Impact of weight loss on circulating IL-1, IL-6, IL-8, TNF-α, VEGF-A, VEGF–C and midkine in gastroesophageal cancer patients

Krzystek−Korpacka, Małgorzata; Matusiewicz, Małgorzata; Diakowska, Dorota; Grabowski, Krzysztof; Blachut, Katarzyna; Kustrzeba−Wójcicka, Irena; Banaś, Teresa

doi:10.1016/j.clinbiochem.2007.07.013

Cited by 62 publications

(50 citation statements)

References 43 publications

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“…[11][12][13][14][15][16] IL-1b, IL-6, and TNFa are produced by tumor cells both in animal models of cachexia [17] and in cancer patients with CACS. [18] In cancer patients, the production of pro-inflammatory cytokines -an expression of systemic inflammation -may lead to an acute-phase response [19] characterized by an increase in acute-phase proteins [20] and by decreased synthesis of albumin, pre-albumin, and transferrin. [9,10] As a consequence of the acute-phase response, degradation of skeletal muscle proteins occurs, causing muscle atrophy.…”

Section: Introductionmentioning

confidence: 99%

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

et al. 2012

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Background and Objective: In patients with advanced cancer, cachexia correlates with low performance status and poor quality of life. In addition, cachexia may be associated with reduced response to chemoradiotherapy and a poor prognosis in cancer patients. Nearly all forms of cachexia are closely associated with chronic inflammation and elevated levels of inflammatory and pro-inflammatory circulating factors, including C-reactive protein (CRP), which is considered a valid laboratory and clinical marker. Among the different pathways involved in the production of inflammatory cytokines and chemokines, the vitamin Dvitamin D receptor (VDR) axis plays a fundamental role.In this study, we explore the possible association between CRP and key factors pertaining to the vitamin D axis -in particular, VDR gene polymorphisms -in cancer patients with cachexia. Although certain tumor types are more commonly associated with cachexia, even within the same tumor type there are significant differences in the extent and duration of cachexia. Such variations may be due to polymorphisms of the VDR gene that could lead to cachexia-prone genotypes or to cachexia-resistant genotypes. Identification of such genotypes could be very helpful in the management of cancer patients. Methods: Forty-three cancer patients were recruited by the Nutritional Unit of the Prato Hospital. Data on age, gender, type of cancer, stage of cancer, and nutritional assessment, as well as transferrin, ferritin, albumin, and CRP levels, were collected. Genomic DNA was extracted from peripheral blood leukocytes and amplified by polymerase chain reaction. BsmI, ApaI, TaqI, and FokI polymorphisms of the VDR gene were investigated using the respective restriction enzymes. For the different VDR polymorphisms, the absence or presence of the restriction sites were designated with capital or small letters, respectively. For example, for the BsmI polymorphism, the presence of the undigested fragment identified the B allele, whereas the presence of the digested fragment identified the b allele. Results: Cancer patients with cachexia have higher CRP levels compared with non-cachectic cancer patients, independently from the genotype. In cachectic patients, the presence of specific VDR BsmI and TaqI alleles was associated with higher CRP levels. In particular, the VDR b and T alleles were more frequent in cachectic cancer patients with elevated CRP levels than in cachectic patients with normal CRP levels. Conclusion: From these results, we hypothesize that there is an association between BsmI and TaqI VDR gene polymorphisms and the cachectic syndrome. In particular, we propose that in cancer patients, the concomitance of b and T alleles with elevated CRP levels may represent an early clinical predictor for the development of a more aggressive form of cachexia.

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Section: Introductionmentioning

confidence: 99%

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

et al. 2012

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“…IL-8 induces the full pattern of responses observed in chemotactically stimulated neutrophils, that is, activation of the motile apparatus and directional migration, expression of surface adhesion molecules, release of storage enzymes and production of reactive oxygen metabolites [38] . IL-6 and IL-8 are reported to participate in the development of cancer-related cachexia [39] , although the participation of IL-8 has not been confirmed in COPD-related body weight loss. In this study, PLA2G2D -Ser enhanced the expression of IL-6 and IL-8, compared with PLA2G2D -Gly.…”

Section: Discussionmentioning

confidence: 99%

Gly80Ser Polymorphism of Phospholipase A2-IID Is Associated with Cytokine Inducibility in A549 Cells

Igarashi

Shibata²,

Yamauchi³

et al. 2009

Respiration

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Background: The Gly80Ser polymorphism in phospholipase A2-IID (PLA2G2D, NCBI SNP reference: rs584367) is associated with a loss in body weight in patients with chronic obstructive pulmonary disease (COPD). The T allele missense mutation results in the 80th amino acid of the PLA2G2D protein changing from a glycine (Gly; C allele) to a serine (Ser; T allele). COPD patients carrying Ser lose a significant amount of weight compared with those carrying Gly. The mechanism for this weight loss following carriage of this Ser allele has not been clarified. Objectives: We aimed to evaluate whether this allelic change alters PLA2 enzymatic activity and/or pro-inflammatory cytokine inducibility. Methods: A549 cells (a human pulmonary epithelial cell line) were transfected with PLA2G2D-Gly or PLA2G2D-Ser. We evaluated PLA2 activity and cytokine expressions in these cells. Results: The enzymatic activity of sPLA2 in A549-PLA2G2D-Ser cells did not differ from the A549-PLA2G2D-Gly cells. A549-PLA2G2D-Ser cells spontaneously produced higher levels of interleukin (IL)-6 and IL-8 than A549-PLA2G2D-Gly cells. Upon tumor necrosis factor-α stimulation, IL-6 and IL-8 mRNA and protein levels in A549-PLA2G2D-Ser cells were elevated compared with those of A549-PLA2G2D-Gly cells. Upon hydrogen peroxide stimulation, IL-8 mRNA and protein levels in A549-PLA2G2D-Ser cells were higher than those of A549-PLA2G2D-Gly cells. Conclusions:PLA2G2D-Ser enhances the expression of IL-6 and IL-8 compared with PLA2G2D-Gly. This enhanced cytokine expression observed with the allelic change in PLA2G2D may be associated with the body weight loss seen in COPD patients.

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“…[13,14] Moreover, in studies about cachexia in patients with gastroesophageal cancer, it has been demonstrated that other pro-inflammatory cytokines such as IL-8 and vascular endothelial growth factor-A (VEGF-A) might be effective as well. [15] Recently, inadequate oral intake, weight loss, and systemic inflammation have been suggested to be important factors in identifying cachectic cancer patients, particularly those with esophageal carcinoma. [16] Nevertheless, the relationship between weight loss and acute phase reactants in cancer-related cachexia has been reported only in lung cancer, pancreatic cancer, and melanoma.…”

Section: Discussionmentioning

confidence: 99%

Prognostic importance of serum CRP, prealbumin, and transferrin levels in patients with advanced stage esophageal cancer

Aydın¹

2011

Turkish J Thorac Cardiovasc Surg

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Amaç: Bu çalışmada stent takılarak tedavi edilen ileri evre özofagus kanserli hastalarda serum C-reaktif protein (CRP), prealbumin ve transferrin düzeylerinin prognostik değeri araştırıldı. Ça lış ma pla nı: Temmuz 2007 ve Aralık 2008 tarihleri arasında gerçekleştirilen prospektif randomize bir çalış-mada lokal olarak ilerlemiş hastalık veya uzak organ metastazı nedeniyle stent takılarak tedavi edilen ardışık 61 hastada, stent takılmadan 1-3 gün önce serum CRP, prealbumin ve transferrin düzeyleri çalışıldı. Tüm hastalar ölünceye kadar takip edildi. Bul gu lar: Stent tüm hastalarda başarı ile takılarak oral alım tekrar sağlandı. İşleme bağlı mortalite gözlenmedi. Hastaların ortalama sağkalım süresi 164.3±120.3 gün (dağılım 15-450 gün) idi. Serum CRP seviyesi ≥10 mg/L olan hastalarda (n=38) ortalama sağkalım 103.2±82.3 gün iken serum CRP seviyesi <10 mg/L olan hastalarda (n=23) ortalama sağkalım 265.4±121.2 gün idi. Serum prealbumin seviyesi ≥15 mg/L olan hastalarda (n=28) ortalama sağkalım 237.5±132.7 gün iken serum prealbumin seviyesi <15 mg/L olan hastalarda (n=33) ortalama sağkalım 102.3±79.6 gün idi. Serum transferrin seviyesi ≥200 mg/L olan hastalarda (n=25) ortalama sağkalım 211.6±130.2 gün iken serum transferrin seviyesi <200 mg/L olan hastalarda (n=36) ortalama sağkalım 131.5±113.8 gün idi. Referans serum CRP, prealbumin ve transferrin seviyelerinin sağ-kalımla ilişkisi istatistiksel olarak anlamlı idi (sırasıyla p<0.001, p<0.001 ve p= 0.003). So nuç: İleri evre özofagus kanserli hastalarda özofageal stent uygulamasından önce serum CRP, prealbumin ve transferrin düzeyleri kolaylıkla saptanabilir ve hastaların prognozları hakkında fikir elde edilebilir.Anah tar söz cük ler: C-reaktif protein; özofagus kanseri; prealbü-min; sağkalım; transferrin.Background: This study investigated the prognostic value of serum C-reactive protein (CRP), prealbumin, and transferrin levels in patients with advanced stage esophageal cancers treated with stent placement. Methods: In a prospective, randomized study conducted between July 2007 and December 2008, serum CRP, prealbumin, and transferrin levels were determined 1-3 days prior to stent placement in 61 consecutive patients who underwent stent placement due to locally advanced disease or distant organ metastasis. All patients were followed until death. Results:The stent was successfully placed in all patients and oral intake was restored. There was no procedure-related mortality. The mean survival period of the patients was 164.3±120.3 days (range 15 to 450 days). Whereas the mean survival period was 103.2±82.3 days in patients with a serum CRP level ≥10 mg/L (n=38), it was 265.4±121.2 days in patients with a serum CRP level <10 mg/L (n=23). While the mean survival period was 237.5±132.7 days in patients with a serum prealbumin level ≥15 mg/L (n=28), the mean survival period was 102.3±79.6 days in patients with a serum prealbumin level <15 mg/L (n=33). The mean survival period was 211.6±130.2 days in patients with a serum transferrin level ≥200 mg/L (n=25) while the mean ...

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Impact of weight loss on circulating IL-1, IL-6, IL-8, TNF-α, VEGF-A, VEGF–C and midkine in gastroesophageal cancer patients

Cited by 62 publications

References 43 publications

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

Gly80Ser Polymorphism of Phospholipase A2-IID Is Associated with Cytokine Inducibility in A549 Cells

Prognostic importance of serum CRP, prealbumin, and transferrin levels in patients with advanced stage esophageal cancer

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