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Boussios S, Sheriff M, Ovsepian SV. Molecular Biology of Cancer-Interplay of Malignant Cells with Emerging Therapies. Int J Mol Sci 2024; 25:13090. [PMID: 39684799 DOI: 10.3390/ijms252313090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 11/26/2024] [Indexed: 12/18/2024] Open
Abstract
Cancer is currently one of the leading causes of death worldwide, and according to data from the World Health Organization reported in 2020, it ranks as the second leading cause of death globally, accounting for 10 million fatalities [...].
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Affiliation(s)
- Stergios Boussios
- Faculty of Medicine, Health and Social Care, Canterbury Christ Church University, Canterbury CT1 1QU, UK
- Faculty of Life Sciences & Medicine, School of Cancer & Pharmaceutical Sciences, King's College London, Strand, London WC2R 2LS, UK
- Kent Medway Medical School, University of Kent, Canterbury CT2 7LX, UK
- AELIA Organization, 9th Km Thessaloniki-Thermi, 57001 Thessaloniki, Greece
- Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK
| | - Matin Sheriff
- Department of Urology, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK
| | - Saak V Ovsepian
- Faculty of Engineering and Science, University of Greenwich London, Chatham Maritime, Gillingham ME4 4AG, UK
- Faculty of Medicine, Tbilisi State University, Tbilisi 0179, Georgia
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2
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Koning T, Calaf GM. Association of Inflammation and Immune Cell Infiltration with Estrogen Receptor Alpha in an Estrogen and Ionizing Radiation-Induced Breast Cancer Model. Int J Mol Sci 2024; 25:8604. [PMID: 39201290 PMCID: PMC11354366 DOI: 10.3390/ijms25168604] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 07/26/2024] [Accepted: 08/03/2024] [Indexed: 09/02/2024] Open
Abstract
Breast cancer is the most diagnosed cancer in the world, and it is the primary cause of cancer death for women. The risk of breast cancer is increased by endogenous factors like hormones and exogenous factors like radiation exposure that causes damage to the mammary epithelial cells leading to an inflammatory response. Chronic inflammation creates a microenvironment composed of, among other factors, chemokines, and interleukins, which promote cancer. The gene expression of the interleukin 1 receptor type 1, the interleukin 1 receptor antagonist, the Interleukin 1 Receptor Accessory Protein, the interleukin 6 cytokine family signal transducer, the C-X-C motif chemokine ligand 3, the C-X-C motif chemokine ligand 5, and the C-X-C motif chemokine ligand 6 were analyzed in an estrogen and radiation experimental breast cancer model. Furthermore, the expression of these genes was correlated with immune cell infiltration, estrogen receptor expression, and their clinical relevance in breast cancer patients based on data provided by The Cancer Genome Atlas database online. Results given by the experimental breast cancer model showed that all genes related to inflammation respond to ionizing radiation alone or in combination with estrogen. On the other hand, the immune response depended on the breast cancer type and on the expression of the gene that encoded the estrogen receptor. Finally, the importance of the expression of these genes in breast cancer is such that high IL1R1 or IL1RAP is strongly related to patient survival. These findings may help to improve the understanding of the role of immune molecules in carcinogenesis and enhance therapeutic approaches.
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Affiliation(s)
| | - Gloria M. Calaf
- Instituto de Alta Investigación, Universidad de Tarapacá, Arica 1000000, Chile;
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Aarstad HH, Moe SEE, Lybak S, Bruserud Ø, Tvedt THA, Aarstad HJ. Plasma IL-1 and IL-6 Family Cytokines with Soluble Receptor Levels at Diagnosis in Head and Neck Squamous Cell Carcinoma: High Levels Predict Decreased Five-Year Disease-Specific and Overall Survival. Cancers (Basel) 2024; 16:1484. [PMID: 38672565 PMCID: PMC11048558 DOI: 10.3390/cancers16081484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 04/09/2024] [Accepted: 04/12/2024] [Indexed: 04/28/2024] Open
Abstract
Activation of the acute-phase cascade (APC) has been correlated with outcomes in various cancers, including head and neck squamous cell carcinoma (HNSCC). Primary drivers of the APC are the cytokines within the interleukin-6 (IL-6) and IL-1 families. Plasma levels of IL-6 family cytokines/soluble receptors (IL-6, IL-27, IL-31, OSM, CNTF, soluble (s-)gp130, s-IL-6Rα) and IL-1 family members (IL-1RA, s-IL-33Rα) were determined at diagnosis for 87 human papillomavirus (HPV)-negative (-) HNSCC patients. We then studied the 5-year Disease-Specific Survival (DSS) and Overall Survival (OS). Increased plasma levels of IL-6 (p < 0.001/p < 0.001) (DSS/OS), IL-31 (p = 0.044/p = 0.07), IL-1RA (p = 0.004/p = 0.035), soluble (s)-IL-6Rα p = 0.022/p = 0.035), and s-gp130 (p = 0.007/p = 0.003) at diagnosis were predictors of both OS and DSS from HPV(-) HNSCC patients. The cytokine DSS/OS predictions were associated with TNM stage and smoking history, whereas the soluble receptors IL-6Rα, gp130, and IL33Rα more uniquely predicted DSS/OS. Clinically, IL-6 levels above 2.5 pg/mL yielded 75% specificity and 70% sensitivity for DSS. In conclusion, high plasma levels of IL-6, IL-31, and IL-1RA, as well as the soluble receptors IL-6Rα, gp130, and IL33Rα, predicted clinical outcome. This shows their potential as candidates for both general therapy and immune therapy stratification, as well as being future platforms for the development of new immunotherapy.
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Affiliation(s)
- Helene Hersvik Aarstad
- Department of Otolaryngology/Head and Neck Surgery, Haukeland University Hospital, 5009 Bergen, Norway; (H.H.A.); (S.E.E.M.); (S.L.)
- Department of Surgery, Haraldsplass Deaconal Hospital, 5009 Bergen, Norway
| | - Svein Erik Emblem Moe
- Department of Otolaryngology/Head and Neck Surgery, Haukeland University Hospital, 5009 Bergen, Norway; (H.H.A.); (S.E.E.M.); (S.L.)
| | - Stein Lybak
- Department of Otolaryngology/Head and Neck Surgery, Haukeland University Hospital, 5009 Bergen, Norway; (H.H.A.); (S.E.E.M.); (S.L.)
- Department of Clinical Medicine, Faculty of Medicine, University of Bergen, 5007 Bergen, Norway
| | - Øystein Bruserud
- Section for Haematology, Department of Medicine, Haukeland University Hospital, 5009 Bergen, Norway
| | | | - Hans Jørgen Aarstad
- Department of Otolaryngology/Head and Neck Surgery, Haukeland University Hospital, 5009 Bergen, Norway; (H.H.A.); (S.E.E.M.); (S.L.)
- Department of Clinical Medicine, Faculty of Medicine, University of Bergen, 5007 Bergen, Norway
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Baghaie L, Haxho F, Leroy F, Lewis B, Wawer A, Minhas S, Harless WW, Szewczuk MR. Contemporaneous Perioperative Inflammatory and Angiogenic Cytokine Profiles of Surgical Breast, Colorectal, and Prostate Cancer Patients: Clinical Implications. Cells 2023; 12:2767. [PMID: 38067195 PMCID: PMC10706122 DOI: 10.3390/cells12232767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 11/29/2023] [Accepted: 12/02/2023] [Indexed: 12/18/2023] Open
Abstract
Surgery-induced tumor growth acceleration and synchronous metastatic growth promotion have been observed for decades. Surgery-induced wound healing, orchestrated through growth factors, chemokines, and cytokines, can negatively impact patients harboring residual or metastatic disease. We provide detailed clinical evidence of this process in surgical breast, prostate, and colorectal cancer patients. Plasma samples were analyzed from 68 cancer patients who had not received treatment before surgery or adjuvant therapy until at least four weeks post-surgery. The levels of plasma cytokines, chemokines, and growth factors were simultaneously quantified and profiled using multiplexed immunoassays for eight time points sampled per patient. The immunologic processes are induced immediately after surgery in patients, characterized by a drastic short-term shift in the expression levels of pro-inflammatory and angiogenic molecules and cytokines. A rapid and significant spike in circulating plasma levels of hepatocyte growth factor (HGF), interleukin-6 (IL-6), placental growth factor (PLGF), and matrix metalloproteinase-9 (MMP-9) after surgery was noted. The rise in these molecules was concomitant with a significant drop in transforming growth factor-β1 (TGF-β1), platelet-derived growth factor (PDGF-AB/BB), insulin-like growth factor-1 (IGF-1), and monocyte chemoattractant protein-2 (MCP-2). If not earlier, each plasma analyte was normalized to baseline levels within 1-2 weeks after surgery, suggesting that surgical intervention alone was responsible for these effects. The effects of surgical tumor removal on disrupting the pro-inflammatory and angiogenic plasma profiles of cancer patients provide evidence for potentiating malignant progression. Our findings indicate a narrow therapeutic window of opportunity after surgery to prevent disease recurrence.
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Affiliation(s)
- Leili Baghaie
- Department of Biomedical & Molecular Sciences, Queen’s University, Kingston, ON K7L 3N6, Canada; (L.B.); (F.H.); (F.L.)
| | - Fiona Haxho
- Department of Biomedical & Molecular Sciences, Queen’s University, Kingston, ON K7L 3N6, Canada; (L.B.); (F.H.); (F.L.)
- Dermatology Residency Program, the Cumming School of Medicine, University of Calgary, Calgary, AB T2T 5C7, Canada
| | - Fleur Leroy
- Department of Biomedical & Molecular Sciences, Queen’s University, Kingston, ON K7L 3N6, Canada; (L.B.); (F.H.); (F.L.)
- Faculté de Médecine, Maïeutique et Sciences de la Santé, Université de Strasbourg, F-67000 Strasbourg, France
| | - Beth Lewis
- ENCYT Technologies Inc., Membertou, NS B1S 0H1, Canada; (B.L.); (A.W.); (S.M.)
| | - Alexander Wawer
- ENCYT Technologies Inc., Membertou, NS B1S 0H1, Canada; (B.L.); (A.W.); (S.M.)
| | - Shamano Minhas
- ENCYT Technologies Inc., Membertou, NS B1S 0H1, Canada; (B.L.); (A.W.); (S.M.)
| | - William W. Harless
- ENCYT Technologies Inc., Membertou, NS B1S 0H1, Canada; (B.L.); (A.W.); (S.M.)
| | - Myron R. Szewczuk
- Department of Biomedical & Molecular Sciences, Queen’s University, Kingston, ON K7L 3N6, Canada; (L.B.); (F.H.); (F.L.)
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Ji S, Liu Y, Yan L, Zhang Y, Li Y, Zhu Q, Xia W, Ge S, Zhang J. DIA-based analysis of the menstrual blood proteome identifies association between CXCL5 and IL1RN and endometriosis. J Proteomics 2023; 289:104995. [PMID: 37657716 DOI: 10.1016/j.jprot.2023.104995] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 07/23/2023] [Accepted: 08/18/2023] [Indexed: 09/03/2023]
Abstract
Endometriosis is a gynecological disease related to menstruation that affects nearly 10% of reproductive-age women. However, so far, there are no reliable diagnostic biomarkers for endometriosis, causing a delay in diagnosis of 6.7 ± 6.2 years. Menstrual blood is a non-invasive source of endometrial tissue that can be analyzed for biomarkers of endometriosis. In this study, menstrual blood samples were collected from women with (n = 8) and without (n = 8) endometriosis. Data Independent Acquisition (DIA)-based mass spectrometry and bioinformatic analysis were used to quantify and identify differentially expressed proteins (DEPs) using the thresholds of fold change >1.5 and P value <0.05. A total of 95 DEPs were identified in menstrual blood from women with endometriosis compared to women without endometriosis, of which 64 were up-regulated and 31 were down-regulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to functionally annotate DEPs. Protein-protein interaction (PPI) network analysis was then conducted to identify hub genes and the MCODE plugin placed CXCL1, CXCL3, CXCL5, CCL18, and IL1RN in the most significant cluster network. The expression of the above candidate proteins was confirmed by enzyme-linked immunosorbent assay (ELISA), among which CXCL5 and IL1RN protein expression was increased in patients with endometriosis, indicating that CXCL5 and IL1RN in menstrual blood may be useful biomarkers to diagnose endometriosis from non-invasive samples. SIGNIFICANCE: Endometriosis is a common gynecological disease that causes discomfort in many women. Unfortunately, the diagnosis of endometriosis is frequently delayed due to a lack of reliable non-invasive biomarkers. To our knowledge, this is the first time that DIA-MS was used to characterize the proteome and identify the differentially expressed proteins in menstrual blood from women with endometriosis. The results, as confirmed by ELISA, showed that CXCL5 and IL1RN protein expression is significantly increased in patients with endometriosis, indicating that these proteins can be used as biomarkers for endometriosis. This study contributes to the identification of putative endometriosis biomarkers from non-invasive samples and lays the groundwork for future research into the roles of CXCL5 and IL1RN in the pathogenesis of endometriosis.
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Affiliation(s)
- Sifan Ji
- Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No. 910, Hengshan Rd, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai 200030, China
| | - Yuan Liu
- Department of Pathology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No. 910, Hengshan Rd, Shanghai 200030, China
| | - Li Yan
- Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No. 910, Hengshan Rd, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai 200030, China
| | - Yiqin Zhang
- Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No. 910, Hengshan Rd, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai 200030, China
| | - Yamei Li
- Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No. 910, Hengshan Rd, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai 200030, China
| | - Qian Zhu
- Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No. 910, Hengshan Rd, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai 200030, China
| | - Wei Xia
- Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No. 910, Hengshan Rd, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai 200030, China
| | - Shunna Ge
- Department of Central Laboratory, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No. 910, Hengshan Rd, Shanghai 200030, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai 200030, China.
| | - Jian Zhang
- Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No. 910, Hengshan Rd, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai 200030, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai 200030, China.
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Feng S, Li Z, Liu M, Ye Q, Xue T, Yan B. Postoperative serum interleukin-6 levels correlate with survival in stage I-III colorectal cancer. BMC Gastroenterol 2023; 23:156. [PMID: 37194025 PMCID: PMC10186764 DOI: 10.1186/s12876-023-02800-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 05/04/2023] [Indexed: 05/18/2023] Open
Abstract
AIMS The preoperative serum levels of inflammatory mediators, including C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6), have been demonstrated to be correlated with patient outcomes in colorectal cancer (CRC); however, the prognostic role of these levels has been less well-studied in postoperative settings. MATERIALS AND METHODS A total of 122 stage I-III CRC patients were retrospectively enrolled. Serum levels of CRP, PCT and IL-6 were measured after surgery, and their prognostic value was evaluated. Kaplan-Meier analysis was used to determine the differences in disease-free survival (DFS) and overall survival (OS) between patients with different levels of these mediators, and the Cox proportional hazards model was used to estimate the risk factors. RESULTS In contrast to CRP and PCT, only the level of IL-6 was significant in predicting DFS (P = 0.01) but not OS (P = 0.07). A total of 66.39% (81/122) of patients were assigned to the low IL-6 group and no significant differences were found in the collected clinicopathological parameters among the low or high IL-6 subgroups. The level of IL-6 was negatively correlated with postoperative (1 w) (R=-0.24, P = 0.02) absolute lymphocyte counts. Patients with low levels of IL-6 had better DFS (log rank = 6.10, P = 0.01) but not OS (log rank = 2.28, P = 0.13). Finally, the level of IL-6 was an independent risk factor for DFS (HR: 1.81, 95% CI: 1.03-3.15, P = 0.04). CONCLUSIONS Compared to CRP and PCT, the level of IL-6 was observed to be the only significant factor in predicting the prognosis of stage I-III CRC patients after surgery, and a low level of IL-6 was associated with good DFS.
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Affiliation(s)
- Shouhan Feng
- Department of Oncology, Huzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Huzhou city of Zhejiang Province, 313000, P.R. China
| | - Zeshi Li
- Department of Critical Care Medicine, Hainan Hospital of PLA General Hospital, Sanya city of Hainan province, 572000, P.R. China
| | - Mei Liu
- Department of Tumor Chemotherapy, Haikou People's Hospital, Haikou city of Hainan province, 570208, P.R. China
| | - Qianwen Ye
- Department of Oncology, Hainan Hospital of PLA General Hospital, No. 80 of Jianglin Road, Haitang District of Sanya city, Hainan province, 572000, P.R. China
| | - Tianhui Xue
- Department of Oncology, Hainan Hospital of PLA General Hospital, No. 80 of Jianglin Road, Haitang District of Sanya city, Hainan province, 572000, P.R. China
| | - Bing Yan
- Department of Oncology, Hainan Hospital of PLA General Hospital, No. 80 of Jianglin Road, Haitang District of Sanya city, Hainan province, 572000, P.R. China.
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Parameters of Metabolic Response to Surgical Trauma Induced via Unilateral Total Mastectomy Associated or Not to Ovariohysterectomy in Dogs. Animals (Basel) 2023; 13:ani13050926. [PMID: 36899784 PMCID: PMC10000079 DOI: 10.3390/ani13050926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 02/10/2023] [Accepted: 02/20/2023] [Indexed: 03/08/2023] Open
Abstract
Surgical excision of solid tumors is required for local control of neoplasms. However, surgical trauma can stimulate the release of proangiogenic growth factors, suppressing cell-mediated immunity and favoring the development of micrometastases and progression of residual disease. The present study aimed to evaluate the intensity of the metabolic response to trauma induced via unilateral mastectomy in bitches with mammary neoplasia, the consequences of its joint performance with ovariohysterectomy, and their respective effects on the organic response. Two groups of animals were evaluated in seven perioperative moments, namely, unilateral mastectomy (G1) and unilateral mastectomy associated with ovariohysterectomy (G2). Thirty-two female dogs were selected, ten clinically healthy, and twenty-two diagnosed with mammary neoplasia. Surgical trauma reduced serum concentrations of albumin and interleukin-2 but increased blood levels of glucose and interleukin-6 in the postoperative of G1 and G2 patients. Moreover, serum cortisol levels increased after unilateral mastectomy associated with ovariohysterectomy. Our findings allowed us to conclude that unilateral mastectomy induces significant metabolic alterations in female dogs with mammary neoplasms and its joint performance with ovariohysterectomy increases the organic response to trauma.
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Huang X, Huan Y, Liu L, Ye Q, Guo J, Yan B. Preoperative low absolute lymphocyte count to fibrinogen ratio correlated with poor survival in nonmetastatic colorectal cancer. World J Surg Oncol 2022; 20:309. [PMID: 36153540 PMCID: PMC9508774 DOI: 10.1186/s12957-022-02775-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Accepted: 08/27/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Preoperative absolute lymphocyte count (LC) and fibrinogen (FIB) are useful prognostic indicators in colorectal cancer (CRC). However, the prognostic value of the LC to FIB ratio (LFR) has never been addressed. METHODS A total of 189 nonmetastatic CRC patients after resection were enrolled retrospectively. The significance of the LFR in predicting disease-free survival (DFS) and overall survival (OS) was estimated by receiver operating characteristic curve analysis, and the prognostic efficacy was compared with individual LC and FIB. Patients were assigned to LFR low or high subgroups. Differences in clinicopathological features among these subgroups were calculated, and the survival differences of these subgroups were determined by the Kaplan-Meier analysis. A Cox proportional hazards model was applied to test the risk factors for survival. RESULTS Taking 0.54 as the optimal cutoff point, the LFR had sensitivities of 79.70% and 86.40% and specificities of 52.30% and 51.00% in predicting the DFS and OS, respectively. A total of 109/189 (57.67%) patients were assigned to the LFR low group, and these patients were more likely to be characterized by criteria such as T3 + T4 (P < 0.01), stage 3 (P < 0.01), tumor deposits (P = 0.01), high CEA (P < 0.01), or CA19-9 levels (P = 0.04). And they also displayed worse DFS (log rank = 18.57, P < 0.01) and OS (log rank = 20.40, P < 0.01) than the high LFR group. Finally, the LFR was independently associated with inferior DFS (HR = 0.32, 95% CI: 0.16-0.61, P < 0.01) and OS (HR = 0.23, 95% CI: 0.09-0.55, P < 0.01). CONCLUSIONS The LFR is a useful prognostic indicator in nonmetastatic CRC, and patients with a relatively low LFR had poor survival.
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Affiliation(s)
- Xiang Huang
- Department of Pulmonary Function Test, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200443, People's Republic of China
| | - Yu Huan
- Department of Clinic Laboratory, Hainan Hospital of Chinese PLA General Hospital, Sanya, Hainan Province, 572000, People's Republic of China
| | - Long Liu
- Department Traditional Chinese Medicine, Tianyou Hospital of Tongji University, Shanghai, 200331, People's Republic of China
| | - Qianwen Ye
- Department of Oncology, Hainan Hospital of Chinese PLA General Hospital, Sanya, Hainan Province, 572000, People's Republic of China
| | - Jian Guo
- Department of Pulmonary Function Test, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200443, People's Republic of China.
| | - Bing Yan
- Department of Oncology, Hainan Hospital of Chinese PLA General Hospital, Sanya, Hainan Province, 572000, People's Republic of China.
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Brinkmann J, Zeißler EC, Scharrenberg JS, Schenk J, Majjouti M, Oberste M, Yagdiran A, Scheyerer MJ, Jung N, Siewe J, Mahabir E. The diagnostic value of cytokines for the discrimination of vertebral osteomyelitis and degenerative diseases of the spine. Cytokine 2021; 150:155782. [PMID: 34933239 DOI: 10.1016/j.cyto.2021.155782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 11/24/2021] [Accepted: 12/04/2021] [Indexed: 11/03/2022]
Abstract
Vertebral osteomyelitis (VO) is a primary infection of the endplates of the vertebral bodies with secondary infection of the adjacent intervertebral discs. Diagnosis is often delayed due to unspecific symptoms and a lack of specific infection markers. In this prospective study, we determined the suitability of 27 cytokines for the discrimination of VO and degenerative diseases of the spine and compared its diagnostic potential in relation to the C-reactive protein (CRP), which is widely used as a non-specific inflammation marker in clinical diagnostics. The patients included in this study underwent surgical stabilization of the lumbar and/or thoracic spine with removal of 1 or more affected intervertebral discs, as therapy for VO (n = 16) or for erosive osteochondrosis (EO, control group, n = 20). We evaluated the cytokine and CRP concentrations before (pre-OP = -20-0d where 0 means the day of surgery) and after surgery (post-OP) on days 3-5, 6-11, 40-56, and 63-142. Compared to the control patients pre-OP, a significantly higher elevation of the 4 cytokines IL-6, IL-8, IL-12 (p70), and VEGF as well as CRP were found in the VO patients, showing an area under the curve > 0.80 pre-OP. No significant differences were observed between VO patients with high and low virulent bacteria with respect to all 5 elevated biomarkers. This is the first prospective study in which a broad spectrum of 27 cytokines was analysed via multiplex assay using sera from patients with and without VO. Our results show that, in addition to CRP, 4 different cytokines were significantly altered in VO but not control patients. The results implicate that these candidate cytokines may be used in a multiplex assay for discrimination between VO and degenerative diseases of the spine.
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Affiliation(s)
- Julia Brinkmann
- Comparative Medicine, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Robert-Koch-Straße 21, 50931 Cologne, Germany
| | - Eva-Carina Zeißler
- Comparative Medicine, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Robert-Koch-Straße 21, 50931 Cologne, Germany
| | - Jan Simon Scharrenberg
- Comparative Medicine, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Robert-Koch-Straße 21, 50931 Cologne, Germany
| | - Julia Schenk
- Comparative Medicine, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Robert-Koch-Straße 21, 50931 Cologne, Germany
| | - Mohamed Majjouti
- Comparative Medicine, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Robert-Koch-Straße 21, 50931 Cologne, Germany
| | - Max Oberste
- Institute of Medical Statistics and Computational Biology (IMSB), University of Cologne, Faculty of Medicine and University Hospital Cologne, Robert-Koch-Straße 10, 50931 Cologne, Germany
| | - Ayla Yagdiran
- University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Orthopedics and Trauma Surgery, Kerpener Straße 62, 50937 Cologne, Germany
| | - Max J Scheyerer
- University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Orthopedics and Trauma Surgery, Kerpener Straße 62, 50937 Cologne, Germany
| | - Norma Jung
- University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Kerpener Straße 62, 50937 Cologne, Germany
| | - Jan Siewe
- Faculty of Medicine and University Hospital of Cologne, Joseph-Stelzmann-Straße 20, 50931 Cologne, Germany
| | - Esther Mahabir
- Comparative Medicine, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Robert-Koch-Straße 21, 50931 Cologne, Germany.
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Aarstad HH, Moe SEE, Bruserud Ø, Lybak S, Aarstad HJ, Tvedt THA. The Acute Phase Reaction and Its Prognostic Impact in Patients with Head and Neck Squamous Cell Carcinoma: Single Biomarkers Including C-Reactive Protein Versus Biomarker Profiles. Biomedicines 2020; 8:biomedicines8100418. [PMID: 33066437 PMCID: PMC7602291 DOI: 10.3390/biomedicines8100418] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 09/26/2020] [Accepted: 10/13/2020] [Indexed: 12/12/2022] Open
Abstract
C-reactive protein (CRP) has a prognostic impact in head and neck squamous cell carcinoma (HNSCC). However, the acute phase reaction involves many other proteins depending on its inducing events, including various cytokines that can function as reaction inducers. In the present study, we compared the pretreatment acute phase cytokine profile for 144 patients with potentially curative HNSCC. We investigated the systemic levels of interleukin (IL)6 family mediators (glycoprotein (gp130), IL6 receptor (R)α, IL6, IL27, IL31, oncostatin M (OSM), ciliary neurotrophic factor (CNTF)), IL1 subfamily members (IL1R antagonist (A), IL33Rα), and tumor necrosis factor (TNF)α. Patient subsets identified from this 10-mediator profile did not differ with regard to disease stage, human papilloma virus (HPV) status, CRP levels, or death cause. Increased CRP, IL6, and IL1RA levels were independent markers for HNSCC-related death in the whole patient population. Furthermore, gp130, IL6Rα, and IL31 were suggested to predict prognosis among tumor HPV-negative patients. Only IL6 predicted survival in HPV-positive patients. Finally, we did a clustering analysis of HPV-negative patients based on six acute phase mediators that showed significant or borderline association with prognosis in Kaplan–Meier analyses; three subsets could then be identified, and they differed in survival (p < 0.001). To conclude, (i) HPV-negative and HPV-positive HNSCC patients show similar variations of their systemic acute phase profiles; (ii) the prognostic impact of single mediators differs between these two patient subsets; and (iii) for HPV-negative patients, acute phase profiling identifies three patient subsets that differ significantly in survival.
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Affiliation(s)
- Helene Hersvik Aarstad
- Department of Clinical Science, Faculty of Medicine, University of Bergen, 5021 Bergen, Norway; (H.H.A.); (Ø.B.)
- Department of Otolaryngology/Head and Neck Surgery, Haukeland University Hospital, 5021 Bergen, Norway; (S.E.E.M.); (S.L.)
| | - Svein Erik Emblem Moe
- Department of Otolaryngology/Head and Neck Surgery, Haukeland University Hospital, 5021 Bergen, Norway; (S.E.E.M.); (S.L.)
| | - Øystein Bruserud
- Department of Clinical Science, Faculty of Medicine, University of Bergen, 5021 Bergen, Norway; (H.H.A.); (Ø.B.)
- Section for Hematology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway;
| | - Stein Lybak
- Department of Otolaryngology/Head and Neck Surgery, Haukeland University Hospital, 5021 Bergen, Norway; (S.E.E.M.); (S.L.)
| | - Hans Jørgen Aarstad
- Department of Otolaryngology/Head and Neck Surgery, Haukeland University Hospital, 5021 Bergen, Norway; (S.E.E.M.); (S.L.)
- Department of Clinical Medicine, Faculty of Medicine, University of Bergen, 5021 Bergen, Norway
- Correspondence: ; Tel.: +47-5597-2664
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11
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Najdaghi S, Razi S, Rezaei N. An overview of the role of interleukin-8 in colorectal cancer. Cytokine 2020; 135:155205. [PMID: 32721849 DOI: 10.1016/j.cyto.2020.155205] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 07/08/2020] [Accepted: 07/09/2020] [Indexed: 02/07/2023]
Abstract
Colorectal Cancer (CRC), a common malignancy, is developing globally among people. Mutagenic insults activate peripheral nucleated cells to secrete chemokines in order to cause an inflammatory state. Despite the presence of multi-retrieving factors, elevated production of minor cytokines may speed-up the sever stages of the baseline inflammation targeting normal compensatory mechanism. IL-8 is a pro-inflammatory cytokine that is believed to be up-regulated in CRC to proceed primary condition into tumor behavior via induction of proliferation, angiogenesis and metastasis. Here, we assess the role of IL-8 in every step of CRC from signaling pathway and formation to invasion and discuss around new perspective therapy that targets IL-8 to manage CRC worldwide incidence and survival rate, more precisely.
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Affiliation(s)
- Soroush Najdaghi
- Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Sepideh Razi
- Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Student Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Sheffield, UK.
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12
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Yamaguchi M, Okamura S, Yamaji T, Iwasaki M, Tsugane S, Shetty V, Koizumi T. Plasma cytokine levels and the presence of colorectal cancer. PLoS One 2019; 14:e0213602. [PMID: 30883594 PMCID: PMC6422333 DOI: 10.1371/journal.pone.0213602] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Accepted: 02/25/2019] [Indexed: 02/06/2023] Open
Abstract
Background/Aims Cancer-related activation of cytokine networks are central aspects of tumor development. The goal of the study was to examine the possibility of plasma cytokines for the screening of colorectal cancer (CRC). Methods We carried out a multicenter, hospital-based case-control study in 66 adult Japanese patients with CRC and 87 healthy adult Japanese. A multiplex bead array immunoassay was used to examine 27 different plasma cytokines. Their association with the presence of CRC was evaluated by logistic regression analysis after adjusting for potential confounding factors. Results Thirteen plasma cytokines were notably associated with the presence of CRC (p< 0.05). Receiver operating characteristic analysis revealed that the combinatorial assessment of some of these plasma cytokines showed “good” capability for discriminating between CRC patients and control subjects (area under the curve (AUC): 0.819 for the combination of IL-9, Eotaxin, G-CSF, and TNF-α; 0.832 for the combination of IL-4, IL-8, Eotaxin, IP-10, and TNF-α). Individual cytokine assessments presented lower AUCs (0.657–0.755) than the combinatorial cytokine assessments. Conclusions The levels of several plasma cytokines varied significantly between CRC patients and control subjects, suggesting the possibility of differentially expressed plasma cytokines as potential biomarkers for detecting the presence of CRC. Our results should be validated in other populations.
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Affiliation(s)
- Masaki Yamaguchi
- Shinshu University, Graduate School of Science & Technology, Department of Mechanical Engineering & Robotics, Ueda, Nagano, Japan
- * E-mail:
| | - Shin Okamura
- Shinshu University, Graduate School of Science & Technology, Department of Mechanical Engineering & Robotics, Ueda, Nagano, Japan
| | - Taiki Yamaji
- Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Motoki Iwasaki
- Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Shoichiro Tsugane
- Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Vivek Shetty
- Section of Oral & Maxillofacial Surgery, UCLA Health Sciences Center, Los Angeles, CA, United States of America
| | - Tomonobu Koizumi
- Shinshu University School of Medicine, Department of Comprehensive Cancer Therapy, Matsumoto, Nagano, Japan
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13
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Riondino S, Ferroni P, Zanzotto FM, Roselli M, Guadagni F. Predicting VTE in Cancer Patients: Candidate Biomarkers and Risk Assessment Models. Cancers (Basel) 2019; 11:cancers11010095. [PMID: 30650562 PMCID: PMC6356247 DOI: 10.3390/cancers11010095] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Revised: 12/07/2018] [Accepted: 01/08/2019] [Indexed: 02/07/2023] Open
Abstract
Risk prediction of chemotherapy-associated venous thromboembolism (VTE) is a compelling challenge in contemporary oncology, as VTE may result in treatment delays, impaired quality of life, and increased mortality. Current guidelines do not recommend thromboprophylaxis for primary prevention, but assessment of the patient's individual risk of VTE prior to chemotherapy is generally advocated. In recent years, efforts have been devoted to building accurate predictive tools for VTE risk assessment in cancer patients. This review focuses on candidate biomarkers and prediction models currently under investigation, considering their advantages and disadvantages, and discussing their diagnostic performance and potential pitfalls.
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Affiliation(s)
- Silvia Riondino
- Interinstitutional Multidisciplinary Biobank, IRCCS San Raffaele Pisana, 00166 Rome, Italy.
- Department of Systems Medicine, Medical Oncology, University of Rome Tor Vergata, 00133 Rome, Italy.
| | - Patrizia Ferroni
- Interinstitutional Multidisciplinary Biobank, IRCCS San Raffaele Pisana, 00166 Rome, Italy.
- Department of Human Sciences & Quality of Life Promotion, San Raffaele Roma Open University, 00166 Rome, Italy.
| | - Fabio Massimo Zanzotto
- Department of Enterprise Engineering, University of Rome "Tor Vergata", 00133 Rome, Italy.
| | - Mario Roselli
- Department of Systems Medicine, Medical Oncology, University of Rome Tor Vergata, 00133 Rome, Italy.
| | - Fiorella Guadagni
- Interinstitutional Multidisciplinary Biobank, IRCCS San Raffaele Pisana, 00166 Rome, Italy.
- Department of Human Sciences & Quality of Life Promotion, San Raffaele Roma Open University, 00166 Rome, Italy.
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14
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Doulabi H, Rastin M, Shabahangh H, Maddah G, Abdollahi A, Nosratabadi R, Esmaeili SA, Mahmoudi M. Analysis of Th22, Th17 and CD4 +cells co-producing IL-17/IL-22 at different stages of human colon cancer. Biomed Pharmacother 2018; 103:1101-1106. [PMID: 29710675 DOI: 10.1016/j.biopha.2018.04.147] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Revised: 04/18/2018] [Accepted: 04/19/2018] [Indexed: 12/11/2022] Open
Abstract
T-helper (Th) 22 cells are involved in the immunopathogenesis of inflammatory diseases, but their specific role in the immunopathogenesis of cancer is unknown. In this study, we examined the profile of circulating and intratumoral Th17, Th22 and CD4+ cells co-producing IL-17/IL-22 in colon cancer (CC) patients in relation to tumor staging. Thirty newly diagnosed colon cancer (CC) patients participated in this study. The percentage of Th1 (CD4+IFN-γ+IL-17-IL-22-), Th17 (CD4+IFN-γ-IL-17+IL-22-), Th22 (CD4+IFN-γ-IL-17-IL-22+) and CD4+ cells co-producing IL-17/IL-22 (CD4+IFN-γ-IL-17+IL-22+) in the peripheral blood, tumor and paratumor tissues was assessed by multicolor flow cytometry. The percentage of circulating Th17 and Th22 cells was significantly increased in CC patients compared to that in healthy controls (HCs). In addition, the percentage of infiltrating Th1, Th17, Th22 and CD4+ cells co-producing IL-17/IL-22 was significantly increased in the tumor tissues compared to that in the parartumor tissues. Furthermore, we also found that the percentage of circulating and intratumoral Th17, Th22 and CD4+ cells co-producing IL-17/IL-22 was higher in advanced stages than in early stages. Our findings revealed that Th17, Th22 and CD4+ cells co-producing IL-17/IL-22 were accumulated in colon cancer tissues and may be involved in the tumor development and progression. A better comprehension of the immunopathogenesis of Th17, Th22 and CD4+ cells co-producing IL-17/IL-22 in colon cancer patients would help in the development of novel therapies.
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Affiliation(s)
- Hassan Doulabi
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Immunology and Allergy, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maryam Rastin
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Immunology and Allergy, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Shabahangh
- Endoscopic and Minimally Invasive Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ghodratollah Maddah
- Endoscopic and Minimally Invasive Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Abbas Abdollahi
- Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Reza Nosratabadi
- Department of Immunology, Faculty of Medicine, Immunology of Infectious Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Seyed-Alireza Esmaeili
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Immunology and Allergy, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahmoud Mahmoudi
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Immunology and Allergy, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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15
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Yu Z, Zhang G, Yang M, Zhang S, Zhao B, Shen G, Chai Y. Systematic review of CYFRA 21-1 as a prognostic indicator and its predictive correlation with clinicopathological features in Non-small Cell Lung Cancer: A meta-analysis. Oncotarget 2018; 8:4043-4050. [PMID: 28008142 PMCID: PMC5354811 DOI: 10.18632/oncotarget.14022] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Accepted: 12/02/2016] [Indexed: 12/14/2022] Open
Abstract
AIM To evaluate the value of Cytokeratin 19 fragment for its survival prognostic indicator and predictive correlation with clinicopathological features in Non-small Cell Lung Cancer. METHODS Eligible studies or databases for articles were retrieved via search systematically. Pooled effect was calculated to evaluate the association between Cytokeratin 19 fragment level and long-term overall survival, as well as the tumor clinicopathological features in Non-small Cell Lung Cancer patients. A fixed-effects or random-effects model was used to calculate the Pooled risk ratios (RRs) and corresponding 95 % confidence intervals (CIs). RESULTS Six studies were up to the selection criteria. This meta-analysis indicated that Cytokeratin 19 fragment high level expression correlated with lower 2-year overall survival (RR =0.47; 95%CI: 0.28-0.79), higher Tumor Node Metastasis stage (II+III+IV) (RR =1.43; 95%CI: 1.15-1.76) in Non-small Cell Lung Cancer. The pooled RR estimates indicated that there is no statistical significance of Cytokeratin 19 fragment level expression in the advanced Non-small Cell Lung Cancer (IIIB+IV) (RR =1.43, 95% CI: 0.85-2.43). CONCLUSION Cytokeratin 19 fragment is a negative prognosis indicator and its high level expression indicates higher Tumor Node Metastasis pathological stage (II+III+IV) in Non-small Cell Lung Cancer. In advanced Non-small Cell Lung Cancer, the level of serum Cytokeratin 19 fragment appears to provide more prognostic information than it does for clinical Tumor Node Metastasis stage information. Further studies are required to confirm our results.
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Affiliation(s)
- Zipu Yu
- Department of Thoracic Surgery, 2nd Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Guofei Zhang
- Department of Thoracic Surgery, 2nd Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Maoying Yang
- Department of Thoracic Surgery, 2nd Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Sai Zhang
- Department of Thoracic Surgery, 2nd Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Baiqin Zhao
- Department of Thoracic Surgery, 2nd Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Gang Shen
- Department of Thoracic Surgery, 2nd Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Ying Chai
- Department of Thoracic Surgery, 2nd Affiliated Hospital, Zhejiang University, Hangzhou, China
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16
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Gu J, Dai S, Liu H, Cao Q, Yin S, Lai KP, Tse WKF, Wong CKC, Shi H. Identification of immune-related genes in gill cells of Japanese eels (Anguilla japonica) in adaptation to water salinity changes. FISH & SHELLFISH IMMUNOLOGY 2018; 73:288-296. [PMID: 29269288 DOI: 10.1016/j.fsi.2017.12.026] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Revised: 12/06/2017] [Accepted: 12/17/2017] [Indexed: 06/07/2023]
Abstract
The changes in ambient salinity influence ion and water homeostasis, hormones secretion, and immune response in fish gills. The physiological functions of hormones and ion transporters in the regulation of gill-osmoregulation have been widely studied, however the modulation of immune response under salinity changes is not determined. Using transcriptome sequencing, we obtained a comprehensive profile of osmo-responsive genes in gill cells of Japanese eel (Anguilla japonica). Herein, we applied bioinformatics analysis to identify the immune-related genes that were significantly higher expressed in gill pavement cells (PVCs) and mitochondrial-rich cells (MRCs) in freshwater (FW) than seawater (SW) adapted fish. We validated the data using the real-time qPCR, which showed a high correlation between the RNA-seq and real-time qPCR data. In addition, the immunohistochemistry results confirmed the changes of the expression of selected immune-related genes, including C-reactive protein (CRP) in PVCs, toll-like receptor 2 (TLR2) in MRCs and interleukin-1 receptor type 2 (IL-1R2) in both PVCs and MRCs. Collectively our results demonstrated that those immune-related genes respond to salinity changes, and might trigger related special signaling pathways and network. This study provides new insights into the impacts of ambient salinity changes on adaptive immune response in fish gill cells.
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Affiliation(s)
- Jie Gu
- Institute of Life Science, Jiangsu University, Zhenjiang, Jiangsu, 212000, China
| | - Shuya Dai
- Institute of Life Science, Jiangsu University, Zhenjiang, Jiangsu, 212000, China
| | - Haitao Liu
- Institute of Life Science, Jiangsu University, Zhenjiang, Jiangsu, 212000, China
| | - Quanquan Cao
- College of Life Sciences, Key Laboratory of Biodiversity and Biotechnology of Jiangsu Province, Nanjing Normal University, Nanjing, Jiangsu, 210023, China
| | - Shaowu Yin
- College of Life Sciences, Key Laboratory of Biodiversity and Biotechnology of Jiangsu Province, Nanjing Normal University, Nanjing, Jiangsu, 210023, China
| | - Keng Po Lai
- Department of Chemistry, City University of Hong Kong, Kowloon, Hong Kong
| | | | | | - Haifeng Shi
- Institute of Life Science, Jiangsu University, Zhenjiang, Jiangsu, 212000, China.
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17
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Miranda DO, Anatriello E, Azevedo LR, Cordeiro JFC, Peria FM, Flória-Santos M, Pereira-da-Silva G. Elevated serum levels of proinflammatory cytokines potentially correlate with depression and anxiety in colorectal cancer patients in different stages of the antitumor therapy. Cytokine 2017; 104:72-77. [PMID: 28969939 DOI: 10.1016/j.cyto.2017.09.030] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2016] [Revised: 08/28/2017] [Accepted: 09/25/2017] [Indexed: 12/28/2022]
Abstract
Depression and anxiety, the most important psychological disorders in cancer patients, have now been considered as psychoneuroimmunological disorders, in which peripheral immune activation, through the release of proinflammatory cytokines, is implicated in the variety of behavioral, neuroendocrine and neurochemical alterations associated with these disorders. Along with the tumor itself, cancer treatment can also contribute to exacerbate the production of proinflammatory cytokines. This study aimed to investigate whether proinflammatory cytokine levels are related to depression and anxiety in CRC patients in different stages of the antitumor therapy We evaluated 60 patients in three stages of antitumor therapy (Pre-chemotherapy, Under-chemotherapy and Post-chemotherapy, n=20 in each group) and 20 healthy volunteers by the Hospital Anxiety and Depression Scale (HADS). Serum levels of cytokines were measured by CBA. Depression and/or anxiety were found at clinically relevant levels in CRC patients during all antitumor therapy. Patients in pre-chemotherapy group exhibited the highest concentrations of pro-inflammatory cytokines and the lowest levels of IL-10. In latter stages of treatment, cytokines reached levels similar to the control group. Correlation analysis between HADS score and cytokine serum levels revealed positive associations of anxiety and/or depression with IL-1β, IL-6, IL-8, and TNF-α, and a negative correlation with IL-10, suggesting that cytokines are involved in the pathophysiology of these psychological disorders in CRC patients. A better understanding of the molecular mechanisms involved in these psychological disorders will allow the design of new therapeutic strategies to assist in alleviating such symptoms in cancer patients.
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Affiliation(s)
- Diego O Miranda
- University of São Paulo at Ribeirão Preto College of Nursing, Ribeirão Preto, Brazil
| | - Elen Anatriello
- University of São Paulo at Ribeirão Preto College of Nursing, Ribeirão Preto, Brazil
| | - Lucas R Azevedo
- São Paulo State University, Department of Biology, Institute of Bioscience, Language & Literature and Exact Science, São José do Rio Preto, Brazil
| | - Jessica F C Cordeiro
- University of São Paulo at Ribeirão Preto College of Nursing, Ribeirão Preto, Brazil
| | - Fernanda M Peria
- University of São Paulo at Ribeirão Preto School of Medicine, Department of Internal Medicine, Ribeirão Preto, Brazil
| | - Milena Flória-Santos
- Post-graduate program in Public Health Nursing, University of São Paulo at Ribeirão Preto College of Nursing, Ribeirão Preto, Brazil
| | - Gabriela Pereira-da-Silva
- Post-graduate program in Public Health Nursing, University of São Paulo at Ribeirão Preto College of Nursing, Ribeirão Preto, Brazil.
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18
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Azizieh FY, Alyahya KO, Dingle K. Association of self-reported symptoms with serum levels of vitamin D and multivariate cytokine profile in healthy women. J Inflamm Res 2017; 10:19-28. [PMID: 28360529 PMCID: PMC5364022 DOI: 10.2147/jir.s127892] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Although a large number of studies have investigated possible relationships among serum levels of vitamin D or cytokines with disease progress and prognosis, similar studies on self-reported symptoms are still controversial. The overall objective of this study was to look into the association between serum levels of vitamin D or cytokines with self-reported symptoms related to musculoskeletal pain, sleep disorders, and premenstrual syndrome (PMS) in healthy adult women. SUBJECTS AND METHODS Venous blood samples were collected from 117 healthy adult women, and serum levels of vitamin D, pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-17, IFN-γ, and TNF-α) and anti-inflammatory cytokines (IL-4, IL-10, and IL-13) were measured. Groups were tested for differences in single parameters, pro-:anti-inflammatory cytokine ratios, and differences in multivariate patterns. RESULTS There were no significant associations between serum levels of vitamin D and any of the self-reported symptoms studied. However, serum levels of certain pro-inflammatory cytokines were significantly higher in subjects with musculoskeletal pain (IL-8, P=0.008), sleep disorders (IFN-γ, P=0.02), and PMS (IL-8 and TNF-α, P=0.009 and 0.002, respectively) compared to subjects who reported no symptoms. The pro-:anti-inflammatory cytokine ratios showed pro-inflammatory cytokine dominance in subjects with self-reported symptoms, particularly in the groups with deficient levels of vitamin D. However, the multivariate cytokine-pattern analysis was significantly different between PMS groups only. CONCLUSION These data point to a possible role of pro-inflammatory cytokines as a contributing factor in self-reported symptoms related to musculoskeletal pain, sleep disorders, and PMS.
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Affiliation(s)
- Fawaz Y Azizieh
- Department of Mathematics and Natural Sciences, Gulf University for Science and Technology, International Centre for Applied Mathematics and Computational Bioengineering, West Mishref, Kuwait
| | - Khulood O Alyahya
- Science Department, College of Basic Education, Public Authority for Applied Education and Training, Kuwait City, Kuwait
| | - Kamaludin Dingle
- Department of Mathematics and Natural Sciences, Gulf University for Science and Technology, International Centre for Applied Mathematics and Computational Bioengineering, West Mishref, Kuwait
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Dagenais M, Dupaul-Chicoine J, Douglas T, Champagne C, Morizot A, Saleh M. The Interleukin (IL)-1R1 pathway is a critical negative regulator of PyMT-mediated mammary tumorigenesis and pulmonary metastasis. Oncoimmunology 2017; 6:e1287247. [PMID: 28405519 DOI: 10.1080/2162402x.2017.1287247] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Revised: 01/16/2017] [Accepted: 01/23/2017] [Indexed: 12/22/2022] Open
Abstract
Breast cancer is the most common cancer in women and the second leading cause of female cancer-related deaths worldwide. Inflammation is an established hallmark of tumorigenesis and an important determinant of tumor outcome and response to therapy. With advances in cancer immunotherapy, there is an urgent need to dissect the contribution of specific immune effectors in cancer development. Here, we genetically investigated the role of the Interleukin-1 (IL-1) receptor 1 (IL-1R1) pathway in breast cancer tumorigenesis and metastasis using the MMTV-PyMT mouse model. Our results indicate that IL-1R1 signaling suppresses mammary tumor cell proliferation early in tumorigenesis and curbs breast cancer outgrowth and pulmonary metastasis. We show that PyMT/Il1r1-/- mice had a higher primary tumor burden and increased mortality rate compared with IL-1R1-sufficient PyMT control mice. This phenotype was independent of the inflammatory caspases-1/-11 but driven by IL-1α, as PyMT/Il1a-/- mice phenocopied PyMT/Il1r1-/- mice. Collectively, our results suggest that IL-1α-mediated IL-1R1 signaling is tumor-suppressive in PyMT-driven breast cancer.
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Affiliation(s)
- Maryse Dagenais
- Department of Biochemistry, McGill University , Montréal, Québec, Canada
| | | | - Todd Douglas
- Department of Microbiology and Immunology, McGill University , Montréal, Québec, Canada
| | - Claudia Champagne
- Department of Medicine, McGill University , Montréal, Québec, Canada
| | - Alexandre Morizot
- Department of Medicine, McGill University , Montréal, Québec, Canada
| | - Maya Saleh
- Department of Biochemistry, McGill University, Montréal, Québec, Canada; Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada; Department of Medicine, McGill University, Montréal, Québec, Canada
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Azizieh F, Alyahya KO, Raghupathy R. Association between levels of vitamin D and inflammatory markers in healthy women. J Inflamm Res 2016; 9:51-7. [PMID: 27175089 PMCID: PMC4854309 DOI: 10.2147/jir.s103298] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Background No one can deny that the biological importance of vitamin D is much beyond its classical role in bone metabolism. Several recent publications have highlighted its potential role in the functioning of the immune system. The overall objective of this study was to look into possible correlations between levels of vitamin D and inflammatory markers in sera of healthy adult women. These markers included proinflammatory cytokines (interleukin [IL]-1β, IL-6, IL-8, IL-17, interferon [IFN]-γ, and tumor necrosis factor [TNF]-α), anti-inflammatory cytokines (IL-4, IL-10, and IL-13), as well as C-reactive protein (CRP) as a general indicator of inflammation. Methods Venous blood samples were collected from 118 healthy adult women and serum levels of vitamin D, CRP, proinflammatory cytokines (IL-1β, IL-6, IL-8, IL-17, IFN-γ, and TNF-α), and anti-inflammatory cytokines (IL-4, IL-10, and IL-13) were measured. Results There were no significant direct correlations between serum levels of vitamin D and any of the inflammatory markers measured. However, subjects with deficient levels of vitamin D and high CRP produced significantly higher levels of the proinflammatory cytokines (TNF-α and IL-8) as compared to subjects with low CRP levels with nondeficient and deficient levels of vitamin D. Further, the anti-inflammatory/proinflammatory ratios suggest a role of vitamin D in maintaining an anti-inflammatory environment at low levels of CRP, an association that is weaker at high CRP levels in subjects with subclinical inflammatory situations. Conclusion These data point to a possible role of vitamin D as a contributing factor in balancing cytokines toward an anti-inflammatory role in inflammatory situations.
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Affiliation(s)
- Fawaz Azizieh
- Department of Mathematics and Natural Sciences, Gulf University for Science and Technology, Kuwait City, Kuwait
| | - Khulood O Alyahya
- Science Department, College of Basic Education, Public Authority for Applied Education and Training, Kuwait City, Kuwait
| | - Raj Raghupathy
- Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait
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Chang PH, Pan YP, Fan CW, Tseng WK, Huang JS, Wu TH, Chou WC, Wang CH, Yeh KY. Pretreatment serum interleukin-1β, interleukin-6, and tumor necrosis factor-α levels predict the progression of colorectal cancer. Cancer Med 2016; 5:426-33. [PMID: 26799163 PMCID: PMC4799955 DOI: 10.1002/cam4.602] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Revised: 10/29/2015] [Accepted: 11/05/2015] [Indexed: 12/25/2022] Open
Abstract
The correlations of pretreatment serum concentrations of proinflammatory cytokines such as interleukin (IL)‐1β, IL‐6, and tumor necrosis factor‐α (TNFα) with the clinicopathologic features and progression of colorectal cancer (CRC) were investigated. The pretreatment serum levels of IL‐1β, IL‐6, and TNFα were measured in 164 CRC patients before treatment. The relationships between changes in proinflammatory cytokine and C‐reactive protein (CRP) levels and both clinicopathologic variables and disease progression were examined by univariate and multivariate analysis. Advanced tumor stage was associated with a poorer histologic differentiation, higher CRP level, lower albumin level, and inferior progression‐free survival rate (PFSR). Furthermore, high levels of CRP (>5 mg/L) were associated with proinflammatory cytokine intensity, defined according to the number of proinflammatory cytokines with levels above the median level (IL‐1β ≥10 pg/mL; IL‐6 ≥ 10 pg/mL; and TNFα ≥55 pg/mL). Under different inflammation states, proinflammatory cytokine intensity, in addition to tumor stage, independently predicted PFSR in patients with CRP <5 mg/L, whereas tumor stage was the only independent predictor of PFSR in patients with CRP ≥5 mg/L. Proinflammatory cytokine intensity and the CRP level are clinically relevant for CRC progression. Measurement of IL‐1β, IL‐6, and TNFα serum levels may help identify early cancer progression among patients with CRP <5 mg/L in routine practice.
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Affiliation(s)
- Pei-Hung Chang
- Division of Hemato-oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung and Chang Gung University, College of Medicine, Keelung, Taiwan
| | - Yi-Ping Pan
- Department of Nutrition, Chang Gung Memorial Hospital, Keelung and Chang Gung University, College of Medicine, Keelung, Taiwan
| | - Chung-Wei Fan
- Division of Colorectal Surgery, Chang Gung Memorial Hospital, Keelung and Chang Gung University, College of Medicine, Keelung, Taiwan
| | - Wen-Ko Tseng
- Division of Colorectal Surgery, Chang Gung Memorial Hospital, Keelung and Chang Gung University, College of Medicine, Keelung, Taiwan
| | - Jen-Seng Huang
- Division of Hemato-oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung and Chang Gung University, College of Medicine, Keelung, Taiwan
| | - Tsung-Han Wu
- Division of Hemato-oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung and Chang Gung University, College of Medicine, Keelung, Taiwan
| | - Wen-Chi Chou
- Division of Hemato-oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung and Chang Gung University, College of Medicine, Keelung, Taiwan
| | - Cheng-Hsu Wang
- Division of Hemato-oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung and Chang Gung University, College of Medicine, Keelung, Taiwan
| | - Kun-Yun Yeh
- Division of Hemato-oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung and Chang Gung University, College of Medicine, Keelung, Taiwan
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Reitter EM, Ay C, Kaider A, Pirker R, Zielinski C, Zlabinger G, Pabinger I. Interleukin levels and their potential association with venous thromboembolism and survival in cancer patients. Clin Exp Immunol 2014; 177:253-60. [PMID: 24580121 DOI: 10.1111/cei.12308] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/24/2014] [Indexed: 12/21/2022] Open
Abstract
Cytokines have been found to be elevated in cancer patients and have been associated with worse prognosis in single tumour entities. We investigated the association of eight different cytokines with venous thromboembolism (VTE) and prognosis in cancer patients. The Vienna Cancer and Thrombosis Study (CATS), a prospective study, includes patients with newly diagnosed tumour or disease progression. Patients with an overt infection are excluded. Study end-points are VTE, death, loss to follow-up or study completion. Interleukin (IL) serum levels were measured using the xMAP technology developed by Luminex. Among 726 included patients, no associations between IL levels and VTE were found, with the exception of a trend for IL-1β and IL-6 in pancreatic cancer. Elevated levels of IL-6 [as continuous variable per double increase hazard ratio (HR) = 1·07, 95% confidence interval (CI) = 1·027-1·114, P = 0·001, IL-8 (HR = 1·12, 95% CI = 1·062-1·170, P < 0·001) and IL-11 (HR = 1·37, 95% CI = 1·103-1·709, P = 0·005] were associated with worse survival. In subgroup analyses based on tumour type, colon carcinoma patients, who had higher IL-6 levels, showed a shorter survival (HR = 2·405, 95% CI = 1·252-4·618, P = 0·008). A significant association of elevated IL-10 levels with a decrease in survival (HR = 1·824, 95% CI = 1·098-3·031, P = 0·020) was seen among patients with lung cancer. No correlation between VTE and IL levels was found, but higher IL-6, IL-8 and IL-11 levels were associated with worse survival in cancer patients. Further, elevated IL-6 levels might be a prognostic marker in colorectal cancer and elevated IL-10 levels in lung cancer patients.
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Affiliation(s)
- E-M Reitter
- Clinical Division of Hematology and Hemostaseology, Comprehensive Cancer Center, Vienna, Austria
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Stanilov N, Miteva L, Jovchev J, Cirovski G, Stanilova S. The prognostic value of preoperative serum levels of IL-12p40 and IL-23 for survival of patients with colorectal cancer. APMIS 2014; 122:1223-9. [PMID: 24909386 DOI: 10.1111/apm.12288] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2014] [Accepted: 04/02/2014] [Indexed: 12/14/2022]
Abstract
Colorectal cancer (CRC) patients were previously shown to express a signature of cytokines that contribute to cancer pathogenesis and are detectable in serum. The aim of this study was to evaluate the potential clinical use of circulating cytokine measurements in CRC patients preoperatively as markers for disease outcome. The levels of cytokines IL-12p40 and IL-23 were assessed by ELISA in the sera of 91 patients with previously untreated CRC and then 5-year survival was determined using Kaplan-Meier analyses. The levels of circulating interleukin IL-12p40 significantly decreased with the progression of CRC, whereas the levels of IL-23 remained with no significant differences between disease stages. None of the cytokine levels were influenced by age, gender and colon vs rectum localization. We found that preoperative serum concentration of IL-12p40 cytokine is a good prognostic marker for survival; as for IL-23 levels, we found no outcome prognostic value. In addition, 5-year survival confirmed that tumor grade, bowel wall invasion, lymph node and metastatic status have an impact on overall survival. In conclusion, we believe that our findings show clinical significance of the preoperative serum concentration for IL-12p40 and provide an additional prognostic biomarker for CRC survival.
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Affiliation(s)
- Noyko Stanilov
- Department of Surgery, Neurosurgery and Urology, Faculty of Medicine, Trakia University, Stara Zagora, Bulgaria; Colorectal surgery unit, The Royal London Hospital, London, UK
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Serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinases 2 (TIMP-2) in colorectal cancer patients. Tumour Biol 2014; 35:3793-802. [PMID: 24395652 PMCID: PMC3980035 DOI: 10.1007/s13277-013-1502-8] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2013] [Accepted: 11/29/2013] [Indexed: 11/04/2022] Open
Abstract
The objective of the study was the assessment of serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in patients with colorectal cancer (CRC). The study included 72 CRC patients and 68 healthy subjects. The serum levels of MMP-2 and TIMP-2 were measured using enzyme-linked immunosorbent assay (ELISA) method, whereas tissue expression of MMP-2 and TIMP-2 in cancer cells, interstitial inflammatory cells, and adjacent normal colorectal mucosa were examined by immunohistochemical staining of tumor samples. The serum levels of MMP-2 and TIMP-2 in cancer patients were significantly lower than those in control group, but the percentage of positive immunoreactivity of these proteins were higher in malignant and inflammatory cells as compared to normal tissue. There was a significant correlation between MMP-2 immunoreactivity in inflammatory cells and the presence of distant metastases and between TIMP-2 expression in inflammatory cells and tumor size, nodal involvement, and distant metastases. Area under receiver operating characteristic (ROC) curve (AUC) for serum MMP-2 was higher than for serum TIMP-2. Moreover, positive tissue expression of MMP-2 was a significant prognostic factor for CRC patients’ survival. Our findings suggest that MMP-2 and TIMP-2 might play a role in the process of colorectal cancer invasion and metastasis, but the significance of their interactions with tumor stroma and interstitial inflammatory infiltration in colorectal neoplasia require further elucidation.
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Ferri M, Rossi Del Monte S, Salerno G, Bocchetti T, Angeletti S, Malisan F, Cardelli P, Ziparo V, Torrisi MR, Visco V. Recovery of immunological homeostasis positively correlates both with early stages of right-colorectal cancer and laparoscopic surgery. PLoS One 2013; 8:e74455. [PMID: 24040252 PMCID: PMC3767741 DOI: 10.1371/journal.pone.0074455] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2013] [Accepted: 08/01/2013] [Indexed: 12/18/2022] Open
Abstract
Differences in postoperative outcome and recovery between patients subjected to laparoscopic-assisted versus open surgery for colorectal cancer (CRC) resection have been widely documented, though not specifically for right-sided tumors. We investigated the immunological responses to the different surgical approaches, by comparing postoperative data simultaneously obtained at systemic, local and cellular levels. A total of 25 right-sided CRC patients and controls were managed, assessing -in the immediate followup- the conventional perioperative parameters and a large panel of cytokines on plasma, peritoneal fluids and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) tissue cultures. A general better recovery for patients operated with laparoscopy compared to conventional procedure, as indicated by the analysis of typical pre- and post-surgical parameters, was observed. The synchronous evaluation of 12 cytokines showed that preoperative plasma levels of the proinflammatory cytokines IL-6, IL-8, IL-1β, TNFα were significantly lower in healthy donors versus CRC patients and that such differences progressively increase with tumor stage. After surgery, the IL-6 and IL-8 increases were significantly higher in open compared to laparoscopic approach only in CRC at early stages. The postsurgical whole panel of cytokine levels were significantly higher in peritoneal fluids compared to corresponding plasma, but with no significant differences depending on kind of surgery or stage of disease. Then we observed that, pre- compared to the corresponding post-surgery derived LPS-stimulated PBMC cultures, produced higher supernatant levels of the whole cytokine panel. In particular IL-6 in vitro production was significantly higher in PBMC derived from patients subjected to laparoscopic versus open intervention, but -again- only in CRC at early stages of disease. Our results thus show that laparoscopy compared to open right resection is associated with a shorter compromission of the immunological homeostasis, mainly in early stages of right-CRC patients.
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Affiliation(s)
- Mario Ferri
- Surgical and Medical Department of the Clinical Sciences, Biomedical Technologies and Translational Medicine, Faculty of Medicine and Psychology University of Rome “Sapienza”, Rome, Italy
- Sant’Andrea Hospital, Rome, Italy
| | - Simone Rossi Del Monte
- Surgical and Medical Department of the Clinical Sciences, Biomedical Technologies and Translational Medicine, Faculty of Medicine and Psychology University of Rome “Sapienza”, Rome, Italy
- Sant’Andrea Hospital, Rome, Italy
| | - Gerardo Salerno
- Department of Clinical and Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Faculty of Medicine and Psychology University of Rome “Sapienza”, Rome, Italy
- Sant’Andrea Hospital, Rome, Italy
| | - Tommaso Bocchetti
- Surgical and Medical Department of the Clinical Sciences, Biomedical Technologies and Translational Medicine, Faculty of Medicine and Psychology University of Rome “Sapienza”, Rome, Italy
- Sant’Andrea Hospital, Rome, Italy
| | - Stefano Angeletti
- Surgical and Medical Department of the Clinical Sciences, Biomedical Technologies and Translational Medicine, Faculty of Medicine and Psychology University of Rome “Sapienza”, Rome, Italy
- Sant’Andrea Hospital, Rome, Italy
| | - Florence Malisan
- Laboratory of Immunology and Signal Transduction, University of Rome ‘Tor Vergata’, Rome, Italy
| | - Patrizia Cardelli
- Department of Clinical and Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Faculty of Medicine and Psychology University of Rome “Sapienza”, Rome, Italy
- Sant’Andrea Hospital, Rome, Italy
| | - Vincenzo Ziparo
- Surgical and Medical Department of the Clinical Sciences, Biomedical Technologies and Translational Medicine, Faculty of Medicine and Psychology University of Rome “Sapienza”, Rome, Italy
- Sant’Andrea Hospital, Rome, Italy
| | - Maria Rosaria Torrisi
- Department of Clinical and Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Faculty of Medicine and Psychology University of Rome “Sapienza”, Rome, Italy
- Sant’Andrea Hospital, Rome, Italy
| | - Vincenzo Visco
- Department of Clinical and Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Faculty of Medicine and Psychology University of Rome “Sapienza”, Rome, Italy
- Sant’Andrea Hospital, Rome, Italy
- * E-mail:
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Choi JW, Liu H, Shin DH, Yu GI, Hwang JS, Kim ES, Yun JW. Proteomic and cytokine plasma biomarkers for predicting progression from colorectal adenoma to carcinoma in human patients. Proteomics 2013; 13:2361-74. [PMID: 23606366 DOI: 10.1002/pmic.201200550] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2012] [Revised: 03/28/2013] [Accepted: 03/30/2013] [Indexed: 12/12/2022]
Abstract
In the present study, we screened proteomic and cytokine biomarkers between patients with adenomatous polyps and colorectal cancer (CRC) in order to improve our understanding of the molecular mechanisms behind turmorigenesis and tumor progression in CRC. To this end, we performed comparative proteomic analysis of plasma proteins using a combination of 2DE and MS as well as profiled differentially regulated cytokines and chemokines by multiplex bead analysis. Proteomic analysis identified 11 upregulated and 13 downregulated plasma proteins showing significantly different regulation patterns with diagnostic potential for predicting progression from adenoma to carcinoma. Some of these proteins have not previously been implicated in CRC, including upregulated leucine-rich α-2-glycoprotein, hemoglobin subunit β, Ig α-2 chain C region, and complement factor B as well as downregulated afamin, zinc-α-2-glycoprotein, vitronectin, and α-1-antichymotrypsin. In addition, plasma levels of three cytokines/chemokines, including interleukin-8, interferon gamma-induced protein 10, and tumor necrosis factor α, were remarkably elevated in patients with CRC compared to those with adenomatous polyps. Although further clinical validation is required, these proteins and cytokines can be established as novel biomarkers for CRC and/or its progression from colon adenoma.
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Affiliation(s)
- Jung-Won Choi
- Department of Biotechnology, Daegu University, Kyungsan, Republic of Korea
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Biasi F, Guina T, Maina M, Nano M, Falcone A, Aroasio E, Saracco GM, Papotti M, Leonarduzzi G, Poli G. Progressive increase of matrix metalloprotease-9 and interleukin-8 serum levels during carcinogenic process in human colorectal tract. PLoS One 2012; 7:e41839. [PMID: 22848630 PMCID: PMC3405044 DOI: 10.1371/journal.pone.0041839] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2012] [Accepted: 06/26/2012] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Inflammatory reactions, known to promote tumor growth and invasion, have been found associated with colorectal carcinoma (CRC). Macrophages are the chief component of the inflammatory infiltration that occurs early in the progression from non-invasive to malignant tumor, with a switch from the pro-inflammatory phenotype to the tumor-promoting phenotype. Tumor and stroma are additional sources of inflammation-related molecules. The study aimed to evaluate, during colorectal carcinogenesis from benign to malignant phases: i) the trend of serum levels of IL-8, IL-6, TGFβ1, VEGF and MMPs; ii) the parallel trend of CRP serum levels; iii) derangement of the principal TGFβ1 receptors (TGFβ1RI/RII) in tumor tissues. METHODOLOGY/PRINCIPAL FINDINGS 96 patients with colon adenomas or CRC at different stages of progression, and 17 controls, were recruited. Serum IL-8, IL-6, TGFβ1, VEGF, MMPs and CRP levels were analyzed before endoscopy or surgery. TGFβ1 receptors were evaluated in adenoma biopsies and surgically-removed colorectal adenocarcinomas. Serum levels of IL-8 in adenocarcinoma patients were increased from stage II, when also the enzymatic activity of MMP-9 increased. Of note, the increasing trend of the two serum markers was found significantly correlated. Trend of serum CRP was also very similar to that of IL-8 and MMP-9, but just below statistical significance. TGFβ1 levels were lower at stage III CRC, while IL-6 and VEGF levels had no significant variations. In tissue specimens, TGFβ1 receptors were already absent in about 50% of adenomas, and this percentage of missing receptors markedly increased in CRC stages III and IV. CONCLUSIONS Combined quantification of serum IL-8, MMP-9 and CRP, appears a reliable and advanced index of inflammation-related processes during malignant phase of colorectal carcinogenesis, since these molecules remain within normal range in colorectal adenoma bearing patients, while consistently increase in the blood of CRC patients, even if from stage II only.
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Affiliation(s)
- Fiorella Biasi
- Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano (Turin), Italy
| | - Tina Guina
- Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano (Turin), Italy
| | - Marco Maina
- Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano (Turin), Italy
| | - Mario Nano
- Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano (Turin), Italy
| | - Alessandro Falcone
- Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano (Turin), Italy
| | - Emiliano Aroasio
- Clinical Biochemistry Laboratory, San Luigi Gonzaga Hospital, Orbassano (Turin), Italy
| | - Giorgio Maria Saracco
- Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano (Turin), Italy
| | - Mauro Papotti
- Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano (Turin), Italy
| | - Gabriella Leonarduzzi
- Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano (Turin), Italy
| | - Giuseppe Poli
- Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano (Turin), Italy
- * E-mail:
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Spicer J, Brodt P, Ferri L. Role of Inflammation in the Early Stages of Liver Metastasis. LIVER METASTASIS: BIOLOGY AND CLINICAL MANAGEMENT 2011. [DOI: 10.1007/978-94-007-0292-9_6] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
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Abstract
The clinical successes of targeting angiogenesis provide a basis for trials of interleukin-1 (IL-1) blockade and particularly anti-IL-1beta as an add-on therapy in human metastatic disease. In animal studies for over 20 years, IL-1 has been demonstrated to increase adherence of tumor cells to the endothelium in vitro, and administration of IL-1 to mice increases the number of metastatic colonies and tumor growth. Importantly, reducing endogenous IL-1 activity, particularly IL-1beta, with the naturally occurring IL-1 receptor antagonist (IL-1Ra) reduces both metastasis as well as tumor burden. Inhibition of IL-1 activity prevents in vivo blood vessel formation induced by products released from hypoxic macrophages or vascular endothelial cell growth factor itself. Mice deficient in IL-1beta do not form blood vessels in matrigels embedded with vascular endothelial cell growth factor or containing products of macrophages. Recombinant IL-1Ra (anakinra) has been administered to over 1,000 patients with septic shock resulting in a consistent reduction in all-cause 28-day mortality. Approved for treatment of rheumatoid arthritis, anakinra has a remarkable safety record. Anakinra resulted in decreased blood vessels in the pannus of affected joints in patients with rheumatoid arthritis. Neutralizing monoclonal antibodies to IL-1beta and a soluble receptor to IL-1 are approved for treating chronic inflammatory diseases. Given the availability of three therapeutic agents for limiting IL-1 activity, the safety of blocking IL-1, and the clear benefit of blocking IL-1 activity in animal models of metastasis and angiogenesis, clinical trials of IL-1 blockade should be initiated, particularly as an add-on therapy of patients receiving antiangiogenesis-based therapies.
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Affiliation(s)
- Charles A Dinarello
- Department of Medicine, University of Colorado, 12700 East 19th Ave., B168, Aurora, CO 80045, USA.
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Knüpfer H, Preiss R. Serum interleukin-6 levels in colorectal cancer patients--a summary of published results. Int J Colorectal Dis 2010; 25:135-40. [PMID: 19898853 DOI: 10.1007/s00384-009-0818-8] [Citation(s) in RCA: 227] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/09/2009] [Indexed: 02/04/2023]
Abstract
INTRODUCTION It is now clear that inflammation and cancer initiation and progression are linked. Interleukin-6 (IL-6) is a pleiotropic inflammatory cytokine with described cancer stimulatory and also cancer inhibitory properties. The study's aim was to assess the potential of circulating IL-6 as a prognostic indicator in colorectal cancer. MATERIALS AND METHODS A literature search was conducted using PubMed, restricted to articles published in English language. We compared published results in regard to differences in IL-6 levels between healthy controls and colon cancer patients (seven published results), between patients with increasing tumor stages (eight published results), between patients with differences in tumor size (four published results), and between patients with and without liver (three published results) or lung metastasis (one published result). Furthermore, we reviewed the literature in regard to the possible correlation of IL-6 levels with survival time (five published results) and correlation of IL-6 levels and lymph node involvement (three published results). RESULTS Concerning colon tumors, results are consistent. Colon cancer patients reveal higher serum IL-6 levels than healthy controls. Furthermore, higher IL-6 levels are associated with increasing tumor stages and tumor size, with metastasis and decreased survival. CONCLUSION Therefore, circulating IL-6 might be prognostic indicator in colorectal cancer.
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Affiliation(s)
- Heike Knüpfer
- Institute of Clinical Pharmacology, University of Leipzig, Härtelstrasse 16-18, 04107 Leipzig, Germany.
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Ma LH, Zhou J, Wang ZX, Hu DW, Shi LM, Ao YZ, Zhang HF. Use of preoperative serum VEGF and CRP levels for prediction of postoperative early recurrence in patients with hepatocellular carcinoma. Shijie Huaren Xiaohua Zazhi 2009; 17:3460-3464. [DOI: 10.11569/wcjd.v17.i33.3460] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the correlations between liver cancer recurrence and preoperative serum vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) levels in patient with hepatocellular carcinoma.
METHODS: The levels of serum VEGF and CRP in 32 liver cancer patients, 30 patients with benign liver diseases and 20 healthy controls were measured by enzyme-linked immunosorbent assay (ELISA) and single immunodiffusion, respectively.
RESULTS: The levels of serum VEGF and CRP in hepatocellular carcinoma patients were significantly higher than those in patients with benign liver diseases and healthy controls (VEGF: 432.32 ± 340.57 ng/L vs 158.54 ± 120.58 ng/L and 124.03 ± 51.65 ng/L; CRP: 9.80 ± 0.86 mg/L vs 6.48 ± 0.98 mg/L and 6.12 ± 0.80 mg/L, all P < 0.01). The sensitivity and specificity of preoperative serum VEGF and CRP levels for prediction of postoperative early recurrence in patients with hepatocellular carcinoma were 77.27% and 59.09% as well as 30% and 60%, respectively.
CONCLUSION: Preoperative serum VEGF and CRP levels are potential predictors of postoperative early recurrence in hepatocellular carcinoma patients.
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Szkaradkiewicz A, Marciniak R, Chudzicka-Strugała I, Wasilewska A, Drews M, Majewski P, Karpiński T, Zwoździak B. Proinflammatory cytokines and IL-10 in inflammatory bowel disease and colorectal cancer patients. Arch Immunol Ther Exp (Warsz) 2009; 57:291-294. [PMID: 19578817 DOI: 10.1007/s00005-009-0031-z] [Citation(s) in RCA: 106] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2008] [Accepted: 01/10/2009] [Indexed: 02/07/2023]
Abstract
INTRODUCTION The aim of the study was to describe the levels of circulating monocyte/macrophage pro-inflammatory cytokines (TNF-alpha, IL-1beta IL-6, and IL-8) and an anti-inflammatory cytokine (IL-10) in inflammatory bowel disease (IBD) and colorectal cancer (CRC) patients and healthy controls. MATERIALS AND METHODS The study was conducted on 15 healthy individuals, 20 patients with ulcerative colitis (UC), 12 with Crohn's disease (CD), and 15 with CRC (Dukes' stage B). Blood serum cytokine levels were measured by ELISA. RESULTS The patients with UC had significantly higher levels of the pro-inflammatory cytokines and of circulating IL-10 than the healthy controls. The patients with CD and CRC had the same specific pattern of serum cytokines of significantly elevated levels of the pro-inflammatory cytokines, but the IL-10 levels were within the range found in the healthy individuals. CONCLUSIONS Thus our results demonstrate that both IBD and CRC are linked with an intensified production of a wide array of monocyte/macrophage pro-inflammatory cytokines which is not accompanied by elevated levels of circulating IL-10, except for its insufficiently inhibitory elevation in UC patients.
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Affiliation(s)
- Andrzej Szkaradkiewicz
- Department of Medical Microbiology, University of Medical Sciences, Wieniawskiego 3, 61-712 Poznań, Poland.
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Clinical utility of serum Interleukin-1 receptor antagonist levels as a diagnostic and prognostic assay in surgical patients. Langenbecks Arch Surg 2009; 394:401-2; author reply 403. [DOI: 10.1007/s00423-008-0422-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2008] [Accepted: 08/11/2008] [Indexed: 10/21/2022]
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Harder J, Kummer O, Olschewski M, Otto F, Blum HE, Opitz O. Prognostic relevance of carbohydrate antigen 19-9 levels in patients with advanced biliary tract cancer. Cancer Epidemiol Biomarkers Prev 2008; 16:2097-100. [PMID: 17932358 DOI: 10.1158/1055-9965.epi-07-0155] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Serum carbohydrate antigen 19-9 (CA 19-9) has been identified as biochemical marker for biliary tract cancer (BTC). The purpose of this study was to evaluate its value as a treatment response marker and its value as a prognostic parameter in patients with unresectable BTC. We analyzed 70 patients with BTC treated with chemotherapy. CA 19-9 levels before and after two treatment courses were analyzed with respect to their effect on treatment response. Patients were categorized into two subgroups according to biliary stenting: patients without endoscopic intervention or biliary drainage (non-stent subgroup) and patients with endoluminal stenting (stent subgroup). Pretreatment CA 19-9 levels were prognostic with respect to overall survival for the entire study population. Patients with CA 19-9 levels above the median of 300 units/mL had a nearly 3-fold risk for early death (hazard ratio, 2.92; 95% confidence interval, 1.51-5.64; adjusted P = 0.002) as compared with patients with CA 19-9 levels <or=300 units/mL. An association between CA 19-9 and therapeutic response was observed in the non-stent subgroup (P = 0.001) only. Furthermore, the decrease of CA 19-9 levels after treatment was predictive for improved survival in the non-stent subgroup (adjusted P = 0.018) but not in the stent subgroup. Our results indicate that pretreatment CA 19-9 levels and CA 19-9 decrease after chemotherapy are of prognostic relevance in patients with BTC.
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Affiliation(s)
- Jan Harder
- Department of Medicine II, University Medical Center, Albert-Ludwigs University, Freiburg, Germany.
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Baker EA, El-Gaddal S, Williams L, Leaper DJ. Profiles of inflammatory cytokines following colorectal surgery: Relationship with wound healing and outcome. Wound Repair Regen 2006; 14:566-72. [PMID: 17014668 DOI: 10.1111/j.1743-6109.2006.00163.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Inflammation is an essential component of normal wound healing. This study has correlated systemic (plasma) and local (wound fluid) concentrations of inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor-alpha [TNF-alpha], and IL-1beta) with wound healing and surgical outcome following elective colorectal surgery. Paired plasma and wound fluid samples were collected (n = 44) postoperatively (days 1, 3, 5, 7) and analyzed by enzyme-linked immunosorbent assay (pg/mL). Cytokine levels were significantly greater in drain fluid than plasma on each postoperative day (POD); e.g., POD 1 : IL-6; drain fluid, median, 77,050 pg/mL (range 9,928-456,408); plasma, 241 pg/mL (22-1,333). Daily profiles of IL-6 and TNF-alpha were similar in drain fluid and plasma; IL-6 levels peaked on POD 1 decreasing to POD 7, and TNF-alpha levels increased from PODs 1 to 7. However, IL-1beta in plasma peaked on POD 1 and plateaued, whereas drain fluid showed two peaks (PODs 1 and 7). Only plasma levels of cytokines correlated to clinical parameters; IL-6 levels significantly correlated with postoperative complications; e.g., POD 5, complications 92(1-597) and no complications, 14(2-217). IL-6 also correlated with tumor pathology (Dukes stage, tumor depth, vascular invasion), and TNF-alpha levels correlated with the estimated blood loss during surgery. We conclude that local wound levels of cytokines correlated with the stage of wound healing, whereas systemic levels correlated with postoperative complications and tumor pathology.
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Affiliation(s)
- Elizabeth A Baker
- Professorial Unit of Surgery, University Hospital of North Tees, Stockton on Tees, United Kingdom.
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Kaminska J, Kowalska M, Kotowicz B, Fuksiewicz M, Glogowski M, Wojcik E, Chechlinska M, Steffen J. Pretreatment Serum Levels of Cytokines and Cytokine Receptors in Patients with Non-Small Cell Lung Cancer, and Correlations with Clinicopathological Features and Prognosis. Oncology 2006; 70:115-25. [PMID: 16645324 DOI: 10.1159/000093002] [Citation(s) in RCA: 94] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2005] [Accepted: 01/29/2006] [Indexed: 01/04/2023]
Abstract
OBJECTIVES Cytokines are potential new serum markers, especially desirable for malignancies with poor prognosis like non-small cell lung cancer (NSCLC). METHODS Cytokines, tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6 and IL-8, soluble TNF (sTNF) RI, sTNF RII, soluble IL-2 receptor-alpha, IL-1 receptor antagonist (IL-1ra), IL-10, vascular endothelial growth factor, basic fibroblast growth factor, and macrophage (M-CSF) and granulocyte colony-stimulating factor, as well as tumor markers - carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and CYFRA 21.1 - were assessed in the sera of 103 untreated NSCLC patients, and these cytokines and tumor markers were referred to clinical parameters of the disease and to the overall survival of patients evaluated during a 6-year follow-up. RESULTS Most of the factors analyzed were found to be elevated in the sera of NSCLC patients, and increases in IL-6, IL-8 and sTNF RI were noted in the greatest proportion of stage I patients. Most cytokine/cytokine receptor levels revealed higher sensitivity than the standard tumor markers; IL-6 and IL-1ra levels were significantly different in patients with squamous cell versus adenocarcinoma; IL-6 and IL-10 were related to the tumor size, while IL-6 and M-CSF levels significantly increased with disease progression. A significant prognostic value of pretreatment serum M-CSF and CEA levels in NSCLC patients has been shown, but only M-CSF proved to be an independent prognostic factor. CONCLUSIONS Increased pretreatment serum M-CSF level is a significant independent predictor of poor survival in patients with NSCLC.
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Affiliation(s)
- Janina Kaminska
- Department of Tumor Markers, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warszawa, Poland.
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Lokshin AE, Winans M, Landsittel D, Marrangoni AM, Velikokhatnaya L, Modugno F, Nolen BM, Gorelik E. Circulating IL-8 and anti-IL-8 autoantibody in patients with ovarian cancer. Gynecol Oncol 2006; 102:244-51. [PMID: 16434085 DOI: 10.1016/j.ygyno.2005.12.011] [Citation(s) in RCA: 99] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2005] [Revised: 11/15/2005] [Accepted: 12/06/2005] [Indexed: 01/24/2023]
Abstract
OBJECTIVES In an ongoing effort to identify diagnostic ovarian cancer biomarkers, SEREX (serological analysis of recombinant cDNA expression libraries) technique was employed resulting in detection of 20 known genes, nine ESTs and one novel sequence. Interleukin-8 (IL-8) was one of ovarian cancer-associated antigens identified by SEREX screening. The objective of this study was, therefore, to evaluate the potential importance of circulating anti-IL-8 antibody as ovarian cancer biomarker. METHODS We developed and optimized a new immunofluorescent bead-based assay for detection of anti-IL-8 antibody in blood serum. Circulating IL-8 and anti-IL-8 IgG concentrations were measured in blood sera from 44 patients with early stage (I-II) ovarian cancer, 50 patients with late stage (III-IV) ovarian cancer, 37 patients with benign pelvic masses, and 80 healthy women using the bead-based assay. RESULTS Our data indicate that serum contains IL-8 cytokine, anti-IL-8 antibody, and IL-8:anti-IL-8 complexes. We found that concentrations of IL-8 and anti-IL-8 antibody were elevated in sera of patients with ovarian cancer as compared with healthy controls. Logistic regression analysis of circulating concentrations of anti-IL-8 IgG in patients with stages I-II ovarian cancer versus healthy controls allowed for prediction of early ovarian cancer with 98% specificity, 65.5% sensitivity, 80.3% of patients correctly classified. Combining IL-8 and anti-IL-8 IgG with CA 125 resulted in increased classification power as compared to individual markers analyzed separately. CONCLUSION Thus, IL-8 and anti-IL-8 autoantibody might potentially serve as additional biomarkers for ovarian cancer.
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Affiliation(s)
- Anna E Lokshin
- University of Pittsburgh Cancer Institute, Hillman Cancer Center, University of Pittsburgh, 5117 Centre Avenue, Pittsburgh, PA 15213, USA.
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Fuksiewicz M, Kaminska J, Kotowicz B, Kowalska M, Rubach M, Pienkowski T. Serum cytokine levels and the expression of estrogen and progesterone receptors in breast cancer patients. Clin Chem Lab Med 2006; 44:1092-7. [PMID: 16958602 DOI: 10.1515/cclm.2006.192] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
AbstractClin Chem Lab Med 2006;44:1092–7.
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Affiliation(s)
- Malgorzata Fuksiewicz
- Department of Tumor Markers, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
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Guillem P, Triboulet JP. Elevated serum levels of C-reactive protein are indicative of a poor prognosis in patients with esophageal cancer. Dis Esophagus 2005; 18:146-50. [PMID: 16045574 DOI: 10.1111/j.1442-2050.2005.00474.x] [Citation(s) in RCA: 66] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Despite improved results gained by the combination of neoadjuvant chemotherapy and radiotherapy with surgery, the prognosis for the esophageal carcinoma patient remains poor. There is a need for prognostic markers that can help improve patient selection. The aim of this study was to evaluate whether serum levels of C-reactive protein (CRP) have any influence on the patient prognosis in terms of prediction of chemoradiosensibility, and overall and disease-free survival. Blood samples were obtained at the time of diagnosis in 67 patients with biopsy-proven primary carcinoma of the esophagus. Although not significantly, the mean CRP level was higher than that of 20 patients with benign esophageal pathology who served as controls. No significant correlation could be found between CRP levels and baseline characteristics such as age, gender, histology, cancer localization, tumor depth, lymph node status or metastatic spread. However, patients with CRP levels higher than 6 mg/L were more frequently non-responders to chemoradiotherapy (P = 0.035), had a shorter overall survival (P = 0.061) and a shorter disease-free survival (P = 0.016). It is concluded from these results that pretreatment measurement of serum CRP levels in patients with esophageal cancer could to be used in routine practice as indicators of chemoradiosensibility and prognosis.
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Affiliation(s)
- P Guillem
- Department of Digestive and General Surgery, Lille University Hospital, Lille, France.
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Kaminska J, Nowacki MP, Kowalska M, Rysinska A, Chwalinski M, Fuksiewicz M, Michalski W, Chechlinska M. Clinical significance of serum cytokine measurements in untreated colorectal cancer patients: soluble tumor necrosis factor receptor type I--an independent prognostic factor. Tumour Biol 2005; 26:186-94. [PMID: 16006772 DOI: 10.1159/000086951] [Citation(s) in RCA: 85] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2004] [Accepted: 02/08/2005] [Indexed: 12/26/2022] Open
Abstract
The aim of this study was to exploit the potential clinical use of circulating cytokine measurements in colorectal cancer (CRC) patients. The levels of cytokines and cytokine receptors were assessed by ELISA in the sera of 50 healthy volunteers and 157 patients with previously untreated CRC and then related to clinicopathological features and prognosis. All tumors were verified histologically as colorectal adenocarcinomas and staged according to TNM classification. The levels of circulating interleukin (IL)-6, IL-8, macrophage colony-stimulating factor (M-CSF) and interleukin 1 receptor antagonist (IL-1ra) significantly increased with the clinical stage of CRC, and the levels of IL-6, soluble tumor necrosis factor (sTNF) receptor type I (RI), soluble interleukin 2 receptor alpha and TNFalpha with tumor grade, while IL-6, IL-8, M-CSF, IL-1ra and sTNF RI levels significantly rose with bowel wall invasion. None of the cytokine or soluble cytokine receptor levels were influenced by age, gender and colon versus rectum localization. sTNF RI, IL-8, IL-6 and vascular endothelial growth factor measurements demonstrated the highest diagnostic sensitivity. sTNF RI was found elevated in the greatest percentage of all CRC patients, in the greatest proportion of stage I patients and presented the best diagnostic sensitivity. In addition, the sTNF RI level strongly correlated with tumor grade and invasion and proved to be an independent prognostic factor.
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Affiliation(s)
- J Kaminska
- Department of Tumor Markers, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
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Nikiteas NI, Tzanakis N, Gazouli M, Rallis G, Daniilidis K, Theodoropoulos G, Kostakis A, Peros G. Serum IL-6, TNFalpha and CRP levels in Greek colorectal cancer patients: prognostic implications. World J Gastroenterol 2005; 11:1639-1643. [PMID: 15786541 PMCID: PMC4305945 DOI: 10.3748/wjg.v11.i11.1639] [Citation(s) in RCA: 117] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2004] [Revised: 09/01/2004] [Accepted: 09/30/2004] [Indexed: 02/06/2023] Open
Abstract
AIM The significance of preoperative serum IL-6, TNFalpha and CRP levels in the progression of colorectal cancer (CRC) has not been fully elucidated. Our intention was to investigate their role and identify their prognostic significance. METHODS The IL-6, TNFalpha and CRP levels were measured in 74 CRC patients and the relationships between their elevations and both the clinicopathological factors and prognosis of patients were investigated. Serum concentrations of human IL-6 and TNFalpha were determined by enzyme-linked immunosorbent assay (ELISA). CRP was measured by an immunoturbinometric method. RESULTS Median IL-6, TNFalpha and CRP levels were significantly higher in CRC patients than in normal controls. High levels of serum IL-6, TNFalpha and CRP were correlated with larger tumor size. Furthermore, high IL-6 and high CRP levels were associated with reduced overall survival. CONCLUSION Serum IL-6, TNFalpha and CRP levels definitely increase in CRC patients. Pre-operative serum elevation of IL-6 and CRP was thus found to be predictor of the prognosis of CRC patients. The clinical value of TNFalpha in CRC needs to be further investigated.
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Affiliation(s)
- Nikolaos I Nikiteas
- 2nd Propedeutic Department of Surgery, School of Medicine, University of Athens, Athens 11527, Greece.
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Abdul M, Hoosein N. Relationship of the interleukin-1 system with neuroendocrine and exocrine markers in human colon cancer cell lines. Cytokine 2002; 18:86-91. [PMID: 12096923 DOI: 10.1006/cyto.2001.1019] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Interleukin 1 (IL-1) is known to regulate the proliferation and differentiation of normal and malignant immune cells as well as other cell types. Expression of IL-1 (alpha and beta), IL-1 receptors (RI and RII) and IL-1 receptor antagonist (IL-1RA) was determined by RT-PCR in seven human colon carcinoma cell lines (COLO 320DM, LoVo, SW403, SW1116, SW1417, LS123 and LS174t). Influence of IL-1 on the secretion of the neuroendocrine (NE) differentiation marker chromogranin A (CGA) and the exocrine marker carcinoembryonic antigen (CEA) was examined by Western blotting. Our data indicate that CGA and IL-1RI are expressed by all seven, IL-1 beta by five, IL-1RII and IL-1RA by six lines. IL-1 alpha transcripts were found only in three lines (LoVo, SW1116 and LS174t) and correlated with high CEA levels and aggressive growth behavior. "Pure" NE cell lines (COLO 320DM and LS123) secreted the highest levels of CGA, but the lowest levels of CEA and were IL-1 (alpha and beta) negative. Exogenously added IL-1 caused a decrease in CGA, but an increase in CEA secretion. Our results suggest an inverse relationship between IL-1 and NE differentiation, as well as a direct relationship between IL-1 and CEA expression in colon carcinoma.
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Affiliation(s)
- Mansoor Abdul
- Rumbaugh-Goodwin Institute for Cancer Research, 1850 NW 69th Avenue #5, Plantation, Florida, 33313, USA
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