的生物治疗手段,优化并发展了传统的治疗方法,给肿瘤患者予以新的希望.目前,人们研究肿瘤的热点已经从癌基因转到抑癌基因,在众多抑癌基因中BLCAP是一个新近发现的与膀胱癌、骨肉瘤、宫颈癌等相关的抑癌基因.兹就此BLCAP基因做一综述.     

MicroRNA在恶性肿瘤发生发展中所起作用的研究现状

笔者就MicmRNA在恶性肿瘤发生发展中所起作用的研究现状进行综述.主要内容包括:阐述MicmRNA的牛物学特性和牛物功能,MicmRNA作为癌基因和抑癌基因与肿瘤发生的关系.MicroRNA及上皮细胞-间质转化与肿瘤侵润转移的关系.     

基于癌症和肿瘤基因图谱筛选低级别胶质瘤中潜在抑癌基因的研究

目的基于癌症和肿瘤基因图谱(TCGA)计划数据库的胶质瘤标本信息,探讨较低级别胶质瘤标本中相对低表达的基因与患者预后的关系。方法在TCGA数据库中选取678例胶质瘤患者[包括低级别胶质瘤(LGG)患者512例,胶质瘤母细胞瘤(GBM)166例]的698例胶质瘤标本[包括LGG患者529例,GBM169例]以及5例正常脑组织,分析其基因表达水平数据以及患者的临床资料。用R软件分析筛选在肿瘤中低表达的基因,对其进行基因注释和基因功能富集分析,用STRING和蛋白交互作用分析(Cytoscape)软件构建蛋白相互作用网络,以R软件根据基因表达水平结合患者的临床资料进行生存分析。结果在正常脑组织和胶质瘤标本、LGG和GBM组织均低表达的基因为155个;蛋白互相作用关系中连通性值最大的前20位基因中,得到12个基因的功能富集数据,谷氨酸离子型受体NMDA可能为重要的肿瘤生长信号通路之一。生存分析结果显示,12个基因中有7个基因与患者的生存预后改善有关,差异均有统计学意义(均P<0.05)。结论基于TCGA挖掘数据是一种有效的探索肿瘤抑癌基因的生物信息手段;谷氨酸离子型受体(NMDA)家族可能与胶质瘤的生长和预后明显相关。     

抑癌基因PTEN/MMAC1/TEP1及其在肿瘤中的突变

正常细胞和肿瘤细胞的蛋白质磷酸化及去磷酸化研究一直引人注目。研究表明 ,细胞内蛋白质酪氨酸磷酸化水平受酪氨酸蛋白激酶 (tyrosine proteinkinase,TPK)和蛋白质酪氨酸磷酸酶 (protein tyro-sine phoshatase,PTP)共同调控。多种癌基因的表达产物具有 TPK活性并参与肿瘤形成过程 ,提示PTP可能抑制肿瘤形成。而最近发现的抑癌基因PTEN[1] /MMAC1 [2 ] /TEP1 [3 ] (以下简称 PTEN)编码的蛋白具有双重特异性磷酸酶 (DSP)活性和 PTP活性 ,对 PTEN的定位克隆及功能研究有望给细胞分化发育和肿瘤的分子生物学研究注入新的活力。…     

胰腺癌癌基因和抑癌基因的研究进展

胰腺癌是较难诊断、较难治疗、预后较差的消化系统恶性肿瘤之一.随着分子生物学和现代遗传学的发展,人们已经认识到肿瘤的发生发展是基因改变,即癌基因激活和抑癌基因失活的结果.近年来有关胰腺癌癌基因、抑癌基因的研究取得了较大进展.     

Period1基因功能与肿瘤抑制

Period 1(Per1)基因是Period基因家族的主要成员,是调节机体生理节奏的核心基因.最新研究显示其在肿瘤抑制过程中发挥着重要作用.笔者就近年来关于该基因的结构、功能及其肿瘤抑制作用等方面的研究作一综述.     

MTA家族与乳腺癌关系的研究进展

MTA基因家族是一类重要的肿瘤转移相关基因,它们主要参与组蛋白去乙酰基酶(nucleosome remodeling deacetylase,NuRD) 的组成.组蛋白去乙酰基酶具有核小体重塑活性,对基因转录有抑制作用,并能通过调节雌激素通路途径促进乳腺肿瘤的侵袭和转移,故与乳腺癌关系密切,是研究乳腺癌转移机制和治疗的新靶点.     

p28GANK与肿瘤恶性生物学行学研究进展

肿瘤的恶性生物学行为由多种肿瘤相关基因协同发生作用。p28GANK最初是在肝癌细胞中通过cDNA文库经消减杂交法克隆而获得的肝癌差异表达基因,包括7个ankyrin结构,在哺乳动物中高度保守。研究发现p28GANK在肝癌、食管癌、结肠癌及肺癌等恶性肿瘤中普遍高表达,并可以通过调节肿瘤相关蛋白分子Rb、p53、MDM2等发挥恶性生物学作用,在消化道恶性肿瘤的病理诊断、预后判断具有潜在应用前景,同时也可能成为恶性肿瘤分子靶向治疗的潜在靶点。     

Fox–Fordyce-like disease following laser hair removal appearing on all treated areas

Fox–Fordyce disease is an uncommon inflammatory disease of the apocrine sweat glands. Two recent reports indicated laser hair removal as a novel cause of axillary Fox–Fordyce disease. We report the first case of Fox–Fordyce disease developing in women after completing treatment with a depilatory hair laser appearing in the axillae, umbilicus, and pubis. We describe a case of Fox–Fordyce disease that developed in a 27-year-old woman 3 months after she had completed two LightSheer Diode laser treatments of her axilla, periumbilical region, and bikini area. Clinical and histopathological changes are as well detailed. Laser therapy induces damage to follicular infundibulum, resulting in altered maturation of keratinocytes which led to keratin plugging causing the common pathologic features in Fox–Fordyce disease. Differences in the physiologic features of the anatomic sites, in the susceptibility to laser-induced injury among these areas, or additional factors may contribute to Fox–Fordyce disease.     

Results of Long-Term Follow-Up Observations of Blepharoptosis Correction Using the Palmaris Longus Tendon

BACKGROUND: The frontalis sling procedure is a useful approach for correcting severe blepharoptosis. However, blepharoptosis often recurs after corrective surgery using the tensor fascia lata. Good results without recurrence after a modified Fox method were obtained using the palmaris longus tendon. This study examined the safety and validity of the surgical method using the palmaris longus tendon through long-term follow-up observations. METHODS: To reduce the rate of recurrence, the highest point on the pentagon of the Fox method was fixed to the frontalis fascia and frontalis muscle. It was fixed once again to the area 1 cm above the highest point. This approach remarkably reduces the incidence of recurrence by fixing the pentagon of the Fox method not only to the palmaris longus tendon but also to the frontalis fascia and again to the frontalis muscle. A modified Fox method using the palmaris longus tendon was used to treat 16 eyelids of 10 patients. A senior surgeon performed the procedure in all cases under local anesthesia. RESULTS: The mean follow-up period was 51 months (range = 18-86 months). There was no case of blepharoptosis recurrence and a good field of view was secured after surgery. Long-term follow-up revealed that the visual field had been well secured with a mean MRD1 of 3.1 mm. The eyelids were well maintained without any postoperative adverse reaction such as exposure keratitis. CONCLUSION: The palmaris longus tendon as useful donor material does not lead to recurrence of blepharoptosis, which is often encountered when the tensor fascia lata is used. The modified Fox method using the palmaris longus tendon can be an effective and valid surgical approach that produces both immediate and long-term results.     

Effect of hyperinsulinemia and hyperglycemia on intracellular glucose and fat metabolism in healthy subjects

Hyperinsulinemia and hyperglycemia per se both stimulate glucose uptake and the disposal of glucose by oxidative (Gox) and nonoxidative (Nox) metabolism. However, the intracellular metabolic fate of glucose may not be the same when glucose uptake is stimulated predominantly by either of these mechanisms due to different effects on fat oxidation (Fox). To address this issue, 11 healthy subjects each had four glucose-clamp studies performed in combination with indirect calorimetry to compare Gox, Nox, and Fox at two different rates of glucose uptake (approximately 7 and 10 mg.kg-1 fat-free mass [FFM].min-1) matched at each level by either hyperglycemia or hyperinsulinemia. When glucose uptake was matched at the lower rate (7 mg.kg-1 FFM.min-1), there was less suppression of both FFA (33 vs. 43%, P less than 0.05) and Fox (73 vs. 90%, P less than 0.05) and less stimulation of incremental (above basal) Gox (1.95 vs. 2.49 mg.kg-1 FFM.min-1, P less than 0.025) at low insulin (72 pM) and hyperglycemia (21.8 mM) compared with high insulin (280 pM) and euglycemia (5.1 mM). Matching glucose uptake at the higher rates (10 mg.kg-1 FFM.min-1) required greater than 300 pM of insulin (309 and 632 pM) in both studies and resulted in maximal suppression of FFA (49 vs. 46%, NS) and Fox (both greater than 90%, NS) and similar incremental Gox (2.89 vs. 2.73 mg.kg-1 FFM.min-1, NS) whether at hyperglycemia (15.7 mM) or euglycemia (5.2 mM). Therefore, both hyperinsulinemia and hyperglycemia stimulate glucose uptake and increase intracellular glucose availability, but insulin also regulates Gox by suppression of FFA and Fox. However, when FFA and Fox are maximally suppressed, the rate of glucose uptake, rather than the prevailing insulin level, determines the distribution of intracellular glucose metabolism.     

Successful treatment of areolar Fox‐Fordyce disease with surgical excision and 1550‐nm fractionated erbium glass laser

Fox‐Fordyce disease (FFD) is a rare chronic disorder characterised by persistent inflammation because of the obstruction of apocrine sweat glands, which is a key factor of pathogenesis. The treatment of FFD is known to be difficult, and the modalities of treatment have not yet been widely studied. We report the successful treatment of a case of bilateral areolar FFD by a combination of surgical excision and 1550‐nm fractionated erbium glass laser in an 18‐year‐old woman. The patient presented with a bilateral areolar eruption of multiple, severely pruritic, 3–4 mm skin‐ to grey‐coloured folliculocentric dome‐shaped papules. The initial treatment plan was for bilateral surgical excision of the larger and more highly elevated papules via circumferential dermal excision, which was intended to maintain the areolar contour and minimise distortion. A 1550‐nm fractional erbium glass laser was then used to control the remnant lesions. The patient was recurrence‐free at 14 months after the final laser treatment, and she was fully satisfied with the treatment results.     

邻苯二甲酸酯类化合物与睾丸源性生殖障碍综合征

流行病学研究显示妇女在怀孕期间接触邻苯二甲酸酯类化合物后,所产男婴易患隐睾、尿道下裂、成年期睾丸肿瘤及精液质量低下等症状。这类症状可统称为睾丸源性生殖障碍综合征(testicular dysgenesis syndrome,TDS)。TDS可能是由男性胎儿睾丸的发育在子宫内受到影响不能发育出具有正常功能的睾丸间质(Leydig)细胞和支持(Sertoli)细胞引起的。例如,睾丸间质细胞接触邻苯二甲酸酯类化合物后,睾丸间质细胞的两种产物———睾酮和胰岛素样生长因子3(INSL3)———受到了抑制,两者对于睾丸下降起关键作用。成年期睾丸的胎儿型间质细胞和支持细胞错位可能是精子生成减少的原因。     

Local Recurrence After Mastectomy for Ductal Carcinoma In Situ

Abstract: Local recurrence after mastectomy for invasive cancer generally carries a poor prognosis. Local recurrence after mastectomy for ductal carcinoma in situ (DCIS) is rare and its impact on survival is unknown. Sixty-eight patients were treated with mastectomy for DCIS at the Fox Chase Cancer Center between 1985 and 1996, and only one of these developed a chest wall recurrence. An additional five patients treated with mastectomy at other institutions and referred to Fox Chase after local recurrence were also identified. These six patients had only DCIS as their primary pathology. Four of the six patients were premenopausal (median age 42 years). The median interval to local recurrence was 5.0 years (2.8–9.3 years). The median follow-up from initial diagnosis was 10.5 years (4.3–26.7 years) and 5.2 years (1.4–17.6 years) from recurrence. All of the recurrences were invasive and treatment included wide local excision with radiotherapy in all of the patients followed by adjuvant chemotherapy for the premenopausal patients. None of the patients had metastatic disease at presentation. The disease-free survival from initial recurrence was 83% and 63% at 5 and 10 years, respectively. The 5- and 10-year survival following local recurrence was 80%. One patient died 3.6 years after recurrence with metastatic disease, while a second patient developed metastatic disease 11.8 years after her initial recurrence. The remaining four patients are alive (NED), ranging from 1.4 to 10.7 years following their local recurrence. Local recurrence following mastectomy for DCIS is rare, usually invasive, and may have a long interval to failure. Salvage using conventional multimodality therapy appears to result in long-term survival.     

Analysis of staging and management of patients with sarcoma: a ten-year experience.

Over ten years, 70 patients with soft tissue sarcoma were treated for their primary tumors at the hospital of The Fox Chase Cancer Center. The clinical characteristics of these tumors are correlated with the outcome of various management efforts. The results of these evaluations identify three groups that can provide the basis for future treatment decisions and stratification for randomized studies of management options. The first group of patients, those with small well differentiated tumors, have no systemic spread regardless of the treatment modality used. The second group, those with large (greater than 5 cm) tumors that are moderately or poorly differentiated, do uniformly poorly despite the management techniques used. An intermediate group, those with high grade or large size but not both, have outcomes which may be correlated to treatment modalities.     

Running patterns of transfemoral amputees: a clinical analysis

The challenge of rehabilitating young, healthy transfemoral amputees may extend beyond the boundaries of teaching them to adapt to functional activities of daily living. The goal for several of these amputees is to participate and sometimes even compete in recreational activities, including running. These amputee runners require prosthetic adaptations as well as a comprehensive individualized training programme to ensure that their running is as safe and energy efficient as possible. To help amputees achieve this, clinicians must understand normal and prosthetic locomotion. This paper compares the biomechanical differences between walking and running in normal locomotion and analyses the running modes used by transfemoral amputees. The modified running mode achieved with the Terry Fox Running Prosthesis subjectively "looks" more energy efficient to the observer and "feels" more energy efficient to the user. These assumptions have yet to be confirmed or refuted by a rigorous scientific research study. An outline of the proposed physiotherapy protocol includes the familiarization, treatment, and training phases. Physiotherapists involved in amputation rehabilitation may not be commonly confronted with this level of patient expectation. It is their responsibility to give realistic guidance to these amputees so that they can safely and independently pursue their recreational running activities. This need can best be fulfilled by providing sound clinical advice which has been validated by research findings.     

The public's willingness to discuss their preference for organ donation with family members

We sought to assess the public's willingness to discuss their preference for organ donation with family members and to identify factors associated with willingness to discuss donation. We categorized individuals (N = 4365) with a preference for donation according to their willingness to discuss donation and used ordinal logistic regression analysis to identify factors related to their level of willingness. About half of those who want to donate have discussed this with a family member. Others were at various stages with respect to their commitment to discuss donation. Those in the more committed stages were more likely than others to have signed an organ donor card, to have seen information about organ donation, to be male, to be white or Hispanic, to know about donation issues, and to be comfortable with the idea of their own death. The decision to donate is ultimately made by family members of a suitable candidate for donation, yet nearly half of those who wish to donate have not made their wishes known. Interventions targeted to individuals at different stages of commitment are needed so that more family members can respond in accordance with their loved one's wishes.     

Blood vessel stem cells and wound healing

This article continues the Journal's "Scientific Surgery" series of leaders. The aim of the series, published throughout 2005, has been to highlight areas of bioscience that, while still largely confined to the experimental laboratory, may soon be brought into the clinical domain. In this month's paper Watt and Fox offer an up to date insight into the processes of tissue healing and suggest possible future therapeutic strategies.