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Catalano T, Selvaggi F, Cotellese R, Aceto GM. The Role of Reactive Oxygen Species in Colorectal Cancer Initiation and Progression: Perspectives on Theranostic Approaches. Cancers (Basel) 2025; 17:752. [PMID: 40075600 PMCID: PMC11899472 DOI: 10.3390/cancers17050752] [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: 01/12/2025] [Revised: 02/18/2025] [Accepted: 02/20/2025] [Indexed: 03/14/2025] Open
Abstract
Altered levels of reactive oxygen species (ROS) are recognized as one of the key factors in mediating tumor cell survival in the tissue microenvironment, where they play a role in the initiation, progression and recurrence/relapse of colorectal cancer (CRC). Tumor cells can adapt to oxidative stress (OS) using genetic or metabolic reprogramming in the long or short term. In addition, tumor cells defend themselves through positive regulation of antioxidant molecules, enhancing ROS-driven proliferation. Balanced oxidative eustress levels can influence chemotherapy resistance, allowing tumor cells to survive treatment. Secondary effects of chemotherapy include increased ROS production and redox stress, which can kill cancer cells and eliminate drug resistance. Anticancer treatments based on manipulating ROS levels could represent the gold standard in CRC therapy. Therefore, exploring the modulation of the response to OS in deregulated signaling pathways may lead to the development of new personalized CRC treatments to overcome therapy resistance. In this review, we explore the role of ROS in the initiation and progression of CRC and their diagnostic implications as biomarkers of disease. Furthermore, we focused on the involvement of ROS in different CRC therapeutic options, such as surgery, radiotherapy, theranostic imaging, chemotherapy and immunotherapy and other precision medicine approaches.
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Affiliation(s)
- Teresa Catalano
- Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125 Messina, Italy
| | - Federico Selvaggi
- Villa Serena Foundation for Research, 65013 Città Sant’Angelo, Italy; (F.S.); (R.C.)
| | - Roberto Cotellese
- Villa Serena Foundation for Research, 65013 Città Sant’Angelo, Italy; (F.S.); (R.C.)
| | - Gitana Maria Aceto
- Villa Serena Foundation for Research, 65013 Città Sant’Angelo, Italy; (F.S.); (R.C.)
- Department of Sciences, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy
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Effect of acute isooxic hypercapnia on oxidative activity of systemic neutrophils in endotoxemic rabbits. Cent Eur J Immunol 2021; 46:47-53. [PMID: 33897283 PMCID: PMC8056343 DOI: 10.5114/ceji.2021.105245] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Accepted: 08/27/2020] [Indexed: 12/14/2022] Open
Abstract
Introduction Whether carbon dioxide (CO2) affects systemic oxidative phenomena under conditions of endotoxemia is not sufficiently clarified. The study aimed to assess the impact of moderate acute hypercapnia on the respiratory burst of circulating neutrophils in mechanically ventilated endotoxemic rabbits. Material and methods Twenty-four endotoxemic rabbits were mechanically ventilated with standard or CO2-enriched gas mixture in order to obtain isooxic hypercapnia. At a baseline point and following 180 min of hypercapnic ventilation, luminol-dependent chemiluminescence (CL) of circulating neutrophils and serum 2-thiobarbituric acid reactive substance (TBARS) concentrations were measured. Throughout the study, leukocyte and neutrophil counts, pH status, circulatory parameters and body temperature were also assessed. Results Following 180 min of hypercapnic ventilation, opsonized zymosan (OZ)-stimulated neutrophils showed lower CL vs. the control group (p = 0.004). Other parameters studied were not affected. Conclusions Short-term isooxic hypercapnia in endotoxemic rabbits preserves circulating neutrophil count pattern and reactive oxygen species (ROS) generation, but it may reduce phagocytosis.
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Nakamura H, Koga H, Okazaki T, Urao M, Miyano G, Okawada M, Doi T, Watayo H, Ogasawara Y, Lane GJ, Yamataka A. Does pneumoperitoneum adversely affect growth, development and liver function in biliary atresia patients after laparoscopic portoenterostomy? Pediatr Surg Int 2015; 31:45-51. [PMID: 25326122 DOI: 10.1007/s00383-014-3625-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/07/2014] [Indexed: 12/26/2022]
Abstract
PURPOSE We assessed the effect of high partial pressure of arterial carbon dioxide (PaCO2) due to pneumoperitoneum (PP) on growth (height/weight) and development (gross/fine motor function, receptive/expressive communication, and social interaction), by comparing outcome after portoenterostomy (PE) for biliary atresia (BA) using laparoscopic PE (LPE: n = 13) and open PE (OPE: n = 13) cases performed between 2005 and 2014. METHODS Our PE is based on Kasai's original PE. All data were collated prospectively. RESULTS Differences in duration of follow-up (LPE: 38.8 months; OPE: 38.1 months), jaundice clearance (LPE: 12/13 = 92.3 %; OPE: 9/13 = 69.2 %), survival with the native liver (LPE: 10/13 = 76.9 %; OPE: 9/13 = 69.2 %), incidence of cholangitis, hypersplenism, and incidence of esophageal varices were not significant. Mean intraoperative PaCO2 was significantly higher in LPE (LPE: 50.1 mmHg; OPE: 40.7 mmHg, p < 0.05). Liver function impairment was not statistically different, although LPE results were slightly worse. There was no overall delay in growth observed, although height/weight gain was more consistent in LPE. The pattern of developmental delay observed was similar for LPE and OPE suggesting that developmental delay is not PE-related; in other words, PP is not implicated in developmental delay. CONCLUSIONS PP during LPE would appear to have no adverse effects on overall growth/development and liver function in BA patients.
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Affiliation(s)
- Hiroki Nakamura
- Department of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
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Jiang GQ, Chen P, Qian JJ, Yao J, Wang XD, Jin SJ, Bai DS. Perioperative advantages of modified laparoscopic vs open splenectomy and azygoportal disconnection. World J Gastroenterol 2014; 20:9146-9153. [PMID: 25083088 PMCID: PMC4112867 DOI: 10.3748/wjg.v20.i27.9146] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Revised: 03/16/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate perioperative outcomes in patients undergoing modified laparoscopic splenectomy or open splenectomy and azygoportal disconnection for portal hypertension.
METHODS: This study included 44 patients who underwent modified laparoscopic splenectomy and azygoportal disconnection (MLSD) and 71 who underwent open procedures for portal hypertension. Blood samples were collected before surgery and on days 1, 3, and 7 after surgery. Markers of liver and renal function, C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) were measured, and perioperative variables were compared between the two groups.
RESULTS: The modified laparoscopic group showed significantly better and faster recovery, better liver and renal function, and fewer complications than the open group. CRP, IL-6, and PCT concentrations on postoperative days 1, 3, and 7 were significantly lower in the modified laparoscopic group than in the open group.
CONCLUSION: MLSD was associated with lower inflammatory immune responses, less impairment of liver and renal function, and faster and better recovery.
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Ure B. Enthusiasm, evidence and ethics: the triple E of minimally invasive pediatric surgery. J Pediatr Surg 2013; 48:27-33. [PMID: 23331789 DOI: 10.1016/j.jpedsurg.2012.10.013] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2012] [Accepted: 10/13/2012] [Indexed: 12/16/2022]
Abstract
Minimally invasive techniques are applicable in more than 60% of abdominal and thoracic operations in children. Enthusiasts promoted these techniques for many years. However, level 1 evidence on advantages of minimally invasive surgery in children remains limited. Randomized controlled trials have been conducted for some types of procedures such as laparoscopic appendectomy, fundoplication, pyloromyotomy, and inguinal hernia repair. The results of these studies confirm some advantages of minimally invasive surgery, but for most types of laparoscopic and all types of thoracoscopic procedures, such data remain to be established. This article also focuses on reports on complications and disadvantages which are relevant for final conclusions and recommendations. The ethical implications of the application of new techniques in children are also discussed. On the basis of evidence based data and ethical principles, minimally invasive techniques may be appropriately used in the future.
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Affiliation(s)
- Benno Ure
- Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
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Aminsharifi A, Salehipoor M, Arasteh H. Systemic immunologic and inflammatory response after laparoscopic versus open nephrectomy: a prospective cohort trial. J Endourol 2012; 26:1231-1236. [PMID: 22471699 DOI: 10.1089/end.2012.0110] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
PURPOSE To compare the dynamics of systemic inflammatory indices during laparoscopic nephrectomy (LN) and standard open donor nephrectomy. PATIENTS AND METHODS Participants in this cohort study were 54 adults without a history of renal surgery and no evidence of urinary tract infection who underwent transperitoneal LN (n=29) and open donor nephrectomy (n=25, control group). We recorded demographic characteristics, intraoperative parameters, and changes 24 hours postoperatively in systemic inflammatory and immunologic values (body temperature, concentrations of white blood cell count [WBC], C-reactive protein [CRP], interleukin [IL]-6, and tumor necrosis factor [TNF]-α), and compared the mean changes between groups. RESULTS Mean age was older in the LN group (45.6 vs 30.9 years; P<0.0001), and mean operative time was significantly shorter (83.1 min vs 101.6 min; P=0.004). Mean postoperative increase in IL-6 and body temperature in LN was significantly less than in control: For IL-6, 15.87 vs 29.09 pg/mL, P=0.03; for body temperature, +0.22°C vs +0.71°C, P=0.001). Mean postoperative increases in levels of other inflammatory markers (CRP, TNF-α, WBC) did not differ significantly. No statistical correlation was found between operative time and changes in IL-6, CRP, TNF-α, WBC, or body temperature. CONCLUSION Based on the smaller increase in serum IL-6 as the most important indicator of surgical stress, the surgical trauma-induced immune dysfunction may be less intense after LN than open surgery. This may explain the smooth convalescence after LN.
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Yamataka A, Lane GJ, Cazares J. Laparoscopic surgery for biliary atresia and choledochal cyst. Semin Pediatr Surg 2012; 21:201-10. [PMID: 22800973 DOI: 10.1053/j.sempedsurg.2012.05.011] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Minimally invasive surgery in children has evolved to the extent that complex procedures can be performed with safety and outcome comparable with open surgery, with the advantage of minimal scarring. Here we describe the latest laparoscopic techniques used by us at the Juntendo University Hospital, Japan, for treating biliary atresia and choledochal malformation, with presentation of our postoperative management and discussion of preliminary outcomes.
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Affiliation(s)
- Atsuyuki Yamataka
- Department of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
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Diao M, Li L, Cheng W. Initial experience of single-incision laparoscopic hepaticojejunostomy using conventional instruments for correctable biliary atresia. J Laparoendosc Adv Surg Tech A 2012; 22:615-20. [PMID: 22690690 DOI: 10.1089/lap.2011.0518] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND/PURPOSE Single-incision laparoscopic surgery aims to minimize surgical trauma. Yet there has been no report on its application to the treatment of correctable biliary atresia (BA). We present here our initial mini-series of successful single-incision laparoscopic hepaticojejunostomy (SILH) for correctable BA. PATIENTS AND METHODS We reviewed 4 correctable BA patients (Type I/II, 3/1) who underwent SILH between May and July 2011. Ultrasonography, upper gastrointestinal contrast studies, and blood tests were performed during the follow-up period. The age at operation, operative time, postoperative hospital stay, resumption of full diet, postoperative complications, and perioperative laboratory tests were evaluated. RESULTS The median age at operation was 21 days. The median operative time was 2 hours. Blood loss was minimal. The median follow-up duration was 4.5 months. Jaundice gradually declined after 3-5 days in Type I and 6 days in Type II BA patient. There was no mortality or surgical complication so far. CONCLUSIONS In experienced hands, SILH for treatment of correctable BA is safe and effective.
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Affiliation(s)
- Mei Diao
- Department of Pediatric Surgery, Capital Institute of Pediatrics, Beijing, China
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Yu Y, Kuebler J, Groos S, Metzelder M, Kurpanik S, Ure BM, Vieten G. Carbon dioxide modifies the morphology and function of mesothelial cells and facilitates transepithelial neuroblastoma cell migration. Pediatr Surg Int 2010; 26:29-36. [PMID: 19847444 DOI: 10.1007/s00383-009-2503-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND The response of mesothelial cells to surgical trauma and bacterial contamination is poorly defined. We have recently shown that CO(2) pneumoperitoneum increases systemic metastasis of neuroblastoma cells in a murine model. Thus, we hypothesized that CO(2) alters the morphology and function of mesothelial cells and facilitates transmesothelial tumor cell migration. MATERIALS AND METHODS Murine mesothelial cells were exposed to 100% CO(2) and 5% CO(2) as control. Scanning electron microscopy (SEM) investigations, as well as LPS-induced granulocyte-colony stimulating factor (G-CSF) production and mitochondrial activity (MTT assay) were measured. Transmesothelial migration of neuroblastoma cells (Neuro2a) was determined using a transwell chamber system. RESULTS CO(2) incubation was associated with a significant destruction of the microvillar formation in SEM. Migration studies showed that the barrier function of the mesothelial monolayer decreased. A significantly increased migration of neuroblastoma cells was identified after 100% CO(2) exposure (P < 0.05). Although the conversion of MTT as an indicator of mitochondrial activity was only slightly and not significantly reduced after CO(2) incubation, the release of G-CSF induced by LPS was completely blocked during the incubation with 100% CO(2) (P < 0.05). The capacity of G-CSF release recovered after the incubation. CONCLUSION We observed that peritoneal mesothelial cells lose their typical cell morphology by CO(2) incubation, which is accompanied by facilitated migration of neuroblastoma cells. Moreover, the synthesis of immunological factors is blocked, but this effect is not long lasting. These mechanisms may explain an increased metastasis rate of neuroblastoma cells after CO(2) pneumoperitoneum, which was recently observed in a murine model.
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Affiliation(s)
- Yi Yu
- Department of Pediatric Surgery, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany
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A novel acute anemia model for pharmacological research in mice by compelled acute exercise. Acta Pharmacol Sin 2009; 30:1643-7. [PMID: 19960009 DOI: 10.1038/aps.2009.161] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
AIM To generate a novel acute anemia model by compelled exercise. METHODS Young adult male mice were compelled to perform an acute exercise by electric stimulation for 30 min. Blood was taken from their tails to be used for detection immediately after exercise. RESULTS It was found that the red blood cell (RBC) count, hemoglobin concentration and hematocrit of exhausted mice were lower than that of sedentary mice without electric stimulation. The model is in line with the diagnostic criteria. As the mechanisms of the acute anemia model, it was found that the osmotic fragility of the RBC in model mice increased compared to that of normal mice, and that the deformation index, orientation index, small deformation index, deformability and orientation of RBCs in the model mice were reduced. The glutathione (GSH) levels in blood plasma were decreased. The liver, spleen, kidney had no detectable changes. CONCLUSION To the best of our knowledge, these effects represent the success of a novel anemia model by compelled acute exercise. The oxidative damages on RBC and hemorheological changes are in part the causes of acute anemia in this model.
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