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1
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Samarth N, Gulhane P, Singh S. Immunoregulatory framework and the role of miRNA in the pathogenesis of NSCLC - A systematic review. Front Oncol 2022; 12:1089320. [PMID: 36620544 PMCID: PMC9811680 DOI: 10.3389/fonc.2022.1089320] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 12/02/2022] [Indexed: 12/24/2022] Open
Abstract
With a 5-year survival rate of only 15%, non-small cell lung cancer (NSCLC), the most common kind of lung carcinoma and the cause of millions of deaths annually, has drawn attention. Numerous variables, such as disrupted signaling caused by somatic mutations in the EGFR-mediated RAS/RAF/MAPK, PI3K/AKT, JAK/STAT signaling cascade, supports tumour survival in one way or another. Here, the tumour microenvironment significantly contributes to the development of cancer by thwarting the immune response. MicroRNAs (miRNAs) are critical regulators of gene expression that can function as oncogenes or oncosuppressors. They have a major influence on the occurrence and prognosis of NSCLC. Though, a myriad number of therapies are available and many are being clinically tested, still the drug resistance, its adverse effect and toxicity leading towards fatality cannot be ruled out. In this review, we tried to ascertain the missing links in between perturbed EGFR signaling, miRNAs favouring tumorigenesis and the autophagy mechanism. While connecting all the aforementioned points multiple associations were set, which can be targeted in order to combat NSCLC. Here, we tried illuminating designing synthetically engineered circuits with the toggle switches that might lay a prototype for better therapeutic paradigm.
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Affiliation(s)
| | | | - Shailza Singh
- National Centre for Cell Science, NCCS Complex, Ganeshkhind, SP Pune University Campus, Pune, India
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2
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Iinuma R, Okuda H, Obara N, Matsubara Y, Aoki M, Ogawa T. Increased Monocyte Chemotactic Protein-1 Accompanying Pro-Inflammatory Processes are Associated with Progressive Hearing Impairment and Bilateral Disability of Meniere's Disease. Audiol Neurootol 2021; 27:208-216. [PMID: 34903680 DOI: 10.1159/000518839] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 08/02/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The progression of hearing impairment and the bilateral involvement of Meniere's disease (MD) may depend on the disease duration and aging. Recent studies reported that MD might involve dysfunction of the microvascular circulation damaged due to inflammatory changes. OBJECTIVES The aim of this study was to determine that the progress of the MD's hearing impairment and bilateral disability may be associated with the pathogenesis of several pro-inflammatory processes. PATIENTS AND METHODS We recruited 30 unilateral MD patients (56.8 ± 14.7 years old), 7 bilateral MD patients (65.3 ± 13.9 years old), and 17 age-matched control subjects (53.5 ± 14.4 years old, p > 0.05). We measured the plasma vascular endothelial growth factor (VEGF), plasma interleukin-6 (IL-6), plasma tumor-necrosis factor α (TNFα), and plasma monocyte chemotactic protein-1 (MCP-1). RESULTS The bilateral MD group and the unilateral MD group had higher plasma MCP-1 (204.7 ± 41.0 pg/mL and 169.5 ± 32.0 pg/mL) than the control group (149.2 ± 30.7 pg/mL) (p < 0.05). There was no significant difference in plasma TNFα, IL-6, and VEGF among 3 groups (p > 0.05). There was a strong correlation between the plasma MCP-1 and age in MD patients (r = 0.58, p < 0.01); however, no significant correlation between the plasma MCP-1 and age was found in control subjects (p > 0.05). The plasma MCP-1 significantly correlated with the average hearing level of 500, 1,000, 2,000, and 4,000 Hz, and the maximum slow phase eye velocity in caloric test in the better side (p < 0.05). Also, the plasma MCP-1 showed significant positive correlations with the plasma IL-6 (r = 0.49, p < 0.01) and plasma TNFα (r = 0.32, p < 0.05) in MD group. CONCLUSIONS Our results suggest that the increased plasma MCP-1 accompanying pro-inflammatory processes are associated with the progression of the hearing impairment and the bilateral disability of MD.
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Affiliation(s)
- Ryota Iinuma
- Department of Otolaryngology, Gifu University Graduate School of Medicine, Gifu City, Japan
| | - Hiroshi Okuda
- Department of Otolaryngology, Gifu University Graduate School of Medicine, Gifu City, Japan
| | - Natsuko Obara
- Department of Otolaryngology, Gifu University Graduate School of Medicine, Gifu City, Japan
| | - Yoshitaka Matsubara
- Department of Otolaryngology, Gifu University Graduate School of Medicine, Gifu City, Japan.,Medical IT Support Department, HRS Co., LTD., Nagoya City, Japan
| | - Mitsuhiro Aoki
- Department of Otolaryngology, Gifu University Graduate School of Medicine, Gifu City, Japan.,Center for Healthcare Information Technology (C-HiT), Tokai National Higher Education and Research System, Nagoya City, Japan
| | - Takenori Ogawa
- Department of Otolaryngology, Gifu University Graduate School of Medicine, Gifu City, Japan
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Rather SH, Bhat SA, Bashir A, Dar AM, Zaman M, Nabi N, Shah A, Shah AM. Impact of Surgery on the Hemangiogenic Profile, Especially VEGF Levels, in Lung Cancer Patients. MÆDICA 2021; 16:170-178. [PMID: 34621335 DOI: 10.26574/maedica.2021.16.2.170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Introduction: Lung cancer was considered to be rare at the beginning of the 20th century, but it has now reached almost epidemic proportions. It is the leading cause of cancer deaths in developed countries and is also rising at alarming rates in developing countries. Introduction: Coronavirus disease 2019 (COVID-19) is an emerging viral infection without any approved treatment. Investigational therapies for COVID-19 may cause clinically important drug-drug interactions (DDIs). We aimed to study drug-drug interactions (DDIs) and their risk factors in hospitalised COVID-19 patients. Aim: The aim of our study is to establish an effect on serum levels of vascular endothelial growth factor (VEGF) after surgery in lung cancer patients. Methods:This was a prospective study. For the estimation of VEGF, 50 lung cancer patients were studied. Both preoperative and postoperative levels of VEGF were estimated for all subjects. Blood samples were obtained from all cases both preoperatively and postoperatively (four weeks after surgery). Blood samples of 100 age and sex matched healthy controls were collected from the Outpatient Departments of SKIMS to establish normal serum VEGF levels. Conclusion: Our findings show that serum VEGF levels are higher as the tumor stage progresses and tumor size increases, which explains the lower serum VEGF levels observed by us in the operable patient group.
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Affiliation(s)
| | - Showkat Ali Bhat
- Department of Surgery, SKIMS Medical College, Srinagar, Jandk, India
| | - Arshad Bashir
- Department of Surgery, SKIMS Medical College, Srinagar, Jandk, India
| | - Abdul Majeed Dar
- Department of Cardiovascular Surgery, SKIMS Institute of Medical Scineces Soura, Srinagar, Jandk, India
| | - Muzzafar Zaman
- Department of Surgery, SKIMS Medical College, Srinagar, Jandk, India
| | - Naveed Nabi
- Department of Surgery, SKIMS Medical College, Srinagar, Jandk, India
| | - Aliya Shah
- Department of Microbiology, GMC Srinagar, India
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Landini N, Anania G, Astolfi M, Fabbri B, Guidi V, Rispoli G, Valt M, Zonta G, Malagù C. Nanostructured Chemoresistive Sensors for Oncological Screening and Tumor Markers Tracking: Single Sensor Approach Applications on Human Blood and Cell Samples. SENSORS 2020; 20:s20051411. [PMID: 32143491 PMCID: PMC7085750 DOI: 10.3390/s20051411] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 02/19/2020] [Accepted: 02/27/2020] [Indexed: 12/24/2022]
Abstract
Preventive screening does not only allow to preemptively intervene on pathologies before they can harm the host; but also to reduce the costs of the intervention itself; boosting the efficiency of the NHS (National Health System) by saving resources for other purposes. To improve technology advancements in this field; user-friendly yet low-cost devices are required; and various applications for gas sensors have been tested and proved reliable in past studies. In this work; cell cultures and blood samples have been studied; using nanostructured chemoresistive sensors; to both verify if this technology can reliably detect tumor markers; and if correlations between responses from tumor line metabolites and the screening outcomes on human specimens could be observed. The results showed how sensors responded differently to the emanations from healthy and mutant (for cells) or tumor affected (for blood) samples, and how those results were consistent between them, since the tumoral specimens had higher responses compared to the ones of their healthy counterparts. Even though the patterns in the responses require a bigger population to be defined properly; it appeared that the different macro-groups between the same kind of samples are distinguishable from some of the sensors chosen in the study; giving promising outcomes for further research.
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Affiliation(s)
- Nicolò Landini
- Department of Physics and Earth Sciences, University of Ferrara, Via Saragat 1/C, 44122 Ferrara, Italy; (M.A.); (B.F.); (V.G.); (M.V.); (G.Z.)
- Correspondence:
| | - Gabriele Anania
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy;
| | - Michele Astolfi
- Department of Physics and Earth Sciences, University of Ferrara, Via Saragat 1/C, 44122 Ferrara, Italy; (M.A.); (B.F.); (V.G.); (M.V.); (G.Z.)
- SCENT S.r.l, Via Quadrifoglio 11, 44124 Ferrara, Italy
| | - Barbara Fabbri
- Department of Physics and Earth Sciences, University of Ferrara, Via Saragat 1/C, 44122 Ferrara, Italy; (M.A.); (B.F.); (V.G.); (M.V.); (G.Z.)
| | - Vincenzo Guidi
- Department of Physics and Earth Sciences, University of Ferrara, Via Saragat 1/C, 44122 Ferrara, Italy; (M.A.); (B.F.); (V.G.); (M.V.); (G.Z.)
| | - Giorgio Rispoli
- Department of Life Sciences and Biotechnology, University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy;
| | - Matteo Valt
- Department of Physics and Earth Sciences, University of Ferrara, Via Saragat 1/C, 44122 Ferrara, Italy; (M.A.); (B.F.); (V.G.); (M.V.); (G.Z.)
| | - Giulia Zonta
- Department of Physics and Earth Sciences, University of Ferrara, Via Saragat 1/C, 44122 Ferrara, Italy; (M.A.); (B.F.); (V.G.); (M.V.); (G.Z.)
| | - Cesare Malagù
- Department of Physics and Earth Sciences, University of Ferrara, Via Saragat 1/C, 44122 Ferrara, Italy; (M.A.); (B.F.); (V.G.); (M.V.); (G.Z.)
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Lai Y, Wang X, Zeng T, Xing S, Dai S, Wang J, Chen S, Li X, Xie Y, Zhu Y, Liu W. Serum VEGF levels in the early diagnosis and severity assessment of non-small cell lung cancer. J Cancer 2018; 9:1538-1547. [PMID: 29760791 PMCID: PMC5950582 DOI: 10.7150/jca.23973] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Accepted: 01/21/2018] [Indexed: 12/16/2022] Open
Abstract
Background: Effective biomarkers are essential to the differential diagnosis and severity assessment of non-small cell lung cancer (NSCLC). This study explored the use of the serum vascular endothelial growth factor (VEGF) levels as a biomarker with the aim of achieving better management of NSCLC. Methods: Serum VEGF levels were assayed via enzyme-linked immunosorbent assay in 180 patients with NSCLC, 136 patients with benign pulmonary nodules, and 119 healthy controls. We additionally detected the serum concentration of three traditional biomarkers—carcinoembryonic antigen (CEA), cancer antigen (CA)-125, and cytokeratin 19 fragments (Cyfra 21-1)—to comparatively evaluate the efficiency and diagnostic value of VEGF in patients with NSCLC. We further evaluated the relationship between serum VEGF levels and clinicopathologic parameters. VEGF levels were compared between pro- and post-surgical patients using the Wilcoxon matched-pairs signed-rank test. DNA was isolated from the primary tumors. EGFR mutations were detected by Scorpions amplification refractory mutation system (ARMS). Results: Patients with NSCLC had significantly higher serum concentration of VEGF, compared to those with benign pulmonary nodules and healthy controls (P <0.0001). As a diagnostic biomarker of NSCLC, VEGF had area under the curve values of 0.824 and 0.839, sensitivities of 75.0% and 75.0%, and specificities of 93.3% and 95.6% when compared with healthy people and patients with benign pulmonary nodules, respectively; notably, these values were greater than those of CA125, Cyfra 21-1 and CEA. Furthermore, a model in which VEGF was combined with CEA, CA125, and Cyfra 21-1 was more effective for NSCLC diagnosis than VEGF alone (sensitivity, 85.0% and 84.4; specificity, 90.0% and 91.9% vs. healthy controls and patients with benign pulmonary nodules, respectively). When use to identify early-stage NSCLC, VEGF showed a better diagnostic efficacy than other biomarkers. The pro-surgical VEGF levels were significantly higher than those measured 25-30 days after surgery. Moreover, VEGF concentration differed significantly among cases according to TNM stages and malignant grades (P <0.0001). EGFR mutations and the size of benign pulmonary nodules did not affect the level of serum VEGF significantly. Conclusion: The serum VEGF levels exhibited relatively high sensitivity and specificity for NSCLC, and may therefore be a useful diagnostic biomarker. Furthermore, the serum VEGF levels could be used to assess prognosis and curative effects.
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Affiliation(s)
- Yanzhen Lai
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xueping Wang
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Tao Zeng
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Shan Xing
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Shuqin Dai
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Junye Wang
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Department of thoracic surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Shulin Chen
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xiaohui Li
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ying Xie
- Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yuanying Zhu
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wanli Liu
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, China
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Hu Y, Li B, Shi G, Rong C, Gao G. [Correlation of postoperative serum VEGF levels with platelet counts in non-small cell lung cancer]. ZHONGGUO FEI AI ZA ZHI = CHINESE JOURNAL OF LUNG CANCER 2010; 13:118-21. [PMID: 20673503 PMCID: PMC6000526 DOI: 10.3779/j.issn.1009-3419.2010.02.07] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/23/2009] [Revised: 08/29/2009] [Indexed: 01/07/2023]
Abstract
背景与目的 已有研究表明:非小细胞肺癌(non-small cell lung cancer, NSCLC)患者手术切除原发肿瘤后其血清中血管内皮生长因子(vascular endothelial growth factor, VEGF)浓度显著升高, 血小板可能是血清中VEGF的主要来源。本研究的目的是探讨NSCLC患者术后血清VEGF浓度的动态变化及其与血小板之间的关系。 方法 应用酶联免疫吸附试验(enzyme linked immunosorbent assay, ELISA)检测法, 监测76例非小细胞肺癌患者术前、术后1天及7天血清VEGF的浓度, 同期检测血小板的浓度。 结果 ① NSCLC患者术前、术后1天及7天血清VEGF分别为(842.06±527.24)pg/mL、(1 119.28±609.62)pg/mL、(1 574.09±873.38)pg/mL, 组间比较差异具有统计学意义(P < 0.001);②NSCLC患者术前、术后1天及7天血小板计数分别为(230.42±82.56)×109/L、(196.47±81.48)×109/L、(237.90±86.94)×109/L, 术后1天最低(P < 0.001);③术后7天在血小板高于均数组血清VEGF浓度为(1 842.86±1 006.63)pg/mL, 低于均数组为(1 398.81±734.00)pg/mL, 两组有统计学差异(P=0.043)。 结论 NSCLC患者术后血清VEGF浓度显著升高, 血小板计数高的患者中, 其血清VEGF浓度升高更为明显。
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Affiliation(s)
- Ying Hu
- Department of General, Beijing Chest Hospital, Beijing 101149, China
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Woolard J, Bevan HS, Harper SJ, Bates DO. Molecular diversity of VEGF-A as a regulator of its biological activity. Microcirculation 2009; 16:572-92. [PMID: 19521900 PMCID: PMC2929464 DOI: 10.1080/10739680902997333] [Citation(s) in RCA: 101] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The vascular endothelial growth factor (VEGF) family of proteins regulates blood flow, growth, and function in both normal physiology and disease processes. VEGF-A is alternatively spliced to form multiple isoforms, in two subfamilies, that have specific, novel functions. Alternative splicing of exons 5-7 of the VEGF gene generates forms with differing bioavailability and activities, whereas alternative splice-site selection in exon 8 generates proangiogenic, termed VEGF(xxx), or antiangiogenic proteins, termed VEGF(xxx)b. Despite its name, emerging roles for VEGF isoforms on cell types other than endothelium have now been identified. Although VEGF-A has conventionally been considered to be a family of proangiogenic, propermeability vasodilators, the identification of effects on nonendothelial cells, and the discovery of the antiangiogenic subfamily of splice isoforms, has added further complexity to their regulation of microvascular function. The distally spliced antiangiogenic isoforms are expressed in normal human tissue, but downregulated in angiogenic diseases, such as cancer and proliferative retinopathy, and in developmental pathologies, such as Denys Drash syndrome and preeclampsia. Here, we examine the molecular diversity of VEGF-A as a regulator of its biological activity and compare the role of the pro- and antiangiogenic VEGF-A splice isoforms in both normal and pathophysiological processes.
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Affiliation(s)
- Jeanette Woolard
- Department of Physiology and Pharmacology, Bristol Heart Institute, School of Veterinary Sciences, University of Bristol, Bristol, UK.
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8
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Millar HJ, Nemeth JA, McCabe FL, Pikounis B, Wickstrom E. Circulating human interleukin-8 as an indicator of cancer progression in a nude rat orthotopic human non-small cell lung carcinoma model. Cancer Epidemiol Biomarkers Prev 2008; 17:2180-7. [PMID: 18708412 DOI: 10.1158/1055-9965.epi-07-2915] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Clinically relevant animal models of human cancer are necessary for the evaluation of putative therapeutics. We hypothesized that circulating human lung cancer-associated proteins would correlate with physiologic measurements from an orthotopic H460 human non-small cell lung carcinoma model that we developed in immunodeficient rats. Physiologic measurements and serum samples were collected over time. Serum interleukin-8 (IL-8), p53, vascular endothelial growth factor, and matrix metalloproteinase-9 were quantitated for correlation with physiologic measurements. Matrix metalloproteinase-9 and p53 were not significantly detectable. Circulating vascular endothelial growth factor was detected at high levels in some tumor-bearing animals. Human IL-8 was detectable in all tumor-bearing animals and correlated positively with markers of respiratory acidosis (pH, P = 0.012; TCO(2), P = 0.024; pCO(2), P = 0.007; and HCO(3)(-), P = 0.029) and with surface body temperature (P = 0.001) beginning on day 16 after implantation. IL-8 levels negatively correlated with survival (P < 0.001), indicating an association with tumor burden. Circulating human IL-8 might be a useful, clinically relevant circulating tumor protein marker due to its positive correlation with multiple physiologic variables associated with lung cancer progression.
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Zhou HF, Wu J, Wang CH, Zhang B, Liu D, Wang W, Zhao N. Expression of vascular endothelial growth factor and basic fibroblast growth factor in gastric carcinoma and their significances. Shijie Huaren Xiaohua Zazhi 2006; 14:2087-2092. [DOI: 10.11569/wcjd.v14.i21.2087] [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 expression of vascular endothelial growth factor (VEGF), basic fibro-blast growth factor (bFGF) in serum and tissues of gastric cancer patients and the clinical charac-teristics of gastric cancer.
METHODS: Avidin-biotin system enzyme-linked immunosorbent assay (ABC-ELISA) was used to examine the serum expression of VEGF and bFGF in preoperative gastric cancer patients (n = 73) and healthy individuals (n = 20). Meanwhile, immunohistochemistry was used to detect the expression of VEGF and bFGF in the cancer and cancer-adjacent tissues.
RESULTS: The serum expression of VEGF and bFGF in gastric cancer patients were significantly higher than those in the healthy controls (VEGF: 101.8 ± 53.3 ng/L vs 16.1 ± 22.5 ng/L, P < 0.05; bFGF: 152.9 ± 42.7 ng/L vs 25.0 ± 11.4 ng/L, P < 0.05). The serum expression of VEGF and bFGF were significantly correlated with the depth of invasion, TNM staging, lymph node metastasis and distant metastasis, but not with the age, sex of patients, and pathological types (P < 0.05). The positive rates of VEGF and bFGF expression in gastric cancer tissues were significantly higher than those in the cancer-adjacent tissues (χ2 = 32.1, P < 0.05; χ2 = 17.7, P < 0.05). The tissue expression of VEGF and bFGF were also correlated with the depth of invasion, TNM staging, lymph node metastasis and distant metastasis (P < 0.05), but not with the age, sex of patients, and pathological types. There existed positive correlations between serum and tissue expression of VEGF and bFGF (in serum: r = 0.439, P < 0.01; in tissue: r = 0.391, P < 0.01). The correlation between serum and tissue expression was also significantly positive (VEGF: r = 0.346, P < 0.01; bFGF: r = 0.304, P < 0.01).
CONCLUSION: VEGF and bFGF play important roles in the oncogenesis, progression, metastasis and prognosis of gastric cancer, which may become new tumor markers for preoperative diagnosis, postoperative following-up, metastasis or recurrence monitoring, assessment of anti-angiogenesis drugs.
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Fürstenberger G, von Moos R, Senn HJ, Boneberg EM. Real-time PCR of CD146 mRNA in peripheral blood enables the relative quantification of circulating endothelial cells and is an indicator of angiogenesis. Br J Cancer 2005; 93:793-8. [PMID: 16160694 PMCID: PMC2361631 DOI: 10.1038/sj.bjc.6602782] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Angiogenesis is a fundamental process in tumour growth and metastatic dissemination. Possible surrogate markers for tumour angiogenesis are the amounts of circulating endothelial cells (CEC) in peripheral blood and the plasma concentration of vascular endothelial growth factor (VEGF). We tested the suitability of real-time PCR for CD146, an endothelial cell-specific antigen, to quantify CEC numbers in comparison to a flow cytometry quantification. Real-time PCR of CD146 mRNA showed high sensitivity and linearity for the quantification of cultivated primary endothelial cells added in different amounts to blood samples. Circulating endothelial cell numbers were quantified in peripheral blood samples of breast cancer patients and healthy controls by four-colour flow cytometry analysis and CD146 real-time PCR, and VEGF plasma concentrations were measured by ELISA. The amounts of CEC detected with both methods correlated significantly and CEC numbers were significantly increased in newly diagnosed breast cancer patients compared to healthy controls. Vascular endothelial growth factor concentrations correlated significantly with CEC numbers, but there was no significant difference in VEGF levels between breast cancer patients and healthy controls indicating that VEGF plasma levels cannot be used as surrogate marker for tumour angiogenesis. Taken together, the quantification of CEC by CD146 real-time PCR showed equivalent results to the flow cytometry analysis. Thus, CD146 real-time PCR may be an easy and reliable approach to quantify CEC in peripheral blood samples and could facilitate the integration of CEC measurements in clinical studies exploring the efficacy of antiangiogenic therapies.
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Affiliation(s)
- G Fürstenberger
- Center for Tumor Detection and Prevention, St Gallen, Switzerland.
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11
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Shimanuki Y, Takahashi K, Cui R, Hori S, Takahashi F, Miyamoto H, Fukurchi Y. Role of serum vascular endothelial growth factor in the prediction of angiogenesis and prognosis for non-small cell lung cancer. Lung 2005; 183:29-42. [PMID: 15793665 DOI: 10.1007/s00408-004-2521-4] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/20/2004] [Indexed: 01/04/2023]
Abstract
Although vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 are involved in angiogenesis of various cancers, clinical utility of preoperative serum concentration of these molecules in non-small cell lung cancer (NSCLC) has not yet been elucidated. In this study, we determined the concentration of VEGF, MMP-9 and various other tumor markers in serum prior to surgery and evaluated the results compared with intratumoral vasculature to isolate a valuable marker in determining the prediction of angiogenesis in NSCLC. Among these molecules and serum tumor markers, circulating serum VEGF was identified to markedly correlate with microvessel density (MVD) of the resected tumor specimens. Moreover, overall survival of patients with low VEGF levels (< or =326 ng/ml) was significantly greater than that of patients with high VEGF levels (>326 ng/ml), while patients with low MMP-9 levels (< or =189 ng/ml) and those with high MMP-9 levels (>189 ng/ml) revealed similar overall survival. Conclusively, preoperative concentration of serum VEGF may be the most valuable marker in the prediction of intratumoral angiogenesis and prognosis of patients with NSCLC.
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Affiliation(s)
- Yuri Shimanuki
- Department of Respiratory Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
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12
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Lü F, Qin ZY, Yang WB, Qi YX, Li YM. A DNA vaccine against extracellular domains 1-3 of flk-1 and its immune preventive and therapeutic effects against H22 tumor cell in vivo. World J Gastroenterol 2004; 10:2039-44. [PMID: 15237430 PMCID: PMC4572329 DOI: 10.3748/wjg.v10.i14.2039] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To construct a DNA vaccine against extracellular domains 1-3 of fetal liver kinase-1 (flk-1), and to investigate its preventive and therapeutic effect against H22 cell in vivo.
METHODS: Flk-1 DNA vaccine was produced by cloning extracellular domains 1-3 of flk-1 and by inserting the cloned gene into pcDNA3.1 (+). Fifteen mice were divided into 3 groups and inoculated by vaccine, plasmid and saline respectively to detect specific T lymphocyte response. Thirty Mice were equally divided into preventive group and therapeutic group. Preventive group was further divided into V, P, and S subgroups, namely immunized by vaccine, pcDNA3.1 (+) and saline, respectively, and attacked by H22 cell. Therapeutical group was divided into 3 subgroups of V, P and S, and attacked by H22, then treated with vaccine, pcDNA3.1 (+) and saline, respectively. The tumor size, tumor weight, mice survival time and tumor latency period were compared within these groups. Furthermore, intratumoral microvessel density (MVD) was assessed by immunohistochemistry.
RESULTS: DNA vaccine pcDNA3.1 (+) flk-1-domains 1-3 was successfully constructed and could raise specific CTL activity. In the preventive group and therapeutic group, tumor latency period and survival time were significantly longer in vaccine subgroup than that in P and S subgroups (P < 0.05); the tumor size, weight and MVD were significantly less in vaccine subgroup than that in P and S subgroups (P < 0.05). The survival time of therapeutic vaccine subgroup was significantly shorter than that of preventive vaccine subgroup (P < 0.05); the tumor size, and MVD of therapeutic vaccine subgroup were significantly greater than that of preventive vaccine subgroup (P < 0.05).
CONCLUSION: DNA vaccine against flk-1 domains 1-3 can stimulate potent specific CTL activity; and has distinctive prophylactic effect on tumor H22; and also can inhibit the tumor growth in vivo. This vaccine may be used as an adjuvant therapy because it is less effective on detectable tumor.
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Affiliation(s)
- Fan Lü
- Department of General Surgery, Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
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Abstract
BACKGROUND VEGF is an important factor for angiogenesis. Although many previous studies have reported an increased serum VEGF concentration in various malignant tumors, there are few studies on the relationship between serum VEGF concentration and its prognosis. This study investigated whether serum VEGF concentration is a prognostic indicator for lung cancer. METHODS Using the ELISA kit, we measured the serum VEGF concentrations of 86 patients diagnosed with lung cancer on histologic examination. With a cut off value of 686 pg/mL, the patients were classified as low-concentration (< 686 pg/mL, n=58) or high-concentration (> or = 686 pg/mL, n=28) based on their mean serum VEGF concentration values to compare survival rates, and serum VEGF concentrations for different histologic types and stages. RESULTS There was no significant difference in serum VEGF concentration based on stage and histologic type between the two groups. Moreover, there was no significant difference in survival rate between the high-concentration and low-concentration groups (p=0.86). CONCLUSION This study demonstrates that serum VEGF concentration is not associated with the prognosis of lung cancer.
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Affiliation(s)
| | - Seung Sei Lee
- Correspondence to : Seung Sei Lee, M.D., Department of Internal Medicine, kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 108, Pyung-dong, Jongro-ku, Seoul, 110-746, Korea Tel : 82-2-2001-2084, Fax : 82-2-2001-204, E-mail :
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14
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Fong KM, Sekido Y, Gazdar AF, Minna JD. Lung cancer. 9: Molecular biology of lung cancer: clinical implications. Thorax 2003; 58:892-900. [PMID: 14514947 PMCID: PMC1746489 DOI: 10.1136/thorax.58.10.892] [Citation(s) in RCA: 94] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
It has been hypothesised that clinically evident lung cancers have accumulated many different genetic or epigenetic abnormalities in oncogenes and/or tumour suppressor genes. This notion has important clinical ramifications. Recent developments in our knowledge of the molecular biology of lung cancer are reviewed, with particular reference to genetic abnormalities in tumour suppressor gene inactivation and overactivity of growth promoting oncogenes. These changes lead to the "hallmarks of lung cancer". These hallmarks are the new rational targets for early detection, prevention, and treatment of lung cancer.
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Affiliation(s)
- K M Fong
- The Prince Charles Hospital, Rode Road, Chermside, Brisbane 4032, Australia
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