Skp2蛋白在非小细胞肺癌中的表达及其与c-myc蛋白表达的关系

目的　研究Skp2、c myc蛋白在非小细胞肺癌组织中的表达 ,探讨它们之间的关系及其临床意义。方法　采用免疫组化技术检测Skp2、c myc蛋白在 42例非小细胞肺癌、10例肺良性疾病和 8例癌旁不典型增生组织中的表达。结果　肺癌组织中Skp2蛋白阳性率为 2 4.83 %± 13 .64 % ,显著高于肺良性疾病组织(3 .0 7%± 1.3 2 % ) (P <0 .0 0 1) ,也显著高于癌旁不典型增生组织 (13 .89%± 3 .95 % ) (P <0 .0 5 )。Skp2蛋白阳性率与细胞分化程度、TNM分期及淋巴结转移有密切关系 ,但与肿瘤组织学类型无明显关系。肺癌组织中Skp2与c myc表达呈显著正相关 (r =0 .44 8,P =0 .0 0 3 ) ,二者同时高表达率为 3 8.1% (16/4 2 ) ,同时高表达率与肺癌组织学类型、细胞分化程度以及淋巴结转移无明显关系 ,但与临床分期有密切关系 (P <0 .0 5 )。结论　Skp2蛋白的过度表达可能在非小细胞肺癌的发生发展中起重要作用 ,并可能与c myc蛋白协同作用。     

肺癌组织中肿瘤浸润树突状细胞对预后的影响

目的　研究肺癌组织中肿瘤浸润树突状细胞 (TIDC)的浸润程度对预后的影响。方法将S 10 0蛋白作为TIDC的特异性标记物 ,应用SABC免疫学方法检测肺癌组织中TIDC的分布。结果38例肺腺癌中 ,TIDC显著浸润 15例 ,5年生存率为 6 0 0 % ;轻度浸润 2 3例 ,5年生存率 2 1.7%。 44例鳞癌中 ,TIDC显著浸润 18例 ,5年生存率 6 1.1% ;轻度浸润 2 6例 ,5年生存率 19.2 %。经Log rank检验 ,无论肺腺癌和鳞癌 ,TIDC显著浸润组和轻度浸润组的 5年生存率之间差异有显著性。结论　肺癌组织中TIDC显著浸润者的预后明显好于轻度浸润者。     

人肺癌中FHIT基因表达的临床病理生理意义及与预后的关系研究

目的　研究FHIT基因表达与人肺癌临床病理生理特征和预后的关系 ,探讨FHIT基因在人肺癌发生、发展过程中的可能作用。方法　应用免疫组化法检测了 1 66例肺癌组织标本及其癌旁肺组织和 37例肺良性病变组织中FHIT基因的表达水平。结果　肺癌组织中FHIT基因表达阳性率 (63 .0 3 %± 2 6 .41 % )显著低于癌旁组织 (83 .74%± 1 7.46 % ) ,而癌旁组织又显著低于肺良性病变组织 (92 .98%± 5 .56 % ) (P <0 .0 1 ) ;肺癌组织中FHIT基因表达水平降低与肺癌组织学类型、细胞分化程度 ,患者P TNM分期、淋巴结转移程度存在相关性 (P <0 .0 5) ;吸烟组肺癌患者的肺癌组织中FHIT基因表达阳性率 (55 .1 4 %± 2 7.55 % )明显低于非吸烟组 (71 .93%± 2 2 .0 5 % ) (P <0 .0 1 ) ;FHIT基因低表达组肺癌患者的术后长期生存率显著低于高表达组 (P <0 .0 5)。结论　FHIT基因的表达下降可能与肺癌的发生、发展过程有关。吸烟是导致肺癌患者FHIT基因表达下降的重要原因之一。     

蛋白酪氨酸磷酸酶与肺癌组织学类型的关系

目的　探索蛋白酪氨酸磷酸酶与肺癌组织学类型的关系。方法　用免疫组织化学技术 (LSAB法 )检测肺良性病变和肺癌组织中蛋白酪氨酸磷酸酶的表达。结果　蛋白酪氨酸磷酸酶阳性率在 3 4例肺良性病变的支气管粘膜上皮细胞为 95 .0 3 %± 2 .10 % ,12 1例肺癌为 43 .5 9%± 14 .41% ;46例腺癌为 47.5 7%±16.2 6% ,48例鳞癌为 40 .5 9%± 14 .0 4% ,2 7例腺鳞癌为 42 .13 %± 9.84% ;2 1例低分化鳞癌为 3 1.63 %±10 .3 4 % ,18例中分化鳞癌为 41.3 9%± 9.3 5 % ,9例高分化鳞癌为 5 9.90 %± 8.61% ;16例低分化腺癌为3 4 .14 %± 12 .5 3 % ,2 6例中分化腺癌为 5 2 .10 %± 12 .19% ,4例高分化腺癌为 63 .0 5 %± 15 .84%。蛋白酪氨酸磷酸酶阳性率在肺良性病变与肺癌间 ,以及低分化肺癌与高分化肺癌间的差异有显著性 (P <0 .0 1或P <0 .0 5 )。结论　检测蛋白酪氨酸磷酸酶有助于鉴别肺部的良恶性疾病 ,并可能作为预测肺癌预后的指标之一。     

胃癌组织内浸润树突状细胞的临床意义

目的 探讨胃癌组织内浸润树突状细胞（TIDC）的临床意义。方法 以手术切除、福尔马林液固定、石蜡包埋的胃癌标本为研究对象,利用S－100蛋白单克隆抗体标记胃癌组织中浸润的TIDC,分别计数20个高倍视野内的TIDC数量,分为高、低浸润组。结果 在淋巴结转移阳性和远处转移患者中,TIDC低度浸润的比例较高,分别为84．6％,100．0％（P＜0．05）。结论 胃癌组织内TIDC增多可能具有抗肿瘤转移的作用。     

恶性肿瘤特异生长因子和肿瘤浸润性树突状细胞在子宫内膜癌患者中的表达及临床意义

目的:探讨恶性肿瘤特异生长因子(TSFG)和肿瘤浸润性树突状细胞(TIDC)在子宫内膜癌患者中的表达及临床意义。方法:选择2015年1月至2017年1月我院收治的子宫内膜癌患者50例。检测子宫内膜组织中TIDC和血清中TSFG水平,分析TSFG、TIDC在不同临床病理特征患者中的表达。结果:与癌旁组织比较,肿瘤组织中TIDC明显降低(P=0.000);MHC-Ⅱ阳性树突状细胞（DC）(%)明显降低（P=0.000);CD54阳性DC(%)明显降低（P=0.000)。与非淋巴结转移的患者相比,淋巴结转移的患者TIDC、MHC-Ⅱ阳性DC(%)、CD54阳性DC(%)均明显降低,TSFG明显增高(P<0.05)。与临床TNM分期为Ⅰ或Ⅱ期的患者相比,Ⅲ或Ⅳ期的患者TIDC、MHC-Ⅱ阳性DC(%)和CD54阳性DC(%)均明显降低,TSFG明显增高(P<0.05)。与肌层浸润≤1/2的患者相比,肌层浸润>1/2的患者TIDC、MHC-Ⅱ阳性DC(%)和CD54阳性DC(%)均明显降低,TSFG明显增高(P<0.05)。与中、高分化的患者相比,低分化患者组织中TIDC、MHC-Ⅱ阳性DC(%)和CD54阳性DC(%)均明显降低,TSFG明显增高（P<0.05）。结论:TIDC在肿瘤组织中低表达,且多为不成熟的调节性DC细胞。低分化、TNM分期为Ⅲ或Ⅳ期、淋巴结发生转移、肌层浸润>1/2的患者血清中TSFG水平明显升高,而肿瘤组织中TIDC明显降低。提示子宫内膜癌患者血清中TSFG和肿瘤组织中TIDC可作为判断预后的指标。     

内皮抑素在非小细胞肺癌中的表达及其与肺癌临床病理生理特征的关系

目的研究非小细胞肺癌组织中内皮抑素(endostatin)的表达及其与肺癌临床和病理生理特征的关系.方法采用免疫组化LSAB法检测46例肺癌组织、14例肺良性病变组织中endostatin的表达.结果①endostatin在肺癌组织中的表达水平(84.91%±7.65%)显著高于癌旁肺组织(63.70%±12.45%)和肺良性病变组织(40.29%±15.01%)(P＜0.01),癌旁肺组织亦显著高于肺良性病变肺组织(P＜0.01);②endostatin表达水平与肺癌原发肿瘤大小、有无远处转移、细胞分化程度、P-TNM分期均有密切关系(P＜0.05),而与肺癌原发部位、组织学类型、淋巴结转移状态、患者的性别、年龄、吸烟史等均无明显关系(P＞0.05);③多因素相关分析发现endostatin表达水平与原发肿瘤的大小、有无远处转移、P-TNM分期均呈负相关(P＜0.05),与细胞分化程度呈正相关(P＜0.01),与原发肿瘤部位、淋巴结转移状态、组织学类型、性别、年龄、吸烟史均无显著相关性.结论非小细胞肺癌组织中endostatin的表达水平可能是预测肿瘤恶性行为的有用指标.     

抗CD11c磁珠阳性选择法分离肺癌组织浸润树突状细胞

目的：建立抗CDI1c磁珠阳性选择法分离Lewis肺癌模型中肿瘤浸润树突状细胞（tumor infiltrating dendritic cell，TIDC）的方法。方法：在C57BL／6小鼠侧腹壁皮下注射Lewis肺癌细胞（1．0&#215;10^6／只）建立荷瘤小鼠模型。抗CD11c磁珠阳性选择法分离提取TIDC，抗小鼠CD11c-PE标记TIDC，用流式细胞仪检测分离到的细胞纯度；电镜观察细胞形态；抗小鼠MHC-Ⅱ-PE和CD83-FITC或CD86-FITC抗体双标记后，用流式细胞术检测细胞表型。结果：抗CD11c磁珠阳性选择法可在每克Lewis肺癌移植瘤组织中分离到（1．73&#177;0．31）&#215;10^6个TIDC，占肿瘤组织细胞总数的（2．18&#177;0．29）％；TIDC纯度达到96．49％。电镜观察到分离的TIDC具有DC细胞的典型形态特征，其细胞表面MHC-Ⅱ、CD83和CD86分子的表达率分别为（51．25&#177;4．21）％、（3．48&#177;0．34）％和（3．07&#177;0．65）％。结论：抗CD11c磁珠阳性选择法体外分离TIDC具有高效、简便、相对经济实用的优点，有推广价值。     

非小细胞肺癌根治术后放射治疗价值的前瞻性研究

目的　评价术后放疗对根治术后N1与N2 非小细胞肺癌的作用。方法　 1982年 2月至 1995年12月收治的 36 6例小于 6 5岁的N1与N2 非小细胞肺癌病例 ,随机分为术后放疗组 (n =184)和单纯手术组 (n= 182 )。结果　术后放疗组和单纯手术组 5年生存率分别为 43 .4%± 5 .1%和 40 .5 %± 4.6 % (P =0 .5 6 ) ,5年无瘤生存率分别为 42 .9%± 5 .2 %和 38.3 %± 4.5 % (P =0 .2 8)。T3 4 N1M0 患者在术后放疗组的 5年生存率和5年无瘤生存率分别为 5 8.1%± 15 .5 %和 6 5 %± 12 % ,单纯手术组则分别为 39.9%± 10 .2 % (P =0 .0 92 )和40 %± 10 % (P =0 .0 5 7)。术后放疗可明显减少胸内复发 (P <0 .0 1)。结论　术后放疗可减少局部复发 ,对总的生存改善不明显 ,但对T3 4 或N1患者有望获得治疗益处     

非小细胞肺癌CD44V6和C-erbB-2的表达及其意义

目的 :探讨CD44V6及C erbB 2表达与非小细胞肺癌临床病理特征之间的关系。方法 :采用S P免疫组化法检测 132例非小细胞肺癌、6 6例淋巴结转移癌、95例癌旁肺组织和 2 0例正常肺组织CD44V6和C erbB 2表达的情况。结果 :非小细胞肺癌CD44V6阳性表达率为 48 4 8%,明显高于癌旁肺组织 16 84%和正常肺组织 2 0 0 0 %的阳性有效率。CD44V6阳性表达与淋巴结转移状况、TNM分期、肿瘤大小和组织学类型有显著相关性。非小细胞肺癌淋巴结转移组、TNMⅢ期患者、直径>3cm的肿瘤和鳞癌CD44V6阳性表达率分别明显高于无淋巴结转移组、TNMⅠ、Ⅱ期患者、直径≤ 3cm的肿瘤和腺癌。淋巴结转移癌CD44V6阳性表达率明显高于肺原发癌。CD44V6阳性表达与患者的性别、年龄和组织学分级无显著相关性。非小细胞肺癌C erbB 2阳性表达率为 6 1 36 %,明显高于癌旁肺组织 18 95 %和正常肺组织 10 0 0 %的阳性表达率。C erbB 2阳性表达与临床病理特征无显著相关性。结论 :CD44V6阳性表达预示非小细胞肺癌具有较强的侵袭和转移能力 ,CD44V6可作为一项预测非小细胞肺癌转移潜能及判断预后的生物学指标。C erbB 2作为判断非小细胞肺癌预后的指标不理想     

Implications of cancer stem cells in the treatment of cancer

Identification of cancer stem cells (CSCs) in both hematological and solid malignancies suggests that CSCs may be a common phenomenon for most malignancies. Similarly to normal stem cells, CSCs can self-renew and differentiate into progeny cancer cells. Almost all current therapy against cancer targets differentiated cancer cells. CSCs are more resistant to therapy secondary to quiescence, increased expression of antiapoptotic proteins and drug efflux transporters. In this article, we review the current status of CSC research and propose the targeting of CSC cell-surface molecules, signal transduction pathways, the stem cell niche, stem cell differentiation and drug resistance.     

Epilepsy in the cancer patient

Purpose

Epileptic seizures in patients with malignancies usually occur as a consequence of brain metastases from systemic cancer or the presence of a primary brain tumor. Other less-frequent causes include metabolic disorders such as electrolyte abnormalities, hypoglycemia, hypoxia and liver failure, paraneoplastic encephalitis, leptomeningeal carcinomatosis, side effects of certain chemotherapeutic agents, central nervous system infections, and pre-existing epilepsy.

Methods

We reviewed all published literature in the English language regarding the use of antiepileptic drugs in patients with cancer.

Results

In patients with brain metastases or primary brain tumors that had never experienced seizures, prophylactic anticonvulsant treatment is justified only for a period up to 6?months postoperatively after surgical excision of a cerebral tumor, since approximately half of the patients will never develop seizures and the anti-epileptic drugs may cause toxicity and interactions with antineoplastic therapies. For brief prophylaxis, newer antiepileptic drugs such as levetiracetam and oxcarbazepine are superior to older agents like phenytoin. In patients with a malignancy and seizures, certain antiepileptic drugs that express tumor inhibitory properties should be used such as valproic acid and levetiracetam, followed by oxcarbazepine and topiramate that exhibit good tolerance, efficient seizure control and absence of significant interactions with the chemotherapy.

Conclusions

Future clinical trials in patients with cancer and epilepsy should focus on combinations of chemotherapeutic interventions with antiepileptic drugs that demonstrate antineoplastic activities.     

Revisiting the concept of cancer stem cells in prostate cancer

The cancer stem cell (CSC) model proposes that cells within a tumor are organized in a hierarchical lineage relationship and display different tumorigenic potential, suggesting that effective therapeutics should target rare CSCs that sustain tumor malignancy. Here we review the current status of studies to identify CSCs in human prostate cancer as well as mouse models, with an emphasis on discussing different functional assays and their advantages and limitations. We also describe current controversies regarding the identification of prostate epithelial stem cells and cell types of origin for prostate cancer, and present potential resolutions of these issues. Although definitive evidence for the existence of CSCs in prostate cancer is still lacking, future directions pursuing the identification of tumor-initiating stem cells in the mouse may provide important advances in evaluating the CSC model for prostate cancer.     

Male breast cancer in the hereditary nonpolyposis colorectal cancer syndrome

A male member of a large HNPCC kindred, affected by primary malignancies of the breast and colon, was identified. This individual was found to harbor a germline mutation of the MLH1 mismatch repair gene previously shown to segregate with disease in this kindred. The breast tumor exhibited somatic reduction to homozygosity for the MLH1 mutation, and microsatellite instability was evident in the breast tumor. We conclude that hereditary male breast cancer can occur as an integral tumor in the HNPCC syndrome.     

Pain in cancer patients unrelated to the cancer or treatment

The majority of patients with cancer will experience pain in the course of their disease [Kjaer, M. The therapy of cancer pain and its integration into a comprehensive supportive care strategy. Ann. Oncol. 1997, 8 (3), 15-19; Bruera, E.; Lawlor, P. Cancer pain management. Acta Anaesthesiol. Scand. 1997, 41 (1 of 2), 146-153]. Epidemiological studies [Foley, K.M. The treatment of pain in the patient with cancer. CA Cancer J. Clin. 1986, 36 (4), 194-215; Walley, B.A.; Hagen, N.A. The epidemiology of cancer pain. Pain Dig. 1995, (5) 237-244; Portenoy, R.K. Cancer pain: epidemiology and syndromes. Cancer 1989, 63 (11), 2298-2307] generally categorize the pain as 1) directly caused by the neoplastic process or related phenomena; 2) by treatment; or 3) unrelated to the neoplastic process. In approximately 10% of cancer patients who have pain, the pain is unrelated to the disease or treatment and is most often caused by muscles and connective tissue (Twycross, R. Pain Relief in Advanced Cancer; Churchill Livingstone: New York, 1994; 55-61). An overview of pathophysiological mechanisms of muscle pain is presented, followed by a structured protocol to treat frequently encountered pain of muscular origin. The purpose of this article is to provide to the practicing clinicians easy to apply approaches for the treatment of muscle-related pain.