肿瘤相关巨噬细胞在食管癌组织浸润及其对预后的影响

目的:探讨肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)在食管癌组织浸润密度、分布及对预后的影响.方法:应用免疫组化方法检测CD68阳性巨噬细胞在食管癌组织及癌旁正常组织的浸润,比较癌旁正常组织和食管癌组织中巨噬细胞浸润密度,并分析癌组织中TAMs浸润密度、分布对食管癌患者生存时间及预后的影响.结果:食管癌组织TAMs浸润密度明显高于癌旁正常组织(P＜0.05).食管癌间质和癌巢TAMs浸润高密度组5年生存率低于低密度组(P＜0.05);癌间质TAMs浸润高密度组5年生存率明显低于低密度组(P＜0.05);相反,癌巢TAMs浸润高密度组5年生存率高于低密度组(P＜0.05).癌间质和癌巢、癌间质TAMs浸润密度与患者生存时间均呈负相关性(P＜0.05);癌巢TAMs浸润密度与患者生存时间呈正相关(P＞0.05),癌间质及癌巢TAMs浸润密度是独立的预后因素(P均＜0.05).结论:TAMs在食管癌组织中具有较高的浸润密度,且不同微环境的浸润密度不同,与患者生存时间及预后具有相关性.     

肿瘤相关巨噬细胞及CD8+/CD68+细胞比值是影响肺腺癌患者预后的独 立危险因素

目的：探讨CD68+ 肿瘤相关巨噬细胞（TAM）、CD8+ T 细胞、Foxp3+ Treg 细胞等在肺腺癌（LUAD）组织中浸润分布及 其与患者预后的关系。方法：收集2004 年9 月至2009 年4 月间在苏州大学附属第三医院手术切除的93 例LUAD 组织及78 例癌 旁组织,采用组织芯片（TMA）及多重免疫荧光（mIF）技术检测其中的免疫细胞浸润与分布,Wilcoxon 秩和检验比较癌与癌旁组 织、癌巢与间质中浸润水平的差异,χ2 检验分析其浸润水平及CD8+/CD68+细胞比值与临床病理特征的关系,Kaplan-Meier 法和 COX 模型分析影响患者OS 的潜在危险因素。结果：与癌旁组织比较,癌组织中CD68+ TAM、CD8+ T 细胞、Foxp3+ Treg 细胞浸润 水平均显著增加（均P<0.01）,间质CD68+ TAM、CD8+ T 细胞的浸润水平均显著高于癌巢（均P<0.01）。总CD68+ TAM、癌巢及间质 CD68+ TAM 浸润水平与淋巴结转移呈正向关联（均P<0.05）,癌巢CD68+ TAM 浸润水平与T 分期呈正向关联（P<0.05）,间质 CD68+ TAM 浸润水平与病理分级呈正向关联（P<0.05）;癌组织中CD8+/CD68+细胞比值与病理分级、淋巴结转移均呈负向关联（均 P<0.05）。Kaplan-Meier 生存分析显示,LUAD 组织中总CD68+ TAM、癌巢及间质CD68+ TAM 高浸润患者OS 均短于低浸润患者（P<0.05 或P<0.01）、癌组织中CD8+/CD68+细胞比值高患者OS 显著长于低比值患者（P<0.05）。多因素COX 模型分析示,LUAD 患者年龄、TNM 分期及癌组织中CD8+/CD68+ 细胞比值是影响患者预后的独立风险因素（P<0.05或P<0.01）。结论:高度浸润的 CD68+TAM与LUAD的进展、侵袭、转移和不良预后显著关联,而高CD8+/CD68+ 细胞比值是影响LUAD 患者OS 的独立保护因素。     

HER2与CD163在胃癌中的表达及意义

目的 研究人表皮生长因子受体-2(human epidermal growth factor receptor-2,HER2)与M2型巨噬细胞表面标志物分化抗原簇163(cluster of differentiation 163,CD163)在胃癌组织中的表达及意义.方法 应用免疫组织化学方法检测45例胃癌和癌旁组织标本中HER2、CD163和CD68蛋白的表达,并将检测结果与患者临床病理资料相结合进行综合分析.结果 胃癌组织中的CD163+和CD68+细胞数目高于癌旁组织(均P＜0.05),HER2阳性表达在肿瘤pTNM分期、有无淋巴结转移等方面差异有统计学意义(均P＜0.05).CD163+ M2巨噬细胞数在肿瘤pTNM分期方面差异有统计学意义(P＜0.05).HER2蛋白表达与CD163+ M2性巨噬细胞数目存在相关性(r=0.61,P＜0.05).结论 HER2表达强度与M2型巨噬细胞数目存在相关性,二者是判断胃癌诊断、治疗及预后的重要参考指标.     

结直肠腺癌中CD163+巨噬细胞、CD8+T细胞与微血管密度的相关性

摘 要：［目的］ 探讨结直肠腺癌中CD163+巨噬细胞、CD8+T细胞、微血管密度（MVD）的相关性及与患者临床病理因素的关系。［方法］ 通过免疫组化SP法检测61例结直肠腺癌癌组织及远癌组织中CD163+巨噬细胞、CD8+T细胞、CD34的表达水平,分析 CD163+巨噬细胞、CD8+T细胞、MVD的相关性及与患者临床病理因素的关系。［结果］ CD163、CD8、MVD在癌组织及远癌组织中的表达差异具有统计学意义(P均<0.001)。CD163与MVD的表达具有显著正相关性(r=0.615,P<0.001),CD8与MVD的表达具有负相关性(r=-0.320,P=0.012),CD8与CD163的表达具有显著负相关性(r=-0.370,P=0.003)。CD163+巨噬细胞与结直肠腺癌分化程度、淋巴结转移、远处转移、TNM分期相关（P<0.05）,MVD与结直肠腺癌肿瘤位置、分化程度、淋巴结转移、远处转移、TNM分期相关（P<0.05）,CD8+T细胞与患者性别、年龄、肿瘤位置、分化程度、TNM分期、淋巴转移、远处转移均无关（P>0.05）。［结论］ 联合靶向消除TAMs及促进CD8+T细胞的活化与增殖可能对结直肠癌的抗血管生成治疗有一定意义。     

食管癌组织淋巴管与巨噬细胞的关系

目的:探讨影响食管癌组织局部淋巴管数量的因素,为抑制巨噬细胞而达到抑制肿瘤生长和转移的目的提供依据.方法:回顾研究2006年-2011年食管鳞状细胞癌手术患者淋巴结数＞3的病例(n=26)及无淋巴结转移的病例(n=22).石蜡切片行CD68、Ki67和D2-40免疫组化染色,比较巨噬细胞数(CD68+细胞数)、Ki67数(Ki67+细胞比例)和微淋巴管密度,分析微淋巴管密度和巨噬细胞数以及微淋巴管密度和Ki67数的相关.结果:淋巴结转移阴组的巨噬细胞数目明显少于淋巴结转移组(30.77±9.65 vs44.81±14.43,P=0.027).淋巴结转移阴组和淋巴结转移组Ki67增殖数比较无统计学意义[(16.77±8.09)％ vs (18.88±8.08)％,P=0.309].淋巴结转移阴组的微淋巴管密度明显小于淋巴结转移组(11.18 ±2.54 vs 17.38 ±4.52,P=0.025).微淋巴管密度和巨噬细胞数呈正相关(r=0.833,P＜0.01),和Ki67增殖数无相关(r=0.058,P=0.573).结论:食管鳞状细胞癌伴淋巴结转移的肿瘤有更高的巨噬细胞浸润和微淋巴管密度,并且淋巴管数和组织浸润的巨噬细胞数呈正相关.     

食管鳞癌间质中多核巨噬细胞浸润与预后的关系

目的探讨多核巨噬细胞浸润与食管癌的关系及其临床意义。方法观察90例生存5年以上和95例死于1年内的食管鳞癌间质中多核巨噬细胞，淋巴细胞浸润、肿瘤分化、胶原纤维增生、淋巴结内癌转移。结果癌间质中多核巨噬细胞浸润阳性在生存5年组明显高于1年内死亡组（P＜0．01）。肿瘤间质淋巴细胞浸润，淋巴结内癌转移，同时有多核巨噬细胞出现在生存5年以上组亦多于1年内死亡组。结论食管鳞癌间质内多核巨噬细胞浸润是宿主抗肿瘤的重要免疫形态学表现，可作为衡量预后的指标之一。     

人肝细胞癌组织肿瘤相关巨噬细胞的浸润水平及其临床意义

摘 要：［目的］ 通过检测人肝细胞癌组织中肿瘤相关巨噬细胞的浸润水平和特点,探讨肿瘤相关巨噬细胞在肝癌发生、进展中的作用。［方法］ 以CD68分子为巨噬细胞标志,采用免疫组织化学法检测116例肝细胞癌肿瘤组织巨噬细胞的浸润水平和特点。［结果］ 肝细胞癌组织中CD68阳性表达率为94.8%(110/116),而癌旁组织为17.2%(20/116)。巨噬细胞的浸润水平在不同TNM分期、是否存在血管侵袭、淋巴结转移及微卫星病灶分组间均有统计学差异(P<0.05),与患者预后呈负相关(P=0.001)。［结论］人肝细胞癌组织肿瘤相关巨噬细胞呈高浸润状态,且浸润水平与多项临床病理特征和预后密切相关,提示其可能参与了肝癌的发生、进展。     

肿瘤微环境中TAMs及PD-1表达水平与非小细胞肺癌患者预后的相关性

目的 探讨非小细胞肺癌(NSCLC)患者肿瘤微环境中肿瘤相关巨噬细胞(TAMs)、程序性死亡受体1(PD-1)的表达及其与预后的相关性。方法 选取2019年1月至2020年1月商丘市第一人民医院收治的NSCLC患者80例,取肿瘤组织和癌旁正常组织,用免疫组化染色检测组织中TAMs的特异性分子标志物CD163、CD206和PD-1的表达情况,分析肿瘤组织中CD163、CD206表达与PD-1的相关性;分析不同临床病理特征与CD163、CD206和PD-1的关系;进一步用COX回归分析影响NSCLC患者预后的危险因素。结果 NSCLC患者肿瘤组织CD163、CD206和PD-1阳性表达显著高于癌旁正常组织(χ²=36.764,P<0.001;χ²=39.353,P<0.001;χ²=32.028,P<0.001)。NSCLC患者肿瘤组织中TAMs特异性分子标志物CD163、CD206与PD-1表达之间存在显著的正相关性(r=0.281,P=0.030;r=0.339,P=0.008)。NSCLC肿瘤组织中P...     

CD68巨噬细胞浸润对原发性食管小细胞癌预后的影响

目的：探讨不同亚型肿瘤相关巨噬细胞在原发性食管小细胞癌(PESC)中的浸润情况及其与患者临床病理指标和预后的关系。方法：回顾性分析汕头大学医学院附属肿瘤医院2000年1月—2019年12月进行手术治疗且临床病理资料完整的69例PESC患者组织标本。采用免疫组织化学法评估CD68巨噬细胞及CD163巨噬细胞在PESC中的浸润情况，卡方检验和Fisher精确检验分析其与PESC临床病理指标的关系，采用Kaplan-Meier生存分析及多因素Cox回归方法分析各检测指标与患者生存预后的关系。结果：CD68及CD163均在巨噬细胞的胞质或胞膜表达。CD68巨噬细胞与肿瘤T分期有关(χ²=6.336，r=-0.303，P=0.012)，与其他各临床病理指标均无明显相关。PESC患者的pTNM分期、手术淋巴结清扫数目、N分期、辅助性化疗及CD68巨噬细胞浸润情况与总生存期有关(P<0.05)。多因素Cox回归分析结果显示pTNM分期、手术淋巴结清扫数目、CD68巨噬细胞是PESC患者独立的预后因素。与CD68巨噬细胞低浸润组相比，CD68巨噬细胞高浸润患者的死亡风险降低[HR=0.340，95% CI (0.179，0.645)，P=0.001]。结论：CD68巨噬细胞高浸润是PESC患者独立的预后影响因素，CD68巨噬细胞高浸润的患者预后明显优于CD68巨噬细胞低浸润的患者。     

自然杀伤细胞在原发性肝细胞肝癌中的浸润及其与预后的关系

背景与目的：对某些实体瘤研究显示肿瘤高浸润自然杀伤细胞（natural killer cell,NK cell）与癌症患者良好的预后相关。本研究探讨NK细胞在肝癌组织中的浸润分布及对肝细胞肝癌（hepatocellular carcinoma,HCC）患者生存和预后的影响。方法：应用流式细胞术检测肝癌切除组织中浸润的NK细胞的比例,并进一步应用免疫组化方法证实原位CD56＋细胞的分布特点。同时比较CD56＋生田胞浸润密度与肝癌患者生存的关系。结果：肿瘤组织浸润淋巴细胞（tumor-infiltrating lymphocytes,TIL）中NK细胞的比例是（11．8±8．1）％,显著低于周围非肿瘤组织浸润淋巴细胞（nontumor-infiltrating lymphocytes,NIL）中的比例（18．0±7．9）％（P=0．002）;组织原位观察癌巢CD56＋细胞为（2.3±2．6）细胞／视野,也是显著少于癌旁组织的（8．5±4．5）细胞／视野（R0．001）。癌巢NK细胞浸润密度低组患者患者的无瘤生存率（P=0．027）及总体生存率（P=0．005）明显低于浸润密度高组,而癌旁NK细胞浸润密度对二者无影响。多因素分析显示,癌巢NK细胞浸润密度是影响生存的独立预后因素（HR=2．658。P=0．019）。结论：HCC患者癌巢NK细胞浸润减少,其低密度浸润提示预后不良。     

Excretion of nitrates with saliva and urine and nitrite excretion with saliva in patients with chronic gastritis and duodenal ulcer

The study assessed excretion of nitrates in urine and saliva and that of nitrites with saliva of patients suffering gastric and duodenal ulcer. In both study groups, a positive correlation was established between nitrate concentration in saliva, on the one hand, and that in urine, and nitrite level in urine, on the other. The groups failed to show a difference in nitrate concentrations in either urine or saliva. Since retention of nitrates in the body of chronic gastritis patients held as precancer of the stomach proved no higher than that in patients with duodenal ulcer, the authors cast doubt on endogenous nitroso compounds as a cause of gastric cancer in cases of chronic gastritis.     

Pathologic states associated with activation of eosinophils and with eosinophilia

Eosinophils are involved in cytotoxicity against helminths and tumor cells and effect both tissue damage and tissue protection in hypersensitivity reactions. Their migratory patterns and oxidative mechanisms are most similar to those of neutrophils, but their tissue longevity and functional variation are more similar to those of monocytes and macrophages. Their enzyme components and behaviors are only now beginning to be defined, and their biologic functions in pathologic states remain a topic of considerable discussion.     

Assessment of guilt and shame in patients with non-small-cell lung cancer compared with patients with breast and prostate cancer

PURPOSE: Patients with lung cancer might feel more guilt and shame resulting from previous smoking. This study was designed to determine the levels of guilt and shame among patients with non-small-cell lung cancer (NSCLC) compared with breast and prostate cancer. PATIENTS AND METHODS: Surveys were sent to participants 3 times (at enrollment, 2 months, and 6 months). Patients were eligible if they had stage IV NSCLC, breast cancer, or prostate cancer. The survey included tests of generalized guilt, shame, depression, and anxiety as well as guilt, shame, and embarrassment related to one's cancer. RESULTS: One hundred seventy-two participants completed >or= 1 questionnaire: 96 patients with NSCLC, 30 patients with breast cancer, and 46 patients with prostate cancer. Of the patients with NSCLC, 91.7% were current or former smokers versus 67.1% of the comparison patients. A composite score of embarrassment related to one's cancer (perceived cancer-related stigma; PCRS) was higher in patients with NSCLC (P < .01). Mean baseline generalized guilt and shame scores were not different among groups and did not change over time. A history of smoking correlated with increased levels of guilt and shame, regardless of tumor type. A personal identification of past behaviors as contributing to cancer correlated with higher levels of guilt, shame, anxiety, and depression. Of the patients with NSCLC, 29.5% felt that their behaviors contributed to their cancer compared with 10.5% of the comparison patients. CONCLUSION: Patients with NSCLC had higher levels of PCRS than patients with prostate cancer or breast cancer but not higher baseline levels of shame and guilt. Smoking is correlated with higher levels of guilt and shame. A belief that one caused one's own cancer is correlated with higher levels of guilt, shame, anxiety, and depression. These findings could be translated into an increased need for open communication among patients and their providers surrounding issues of cancer causation, guilt, shame, depression, and anxiety.     

Characteristics and survival of patients with non-Hodgkin's lymphoma with and without acquired immunodeficiency syndrome

Our objective was to determine the characteristics and survival of patients with non-Hodgkin's lymphoma (NHL) with and without acquired immunodeficiency syndrome (AIDS). A cancer registry and AIDS registry linkage for San Diego County was performed in October 1998 as part of a national multicentre study. We performed Kaplan-Meier analysis to compare survival in NHL patients with and without AIDS, after matching for age, sex, and race/ethnicity. We performed logistic regression to determine which patient and tumour characteristics were significantly associated with 1-year survival. Of the 4361 cases of NHL, 324 (7%) had AIDS and 4037 (93%) were not known to have AIDS. Patients with AIDS were more likely to have extranodal, high-grade, and disseminated NHL diagnosed by non-histologic means and were less likely to have received chemotherapy. Patients with AIDS and NHL who survived at least 1 year had less advanced disease stage and received chemotherapy. The median survival in patients with AIDS was 4 months (95% confidence interval (CI): 4-5) and 95 months (95% CI: 58-157) in patients without AIDS (P<0.001). Although these patients with AIDS-related NHL were unlikely to survive, the highly active antiretroviral agents currently used may improve outcomes in future patients.     

Outcomes of patients with stage III nonsmall cell lung cancer treated with chemotherapy and radiation with and without surgery

BACKGROUND:

The objective of this study was to identify the factors associated with improved outcome after treatment for stage III nonsmall cell lung cancer (NSCLC).

METHODS:

A retrospective review of stage III NSCLC patients treated at who were treated at the Dana‐Farber Cancer Institute/Brigham and Women's Cancer Center was done with institutional review board approval. Patients were followed for toxicity, local and distant failure, and overall survival. Multivariate Cox logistic regression analysis was used to determine the factors associated with treatment outcome.

RESULTS:

Between August 2000 and November 2006, 144 patients received concurrent chemoradiation (CRT) for stage III NSCLC. Eighty of 144 patients were men (56%), and the median age was 61 years (range, 33‐81 years). Sixty‐two patients (43%) had stage IIIA NSCLC, and 82 patients (57%) had stage IIIB NSCLC. Radiotherapy (RT) was given concurrently with chemotherapy to all patients; 100 patients (69%) received CRT without surgery, and 44 patients (31%) received with neoadjuvant CRT followed by surgical resection. The median RT dose was 60 grays (Gy) (range, 46‐70 Gy). The median follow‐up was 15 months (range, 3‐64 months), the median potential follow‐up was 37 months (range, 12‐84 months), and the median overall survival was 22 months (95% confidence interval, 15‐28 months). The 1‐year and 2‐year survival rates were 68% and 47%, respectively. Among the 44 patients who underwent resection, the median survival was 61 months, and the 2‐year survival rate was 73%. On multivariate analysis, stage at the time of treatment (stage IIIA vs stage IIIB) and use of surgery were the only factors associated with improved outcome (P = .01 and P = .001, respectively).

CONCLUSIONS:

In this retrospective series, those patients who were able to undergo resection appeared to have improved outcome after induction CRT. Cancer 2009. © 2009 American Cancer Society.     

VEGF and EMMPRIN expression correlates with survival of patients with osteosarcoma

Aim

To investigate the clinicopathologic characteristics of Vascular Endothelial Growth Factor (VEGF) and Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) expression in osteosarcoma, and to evaluate the clinical significance of these two markers in the survival of osteosarcoma.

Methods

VEGF and EMMPRIN expression in paraffin-embedded specimens gathered from 65 patients with primary osteosarcoma were detected by the method of immunohistochemistry using antibodies against VEGF and EMMPRIN. The correlation of VEGF and EMMPRIN expression with the clinicopathologic features and with the survival of osteosarcoma was subsequently assessed.

Results

The expression of VEGF and EMMPRIN was detected in 47/65 (72.31%) and 45/65 (69.23%) of patients with osteosarcoma, respectively. Positive expression of VEGF and EMMPRIN was significantly correlated with surgical stage and percentage of dead cells of osteosarcoma. A significant correlation was found between the expression of VEGF and EMMPRIN in osteosarcoma (r = 0.89, p = 0.01). Additionally, surgical stage, percentage of dead cells, VEGF and EMMPRIN expression showed significant influence on overall survival (OS) and disease-free survival (DFS) in univariate analysis. In multivariate analysis, surgical stage (IIA versus IIB/III) and percentage of dead cells (≤90% versus >90%) were significant for DFS and OS. Those patients with VEGF+/EMMPRIN+ co-expression showed significantly shorter OS and DFS compared with VEGF−/EMMPRIN− expression.

Conclusion

According to our study, the overexpression of VEGF or EMMPRIN may be an important feature of osteosarcoma. A combined detection of VEGF/EMMPRIN co-expression may benefit us in prediction of a poor survival of osteosarcoma.     

肽胺哌啶酮联合MP化疗方案治疗多发性骨髓瘤的疗效观察

目的：观察肽胺哌啶酮联合MP方案，即马法兰＋泼尼松（强的松）治疗多发性骨须瘤的疗效及其毒副作用。方法：确诊的多发性骨髓瘤病人12例，肽胺哌啶酮－MP方案；肽胺哌啶酮自MP方案开始持续给药，每晚睡前口服，剂量从每天100mg开始，每周日剂量递增50mg，至病人不能耐受或最高至每日400mg;MP方案每月一个疗程。结果：部分缓解6例（50％），进步3例（25％）。总有效率为9／12（75．0），有效的病人中7例在4周内起效，肽胺哌啶酮每天100－400mg不等，中位剂量每天225mg，常见的副反应为皮疹，便秘，嗜睡、乏力、头昏，水肿等，结论：肽胺哌啶酮＋MP方案治疗多发性骨髓瘤副反应少，耐受性好，且反应率可能提高。