胃肠道肿瘤干细胞的研究进展

近年,肿瘤干细胞作为肿瘤发生、发展的新理论正受到越来越多的关注。在多种肿瘤组织中发现和分离出肿瘤干细胞为证实肿瘤干细胞的存在和干细胞相关特性提供了理论依据。近期研究发现部分胃肠道肿瘤细胞具有干细胞特性,是胃肠道肿瘤发生、发展、逃避常规抗肿瘤治疗的重要原因,为胃肠道肿瘤的治疗提供了新的靶点。本文就肿瘤干细胞,特别是胃肠道肿瘤干细胞的研究进展作一综述。     

肿瘤干细胞的研究进展

肿瘤干细胞是指肿瘤组织中存在的一小群具有自我更新能力和多向分化潜能的细胞。肿瘤干细胞主宰着肿瘤分化、癌细胞增殖、自我更新及血管形成等诸多方面。如果能够有效抑制肿瘤干细胞,就可以从源头上阻断恶性肿瘤的发生、发展。本文对肿瘤干细胞的起源、肿瘤干细胞学说的发展、肿瘤干细胞与肿瘤异质性、转移和耐药的关系以及针对肿瘤干细胞的治疗策略等方面进行综述,为未来肿瘤的诊断和治疗提供新思路。     

肿瘤干细胞的研究进展

如何解决恶性肿瘤的复发和转移问题仍是当前肿瘤治疗中的一大难题.一种新的理论--肿瘤干细胞学说认为,在肿瘤组织中存在着少数具有干细胞性质的细胞群体,这些细胞具有自我更新能力和多向分化潜能,被称为肿瘤干细胞(cancer stem cells,CSCs);CSCs可能是导致恶性肿瘤复发和转移的根本原因.本文就CSCs分离纯化和鉴定的方法和多药耐药机制的研究进展情况进行综述.     

肝癌组织中侧群细胞的检测及初步分析

随着对肿瘤研究的不断深入及对干细胞了解的日益加深,越来越多的研究证实,一些肿瘤组织中存在肿瘤干细胞.由于没有特异性的表面标记分子,迄今为止尚无成熟的肝癌干细胞的分离与鉴定技术,从而导致对肝癌干细胞的研究举步维艰.侧群(SP)细胞有着和组织特异的肿瘤干细胞几乎相同的功能和分子特点,快速的Hoechst 33342染料排斥特性可以应用到多种肿瘤干细胞的分离和纯化中,为肿瘤干细胞研究提供了更为便利的途径.本研究采用Hoechst 33342染色法从肝癌患者的肝癌组织中分离、培养肝癌SP细胞,并对其进行初步分析,为进一步研究其生物学特性奠定基础.     

侧群细胞与肝癌干细胞

肝癌是严重威胁人类生命和健康的一种疾病.其病因和发病机制尚不完全清楚,治疗缺少有效靶点.对肝癌恶性生长、转移及复发机制的研究正在逐渐深入.近年来的研究认为,肿瘤中存在一小群具有自我更新和分化潜能的细胞,即肿瘤干细胞,可能是肿瘤转移和复发的根源.肝癌中应同样存在这样的一群细胞.侧群(side population,SP)细胞是肿瘤细胞中一小部分,具备干细胞的多种特性且易于分离.肝癌组织中SP细胞的鉴定和分离有可能找到肝癌干细胞,有助于肝癌的转移和复发机制的研究,并为肝癌治疗提供有效治疗靶点.     

肝癌干细胞的研究进展

肿瘤干细胞已经被证实存在于一些肿瘤组织中,而肝癌干细胞是否存在仍未得到确切的结果.通过实验,研究人员对于肝癌干细胞的来源提出了两个假说:成熟肝细胞的去分化与肝干细胞的"成熟受阻".目前后者是较为公认的肝癌形成途径.同时,为了得到肝癌干细胞存在的直接证据,研究人员一直致力于其表面标志物的研究,希望通过得到理想的标志物来鉴定分选出肝癌干细胞.SP细胞与肝癌干细胞的研究也是目前研究的热点.因此,肝癌干细胞的研究将会对肝癌的诊断和治疗产生重大的意义.     

结肠癌干细胞标志分子及其功能研究现状

结肠癌干细胞是一小部分存在于结肠癌中具有自我更新、无限增殖和多项分化潜能的肿瘤干细胞,它与结肠癌的复发、转移和治疗耐受有着密切的联系.通过结肠癌细胞表面表达的标志分子如CD133、CD44、CD29、ALDH1和Wnt等从结肠癌中分离得到少部分具有干细胞特性的结肠癌细胞即结肠癌干细胞,以这部分肿瘤干细胞作为肿瘤治疗靶点将为肿瘤治疗带来新的治疗方向.此文就标志分子在结肠癌干细胞筛选及生物学中的功能研究作一回顾,并探讨其作为肿瘤干细胞治疗靶点的可能性.     

甲状腺干细胞的研究进展

甲状腺干细胞是一类具有自我复制能力及具有向甲状腺细胞分化潜能的未分化细胞.近年来,关于甲状腺干细胞的研究日益成熟,已经成功地从胚胎干细胞、甲状腺成体干细胞和骨髓干细胞诱导分化出甲状腺滤泡细胞,这类细胞能够表达甲状腺特征性基因,并具有摄碘功能.甲状腺干细胞的研究为临床甲状腺疾病的治疗,特别是甲状腺干细胞移植奠定了基础.     

肿瘤干细胞与消化道肿瘤的研究进展

研究者发现肿瘤干细胞(CSC)在肿瘤的发生、发展、复发及转移过程中发挥着重要作用.CSC是存在于肿瘤组织中具有干细胞样能力的肿瘤细胞亚群,一个CSC能够产生整个肿瘤组织的(处于不同分化阶段的)所有肿瘤细胞[1].CSC概念的提出为研究肿瘤细胞的生物学特性提供了新思路,并为肿瘤的临床治疗提供了新靶点,目前已逐渐成为肿瘤防治研究的新的热点.     

浅谈甲状腺肿瘤干细胞的起源及作用

甲状腺癌是一种异质性较高的肿瘤, 主要分为低恶性程度的乳头状癌和滤泡状癌, 以及高恶性程度的未分化癌。目前, 有新的假说提出甲状腺肿瘤干细胞(thyroid cancer stem cells, TCSC)在甲状腺肿瘤的发生和转移中起重要作用, 但TCSC的发生来源及在甲状腺肿瘤发展过程中的作用尚不清楚。本文简单介绍了甲状腺癌起源的历史假说, 从干细胞角度综述了甲状腺癌起源及TCSC与免疫系统和肿瘤微环境之间的关系, 并介绍了针对TCSC的治疗策略, 这将为甲状腺癌的治疗提供新思路, 以改善难治性甲状腺癌患者的预后。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.