1.Pathophysiological Role of Hormones and Cytokines in Cancer Cachexia.
Hyun Jung KIM ; Han Jo KIM ; Jina YUN ; Kyoung Ha KIM ; Se Hyung KIM ; Sang Cheol LEE ; Sang Byung BAE ; Chan Kyu KIM ; Nam Su LEE ; Kyu Taek LEE ; Seong Kyu PARK ; Jong Ho WON ; Hee Sook PARK ; Dae Sik HONG
Journal of Korean Medical Science 2012;27(2):128-134
We investigated the role of fasting hormones and pro-inflammatory cytokines in cancer patients. Hormones (ghrelin, adiponectin, and leptin) and cytokines (TNF-alpha, IFN-gamma, and IL-6) were measured by ELISA or RIA in lung cancer and colorectal cancer patients before the administration of cancer therapy, and measurements were repeated every 2 months for 6 months. From June 2006 to August 2008, 42 patients (19 with colorectal cancer and 23 with lung cancer) were enrolled. In total, 21 patients were included in the cachexia group and the others served as a comparison group. No significant difference in the initial adiponectin, ghrelin, TNF-alpha, IFN-gamma, or IL-6 level was observed between groups, although leptin was significantly lower in cachectic patients than in the comparison group (15.3 +/- 19.5 vs 80.9 +/- 99.0 pg/mL, P = 0.007). During the follow-up, the patients who showed a > 5% weight gain had higher ghrelin levels after 6 months. Patients exhibiting elevated IL-6 levels typically showed a weight loss > 5% after 6 months. A blunted adiponectin or ghrelin response to weight loss may contribute to cancer cachexia and IL-6 may be responsible for inducing and maintaining cancer cachexia.
Adiponectin/analysis
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Aged
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Antineoplastic Agents/therapeutic use
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Cachexia/*physiopathology
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Colorectal Neoplasms/drug therapy/*metabolism/mortality
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Cytokines/*analysis
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Female
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Follow-Up Studies
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Ghrelin/analysis
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Humans
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Interferon-gamma/analysis/physiology
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Interleukin-6/analysis
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Leptin/analysis
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Lung Neoplasms/drug therapy/*metabolism/mortality
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Male
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Middle Aged
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Peptide Hormones/*analysis
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Prognosis
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Prospective Studies
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Survival Rate
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Tumor Necrosis Factor-alpha/analysis
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Weight Gain
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Weight Loss
2.Suppression of hepatic tumor growth and metastasis by metronomic therapy in a rat model of hepatocellular carcinoma.
Jeong Won JANG ; Seong Tae PARK ; Jung Hyun KWON ; Chan Ran YOU ; Jong Young CHOI ; Chan Kwon JUNG ; Si Hyun BAE ; Seung Kew YOON
Experimental & Molecular Medicine 2011;43(5):305-312
Although continuous low-dose (metronomic [MET]) therapy exerts anti-cancer efficacy in various cancer models, the effect of long-term MET therapy for hepatocellular carcinoma (HCC) remains unknown. This study assessed the long-term efficacy of MET on suppression of tumor growth and spontaneous metastasis in a rat model of HCC induced by administration of diethylnitrosamine for 16 wk. The rats were divided into 3 groups: MTD group received intraperitoneal (i.p.) injections of 40 mg/kg cyclophosphamide on days 1, 3, and 5 of a 21-day cycle; Control and MET groups received i.p. injections of saline and 20 mg/kg cyclophosphamide twice a week, respectively. Anti-tumor and anti-angiogenic effects and anti-metastatic mechanisms including matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) were evaluated. Twelve wk of MET therapy resulted in a significant reduction in intrahepatic tumors than control or MTD therapy. The MET group had fewer proliferating cell nuclear antigen-positive cells and decreased hypoxia-inducible factor-1alpha levels and microvessel density. Lung metastases were detected in 100%, 80%, and 42.9% in the control, MTD, and MET groups, respectively. MET therapy significantly decreased expression of TIMP-1, MMP-2 and -9. For mediators of pro-MMP-2 activation, MET therapy induced significant suppression in the TIMP-2 and MMP-14 level. The survival in the MET group was significantly prolonged compared to the control and MTD groups. Long-term MET scheduling suppresses tumor growth and metastasis via its potent anti-angiogenic properties and a decrease in MMPs and TIMPs activities. These results provide a rationale for long-term MET dosing in future clinical trials of HCC treatment.
Animals
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Antineoplastic Agents/*administration & dosage/*pharmacology
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Carcinoma, Hepatocellular/chemically induced/*drug therapy/mortality/pathology
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Cell Proliferation/drug effects
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Cyclophosphamide/*administration & dosage/*pharmacology
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Diethylnitrosamine
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Disease Models, Animal
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Gene Expression Regulation, Neoplastic/*drug effects
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Liver Cirrhosis/chemically induced
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Liver Neoplasms/chemically induced/*drug therapy/mortality/pathology
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Lung Neoplasms/drug therapy/pathology/secondary
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Male
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Matrix Metalloproteinases/metabolism
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Neovascularization, Pathologic/enzymology/physiopathology
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Rats
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Rats, Sprague-Dawley
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Survival Analysis
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Tissue Inhibitor of Metalloproteinases/metabolism
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Tumor Burden/drug effects
3.Clinical Predictive Factors associated with First Line EGFR-TKI Efficacy in Advanced NSCLC Patients with EGFR Mutations.
Minjiang CHEN ; Yan XU ; Jing ZHAO ; Wei ZHONG ; Mengzhao WANG
Chinese Journal of Lung Cancer 2019;22(2):99-104
BACKGROUND:
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated some dramatic efficacy in advanced non-small-cell lung cancer (NSCLC) patients with activating EGFR mutation. However, progression-free survivals (PFS) among those patients who were treated with first line EGFR TKIs were inconsistent. The aim of this study is to explore the association of clinical prognostic factors with EGFR-TKI efficacy in advanced NSCLC patients.
METHODS:
The demographic and clinical characteristics of 203 patients with activating EGFR mutation treated with first generation TKI as a first-line therapy were retrospectively reviewed.
RESULTS:
Of the 203 patients enrolled in this study, 139 patients had progression of disease and 63 patients died. The subjects had a median follow up duration of 21.1months and a median PFS of 14.3 months. Partial response (PR) was achieved in 127 (66.1%) patients and stable disease (SD) rate was achieved in 55 (28.6%) patients. In univariate analysis, patients with 2 or higher ECOG score (5.1 vs 16 months, P=0.033), SD as best overall response (9.5 vs 17.9 months, P=0.030), extrathoracic metastasis (11.7 vs 27.5 months, P=0.004), liver metastasis (4.1 vs 16.0 months, P=0.000), bone metastasis (13.3 vs 21.5months, P=0.027) and pulmonary embolism (5.5 vs 16.6 months, P=0.005) had shorter PFS than those without the listed factors. Multivariable Cox regression analysis showed best overall response (HR=1.825, 95%CI: 1.107-3.008, P=0.018) and liver metastasis (HR=1.694, 95%CI: 1.146-5.756, P=0.022) were independent predictive factors of shorter PFS.
CONCLUSIONS
Despite the high efficacy of EGFR-TKI, SD as best overall response and liver metastasis predicts poorer PFS in advanced NSCLC patients with EGFR gene mutations receiving first-line therapy treatment.
Adult
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Aged
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Antineoplastic Agents
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administration & dosage
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Carcinoma, Non-Small-Cell Lung
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drug therapy
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enzymology
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genetics
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mortality
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ErbB Receptors
;
genetics
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metabolism
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Female
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Humans
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Lung Neoplasms
;
drug therapy
;
enzymology
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genetics
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Middle Aged
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Mutation
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Protein Kinase Inhibitors
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administration & dosage
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Retrospective Studies
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Treatment Outcome
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Young Adult