胰腺癌的非手术治疗进展

胰腺癌是一种发病隐匿、进展迅猛且预后极差的恶性肿瘤,治疗以外科手术、化疗和放疗相结合的综合治疗为主,但疗效有限。随着治疗技术的发展以及对胰腺癌分子机制的研究进展,非手术治疗新策略如内镜超声治疗、分子靶向治疗、基因治疗等逐渐引起关注,其可改善患者生存质量和延长生存期。本文就胰腺癌的非手术治疗进展作一综述。     

胰腺癌分子靶向治疗药物及靶点研究进展

作为恶性程度较高的消化道肿瘤之一, 胰腺癌病情进展快、生存率低、死亡率高, 这种现状与起病隐匿、治疗手段局限等多种因素相关。胰腺癌的靶向治疗是近年来研究的热点, 而寻找一种有效且副作用小的靶向药物对改善胰腺癌预后至关重要。本文将围绕胰腺癌分子靶向治疗药物及靶点的研究现状作一综述。     

DNA甲基化与胰腺癌的研究进展

表观遗传学调控机制在肿瘤发生、发展过程中起着重要的作用.DNA甲基化是重要的基因表观修饰方式之一.目前关于胰腺癌发病的分子机制尚未完全阐明,这大大限制了胰腺癌治疗领域的发展.DNA甲基化的研究对明确胰腺癌的发病机制及其早期诊断、靶向治疗等方面具有十分重要的意义.此文就DNA甲基化与胰腺癌关系的研究进展作一综述.     

全基因组表达谱芯片筛选胰腺癌凋亡相关基因

尽管近年来有关胰腺癌分子发病机制的研究已经取得了很大的进展,但目前早期诊断依然很困难,仍缺乏有效的诊治手段.广泛、深入研究胰腺癌发病的分子机制,寻求早期诊断特异性标志物以及特异性治疗靶点等是有效防治胰腺癌、改善其预后的关键.众多研究表明细胞凋亡与胰腺痛发病关系密切[1-2].     

全基因组表达谱芯片筛选胰腺癌凋亡相关基因

尽管近年来有关胰腺癌分子发病机制的研究已经取得了很大的进展,但目前早期诊断依然很困难,仍缺乏有效的诊治手段.广泛、深入研究胰腺癌发病的分子机制,寻求早期诊断特异性标志物以及特异性治疗靶点等是有效防治胰腺癌、改善其预后的关键.众多研究表明细胞凋亡与胰腺痛发病关系密切[1-2].     

超声微泡造影剂与胰腺癌靶向诊断和治疗的研究进展

胰腺癌是恶性程度极高的消化道肿瘤,预后很差,其病因考虑与大量吸烟、糖尿病、慢性胰腺炎、肥胖、基因突变等有关。因胰腺癌起病隐匿,且早期症状不明显,使大多数患者失去手术治疗机会,即使将肿瘤切除,术后极易复发和转移。胰腺癌分子靶向治疗是近年来肿瘤治疗研究的热点。超声微泡造影剂是一种新的安全有效的载体,可从分子水平上介导肿瘤的靶向诊断和治疗。一、靶向超声微泡的研究进展     

肝细胞癌的靶向治疗

近年来,随着肝细胞癌(HCC)分子机制研究深入,靶向治疗也得到了迅猛发展,在延缓和改善患者疾病进展和预后方面作出了巨大贡献。由于HCC的发病机制错综复杂,单一的分子靶向治疗总体临床收益并不理想。因此,近年来靶向联合其他治疗方式的新方案不断出新,并取得了令人鼓舞的成果。就HCC分子靶向治疗药物、研究现状及临床联合应用治疗进展予以简要总结。     

分子靶向药物相关间质性肺病的现状

近年来分子靶向药物越来越多地用于肿瘤治疗,疗效确切,选择性高,不良反应较少。间质性肺病是其少见不良反应,但症状严重、预后差、致死率高,越来越引起人们的重视。本文就分子靶向药物相关间质性肺病的发病、临床表现、发病机制、处理和治疗作一介绍,以提高临床工作者对分子靶向药物相关间质性肺病的警惕和认识。     

胰腺癌细胞生长因子受体及其介导的信号转导通路

生长因子受体及其介导的信号转导异常被认为是肿瘤发生、发展的重要机制 ,成为近年来的研究热点。对胰腺癌细胞的多种生长因子受体及其介导信号的深入研究 ,在阐明胰腺癌的发病机制、预测及靶向治疗方面具有重要意义     

胰腺癌细胞生长因子受体及其介导的信号转导通路

生长因子受体及其介导的信号转导异常被认为是肿瘤发生、发展的重要机制，成为近年来的研究热点。对胰腺癌细胞的多种生长因子受体及其介导信号的深入研究，在阐明胰腺癌的发病机制、预测及靶向治疗方面具有重要意义。     

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.