Association of interleukin-6 levels and neutropenia during gemcitabine monotherapy for advanced pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 178-178 ◽  
Author(s):  
H. Okuyama ◽  
S. Mitsunaga ◽  
K. Nakachi ◽  
I. Ohno ◽  
S. Shimizu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Inflammatory Cytokines ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Serum Levels ◽  
Severe Neutropenia ◽  
Ecog Performance Status ◽  
Tnf Α ◽  
Low Serum ◽  
Pro Inflammatory Cytokines

178 Background: Neutropenia is an important dose-limiting toxicity of gemcitabine (GEM) in patients with advanced pancreatic cancer (PC). Serum haptoglobin, regulated by pro-inflammatory cytokines, is a predictor of neutropenia in PC patients under treatment with GEM. We conducted this study with the aim of identifying the association between serum levels of haptoglobin and cytokines and the risk of development of neutropenia in advanced PC patients receiving GEM therapy. Methods: Serum levels of haptoglobin and pro-inflammatory cytokines (GM-CSF, IFN-γ, IL-1β, IL-2β, IL-6, IL-8, IL-10, IL-12, TNF-α) were measured in 55 patients with advanced PC. All patients (median age: 67 years, male/female: 26/29, ECOG performance status: 0/1/2: 32/21/2,) received GEM monotherapy as the initial treatment for PC. The severity of neutropenia within the first 90 days of the GEM treatment was graded according to the NCI Common Terminology Criteria for Adverse Events, version 3.0. Categorical or and noncategorical data were compared using Student's t test. Multivariate regression analysis was performed using logistic regression modeling. The significance level was set at p<0.05. Results: Grade 0 to 2 (G0/1/2) and grade 3 to 4 (G3/4) neutropenia were observed in 32 patients (58.2%) and 23 patients (41.8%), respectively. The G3/4 neutropenia group showed low serum levels of haptoglobin (mean 144.4 mg/dl vs. 186.7 mg/dl, p=0.097), IL-1β (mean 0.07 pg/ml vs. 0.24 pg/ml, p=0.044), IL-6 (mean 1.13 pg/ml vs. 6.43 pg/ml, p=0.002), IL-8 (mean 18.4 pg/ml vs. 44.8 pg/ml, p=0.015), and TNF-α (mean 6.28 pg/ml vs. 8.86 pg/ml, p=0.017) as compared to the G0/1/2 neutropenia group. Multivariate analysis revealed that only low serum IL-6 was significantly associated with the development of G3/4 neutropenia (OR=0.081, p=0.0011). Conclusions: Low serum IL-6 level was associated with severe neutropenia. Thus, circulating IL- 6 levels may be a predictor of the development of severe neutropenia in advanced PC patients receiving GEM therapy. No significant financial relationships to disclose.

Clinical significance of elevation of the serum IL-6 level in patients with advanced pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 181-181
Author(s):  
S. Mitsunaga ◽  
M. Ikeda ◽  
K. Nakachi ◽  
I. Ohno ◽  
S. Shimizu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Volume ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Japanese Version ◽  
Serum Levels ◽  
Ecog Performance Status ◽  
Reactive Protein ◽  
Treatment Naïve ◽  
Median Change

181 Background: IL-6, one of the pro-inflammatory cytokines, is a recognized mediator of cachexia and cancer cell invasion. It has been reported that elevation of the serum IL-6 level may be associated with deterioration of the clinical condition and tumor progression in advanced pancreatic cancer (PC) patients. The aim of this study was to clarify the clinical features of increased serum IL-6 levels in patients with advanced PC receiving chemotherapy. Methods: Patients with treatment-naïve unresectable PC and no obvious infectious conditions were eligible for this study. Serum levels of IL-6 were measured by an electrochemiluminescence assay. Symptoms were rated numerically from 0 to 10 using the Japanese version of the M. D. Anderson Symptom Inventory. Tumor volume was calculated as the sum of the long diameters of the tumors. The measurements were performed before chemotherapy and at one month after the start of chemotherapy. Results: A total of 87 patients (male/female: 41/46; ECOG performance status: 0/1/2: 59/26/1; media age: 66 years) were enrolled; all patients were administered systemic chemotherapy (gemcitabine [GEM]/GEM+S-1/GEM+other/S-1: 52/11/9/15). The median serum level of IL-6 was 1.3 pg/mL before chemotherapy (at baseline) and 1.8 pg/mL at one-month after the start of chemotherapy. The median change of IL-6 from the baseline was +0.18 pg/mL. Patients with increase of the serum IL-6 level by more than 0.18 pg/mL were assigned to the elevated IL-6 group (n=42; median change in IL-6: +1.66 pg/mL). The elevated IL-6 group showed more sadness (p=0.019), numbness (p=0.008), and gain of body weight (p=0.016) at the baseline as compared to the non-IL-6-elevated group (n=42; median change in IL-6: -0.27 pg/mL). Comparison of the elevated and non-IL-6-elevated groups revealed a greater degree of increase in the tumor volume (p=0.015), deterioration of nausea (p=0.046) and vomiting (p=0.028), neutrophilia (p=0.004), and elevation of the serum C-reactive protein (p=0.011) in the elevated IL-6 group than in the non-IL-6-elevated group. Conclusions: Elevation of the serum IL-6 level may be associated withsymptom deterioration, increase of the tumor mass, and inflammatory reaction in patients with advanced PC. No significant financial relationships to disclose.

Tolerability and clinical outcomes in elderly patients with advanced pancreatic cancer treated with FOLFIRINOX.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 404-404 ◽  
Author(s):  
Taikan Yamamoto ◽  
Yu Sunakawa ◽  
Yutaro Kubota ◽  
Teppei Tagawa ◽  
Yasuhiro Kaga ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Elderly Patients ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
The Elderly ◽  
Elderly Group ◽  
Severe Neutropenia ◽  
Severe Toxicity ◽  
Ecog Performance Status ◽  
Significant Difference

404 Background: FOLFIRINOX, a combination chemotherapy of 5-FU, oxaliplatin, and irinotecan, has contributed to the overall survival (OS) benefit of advanced pancreatic cancer (PC), of which a major concern is severe toxicity such as neutropenia and diarrhea. Some elderly patients (pts) with PC need such an intensive chemotherapy in practical treatment; however, tolerability and efficacy for the regimen in the elderly are not well known. We report a retrospective analysis for toxicity and efficacy of FOLFIRINOX treatment in elderly pts with advanced PC. Methods: We analyzed pts with unresectable/metastatic PC, ECOG performance status 0 or 1, neutrocyte over 1500/mm3, and hemoglobin over 9g/dl, who received FOLFIRINOX as 1st- or 2nd-line therapy between November 2012 and July 2015 in 3 institutes of Showa University, Japan. All pts were divided into two groups, elderly group with pts 65 years of age or older and younger group with pts under 65 years old, then were compared in the toxicity and efficacy of FOLFIRINOX treatment. Results: Fifty-nine pts (median age: 62 years) were enrolled in this study: elderly and younger groups included 26 pts (median age: 70 years) and 33 pts (median age: 57 years), respectively. Severe neutropenia with grade 4 was numerically more frequent in the elderly group compared to the younger group (54% vs. 36%, p = 0.17). However, rate of febrile neutropenia was similar between the groups: 3 (12%) pts for the elderly group and 2 (6%) pts for the younger group. There was no difference in frequency of any grade toxicities, and no FOLFIRINOX treatment-related death was observed in both groups. Response rate was 14% (5/26) for the elderly group and 33% (11/33) for the younger group, with no significant difference (p = 0.22). Median progression-free survival (PFS) and OS were comparable between the elderly and younger groups (5.3 months vs. 5.4 months, log-rank p = 0.47 for PFS; not-reached vs. 10.7 months, long-rank p = 0.49 for OS). Conclusions: Our study suggests that FOLFIRINOX treatment is tolerable and active for the elderly pts with advanced PC, although frequency of severe neutropenia is higher in the elderly compared to the younger pts.

Interleukin-6, Hepcidin, and Other Biomarkers in Anemia of Chronic Disease (ACD) and Chemotherapy-Induced Anemia (CIA): Potential Therapeutic Targets.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2086-2086 ◽  
Author(s):  
Saroj Vadhan-Raj ◽  
Xiao Zhou ◽  
Carlos E. Bueso-Ramos ◽  
Shreyaskumar Patel ◽  
Robert S Benjamin ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Inflammatory Cytokines ◽  
Linear Regression Analysis ◽  
Transferrin Saturation ◽  
Serum Levels ◽  
Serum Samples ◽  
Anemia Of Chronic Disease ◽  
Baseline Serum ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Abstract Abstract 2086 Background: Anemia in patients with malignancies can be multifactorial including anemia of chronic disease (ACD), also known as anemia of inflammation (AI), and chemotherapy (CT)-induced anemia (CIA) from myelosuppression. Although, exact mechanism for ACD is not known, induction of hepcidin, a key iron-regulatory hormone, by Interleukin (IL)-6 and other pro-inflammatory cytokines with resulting hypoferremia and limitation of iron supply to the bone marrow appear to be major contributors to pathogenesis of anemia. Hepcidin reduces iron levels by inducing degradation of the cellular iron exporter, ferroportin. The objective of this study was to examine the levels of various cytokines/regulators that may play role in ACD. Methods: Chemo-naïve patients with sarcoma scheduled to initiate first-line doxorubicin-based chemotherapy had blood samples drawn at baseline, and following chemotherapy (post cycles1, 3 and 6) for analysis of pro-inflammatory cytokines/other biomarkers of anemia. Serum samples were analyzed for IL-1β, IL-6, TNF-α, Hepcidin, hemojuvelin, ferroportin, soluble transferrin receptor (sTFR), and C-reactive protein (CRP) using ELISA techniques (R&D Diagnostics, Uscn Life Science Inc, or Abnova). Correlations between these biomarkers and Hgb levels at baseline and during the study period were calculated by linear regression analysis (SAS 9.2). Results: Of the 49 patients enrolled on to the clinical trial, there were 26 (53%) women and 23 (47%) men, with median age 45 years (range 19–65 years). Twenty-five percent of the patients had Hgb less than 12g/dL (range, 8.9–15.9 g/dL) prior to CT. At baseline, 50% of the pts had hypoferremia with low serum iron and transferrin saturation <20%. Baseline serum levels of IL-6 (r= −0.73, p<0.0001), hepcidin (r= −0.46, p=0.005), CRP (r= −0.46, p=0.003), sTFR (r= −0.32, p=0.064) inversely correlated with hemoglobin levels prior to CT, supporting their role in ACD. During CT (median 4, range; 1–6 cycles), Hgb declined in all pts with 55% requiring PRBC transfusions (77% of pts starting with baseline Hgb < 12 g/dL vs 47% of pts with baseline Hgb > 12 g/dL). Interestingly, as shown below, Hepcidin, IL-6, and sTFR all significantly negatively correlated with Hgb levels during CT. No significant correlation was found for IL-1β, TNF-α, ferroportin, or hemojuvelin levels with Hgb. Conclusions: IL-6 and Hepcidin pathway appears to play an important role in anemia in cancer patients before and during CT. Treatment with novel agents targeting this pathway may provide effective strategies for prevention and treatment of ACD and CIA. Disclosures: Vadhan-Raj: JNJ: Research Funding.

Clinical significance of serum alkaline phosphatase level in advanced pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 183-183 ◽  
Author(s):  
I. Ohno ◽  
S. Mitsunaga ◽  
K. Nakachi ◽  
S. Shimizu ◽  
H. Takahashi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Liver Metastasis ◽  
Prognostic Factor ◽  
Performance Status ◽  
Elevated Serum ◽  
Advanced Pancreatic Cancer ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Bile Stasis ◽  
Low Serum

183 Background: Alkaline phosphatase (ALP) is an enzyme that is elevated by various hepatobiliary diseases. Generally its elevation is thought to indicate bile stasis. There are some reports that show ALP is an important prognostic factor for several cancers such as colon, lung, and gastric cancer. Often it is speculated that ALP elevation indicates bile stasis caused by liver metastasis. However, the significance of ALP elevation in advanced pancreatic cancer (APC) patients is not well evaluated. The aim of this study was to determine the significance of elevated serum ALP as a prognostic factor in patients with APC even without jaundice and liver metastasis. Methods: Serum ALP levels were measured in 393 patients with APC receiving gemcitabine monotherapy before treatment, and according to those levels, patients were subgrouped (ALP<upper normal limit (UNL), UNL-500 U/L, 501-700 U/L, 701-1000 U/L, 1000U/L < ALP). The clinical data of each group were analyzed to see characteristics of elevated ALP patients. The relationship between ALP level and survival, response were also examined. Results: The elevated ALP group included poor performance status (PS>1) patients (41.3%, p=0.001), and associated with low serum albumin (3.31±0.38, p<0.01). The elevated ALP group (median survival time (MST) 112 days) showed significantly worse prognosis and lower disease control rate compared to the normal ALP group (MST 217days) (p<0.001, p<0.001). Multivariate analysis revealed ALP (p<0.001), CRP (p<0.001), ascites (p<0.001), distant metastasis (p=0.003), white blood cell count (p=0.005), PS (p=0.020), AST (p=0.020), and ALT (p=0.020) were independent prognostic factors. Similar results were seen in liver metastasis free patients without jaundice. Conclusions: Elevated serum ALP level correlated with poor performance status and low serum albumin. ALP was also the independent prognostic factor in liver metastasis free APC patients without jaundice. No significant financial relationships to disclose.

scholarly journals Evaluation of pro-inflammatory cytokines in frail Tunisian older adults

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242152
Author(s):  
Sonia Hammami ◽  
Imen Ghzaiel ◽  
Souha Hammouda ◽  
Nabil Sakly ◽  
Mohamed Hammami ◽  
...  
Keyword(s):  
Older Adults ◽  
Inflammatory Cytokines ◽  
Geriatric Assessment ◽  
Nutritional Assessment ◽  
Short Form ◽  
Mini Nutritional Assessment ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

The present study was undertaken to evaluate serum levels of pro-inflammatory cytokines in Tunisian older adults and to examine the relationships between inflammatory marker levels, geriatric, and biochemical parameters. A cross-sectional study was conducted in a population of Tunisian older adults (N = 141, aged 65 and over). Patients were recruited from the Department of Internal Medicine, Fattouma Bourguiba University Hospital (Monastir, Tunisia) and from a nursing home (Sousse, Tunisia). Comprehensive geriatric assessment, history taking and examination including functional and nutritional assessment were done for each participant. Enzyme-linked immunosorbent assay (ELISA) test was used to measure serum cytokine (TNF-α, IL-8, IL-6) levels. The modified Short Emergency Geriatric Assessment score (SEGAm) were used to classify patients as 51 very-frail, 40 frail, and 50 non-frail. The age of the participants (80 men, 61 women) ranged from 65 to 97 years. Serum levels of TNF-α, IL-8 and C-reactive protein (CRP) were significantly higher in very-frail participants compared to frail and non-frail ones. However, no significant differences in IL-6 levels were detected among frailty groups. After adjustment for age, CRP and IL-8 levels remained significantly associated with frailty. Analysis of the receiver operating characteristic (ROC) curve corresponding to IL-8 showed an area under the curve of 0.7 (p = 0.003; 95% CI [0.58–0.81]) and a predictive threshold of 5.27 pg/ml. Positive correlations were found between frailty score, IL-6, and IL-8 levels. In addition, a significant positive correlation was observed between IL-8 levels and Timed Up and Go test results. However, a negative correlation was observed between Mini Nutritional Assessment Short-Form score, IL-6 and CRP levels, as well as between Activities of Daily Living score and serum levels of TNF-α, IL-6, and CRP. In conclusion, the key findings of this study collectively support a role of pro-inflammatory cytokines, TNF-α, CRP, and especially IL-8 in the development of frailty in older adults.

Identification of prognostic factors for patients with advanced pancreatic cancer by proteomics

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4615-4615
Author(s):  
J. Matsubara ◽  
M. Ono ◽  
H. Ueno ◽  
T. Okusaka ◽  
J. Furuse ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Prediction Model ◽  
Statistical Significance ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Information Criterion ◽  
Survival Prediction ◽  
Current Standard ◽  
Ecog Performance Status ◽  
Wbc Count

4615 Background: Gemcitabine monotherapy is the current standard for patients with advanced pancreatic cancer (PC). Its efficacy, however, varies significantly depending on individuals. This study was aimed at discovering a new diagnostic biomarker that can estimate the outcome of patients after receiving the therapy. Methods: All patients included in this study (304 patients) had metastatic PC and received at least two cycles of gemcitabine monotherapy. We compared the baseline plasma proteome between representative 29 short-term survivors (survived for less than 100 days) and 31 long-term survivors (survived for more than 400 days) using quantitative mass spectrometry (MS). Results: Among a total of 45,277 peptide peaks, we identified 637 peaks whose intensities were significantly different (p<0.001, Welch's t-test). The 2 MS peaks with the highest statistical significance (p=2.57×10-4 and 5.03×10-4) were revealed to be derived from α1-antitrypsin (AT) and α1-antichymotrypsin (ACT), respectively, by tandem MS. The levels of AT and ACT, WBC count, platelet count, alkaline phosphatase, and ECOG performance status were selected using a forward stepwise procedure by Akaike's information criterion, and a scoring system (nomogram) was constructed to estimate the prognosis of individual patients. Among the selected parameters the AT level was found to be the second most significant contributor to the nomogram (p=0.0003; Table ). This survival prediction model was internally validated using a bootstrap approach with 200 resamples. Conclusions: Our survival prediction model including values of AT and ACT seems to have high practical utility and may lead to tailoring the treatment of patients with advanced PC. Modification of therapeutics may need to be taken into consideration for patients with increased AT and ACT. [Table: see text] [Table: see text]

Phase I trial of enzalutamide in combination with gemcitabine and nab-paclitaxel for the treatment of advanced pancreatic cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 467-467
Author(s):  
Amit Mahipal ◽  
Gregory M. Springett ◽  
Nancy Burke ◽  
Barbara Bertels ◽  
Georgine Wapinsky ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Dose Level ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Stage Iv ◽  
Ecog Performance Status ◽  
Treatment Standard ◽  
Cancer Models ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Grade 3

467 Background: Despite recent advances, patients with metastatic pancreatic cancer have a very poor prognosis with a median survival of less than 1 year. Sex steroid hormones may play an important role in the growth and progression of pancreatic cancer. Anti-androgen drugs have demonstrated to have activity in pre-clinical pancreatic cancer models. In this Phase 1a/Ib trial, we evaluated the safety and tolerability of the combination of enzalutamide, a novel androgen receptor (AR) antagonist with gemcitabine and nab-paclitaxel. Methods: Pts with histologically confirmed metastatic pancreatic adenocarcinoma were included in this trial as a first-line treatment. Standard 3+3 dose escalation design was used to evaluate 2 dose levels of enzalutamide: 80 mg and 160 mg daily. Gemcitabine 1,000 mg/m2 was administered IV on days 1, 8 and 15 of 28-day cycle. The dose of nab-paclitaxel was 125 mg/m2 IV on days 1, 8 and 15. The DLT period was 28-days or until the beginning of the second cycle. Imaging studies were performed every 2 cycles. Results: Eight pts with stage IV pancreatic cancer have been enrolled in this trial, 5 pts at the first dose level and 3 pts at the second dose level. The median age was 64 years (50-80 years). All pts were male with an ECOG performance status of 1. Five pts had liver metastases. One patient was non-evaluable for DLT. No DLTs have been observed. Grade 3 treatment related AEs include febrile neutropenia (n=1), Neutropenia (n=1), ALT elevation (n=1). Grade 2 anemia and thrombocytopenia was seen in one patient. Grade 1 AEs included anemia (n=2), neutropenia (n=4), thrombocytopenia (n=3), diarrhea (n=1), fatigue (n=2), pruritis (n=1), nausea (n=1), hyponatremia (n=1) and AST elevation (n=1). Three pts had restaging studies performed and all had stable disease by RECIST criteria. There were decreases in size of target lesions in all the 3 patients along with a decrease in CA 19-9 levels. Conclusions: Enzalutamide at the dose of 160 mg daily is safe to administer in combination with gemcitabine and nab-paclitaxel. No unexpected toxicity has been observed. Cytopenias secondary to chemotherapy is common. Preliminary signals of efficacy were observed with this combination. Clinical trial information: NCT02138383.

scholarly journals Immunomodulatory Effect of Vitamin C on Proinflammatory Cytokines Production in Ossimi Lambs (Ovis aries) with Pneumonic Pasteurellosis

Animals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3374
Author(s):  
Mohamed Abdo Rizk ◽  
Shimaa Abd El-Salam El-Sayed ◽  
Doaa Salman ◽  
Basma H. Marghani ◽  
Hossam Elshahat Gadalla ◽  
...  
Keyword(s):  
Vitamin C ◽  
Inflammatory Cytokines ◽  
Interleukin 1 ◽  
Serum Levels ◽  
Ovis Aries ◽  
Necrosis Factor Alpha ◽  
Pneumonic Pasteurellosis ◽  
Tnf Α ◽  
The Impact ◽  
Pro Inflammatory Cytokines

In this study, we have investigated the impact of vitamin C on the production of pro-inflammatory cytokines (interleukin 1 β (IL-1 β), interleukin 6 (IL-6), interleukin 12p40 (IL-12p40), interferon gamma (IFNγ), and tumor necrosis factor alpha (TNF-α)) in lambs naturally infected by pneumonic pasteurellosis. Of 37 lambs, 18 lambs were identified to have pneumonic pasteurellosis and randomly allocated into two equal groups. Single subcutaneous dose of tulathromycine alone (2.5 mg kg−1) or tulathromycine combined with vitamin C (3 gm kg−1) were administrated to the diseased lambs. The serum levels of IL-1β, IL-6, IFN-γ, and TNF-α were returned to the normal levels in pneumonic lambs treated with the combination therapy. The obtained results indicate the selective influences of vitamin C on pro-inflammatory cytokines production in sera of lambs with pneumonic pasteurellosis and highlights the value of vitamin C as a potential anti-inflammatory drug and ideal immunomodulatory agent.

scholarly journals Clinical and Tumor Characteristics of Patients with High Serum Levels of Growth Differentiation Factor 15 in Advanced Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4842
Author(s):  
Hidetaka Suzuki ◽  
Shuichi Mitsunaga ◽  
Masafumi Ikeda ◽  
Takao Aoyama ◽  
Kazumi Yoshizawa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Liver Metastasis ◽  
Group Performance ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Serum Levels ◽  
Pancreatic Disease ◽  
High Serum ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor

We aimed to evaluate the association of circulating growth differentiation factor 15 (GDF-15) with cachexia symptoms and the biological activity of advanced pancreatic cancer (APC). Treatment-naïve patients with liver metastasis of APC or with benign pancreatic disease were retrospectively analyzed. Clinical data, blood samples, and biopsy specimens of liver metastasis were collected prior to anti-cancer treatment. Serum GDF-15 levels and multiple protein expressions in lysates extracted from liver metastasis were measured by enzyme-linked immuno-sorbent assay and reverse-phase protein array, respectively. The cut-off for serum GDF-15 was determined as 3356.6 pg/mL, the mean plus two standard deviations for benign pancreatic disease. The high-GDF-15 group was characterized as showing low Karnofsky performance status (KPS) (p = 0.037), poor Eastern Cooperative Oncology Group performance status (ECOG-PS) (p = 0.049), severe appetite loss (p = 0.011), and high serum levels of carbohydrate antigen 19-9 (p = 0.019) and C-reactive protein (p = 0.009). Tumors of the high-GDF-15 group expressed high levels of phosphorylated (p)JNK (p = 0.007) and pAkt (p = 0.040). APC patients with high serum GDF-15 showed signatures of cachexia and activation of the signaling pathways involving Akt and JNK in the tumor. This study indicated circulating GDF-15 could be associated with cachectic symptoms in APC.

scholarly journals Beneficial effects of diacerein on adipokines and pro-inflammatory cytokines involved in diet-induced nonalcoholic steatohepatitis in rats

2017 ◽  
Vol 6 (4) ◽  
pp. 811 ◽  
Author(s):  
Omaima M. Abd Allah
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Inflammatory Cytokines ◽  
Blood Lipids ◽  
Fasting Blood Glucose ◽  
Liver Weight ◽  
Serum Levels ◽  
Beneficial Effects ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Background: Non-alcoholic steatohepatitis (NASH) is considered as a progressive liver disease, so effective therapies are needed to ameliorate hepatic steatosis, inflammation and fibrosis, and to prevent the progression to cirrhosis and hepatocellular carcinoma. Diacerein is an anti-inflammatory drug that inhibits the synthesis and activity of pro-inflammatory cytokines. The present study was designed to investigate the effect of diacerein on pro-inflammatory cytokines as well as adipokines involved in diet-induced NASH rat model.Methods: Thirty-two adult male rats were divided into four groups: control, diacerein-treated, NASH-untreated and NASH+diacerein-treated groups. NASH was induced by feeding rats with high-fat and high-cholesterol diet for 12 weeks. Body weight, liver weight, fasting blood glucose and insulin levels for estimation of insulin resistance, blood lipids, alanine transaminase, and aspartate aminotransferase were evaluated. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), adiponectin, visfatin and leptin were also detected. Histopathological examination of liver sections was performed.Results: Diacerein significantly reduced liver weight, fasting blood glucose, insulin level, transaminases and ameliorates insulin resistance with favourable effects on blood lipids. These results were accompanied with a significant reduction in serum levels of TNF-α, IL-1β, IL-6, and visfatin, while, adiponectin was significantly increased and leptin was insignificantly affected. Liver sections revealed that diacerein reduced steatosis and lobular inflammatory grades.Conclusions: These data suggest that diacerein administration may have a potential usefulness in the prevention of NASH as a possible result of inhibition of pro-inflammatory cytokines and the beneficial effects on adipokines especially adiponectin and visfatin.

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