Effect of IL-6 elevation in malignant pleural effusion on hyperfibrinogenemia in lung cancer patients

BACKGROUND: The involvements of interleukin-6 (IL-6) and fibrinogen in cancer development were elucidated independently, irrespective of IL-6 activity to induce fibrinogen. This study was undertaken to clarify the clinicopathological association of these molecules in lung cancer patients with malignant pleurisy. METHODS: IL-6, fibrinogen and the related molecules in blood and pleural effusion of 38 patients were assayed at 3-day intervals. RESULTS: IL-6 levels were elevated in sera of 27 cases (71.1%) and in all the effusions with mean values of 20.5 and 9970.5 pg/ml, respectively. Their correlation in 22 cases who were examined on the same day was statistically strong (r = 0.902, p < 0.0001). Occasional elevations of tumor necrosis factor-alpha were independent of IL-6 elevation. Levels of plasma fibrinogen, fibrin(ogen) degradation products (FDP) and C-reactive protein (CRP) were more frequently elevated in the IL-6-elevated cases than those without IL-6 elevation. In all pleural effusions, fibrinogen levels were significantly decreased to <150 mg/dl with large elevations of FDP level. Immunocytologically, IL-6 was detected in cancer cells in 16 cases of adenocarcinoma in addition to host pleural cells, but its cellular positivity was not reflected in the IL-6 level in each pleural effusion. CONCLUSION: Compared with lung cancer patients without malignant pleurisy, IL-6, fibrinogen, FDP and CRP levels in patients with malignant pleurisy were increased more frequently in their peripheral blood. These were basically attributed to systemic leakage of IL-6 from the affected pleural cavity, in which plasma fibrinogen induced in response to serum IL-6 was exudated and degraded predominantly to FDP.     

Elevation of preoperative serum C-reactive protein level is related to poor prognosis in esophageal squamous cell carcinoma

BACKGROUND AND OBJECTIVES: An increased serum C-reactive protein (CRP) level was found in patients with various malignant tumors and was associated with poor prognosis. The aim of this study was to analyze the clinicopathological significance and the prognostic value of preoperative CRP levels in patients with esophageal squamous cell carcinomas. PATIENTS AND METHODS: The preoperative CRP level was measured by enzyme-linked immunosorbent assay (ELISA) in 150 patients with primary esophageal squamous cell carcinomas. All patients underwent radical surgery without any preoperative therapy. The patients were divided into two groups using a cut-off value of 1.0 mg/dl. The pathological classifications of the tumor were examined according to the TNM/UICC classification. The associations between the clinicopathological factors and CRP level were determined. The prognostic value of CRP was determined using Cox's proportional hazards model. RESULTS: Thirty-five patients (23%) showed high CRP levels (more than 1.0 mg/dl). Statistically significant differences in CRP levels were observed depending on tumor depth (P = 0.022) and TNM/UICC stage (P = 0.001). A high CRP level was associated with poor survival (P = 0.005) and was confirmed by multivariate analysis. CONCLUSIONS: A high CRP level is associated with tumor progression and poor survival in patients with esophageal squamous cell carcinoma.     

Hyperfibrinogenemia is a useful predictor for lymphatic metastasis in human gastric cancer

BACKGROUND: Although abnormal hemostasis has been described in cancer patients, the precise association between the plasma fibrinogen level and lymphatic metastasis has not been reported in a large-scale clinical study. METHODS: Preoperative plasma levels of fibrinogen as well as C-reactive protein (CRP) and carcinoembryonic antigen (CEA) were retrospectively examined in 649 patients who underwent surgery for gastric cancer, and the correlation between these factors and nodal status was evaluated. RESULTS: Plasma fibrinogen level in patients with gastric cancer showed a positive association with nodal classification (P < 0.0001). Hyperfibrinogenemia (>310 mg/dl) as well as high CEA (>5 ng/ml) and CRP (>0.3 mg/dl) showed a significant association with nodal metastasis in univariate analysis. Multivariate analysis revealed that hyperfibrinogenemia had an independent association with nodal metastasis (odds ratio, 2.004 (1.140-3.521); P = 0.0157), whereas CEA and CRP were not independent factors. Hyperfibrinogenemia showed an independent association even in advanced cancer [odds ratio 2.611 (1.404-4.854), P = 0.0024, n = 319]. When the 649 gastric cancers were classified into intestinal-type and gastric-type adenocarcinomas, plasma fibrinogen level was correlated with nodal metastasis only in the intestinal-type. CONCLUSIONS: Our results suggest that hyperfibrinogenemia may provide favorable circumstances for cancer cells to metastasize via the lymphatic system. Preoperative plasma fibrinogen level is a useful predictor of lymphatic metastasis in intestinal-type gastric cancer.     

Elevations of serum C-reactive protein occur independently of circulating interleukin-6 concentrations in patients with lung-cancer

It has been suggested that a proportion of patients with cancer have an ongoing acute phase response indicated by a raised C-reactive protein (CRP). To examine whether an acute phase protein response is associated with circulating interleukin-6 (IL-6) concentrations in patients with lung cancer, we measured serum levels of CRP and interleukin (IL)-6 in 176 patients with lung cancer and 48 patients with other pulmonary diseases (28 diffuse pulmonary infiltrates, 15 benign lung tumors, and 5 bronchial asthmas). Serum CRP was detectable (greater-than-or-equal-to 2.5 mg/liter) in 57.4% of patients with lung cancer, 78.6% of patients with diffuse pulmonary infiltrates, 46.7% of patients with benign lung tumors, and 40.0% of patients with bronchial asthma. Serum IL-6 was detectable in all patients by a highly sensitive enzyme-immunoassay, the concentration ranging from 0.126 to 35.115 pg/ml. Although there was no significant difference in serum IL-6 levels among the histologic types of lung cancer, the IL-6 concentration was significantly higher in patients with advanced cancers than in those with early ones. Correlation analyses showed that there was no significant relationship between the CRP and IL-6 concentrations in the 176 patients with lung cancer (r=0.212, P=0.1243), while a highly significant correlation between both levels was observed in the 28 patients with diffuse pulmonary infiltrates (r=0.783, P=0.0005). These results indicate that the serum IL-6 level in patients with lung cancer is closely associated with the disease stage, but that a raised CRP concentration occurs independently of circulating IL-6 concentrations in patients with lung cancer.     

Plasma fibrinogen and serum C-reactive protein are associated with non-small cell lung cancer

OBJECTIVES: There is an association between coagulation and lung cancer. Therefore, pre-operative plasma fibrinogen and serum C-reactive protein (CRP) concentration were assessed to determine their association with tumour characteristics and to ascertain any role in patient selection for curative resection. METHODS: These parameters were compared with tumour size, pTNM stage, and possibility of complete resection in 93 patients with non-small cell lung cancer who underwent surgical resection. RESULTS: Plasma fibrinogen concentration (r(s)=0.34, P=0.001) and serum CRP concentration (r(s)=0.34, P=0.001) were positively correlated with maximum pathological tumour size. A higher plasma fibrinogen concentration was associated with squamous cell carcinoma versus adenocarcinoma (4.5+/-0.13 g/L versus 3.6+/-0.28 g/L; P=0.008), with a trend towards a similar association for CRP (P=0.06). Pathological T stage was also associated with mean plasma fibrinogen and serum CRP concentration (P=0.01 and 0.04, respectively), but pN stage was not associated with either parameter. Incomplete resection occurred in 23% of patients with plasma fibrinogen > 5 g/L or serum CRP > 40 mg/L (versus only 8% when fibrinogen < or = 5 g/L and CRP < or = 40 mg/L; P=0.09). CONCLUSIONS: Plasma fibrinogen and serum CRP are associated with tumour characteristics. High values were associated with inability to achieve complete resection which may refine patient selection for thoracotomy when used with other staging modalities. Attempted resection may be justified in a patient of borderline fitness who has favourable plasma fibrinogen and serum CRP concentration, where a high resection rate is possible. As the relationship was with T stage rather than N stage it may be complimentary to PET scanning, which has only marginally better accuracy for T stage than CT scanning.     

Serum Levels of IL-lβ, IL-6, TNF-α, sTNF-RI and CRP in Patients with oral cavity cancer

Pro-inflammatory cytokines, such as interleukin-lβ (IL-lβ), interleukin-6 (IL-6) and tumor necrosis factor- (TNF-α) play an essential role in the regulation of immune response to, and may have prognostic significance in, cancer. The aim of this study was to examine the relationship between the serum levels of IL-lβ, IL-6 and TNF-α as well as the concentrations of soluble TNF receptor I (sTNF-RI) and C-reactive protein (CRP) in patients with squamous cell carcinoma of oral cavity. Results obtained were confronted with squamous cell carcinoma antigen (SCO concentrations. IL-lβ IL-6 and TNF-α serum levels as well as sTNF-RI and CRP concentrations were higher in patients than in controls. The increased serum levels appeared to be related to the clinical stage of disease. There was a correlation between IL-lβ and sTNF-RI. IL-6 and IL-lβ correlated with CRP levels. The mean concentrations of SCC were also elevated. IL-6 and sTNF-RI seemed to be the most sensitive parameters in early stages and may be used as additional markers in oral cancer     

Serum levels of leptin and proinflammatory cytokines in advanced-stage non-small cell lung cancer

In this study, we aimed to investigate the diagnostic and prognostic roles and the effects of chemotherapy of serum proinflammatory cytokines consisting of IL-6, TNF-alpha, CRP, and leptin levels in patients with advanced-stage non-small cell lung cancer. Twenty-eight patients newly diagnosed of non-surgical advanced non-small cell lung cancer and 15 healthy controls were included. All patients with good performance status were treated with combination therapy consisting of cisplatin plus vinorelbine chemotherapy. Blood samples were obtained in fasting conditions before chemotherapy first and after two cycles of chemotherapy. IL-6 and TNF-alpha immunoassays employ the quantitative sandwich enzyme immunoassay technique. Leptin (Sandwich) ELISA is a solid-phase enzyme-linked immunosorbent assay based on the sandwich principle. CRP is a photometric immunoturbidimetric test. Most of the patients were elderly, male predominance, good performance status, and no or less than 10% weight loss. Higher serum TNF-alpha (p < 0.001) and CRP (p < 0.001), and lower leptin (p = 0.021) levels in patients than in controls. Serum IL-6 cytokine (p = 0.693) levels were not significantly different. No statistically significant relationships between investigated serum parameters and various characteristics of patient and disease. Likewise, serum levels of leptin, IL-6, TNF-alpha, and CRP were all similar in lung cancer patients independently from severity of weight loss (p > 0.05). A direct relationship was found between serum IL-6 and TNF-alpha levels (r = 0.530, p = 0.004). We found that both serum leptin (p = 0.046) and IL-6 (p = 0.002) levels were decreased owing to the chemotherapy effect independently from chemotherapy response. However, serum TNF-alpha and CRP levels were not changed by the chemotherapy effect. The stage of the disease, serum LDH levels, performance status, and responsiveness to chemotherapy yielded prognostic value. Only serum IL-6 levels out of the parameters showed a trend (p = 0.06) related to a worse prognosis.     

Serum level of interleukin 6 as a prognosis factor in metastatic renal cell carcinoma.

Interleukin (IL) 6 was measured in the serum of 138 patients with metastatic renal carcinoma before the initiation of IL-2 treatment. IL-6 was detectable in 66 patients with renal cancer (48%) and in only 8 of 70 normal adults (11%). Serum C reactive protein (CRP) and IL-6 levels are correlated, suggesting that IL-6 is involved in CRP increase in these patients. The interval between diagnosis of the primary tumor and metastasis was shorter in patients with a detectable serum IL-6 and/or serum CRP level greater than 50 mg/liter. Serum IL-6 and CRP levels were higher in subgroups of patients previously defined as having a poor life expectancy according to the Eastern Cooperative Oncology Group criteria. Pretreatment concentrations of IL-6 and CRP were higher in patients who experienced progressive disease after IL-2 treatment. Patients with detectable IL-6 had a shorter survival from the beginning of IL-2 treatment than patients without circulating IL-6 (median, 8 versus 16 months). Similarly, the median survival from the beginning of IL-2 therapy of patients with CRP levels greater than 50 mg/liter was 6 months, compared to 16 months in those with CRP levels below this threshold. None of the 21 patients with serum IL-6 concentrations greater than 300 pg/ml achieved response to any of the three IL-2 regimens. This subgroup has a median survival of 5 months after IL-2 treatment and consisted of 15% of the patients in our series. These results indicate that serum IL-6 and CRP levels are adverse prognosis factors in patients with metastatic renal cell carcinoma. Serum IL-6 level could help in the selection or stratification of the patients in future IL-2 trials.     

凝血功能与肺癌分期及病理分型的关系

目的 研究肺癌患者的凝血功能与肿瘤病理类型及分期的关系,并探讨其临床意义。方法 收集南京医科大学第一附属医院胸心外科2012年1月至2012年6月连续76例行手术治疗的肺癌患者,检测患者血浆组织因子（TF）、D-二聚体、血浆纤维蛋白原（FIB）、纤维蛋白原降解产物（FDP）水平及血小板（PLT）计数,按不同病理类型及术后分期对以上指标进行比较。结果 Ⅲ期、Ⅳ期患者的血浆D-二聚体、TF水平明显高于Ⅱ期患者,差异有统计学意义（P＜0.05） 。肺腺癌患者TF、D-二聚体水平明显高于肺鳞癌患者,差异有统计学意义（P＜0.05）。结论 肺癌患者凝血功能与病理类型、肿瘤分期有关,早期发现并改善高凝状态,可能对肺癌预后有意义。     

Cyclooxygenase-2 Expression is not a Marker of Poor Survival in Lung Cancer

Objective: Cyclooxygenase-2 (COX-2) has been claimed to play role in carcinogenesis and be related to a badprognosis in tumours. The aim of this study was to investigate the relationship between COX-2 expression andclinical and pathological parameters in early and advanced stage lung cancer patients. Materials and Methods: Atotal of 73 patients with lung cancer (27 adenocarcinomas, 33 squamous cell carcinomas, 4 large cell carcinomasand 9 small cell cancer) were analysed retrospectively. COX-2 expression was evaluated by immunohistochemistryin resection materials or lung biopsies. Tumor cells demonstrating more intense staining than smooth muscle andendothelial cells were recorded as COX-2 positive. We investigated the correlation between increased COX-2expression and histological type of the tumor, the stage of the disease and survival. Results: COX-2 expressionwas observed in 55% of the adenocarcinomas, 45% of the squamous cell carcinomas and 22% of the small cellcarcinomas. No correlation was apparent between COX-2 expression and disease stage, histological type and thesurvival. Conclusion: The results of this study do not support COX-2 expression as an independent prognosticfactor in lung cancer. However, since results of the literature are different, further studies made in larger seriesare needed.     

Primary tumor levels of interleukin-6 in relation to tumor burden in human breast-cancer

To examine whether tissue levels of interleukin 6 (IL-6) are associated with the clinicopathologic status in human breast cancer, immunoreactive IL-6 concentration was measured in tumor extracts of 75 breast cancer patients. IL-6 was detectable in 69 of 75 tumor extracts by enzyme-linked immunosorbent assay, the concentration ranging from 10 to 10.690 pg/mg protein. When breast cancer specimens were categorized into four groups in terms of clinical stage of disease at diagnosis, IL-6 concentration (mean +/- SE) in tissue extracts was significantly higher in stage IV patients (2859 +/- 840 pg/mg protein) than in stage I-III patients (344 +/- 117, 350 +/- 150 and 564 +/- 230 pg/mg protein, respectively). Correlation analyses between IL-6 concentration and clinicopathologic factors showed that tissue levels of IL-6 were significantly higher in patients with distant metastasis compared with those without. Furthermore, IL-6 concentration was significantly higher in tumors of more than 5.0 cm in size as compared to less than 5.0 cm. However, no significant association was found between IL-6 concentration and age, histological type, histological grade, lymph node involvement, or hormone receptor status. These results suggest that primary tumor levels of IL-6 are closely associated with clinical stage in human breast cancer.     

胃癌患者血清炎性因子水平的检验分析

目的:探讨胃癌患者血清炎性因子的表达水平检测在其临床诊治中的意义。方法:选取92例胃癌患者为观察组,并选择同期105例发生胃良性病变的患者作为良性病变对照组,同期76例急性胃炎和胃溃疡合并作为急性炎症对照组,对三组患者的肿瘤坏死因子-α（TNF-α）、中期因子（MK）、白细胞介素（IL）-6、白细胞介素（IL）-8和C-反应蛋白（CRP）表达水平进行检测,比较上述血清炎性因子在三组中的表达情况。结果:胃癌患者TNF-α、MK、IL-6、IL-8、CRP等血清炎性因子水平分别为（15.7±2.1）ng·L-1、（616.5±254.6）pg·ml-1、（12.6±2.4）ng·L-1、（234.3±31.4）ng·L-1、（12.3±2.6）mg·L-1,与胃良性病变组和急性炎症对照组比较,均明显增高,差异有统计学意义（P<0.05）。胃良性病变组上述血清炎性因子水平和急性炎症对照组比较,差异无统计学意义（P>0.05）。TNF-α、MK、IL-6、IL-8、CRP等血清炎性因子在胃癌组III期-IV期和发生淋巴结转移患者的表达水平,分别与I期-II期和无淋巴结转移患者相比显著增高,差异有统计学意义（P<0.05）。结论:TNF-α、MK、IL-6、IL-8、CRP等血清炎性因子与胃癌的发生和进展具有一定的相关性,有进一步扩大研究的价值。     

A Comparison of the Characteristics of Cytokine Storm between Lichen Planus and Oral Squamous Cell Carcinoma

Introduction: Lichen planus (LP) is a relatively common chronic mucocutaneous disease that affects the skin and mucous membranes, including oral mucosa. The etiology of the disease is unknown. Some evidence suggests that the immune system and inflammation may play a role in the formation and progression of lichen planus. Some authorities believe that LP is a precancerous condition. The purpose of this study was to investigate the serum levels of the inflammatory cytokines CRP, IL-1, IL-6, and TNF- in patients with oral lichen planus and oral squamous cell carcinoma (OSCC), as well as to assess the relationship between these cytokine levels and clinical symptoms. Methods: A total of 75 subjects, with 25 in each group of oral lichen planus, healthy control, and oral squamous cell carcinoma, participated in this cross-sectional study. Serum levels of IL-1α, TNF-α, IL-6, and CRP were determined and compared. In comparison to the healthy control group, the lichen planus and oral squamous cell carcinoma groups had higher levels of CRP, IL-1α, IL-6, and TNF-α. Results: We discovered that the mean mRNA and protein levels of CRP, IL-1α, IL-6, and TNF-α were significantly higher in the blood and tissue of lichen planus and OSCC patients than in normal controls. Conclusion: Higher levels of CRP, IL-1α, IL-6, and TNF-α may be linked to OLP and oral carcinogenesis. More research with larger groups is required.     

Combination chemotherapy with cis-platinum, adriamycin and mitomycin C (PAM) in the treatment of non-small cell carcinoma of the lung

Twenty-three patients with inoperable non-small cell lung cancer were treated with a combination chemotherapy of CDDP 100 mg/m2, ADM 30 mg/m2 and MMC 8 mg/m2 (PAM). Ten cases were adenocarcinoma, 9 cases were squamous cell carcinoma and 4 cases were large cell carcinoma. In 21 evaluable cases, partial response was obtained in 47.6%. (The response rates were 40.0% in patients with adenocarcinoma, 50.0% in those with squamous cell carcinoma and 66.7% in those with large cell carcinoma.) Leukocytopenia of less than 4,000/mm3 occurred in 100% of cases, thrombocytopenia of less than 100,000/mm3 occurred in 81.0%, and anemia(fall in hemoglobin over 2.0 g/dl) occurred in 66.7%. A transient elevation of Cr (over 1.5 mg/dl) and/or BUN (over 30 mg/dl) was observed in 23.8%. Nausea and vomiting occurred in almost all patients. No death occurred due to toxicity of PAM. These results demonstrate that PAM is an effective combination chemotherapy in patients with non-small cell carcinoma of the lung.     

Interleukin-6 predicts recurrence and survival among head and neck cancer patients

BACKGROUND: Increased pretreatment serum interleukin (IL)-6 levels among patients with head and neck squamous cell carcinoma (HNSCC) have been shown to correlate with poor prognosis, but sample sizes in prior studies have been small and thus unable to control for other known prognostic variables. METHODS: A longitudinal, prospective cohort study determined the correlation between pretreatment serum IL-6 levels, and tumor recurrence and all-cause survival in a large population (N = 444) of previously untreated HNSCC patients. Control variables included age, sex, smoking, cancer site and stage, and comorbidities. Kaplan-Meier plots and univariate and multivariate Cox proportional hazards models were used to study the association between IL-6 levels, control variables, and time to recurrence and survival. RESULTS: The median serum IL-6 level was 13 pg/mL (range, 0-453). The 2-year recurrence rate was 35.2% (standard error, 2.67%). The 2-year death rate was 26.5% (standard error, 2.26%). Multivariate analyses showed that serum IL-6 levels independently predicted recurrence at significant levels [hazard ratio (HR) = 1.32; 95% confidence interval (CI), 1.11 to 1.58; P = .002] as did cancer site (oral/sinus). Serum IL-6 level was also a significant independent predictor of poor survival (HR = 1.22; 95% CI, 1.02 to 1.46; P = .03), as were older age, smoking, cancer site (oral/sinus), higher cancer stage, and comorbidities. CONCLUSIONS: Pretreatment serum IL-6 could be a valuable biomarker for predicting recurrence and overall survival among HNSCC patients. Using IL-6 as a biomarker for recurrence and survival may allow for earlier identification and treatment of disease relapse.     

盐酸埃克替尼治疗EGFR突变型老年非小细胞肺癌的临床疗效与安全性分析

目的:探讨盐酸埃克替尼治疗EGFR突变型老年非小细胞肺癌的临床疗效及安全性。方法:选择2015年4月至2017年6月接受治疗的EGFR突变型老年非小细胞肺癌患者110例,随机数字法分为对照组（n=55例）和观察组（n=55例）。对照组采用吉非替尼治疗,观察组采用盐酸埃克替尼治疗,采用酶联免疫吸附试验测定两组患者血清C反应蛋白（CRP）、血清淀粉样蛋白A（SAA）、白细胞介素-6（IL-6）及白细胞介素-2受体（IL-2R）水平,比较两组患者临床疗效及安全性。结果:观察组治疗4周后有效率为34.55%,高于对照组25.45%（P<0.05）;两组患者治疗前炎症因子水平差异无统计学意义（P>0.05）;两组化疗后CRP、SAA、IL-6及IL-2R水平均得到提高;观察组治疗4周后CRP、SAA、IL-6及IL-2R水平,均低于对照组（P<0.05）;观察组治疗4周后药物毒副反应发生率为21.82%,低于对照组的32.73%（P<0.05）。结论:将盐酸埃克替尼用于治疗EGFR突变型老年非小细胞肺癌患者有助于提高临床疗效,降低炎症因子水平,安全性较高,值得推广应用。     

CRP, TNFα, IL-1ra, IL-6, IL-8 and IL-10 in blood serum of colorectal cancer patients

Blood serum cytokines: TNFalpha, IL-1ra, IL-6, IL-8, IL-10 as well as CRP were investigated in patients with colorectal cancer, prior treatment and 1, 10 and 42 days after surgery. There was an increase of the levels of CRP, IL-6 and IL-10 in most patients 24 hours after surgery. The levels of IL-1ra were elevated in patients in stage C and in several patients in stage B of the disease and there was a decrease of circulating TNFalpha in stage B patients. On day 10 and 42 after surgery, the levels of cytokines followed various patterns.     

The influence of blood arterial oxygen condition on the tumor response to preoperative radiation therapy in oral cancer patients

The relationship between clinicopathological factors and response of radiation therapy in oral squamous cell carcinoma has been studied. It has been suggested that factors such as tumor site, extent and tumor differentiation determine the response to radiation therapy. It is known that oxygenation is related to the therapeutic effects of radiation therapy. However, there are few reports on the relationship between oxygen condition and the response to radiation therapy. The present study was carried out to assess whether any clinicopathological factors, including an evaluation of the oxygen condition can be used to predict the effects of preoperative radiation therapy in oral squamous cell carcinomas. Forty-seven patients with oral cancer treated with external radiation therapy preoperatively were evaluated. There were no significant differences in response to the radiation with respect to age, sex, tumor site, stage, macroscopic shape of tumors, and the histological factors. The hemoglobin (Hb) and arterial oxygen content (CaO(2)) levels of favorable cases (Hb: 14.4 g/dl, CaO(2) 19.1 ml/dl) were significantly higher than those of unfavorable cases (Hb: 11.0 g/dl, CaO(2): 16.1 ml/dl). These findings suggest that oxygen conditions of oral cancer patients predict tumor response to preoperative radiation therapy.     

Quantitative evaluation of oxidative stress, chronic inflammatory indices and leptin in cancer patients: correlation with stage and performance status

In advanced cancer patients, the oxidative stress could take place either at the onset of disease or as a function of disease progression. To test this hypothesis, the following parameters were investigated: the erythrocyte activity of the enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), the serum activity of glutathione reductase (GR) and the serum total antioxidant status (TAS). The total antioxidant capacity of plasma LMWA was evaluated by the cyclic voltammetry methodology. We further determined the serum levels of proinflammatory cytokines (IL-6 and TNFalpha), IL-2, leptin and C-reactive protein (CRP). All of these parameters have been correlated with the most important clinical indices of patients such as Stage of disease, ECOG PS and clinical response. Eighty-two advanced stage cancer patients and 36 healthy individuals used as controls were included in the study. Our findings show that SOD activity was significantly higher in cancer patients than in controls and GPx activity was significantly lower in cancer patients than in controls. Serum values of IL-6, TNFalpha and CRP were significantly higher in patients than in controls. Serum leptin values of cancer patients were significantly lower than controls. SOD activity increased significantly from Stage II/ECOG 0-1 to Stage IV/ECOG 0-1, whereas it decreased significantly in Stage IV/ECOG 3. GPx activity decreased significantly in Stage IV/ECOG 2-3. An inverse correlation between ECOG PS and serum leptin levels was found. Serum levels of IL-2 decreased from Stage II/ECOG 0-1 to Stage IV/ECOG 2-3. A direct correlation between Stage/ECOG PS and serum levels of both IL-6 and CRP was observed. Cisplatin administration induced a significant increase of GPx after 24 hr. In conclusion, this is the first study that shows that several "biological" parameters of cancer patients such as antioxidant enzyme activity, cytokines, leptin and CRP strictly correlate with the most important clinical parameters of disease such as Stage and ECOG PS.     

Association of serum IL-6 levels with comprehensive geriatric assessment variables in a population of elderly cancer patients

The primary aim of this study was to find whether any association exists between serum levels of proinflammatory cytokines, mainly IL-6, and the most important comprehensive geriatric assessment (CGA) variables such as functional status, cognitive functions and nutrition in a population of elderly cancer patients. The secondary aims were to find whether any difference existed between: i) age groups, ii) performance status scores, iii) patients who had lost weight versus those who had not. Eighty-four elderly patients with advanced cancer were included in the study (stage III 15.4%, and stage IV 72.6%). Serum levels of IL-6 and CRP were significantly higher in elderly than in the other adult cancer patients. Among the CGA variables investigated, the most affected were functional status assessed by IADL, cognitive functions by MMSE and nutrition. The ECOG PS was shown to be significantly associated with all the dimensions of CGA investigated: poor PS (>/=2) corresponded to severe disabilities. As for the relationship of serum IL-6 with CGA variables, the strongest correlations were between IL-6 and functional status assessed by both Katz ADL (p=0.0003), IADL (p=0.0070) and nutrition (p=0.0013). Moreover, we observed an association, although not statistically significant, between functional disability (ADL and IADL) and high IL-6 levels in individuals with weight loss. IL-6 levels seem to be independently associated with all CGA variables investigated in the present study in a population of elderly cancer patients. Because the most important CGA variables, in particular functional status, have been observed to be strongly associated with survival, the present study, confirming our previously reported ones, suggests that IL-6 may be a reliable marker of disease outcome and supports the feasibility of using IL-6 as a sensitive outcome marker in studies based on novel approaches aiming at modifying age- and cancer-related biologic mechanisms.