肿瘤微环境的细胞成分在结直肠癌肝转移中的研究进展

结直肠癌是以高发病率和高死亡率为特征的消化系统恶性肿瘤，肝脏是结直肠癌最常见的转移部位。近年来结直肠癌肝转移的综合治疗虽得到广泛发展，但许多方案的使用对晚期患者预后仍不尽如人意，结直肠癌肝转移发生发展中的作用机制和针对性的治疗手段仍需进一步探索。肿瘤微环境已被证明在结直肠癌肝转移中发挥重要作用，而其中肿瘤微环境相关细胞的作用不可忽视，由于肿瘤微环境内的相关细胞在遗传上是稳定的，因此可能成为一种有吸引力的治疗靶点。有关肿瘤微环境相关细胞与结直肠癌肝转移关系的相关报道日益增多，现就近年来肿瘤微环境中的细胞成分与结直肠癌肝转移的研究进展作一综述。     

高龄结直肠癌肝转移Ⅰ期手术切除患者的围手术期处理

结直肠癌是常见的消化道肿瘤.对于结直肠癌肝转移患者许多人主张对原发灶和转移灶分次切除[1].但有研究表明,结直肠癌肝转移患者积极Ⅰ期切除原发肿瘤和肝脏转移癌的手术并发症少,在死亡率方面与分次切除无显著差异;     

CCL2表达与同时性结直肠癌肝转移的相关性分析

目的观察结直肠癌原发瘤CCL2表达与同时性结直肠癌肝转移的相关性。 方法检索1999年1月至2003年12月中国医学科学院肿瘤医院临床病理资料完整的结直肠癌病例,最终197例纳入研究。其中对照组104例,同时性肝转移组93例。对照病例定义为结直肠癌术后随访5年以上没有复发转移者。采用免疫组织化学法检测结直肠癌原发瘤CCL2表达,单因素和多因素分析CCL2和临床病理因素与结直肠癌肝转移的相关性。 结果多因素分析显示,肿瘤大小、淋巴结分期、CEA和CCL2表达是预示结直肠癌肝转移的独立危险因素(P<0.05),CCL2高表达者肝转移风险是低表达者的5.828倍(95% CI：2.212～15.355)。CCL2与其他临床病理因素的相关性分析表明,CCL2表达仅与肝转移相关(P<0.05),与肿瘤浸润深度、淋巴结分期和CEA均未见统计学差异(P>0.05)。 结论同时性结直肠癌肝转移与肿瘤大小、淋巴结分期、CEA和CCL2表达密切相关。结直肠癌肝转移中CCL2的作用机制可能与常见临床病理因素不同。     

结直肠癌肝转移评估方法的研究进展

结直肠癌的发病率近年来呈明显上升趋势。肝转移是结直肠癌患者死亡的主要原因之一,对其进行早期诊治是提高患者生存率的重要手段。结直肠癌肝转移是一个多步骤参与的过程,涉及诸多基因、分子的变化,对相关物质进行检测,有助于早期评估结直肠癌肝转移的风险。本文就结直肠癌肝转移评估方法的研究进展作一综述。     

结直肠癌寡转移的放射治疗策略

结直肠癌寡转移是目前研究的重要领域之一。肝转移、肺转移及多部位寡转移的立体定性放射治疗研究逐步开展。直肠癌寡转移患者的盆腔放疗,国际上已经形成了推荐转移性直肠癌接受盆腔放疗的多学科共识。     

结直肠癌肝转移的手术治疗进展

肝转移是结直肠癌患者的主要死亡原因之一。15％～25％的结直肠癌患者在发现原发灶的同时确定有肝转移,另外有25％的结直肠癌患者将来会出现异时性肝转移,其中20％-35％的患者肝脏为惟一转移部位。孤立性肝脏转移未经治疗的结直肠癌患者中位生存期为5～9个月。不过,临床上发现,某些比较早期的结直肠癌就已出现肝转移,分化比较好的结直肠癌似乎更容易发生肝转移。因此,结直肠癌出现肝转移并不意味着失去治愈机会。目前手术切除仍然是结直肠癌肝转移的主要治疗手段。现将其手术治疗进展情况综述如下。     

结直肠癌肝转移同期肝切除的原则剖析

结直肠癌(CRC)是常见的消化系统恶性肿瘤,其发病率及病死率逐年升高,肝脏是其最常见转移部位。手术治疗是目前治疗结直肠癌肝转移最有效的方法。对于结直肠癌肝转移同期肝切除的手术时机的选择一直是外科医生争论的话题。诸如围手术期化疗或者一些其他新的方法,都可以影响手术时机的选择。随着对结直肠癌肝转移研究的不断深入以及外科手术技巧的不断进步,目前对于同期肝切除的原则仍在很大程度上依赖于新辅助化疗、外科医生对于可切除性的判断以及病人的体质。笔者综述了近些年来对于结直肠癌肝转移同期肝切除的原则剖析,并加以分析。     

人结肠鳞癌直肠鳞腺癌SCID鼠原位移植高转移模型的建立及生物学特性的研究

目的建立人结肠鳞癌直肠鳞腺癌SCID鼠原位移植高转移模型,为探讨理想的治疗结直肠癌肝转移和预防结直肠癌根治术后肝转移的方法提供实验工具.方法采用组织学完整的结直肠癌手术标本植入SCID鼠结直肠(粘膜层)壁内,观察原位移植的成瘤、移植瘤的侵袭和转移及其形态学特性(光镜、电镜、免疫组织化学).结果两株人结直肠癌SCID鼠均获原位移植成功.人直肠鳞癌SCID鼠原位移植模型HCS-HMN-1已传至19代,人直肠鳞腺癌SCID鼠原位移植模型HRSA-HMN-2已传至23代,共移植SCID鼠223只,其移植生长率和自发转移率及液氮冻存复苏成活率均为100%,移植瘤在结直肠内呈广泛原位侵袭性生长、淋巴结转移、肝转移和全腹腔癌病.并具有分泌CEA的功能.移植瘤细胞病理学和电镜观察、流式细胞仪DNA含量检测及染色体核型分析与瘤源人结直肠癌细胞完全一致.结论本研究所建立的两株人结直肠癌SCID鼠高转移模型完整模拟了人结直肠癌侵袭和转移的临床过程,为进一步研究结直肠癌肝转移治疗和预防结直肠癌根治术后肝转移的方法提供了理想的实验动物模型.     

术前血清CEA、CA19-9、CA50联合检测在结直肠癌肝转移预测中的应用

目的研究术前血清CEA、CA19-9、CA50联合检测在结直肠癌肝转移预测中的应用价值。 方法选择2015年1月至2017年1月在中国医学科学院肿瘤医院接受手术治疗的结直肠癌患者316例为研究对象,其中结直肠癌伴有肝转移的患者158例作为实验组,并按照性别、年龄等匹配结直肠癌不伴有肝转移的患者158例作为对照组。对所有患者的术前血清癌胚抗原（CEA）、糖类抗原19-9（CA19-9）以及糖类抗原50（CA50）进行检测,采用单因素及多因素分析以上肿瘤标志物单独或联合检测在结直肠癌肝转移中的预测价值。 结果单因素及多因素分析结果表明,术前血清CEA、CA19-9、CA50升高与结直肠癌发生肝转移显著相关（P<0.05）,CEA、CA19-9、CA50单独预测结直肠癌肝转移的敏感度分别为62.7%、57.4%、67.1%;特异度分别为58.2%、53.5%、56.6%。CEA、CA19-9、CA50联合诊断预测直肠癌肝转移的敏感度和特异度分别为74.3%、76.3%。 结论术前血清CEA、CA19-9、CA50升高是结直肠癌肝转移的独立预测因素,但三者单独预测结直肠癌肝转移的敏感度和特异度均较低。三者联合检测对于预测结直肠癌肝转移的敏感度和特异度均较高,可以作为结直肠癌肝转移的预测模型。     

MACC1在肿瘤发生、发展中的作用及其表达调控机制

结肠癌转移相关基因1(MACC1)是新近发现的与结直肠癌转移密切相关的基因之一,在其他肿瘤转移中也发挥了重要作用。一些细胞信号转导通路或生物分子可能参与了MACC1的表达调控以及MACC1促进肿瘤侵袭转移的相关机制。然而,目前对MACC1的表达调控机制和通路尚未完全阐明。本文就MACC1在肿瘤发生、发展中的作用及其表达调控机制作一综述。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

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.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

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.     

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.     

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.