血清中 MMP-9、TIMP-1表达水平与肺癌病理特征的关系分析

目的：检测肺癌患者血清MMP-9、TIMP-1水平变化,探讨其与肺癌患者病理特征的关系。方法选取80例肺癌患者为研究对象,另选取30例正常健康者为对照组,ELISA法测定肺癌患者及正常者血清中MMP-9、TIMP-1水平,比较两组之间差异。结果肺癌患者血清MMP-9、TIMP-1水平均显著高于正常者（ P＜0．01）,肺癌患者血清中MMP-9、TIMP-1表达水平与肺癌病理类型、病理分化程度无关（P＞0．05）,与肿瘤体积大小、TNM分期、淋巴结转移、远处转移相关,肿瘤≥3 cm患者血清中MMP-9、TIMP-1水平明显高于肿瘤≤3 cm的患者;Ⅲ＋Ⅳ期患者血清中MMP-9、TIMP-1水平明显高于Ⅰ＋Ⅱ期患者;淋巴结转移患者血清中MMP-9、TIMP-1水平明显高于无淋巴结转移患者;远处转移患者血清中MMP-9、TIMP-1水平明显高于无远处转移患者;肺癌患者MMP-9表达与TIMP-1表达呈正相关（γ＝0．634,P＜0．05）。结论 MMP-9、TIMP-1在肺癌患者中表达与TNM分期、淋巴结转移、远处转移相关,在肺癌侵袭转移中有重要作用,可监测病情发展。     

IL-8和MMP-9在非小细胞肺癌患者组织及血清中表达水平的研究

背景与目的 白细胞介素-8(interleukin-8, IL-8)曾被认为是一种具有趋化作用的炎症因子,近年的研 究认为它和基质金属蛋白酶-9(matrix metalloproteinase-9, MMP-9)均为与肿瘤生长和转移密切相关的细胞因子,本 研究通过检测IL-8、MMP-9在非小细胞肺癌患者组织和血清中的表达,研究二者与临床病理特征之间的联系,分析 肺癌组织和血清中IL-8、MMP-9表达的相关性,并探讨IL-8、MMP-9作为肿瘤标志物评估非小细胞肺癌患者病情进 展程度的效能.方法 应用酶联免疫吸附实验(enzyme-linked immunosorbent assay, ELISA)检测141例非小细胞肺癌患 者、40例健康人和40例肺良性疾病患者血清中IL-8、MMP-9的水平.采用免疫组化SP法检测95例非小细胞肺癌、21 例良性疾病肺组织及25例正常肺组织中IL-8和MMP-9的表达.结果 IL-8、MMP-9在非小细胞肺癌患者血清和组织的 表达水平明显高于肺良性疾病对照组和健康对照组,其差异有统计学意义,且随着临床病理分期的升高而升高.在 肺癌患者组织和血清中,IL-8与淋巴转移均有较强的相关性,在肺癌组织中IL-8和MMP-9的表达具有很强的相关性 (r=0.765).结论 IL-8、MMP-9表达水平与非小细胞肺癌的进展密切相关,特别是IL-8与肺癌的淋巴转移具有明显 的相关性,其机制可能是通过上调MMP-9实现的.     

非小细胞肺癌患者外周血有核细胞miR-205-5p水平及其临床意义

目的: 探讨非小细胞肺癌患者外周血有核细胞miR-205-5p 的表达水平是否可作为分子标志物。方法: 收集昆明医科大学第三附属医院2011 年6 月至2012 年6 月非小细胞肺癌首诊患者60 例,其中无远处转移患者30 例,有远处转移患者30例。另外收集健康志愿者30 例作为对照组。qPCR技术检测人支气管上皮细胞BEAS-2B、云南个旧肺鳞癌细胞YTMLC-90、云南宣威肺腺癌细胞XWLC-05 以及人外周血有核细胞的表达水平。分析外周血有核细胞miR-205-5p 的表达水平与非小细胞肺癌患者血清标志物水平、TNM分期、淋巴结转移、远处转移等临床病理参数的相关性。结果：miR-205-5p 在BEAS-2B细胞中表达水平低（0.820 8±0.255 3）,而在YTMLC-90（17.507 2±1.906 3）和XWLC-05（5.725 2±1.012 0）细胞中表达水平明显升高,差异有统计学意义(P<0.05);miR-205-p 在健康人外周血中的表达水平显著低于无转移的以及转移的非小细胞肺癌患者（1.073 0 vs 3.658 8、19.6324,均P<0.01）。外周血有核细胞miR-205-5p 的阳性表达率与非小细胞肺癌患者性别、年龄、淋巴结转移、病理类型和血清肿瘤标志物水平（CEA、CA125、CA242）无关(P>0.05),而与患者远处转移、TNM分期、血清肿瘤标志物CA153 水平明显相关(P<0.01)。结论：miR-205-5p表达水平异常升高可能作为非小细胞肺癌患者转移相关的分子标志物。     

非小细胞肺癌中RECK基因的表达及其与MMP-9的关系

目的：探讨非小细胞肺癌组织中RECK和MMP-9蛋白的表达和相关性。方法：采用免疫组化SP法检测RECK和MMP-9在48例肺癌组织和癌旁正常肺组织中的表达情况。结果：肺癌组织中RECK表达阳性率为29．2％（14／48）,癌旁正常肺组织中阳性表达率为85．7％（42／48）,两组比较差异有统计学意义（P〈0．05）。肺癌组织中MMP-9表达阳性率为68．8％（33／48）,癌旁正常肺组织中阳性表达率为16．7％（33／48）,两组比较差异有统计学意义（P〈0．05）。RECK和MMP-9的表达与淋巴结转移和TNM分期有关,而与患者年龄、性别、肿瘤大小、组织学分化程度无关。与无淋巴结转移和Ⅰ、Ⅱ期的肺癌组织相比,在有淋巴结转移和Ⅲ期的肺癌组织中,RECK表达降低,而MMP-9表达增高（P〈0．05）。RECK和MMP-9的表达经x2检验有负相关关系（χ^2=8．263,r=-0．437,P〈0．05）。结论：RECK蛋白在肺癌中低表达,MMP-9蛋白高表达,二者可能参与了肺癌的发生,在肺癌的侵袭和转移中发挥重要作用,并且具有协同作用。     

血清ProGRP、NSE和MMP-9在肺癌中的表达及意义

摘 要：［目的］ 探讨血清肿瘤标志物胃泌素释放肽前体(ProGRP)、神经特异性烯醇化酶(NSE)、基质金属蛋白酶-9(MMP-9)在肺癌诊断中的价值及意义。［方法］ 采用电化学发光法和ELISA法检测50例小细胞肺癌(SCLC)患者、70例非小细胞肺癌(NSCLC)患者和40例肺良性病变者血清中ProGRP、NSE及MMP-9水平。［结果］ SCLC组和NSCLC组血清ProGRP、NSE及MMP-9水平显著性高于肺良性病变组(P＜0.05)。在SCLC组中,ProGRP、NSE和MMP-9在广泛期和有淋巴结转移者高于局限期和无淋巴结转移者(P＜0.05);NSCLC组患者中,ProGRP、NSE和MMP-9在肿瘤TNM分期Ⅲ~Ⅳ期和淋巴结转移者显著性高于肿瘤TNM分期Ⅰ~Ⅱ期和无淋巴结转移者(P＜0.05)。ProGRP、NSE、 MMP-9诊断肺癌曲线下面积(AUC)分别为0.973（95%CI：0.953-0.994),0.890（95%CI：0.840~0.940),0.830（95%CI：0.769~0.891）。［结论］ 检测ProGRP、NSE、MMP-9能够提高肺癌的诊断水平,血清ProGRP、NSE和MMP-9可作为肺癌诊断标志物。     

肺癌分期的PET/CT表现与血清VEGF表达的关系

目的：探讨肺癌TNM分期的PET／CT成像表现特点与血清VEGF蛋白表达水平的关系。方法：53例肺癌患者治疗前，对其进行PET／CT检查，再用酶联免疫夹心法检测血清VEGF蛋白的表达水平．分析肺癌的T分期和转移（淋巴结和远处转移）的PET／CT表现特征与血清VEGF表达的关系。结果：经PET／CT成像分析．其中T1 11例、T2 9例、T3 18例、T4 15例；纵隔淋巴结转移22例，9例患者有远处转移.肺癌患者的血清VEGF表达的平均水平为（378．02±180．79）ng／L，与正常健康人组差异有统计学意义（P〈0．05）。在不同的低T分期（T1与T2）患者中，血清VEGF表达水平无显著性差异，而低T分期（T1与T2）患者与高T分期（T3与T4）患者中的血清VEGF表达差异有统计学意义（P〈0．05）。纵隔淋巴结转移组血清VEGF表达水平为（561．50±104．55）ng／L．与非淋巴结转移组间比较差异有统计学意义（t=12．21，P〈0．05）：远处转移组血清VEGF表达水平为（614．11±158．81）ng／L．血清VEGF的表达明显与远处转移相关（t=5．30，P〈0．05）。结论：1）肺癌患者血清VEGF水平呈高表达；2）肺癌患者VEGF的表达水平与发生淋巴结转移和远处转移有关；3）随着肺癌TNM分期增加，血清VEGF蛋白表达增强，     

非小细胞肺癌患者血清中ADAM8和CEA的表达及意义

背景与目的肺癌是目前世界上最常见的恶性肿瘤,死亡率在各类肿瘤中居首位,本文拟研究ADAM8和CEA在非小细胞肺癌患者血清中的表达规律,探讨ADAM8和CEA对非小细胞肺癌的诊断价值。方法应用酶联免疫吸附试验方法检测62例非小细胞肺癌患者、27例良性肺病患者和32例健康体检者血清中的ADAM8蛋白表达水平,同时用放射免疫分析法检测以上所有研究对象血清中CEA的蛋白表达水平。结果血清ADAM8、CEA水平在NSCLC组均高于良性肺病组和正常对照组,差异有统计学意义(P<0.01),良性肺病组中这两种标志物表达水平比正常对照组略高,但差异无统计学意义(P>0.05);ADAM8在腺癌患者中表达水平与鳞癌相比差异无统计学意义(P>0.05),而CEA在腺癌患者中表达水平比鳞癌高,差异有统计学意义(P<0.05);Ⅲ-Ⅳ期NSCLC患者血清中ADAM8和CEA的表达水平均高于Ⅰ-Ⅱ期患者,差异均有统计学意义(P<0.01);伴有淋巴结转移NSCLC患者血清中ADAM8和CEA的表达水平均高于不伴有淋巴结转移者,差异均具有统计学意义(P<0.01);单项检测ADAM8、CEA对NSCLC的敏感性分别为77.4%、71.0%,特异性分别为90.6%、84.4%,联合检测敏感性提高到91.9%,但特异性下降到75.0%。结论ADAM8在非小细胞肺癌患者血清中的过度表达表明其与肺癌的发展有着密切的关系,联合检测ADAM8和CEA对非小细胞肺癌的诊断有一定的辅助价值。     

Trx-1和COX-2在非小细胞肺癌中的表达及意义

目的探讨硫氧化还原蛋白1(thioredoxin,Trx-1)和COX-2在非小细胞肺癌中的表达及其临床意义。方法免疫组织化学方法检测63例非小细胞肺癌组织和20例癌旁正常肺组织中Trx-1和COX-2的表达。结果63例非小细胞肺癌组织中Trx-1和COX-2均呈高表达,分别为63.5%（40/63）和59.1%（37/63）,20例正常肺组织Trx-1阳性3例,COX-2阳性2例,差异具有统计学意义(P<005)。Trx-1在低分化癌组织中阳性表达率高于中高分化癌组织,差异具有统计学意义(P<0.05);在不同TNM分期的非小细胞肺癌组织中,阳性表达率差异具有统计学意义(P< 0.05),在有淋巴结转移的癌组织中阳性表达率高于无淋巴结转移者,差异具有统计学意义(P<0.05)。COX-2的表达与TNM分期及淋巴结转移差异具有统计学意义(P<0.05)。结论Trx-1和COX-2的表达与非小细胞肺癌患者预后密切相关。     

血清HIF-1α、MMP-9水平与皮肤鳞癌患者手术治疗预后的相关性

目的 探讨血清缺氧诱导因子-1α(HIF-1α)、基质金属蛋白-9(MMP-9)水平与皮肤鳞癌患者手术治疗预后的相关性。方法 选择83例皮肤鳞癌(SCC)患者作为观察组，同时选取同期体检健康者90例作为对照组。采集2组受试者外周静脉血5 ml,采用酶联免疫吸附法测定血清HIF-1α、MMP-9水平。比较2组的血清HIF-1α、MMP-9水平，分析皮肤鳞癌患者血清HIF-1α、MMP-9水平与临床病理特征关系。SCC患者术后随访24个月，统计生存率，分析HIF-1α、MMP-9与患者预后的相关性。结果 观察组HIF-1α、MMP-9水平高于对照组，差异有统计学意义(P<0.05)。TNM分期中的Ⅱ期+Ⅲ期、组织学分级低分化、有淋巴结转移患者的HIF-1α、MMP-9水平高于TNM分期中的0期+Ⅰ期、组织学分级高+中分化、无淋巴结转移患者，差异有统计学意义(P<0.05)。术后随访24个月，83例SCC患者中死亡13例；死亡组患者的HIF-1α、MMP-9水平高于生存组，差异有统计学意义(P<0.05);经COX多因素分析发现，血清HIF-1α、MMP-9水平高是患者预后...     

血清MMP-9在肺癌侵袭和转移中的意义

摘 要：［目的］ 研究基质金属蛋白酶-9(matrix metalloproteinase 9,MMP-9)在肺癌患者侵袭和转移中的意义。［方法］ 收集肺癌患者血清70例,健康体检者血清60例,通过酶联免疫吸附法(ELISA)检测血清样本中MMP-9的表达水平。［结果］ MMP-9在肺癌患者血清中的含量明显高于健康人群;且有淋巴结转移组血清MMP-9水平显著性高于无淋巴结转移组;在不同病理类型肺癌组间MMP-9水平差异无统计学意义。［结论］ MMP-9可以作为临床判断肺癌侵袭和转移的生物学指标。     

Circadian-rhythm of tumor growth in non-vascularized tumor

Circadian-Rhythms of tumor growth rates of Walker-256 implanted in the dorsum side of hind paw of Wistar rats (Male 5-6 weeks age) were observed. Tumor size was measured at 7 A.M. and 7 P.M. The tumor growth rate was determined by the following method. Rday = T (P.M.)/T (A.M.). Rnight = T (A.M.)/T (previous P.M.). Rday and Rnight: Tumor growth rate during day and night, respectively. T: Tumor size. The tumor growth rate, for those less than 750 mm3 in size and in which tumor vessels did not form yet, was 0.10 +/- 0.5 on Rday, 0.29 +/- 0.12 on Rnight (p less than 0.05). Tumors of more than 1,500 mm3 forming tumor vessels did not show a significant difference in the degree of the tumor growth rate (Rday: 0.14 +/- 0.07; Rnight: 0.212 +/- 0.05) (p greater than 0.05). Tumors in which vessels were injured and showed microvascular disturbance due to MMC (A. i) or thermochemotherapy using warmed physiological saline injected into tumor vessels after chemotherapy, were damaged on Rday and enhanced on Rnight for 3-7 days after these kinds of treatment. The tumor in unformed tumor vessels or damaged types showed, rapid size increase at night. Therefore, the Circadian-Rhythm tumor vessels in microtumor or damaged tumor may be treated with antimetabolic agents such as 5-FU at night for inhibition of microtumor or micrometastatic tumor.     

肿瘤抗原在肿瘤研究中的应用

近年来随着肿瘤抗原筛选鉴定方法的多样化,已鉴定出了大量的肿瘤抗原,抗原的分类越来越全面,肿瘤抗原的基础性研究已经深入到其他学科,肿瘤抗原的检测诊断则在临床上应用越来越广泛,而针对不同抗原的免疫治疗也更加具体可行.     

肿瘤血管生成调节与肿瘤治疗

肿瘤血管生成是一个非常复杂的过程，涉及到多种因子的调节。针对肿瘤血管生成的治疗对策在目前肿瘤治疗中具有十分重要的意义。本文就影响肿瘤血管生成的各种调节因子、抗血管生成的主要治疗靶标及研发现状作一综述，为肿瘤治疗的抗血管生成新靶标的设计研究提供信息。     

The inhibition of tumor growth by tumor mass

Evidence suggests that a tumor behaves, in its pattern of growth, like an integrated organ rather than a collection of independently growing cells. Tumor growth tends to slow progressively as size increases and to undergo compensatory growth after partial resection. Consequently, therapies that reduce tumor mass may tend to accelerate the growth of the remaining tumor and tumor metastases. An approach to therapy based upon a simulated increase in tumor mass may be worthy of consideration.     

伴性索分化的低度恶性子宫内膜间质肉瘤1例并文献复习

目的:探讨伴性索分化的低度恶性子宫内膜间质肉瘤的临床病理特征、生物学行为及预后。方法:对1例伴性索分化的低度恶性子宫内膜间质肉瘤的临床、病理和免疫学表型进行观察、分析及文献复习。结果:结合组织学特点及免疫组化结果,诊断为伴性索分化的低度恶性子宫内膜间质肉瘤。结论:伴性索分化的低度恶性子宫内膜间质肉瘤是一种极其少见的现象。其诊断依赖于组织病理学、免疫组化,并须结合其临床资料。     

Granulosa cell tumor of the ovary: tumor review

Granulosa cell tumors of the ovary are rare neoplasms that originate from sex-cord stromal cells. The long natural history of granulosa cell tumors and their tendency to recur years after the initial diagnosis are the most prominent of their characteristics. The secretion of estradiol is the reason for signs at presentation such as vaginal bleeding and precocious puberty. Abdominal pain and hemoperitoneum, which occasionally can occur, are attributable to tumor rupture. The most common finding in pelvic examination is a tumor mass, which is subsequently confirmed with imaging techniques. Surgery is the mainstay of initial management for histological diagnosis, appropriate staging, and debulking. A more conservative unilateral salpingo-oophorectomy is indicated in patients with stage I disease and patients of reproductive age. Total abdominal hysterectomy with bilateral salpingo-oophorectomy is the appropriate surgical treatment for postmenopausal women and those with more advanced disease. The stage of disease is the most important prognostic factor associated with the risk of relapse. There are no clear conclusions regarding the role of postoperative chemotherapy or radiotherapy in stage I disease and in those with completely resected tumor. The use of adjuvant chemotherapy or radiotherapy has sometimes been associated with prolonged disease-free survival and possibly overall survival. Chemotherapy is the treatment of choice for patients with advanced, recurrent, or metastatic disease, and BEP (bleomycin, etoposide, and cisplatin) is the preferred regimen. Although the overall rate of response to treatment is high, the impact of treatment on disease-free or overall survival is unknown. Prolonged surveillance is mandatory because tumors tend to recur years after the initial diagnosis.     

肿瘤免疫抑制微环境对肿瘤免疫治疗作用的研究进展

肿瘤免疫抑制微环境是肿瘤微环境中起抑制免疫功能的部分。其组成包括抑制性细胞和抑制性细胞因子。近年来,因其在肿瘤免疫中的重要作用,CAR－T和PD－1／PD－L1信号通路已成为免疫治疗的研究热点,它们可通过不同的机制产生免疫抑制作用,从而促进肿瘤进展。因此,针对以上机制采取更有效的抗肿瘤疗法有可能减缓肿瘤进展。本文现就免疫抑制微环境对CAR－T疗法和PD－1／PD－L1信号通路在抗肿瘤过程中的作用进行综述。     

Detection of circulating tumor cells and of tumor DNA in plasma during tumor progression in rats

The role and clinical significance of circulating tumor cells and of tumor DNA in the plasma have not yet been clarified. In the present study, we compared rates of detection of tumor-derived DNA in the buffy coat to those in plasma from tumor-bearing rats, and we attempted to correlate these rates with the progression of tumors. We injected DHD/K12-PROb cancer cells subcutaneously into BD-IX rats and divided the animals into six groups according to the time between the injection of tumor cells and euthanasia. After euthanasia, macroscopic metastases were assessed and samples of blood and lung were collected. We used mutant allele-specific amplification by PCR to detect tumor-derived DNA. We detected tumor DNA in lung samples from the first week after inoculation, in plasma from the third week and in the buffy coat from the fifth week. All animals analyzed on the 11th week had macro- or micrometastases in their lungs. Regardless of group, the rate of PCR-positive plasma samples was significantly higher than that of circulating tumor cells (P=0.005). In animals with metastases, this difference was also statistically significant (P=0.008). However, neither the detection of tumor DNA in the plasma nor the presence of circulating tumor cells was strongly correlated with the presence of metastases. Thus, cell-free tumor DNA was detected sooner and more frequently than circulating tumor cells and the dissemination of tumor DNA in the plasma seems to be much more common than detectable hematogenic tumor cells during the spread of colorectal cancer.     

Adenocarcinoid tumor of appendix presenting as unilateral Krukenberg tumor

We report a case of adenocarcinoid tumor of the appendix that presented initially as a unilateral Krukenberg tumor (a signet ring cell mucinous adenocarcinoma with prominent cellular stroma). The primary tumor in the appendix was discovered 10 months later at the time of a "second look" laparotomy. The ovarian metastasis showed both goblet cell elements and tubular formations with numerous argyrophilic cells, indicating that both components of these tumors may metastasize, a finding at variance with the conclusions of some authors who suggest that only the mucinous component may metastasize. Theories of histogenesis of these tumors are discussed, and 12 previously reported cases presenting as Krukenberg tumors (all bilateral) are reviewed. Because the primary tumor in the appendix may be small and easily missed, appendectomy is recommended in all patients with Krukenberg tumors when another primary site cannot be identified at the time of surgery.     

肿瘤相关巨噬细胞的极化与肿瘤的发展

肿瘤相关巨噬细胞（TAM）在肿瘤微环境中扮演重要角色,它包含了两种可以相互极化的亚型:M1型(经典活化巨噬细胞)和M2型（替代活化巨噬细胞）。M1型TAM发挥着抑制肿瘤生长的作用,而M2型TAM对肿瘤的发生发展起促进支持作用。在特定的肿瘤微环境中,M2型TAM占据主导地位,促进肿瘤的发展。基于肿瘤相关巨噬细胞两种亚型的功能特点,如何诱导M2型向M1型极化是目前的研究热点,也将是肿瘤治疗的一个重要靶点。