scholarly journals Blood cytokine analysis suggests that SARS-CoV-2 infection results in a sustained tumour promoting environment in cancer patients

Author(s):  
Fien HR De Winter ◽  
An Hotterbeekx ◽  
Manon Huizing ◽  
Angelina Konnova ◽  
Erik Fransen ◽  
...  

Cytokines, chemokines and (angiogenic) growth factors (CCGs) have been shown to play an intricate role in the progression of both solid and haematological malignancies. Recent studies have shown that SARS-CoV-2 infection leads to worse outcome in cancer patients, especially in haematological malignancy patients. Here, we investigated how SARS-CoV-2 infection impacts the already altered CCG levels in solid or haematological malignancies, specifically whether there is a protective effect or rather a potentially higher risk for major COVID-19 complications in cancer patients due to elevated CCGs linked to cancer progression. Serially analysing immune responses with 55 CCGs in cancer patients under active treatment with or without SARS-CoV-2 infection, we first showed that cancer patients without SARS-CoV-2 infection (n=54) demonstrate elevated levels of 35 CCGs compared to the non-cancer, non-infected control group of health care workers (n=42). Of the 35 CCGs, 19 were common to both solid and haematological malignancy groups and comprised previously described cytokines such as IL-6, TNF-α, IL-1Ra, IL-17A, and VEGF, but also several less well described cytokines/chemokines such as Fractalkine, Tie-2, and T cell chemokine CTACK. Importantly, we show here that 7 CCGs are significantly altered in SARS-CoV-2 exposed cancer patients (n=52). Of these TNF-α, IFN-β, TSLP and sVCAM-1, identified to be elevated in haematological cancers, are also known tumour-promoting factors. Longitudinal analysis conducted over 3 months showed persistence of several tumour-promoting CCGs in SARS-CoV-2 exposed cancer patients. These data urge for increased vigilance for haematological malignancy patients as a part of long COVID follow-up.

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5718
Author(s):  
Fien H.R. De Winter ◽  
An Hotterbeekx ◽  
Manon T. Huizing ◽  
Angelina Konnova ◽  
Erik Fransen ◽  
...  

Cytokines, chemokines, and (angiogenic) growth factors (CCGs) have been shown to play an intricate role in the progression of both solid and haematological malignancies. Recent studies have shown that SARS-CoV-2 infection leads to a worse outcome in cancer patients, especially in haematological malignancy patients. Here, we investigated how SARS-CoV-2 infection impacts the already altered CCG levels in solid or haematological malignancies, specifically, whether there is a protective effect or rather a potentially higher risk for major COVID-19 complications in cancer patients due to elevated CCGs linked to cancer progression. Serially analysing immune responses with 55 CCGs in cancer patients under active treatment with or without SARS-CoV-2 infection, we first showed that cancer patients without SARS-CoV-2 infection (n = 54) demonstrate elevated levels of 35 CCGs compared to the non-cancer, non-infected control group of health care workers (n = 42). Of the 35 CCGs, 19 were common to both the solid and haematological malignancy groups and comprised previously described cytokines such as IL-6, TNF-α, IL-1Ra, IL-17A, and VEGF, but also several less well described cytokines/chemokines such as Fractalkine, Tie-2, and T cell chemokine CTACK. Importantly, we show here that 7 CCGs are significantly altered in SARS-CoV-2 exposed cancer patients (n = 52). Of these, TNF-α, IFN-β, TSLP, and sVCAM-1, identified to be elevated in haematological cancers, are also known tumour-promoting factors. Longitudinal analysis conducted over 3 months showed persistence of several tumour-promoting CCGs in SARS-CoV-2 exposed cancer patients. These data demonstrate a need for increased vigilance for haematological malignancy patients as a part of long COVID follow-up.


2014 ◽  
Vol 32 (31_suppl) ◽  
pp. 189-189 ◽  
Author(s):  
Clelia Madeddu ◽  
Giulia Gramignano ◽  
Luciana Tanca ◽  
Maria Cristina Cherchi ◽  
Carlo Aurelio Floris ◽  
...  

189 Background: Cancer progression is characterized by specific energy metabolism alterations and by symptoms including fatigue, anorexia, nausea, depression, which results in cachexia syndrome and compromised quality of life (QL). This condition is often associated to anemia (cancer-related anemia, CRA), which negatively impacts patient QL and disease outcome. Methods: Adult advanced cancer patients with cachexia (i.e., weight loss > 5% in the previous 6 months) and CRA were randomly assigned (1:1 by computer generated list) to receive 3 months of a combined approach consisting of celecoxib (200 mg/day), L-carnitine (2 g/day), curcumin (Meriva) (4 g/day) and lactoferrin (200 mg/day) or placebo. The rationale for selecting these agents was: L-carnitine for modulating cell energy metabolism; celecoxib for counteracting inflammation, which is a key feature of cachexia; curcumin for its antiinflammatory and antioxidant action, without disregarding its action on the NF-kB and JAK-STAT pathway and the related synthesis of proinflammatory cytokines; lactoferrin for its ability to regulate iron metabolism in anemic cancer patients. Primary endpoints were improvement of lean body mass (LBM), appetite, fatigue and anemia. Additionally, we assessed the impact of treatment on the main metabolic/inflammatory and iron metabolism parameters: C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, leptin, reactive oxygen species (ROS), glutathione peroxidase, serum iron, ferritin, hepcidin and erythropoietin (EPO). Results: From January 2013 to March 2014, 66 patients have been enrolled. The combination arm was more effective than placebo arm in improving body weight, LBM, appetite, fatigue, and anemia. Among secondary parameters IL-6, TNF-α, CRP, ROS, ferritin, hepcidin and EPO decreased, while leptin increased significantly in the combination arm. No significant changes were observed in the placebo arm. Conclusions: To date a standard effective treatment of cancer cachexia is lacking. Our combined multitargeted approach was able to improve the nutritional and immunometabolic alterations of cachexia, ameliorate patient QL and correct CRA.


Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 341-349
Author(s):  
Amichay Meirovitz ◽  
Lea Baider ◽  
Tamar Peretz ◽  
Samir Stephanos ◽  
Vivian Barak

BACKGROUND: Cancer progression is associated with significant systemic clinical manifestations including cachexia induced weight loss and anorexia. Pentoxifylline (PTX) is a drug that has been shown to have multiple beneficial effects in cancer patients through its anti-inflammatory properties. MAIN OBJECTIVE: To evaluate PTX effects on colon cancer patients treated with chemotherapy. PATIENTS and METHODS: Forty metastatic colon cancer patients receiving chemotherapy were enrolled in this randomized study. 17 patients were treated with a full dose of PTX (400 mg TID), 9 patients with a reduced dose PTX (200 mg TID) and 23 served as controls (no PTX). RESULTS: Follow-up evaluations of patients included the following: physical examination; leukopenia determination; weight determination; stomatitis determination; and survival rate. Patients treated with PTX (both full and reduced doses), experienced a significant increase in weight and a reduction in stomatitis relative to the control group. Treatment with PTX also significantly increased patient survival rate. All patients treated with PTX, had a median overall survival (OS) rate of 20.4 months as compared to 13.2 months in the control group. CONCLUSIONS: PTX treatment of colon cancer patients, in addition to chemotherapy, significantly improved survival rates, induced weight gain and reduced stomatitis occurrence –all important parameters of cachexia.


2015 ◽  
Vol 90 (5) ◽  
pp. 547-554 ◽  
Author(s):  
W.N. Onkoba ◽  
M.J. Chimbari ◽  
J.M. Kamau ◽  
S. Mukaratirwa

AbstractTo improve diagnostic tools, immunotherapies and vaccine development for trichinellosis surveillance and control there is a need to understand the host immune responses induced during infection with Trichinella zimbabwensis, a tissue-dwelling nematode. In this study, we sought to determine immune responses induced in mice during T. zimbabwensis infection. The parasite strain used (Code ISS1209) was derived from a naturally infected crocodile (Crocodylus niloticus) and is the main Trichinella species prevalent in southern Africa. Sixty 6- to 8-week-old female BALB/c mice were randomly assigned to two equal groups: T. zimbabwensis-infected (n= 30) and the non-infected control group (n= 30). Levels of serum tumour necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), interleukin-4 (IL-4) as well as parasite-specific IgM, IgG, IgG1, IgG2a, IgG2b and IgG3 antibody responses were determined using enzyme-linked immunosorbent assay (ELISA). The cytokines and antibodies provided information on T-helper 1 (Th1)- and Th2-type, T-regulatory and antibody responses. Results showed that during the intestinal stage of infection, higher levels of parasite-specific IgM, IgG, IgG1 (P <  0.05) and IL-10 and TNF-α (P <  0.001) were observed in the Trichinella-infected group compared with the non-infected control group. In the parasite establishment and tissue migration phases, levels of IgG1 and IgG3 were elevated (P <  0.001), while those of IgM (P <  0.01) declined on days 21 and 35 post infection (pi) compared to the enteric phase. Our findings show that distinct differences in Th1- and Th2-type and T-regulatory responses are induced during the intestinal, tissue migration and larval establishment stages of T. zimbabwensis infection.


Parasitology ◽  
2009 ◽  
Vol 137 (7) ◽  
pp. 1079-1088 ◽  
Author(s):  
J. M. R. PINHO ◽  
F. C. CARDOSO ◽  
D. O. LOPES ◽  
C. S. PINHEIRO ◽  
M. V. CALIARI ◽  
...  

SUMMARYProteins associated with the schistosome tegument are of great importance for the development of new intervention strategies since they may be exposed on the surface of the parasite. Herein, we have isolated a cDNA clone encoding for theSchistosoma mansoniSmIg and its recombinant protein was tested as a potential vaccine candidate. Initially, its amino acid sequence was analysed by bioinformatics and shown to possess an N-terminal signal peptide, a C-terminal transmembrane helix, 4 glycosylation sites, an immunoglobulin conserved domain and 73% similarity with a hypotheticalS. japonicumprotein of unknown function. SmIg was produced byE. colias a recombinant protein (rSmIg) and its protective effectiveness was evaluated againstS. mansoniinfection with 100 cercariae in a murine model. Mice immunized with rSmIg induced an immune response characterized by dominant IgG1 isotype and significant levels of IFN-γ, TNF-α, IL-10 and IL-4. Although immunogenic, the recombinant vaccine failed to induce worm burden reduction when compared to the infected control group. However, rSmIg-immunized mice had significant reductions of liver granuloma volume and fibrosis content by 31·8% and 49%, respectively. In conclusion, SmIg is a new tegument protein fromS. mansonithat plays an important role in reducing pathology induced by parasite infection.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Lizhen Gao ◽  
Jia Lv ◽  
Linlin Hou ◽  
Yuchao Yuan ◽  
Qiuhua Wan

Objective. This study was aimed to investigate the clinical effect of Chinese herbal decoction combined with basic chemoradiotherapy and nursing intervention in the treatment of cervical cancer and the effect on serum carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), and tumor necrosis factor-α (TNF-α) levels. Methods. A total of 200 cervical cancer patients in our hospital from June 2015 to November 2018 were selected and randomly divided into a study group and a control group. The control group was given chemoradiotherapy and psychological nursing treatment, and the study group was given self-made Chinese herbal decoction on the basis of the control group. The clinical efficacy and serum CEA, CA125, and TNF-α levels were assessed. Results. After treatment, the total effective rate of the study group was significantly higher than that of the control group. The levels of serum CEA, CA125, and TNF-α were decreased in the two groups after treatment, and the decrease in the study group was more significant than that in the control group. After treatment, CD3+ and CD4+ levels were increased compared with those before treatment, and the increase in the study group was also more obvious than that of the control group. The level of CD8+ was decreased compared with before treatment, and the decrease in the study group was more notable than that of the control group. The two-year cumulative survival rate of the study group was markedly higher than that of the control group. The quality-of-life of patients treated for 3 months, 1 year, and 2 years was dramatically improved compared to before treatment. The incidence of adverse reactions in the study group was lower than that of the control group. Conclusion. The treatment of basic chemoradiotherapy and psychological nursing intervention combined with Chinese herbal decoction on cervical cancer patients can improve the clinical treatment effects, improve the patient’s body immunity, reduce serum CEA, CA125, and TNF-α levels, prolong survival time, improve life quality, and reduce the incidence of adverse reactions, and it is worthy of clinical promotion.


2018 ◽  
Vol 34 ◽  
pp. 113-115 ◽  
Author(s):  
Wen-Juan Liu ◽  
Xiao-Dan Wang ◽  
Wei Wu ◽  
Xiao Huang

Objective: To study the correlation between depression and blood cytokine levels in lung cancer patients.Methods: 92 patients with advanced lung cancer were evaluated for depression using the scoring index of depression self-rating scale. Lack of depression (n=24), mild depression (n=45), and moderate depression (n=23) were found in the cohort. Meanwhile, 40 healthy subjects were selected as the control group. The levels of IL-10, IL-6, IL-8, and TNF-α in each group were detected by sandwich enzyme-linked immunosorbent assays, and their correlation with the degree of depression was analyzed.Results: The levels of IL-10, IL-6, IL-8, and TNF-α were all higher than those in the control group (P<0.05). Moreover, the depression statuses of patients with lung cancer were positively correlated with IL-10, IL-6, and TNF-α levels (r = 0.705, 0.301, and 0.446, P<0.01); however, the level of IL-8 was not relevant (r=0.136, p>0.05).Conclusion: Serum levels of IL-10, IL-6, and TNF-α are associated with depression scoring in patients with lung cancer.


2018 ◽  
Vol 25 (6) ◽  
Author(s):  
Z. Y. Zhu ◽  
J. X. Xue ◽  
L. X. Yu ◽  
W. H. Bian ◽  
Y. F. Zhang ◽  
...  

Background Reducing inflammatory factors in wound exudate is a promising treatment approach for healing wounds in postsurgical breast cancer patients. Traditional Chinese Medicine (tcm) treatments have been shown to be beneficial and safe for optimal regulation of oxidative stress during the postoperative period. In the present clinical trial, we evaluated the effectiveness of a promising Chinese herbal formula, San Huang decoction [shd (Radix astragali, Radix et rhizoma rhei, and Rhizoma curcuma longa, 3:1:1; supplemental Table 1)], on wound inflammatory response after mastectomy.Methods The study randomized 30 patients with breast cancer who fulfilled the inclusion and exclusion criteria to either a treatment (n = 15) or a control group (n = 15). Patients in the treatment group received liquid shd, taken twice daily with or without food. Treatment was given for 1 day before surgery and for 7 days postoperatively. Participants in the control group received a placebo on the same schedule as the treatment group. Outcomes measured in every subject included clinical tcm and wound inflammation symptom scores, daily and total amounts of drainage fluid, and levels of inflammatory factors in the exudate [tumour necrosis factor α (tnf-α), interleukins 6 (il-6), 8 (il-8), and 2R (il-2R), human C-reactive protein (crp)] at 2 hours and on days 1, 3, and 7 postoperatively.Results The total amount of drainage fluid over 7 days was significantly lower in the treatment group (572.20 } 93.95 mL) than in the control group (700.40 } 107.38 mL). The tcm symptom score was also lower in treatment group (day 7: 1.87 } 0.83 vs. 4.80 } 3.61, p = 0.049), as was the inflammatory symptom score (day 7: 0.67 } 0.72 vs. 3.67 } 2.50, p = 0.001). Levels of tnf-α, il-6, il-8, il-2R, and crp in drainage fluid were significantly lower with shd treatment.Conclusions Perioperative treatment with shd effectively lessened postoperative exudate and ameliorated inflammatory symptoms in patients who underwent surgery for breast cancer..


2018 ◽  
Vol 40 (4) ◽  
pp. 323-327 ◽  
Author(s):  
F Tas ◽  
S Karabulut ◽  
K Erturk ◽  
D Duranyildiz

Aim: Caveolin-1 plays a significant role in the pathogenesis of various carcinomas and its expression affects the survival of cancer patients. However, the molecular function of caveolin-1 and its possible clinical importance has remained uncertain in gastric cancer. No clinical trial has examined serum caveolin-1 levels in gastric cancer patients so far, instead all available results were provided from studies conducted on tissue samples. In the current study, we analyzed the soluble serum caveolin-1 levels in gastric cancer patients, and specified its associations with the clinical factors and prognosis. Material and Methods: Sixty-three patients with pathologically confirmed gastric cancer were enrolled into the trial. Serum caveolin-1 concentrations were detected by ELISA method. Thirty healthy subjects were also included in the study. Results: The median age of patients was 62 years, ranging from 28 to 82 years. The serum caveolin-1 levels in gastric cancer patients were significantly higher than those in control group (p < 0.001). The common clinical parameters including patient age, sex, lesion localization, histopathology, histological grade, disease stage, and various serum tumor markers (e.g. LDH, CEA, and CA 19.9) were not found to be associated with serum caveolin-1 levels (p > 0.05). Similarly, no correlation existed between serum caveolin-1 concentration and chemotherapy responsiveness (p = 0.93). Furthermore, serum caveolin-1 level was not found to have a prognostic role (p = 0.16). Conclusion: Even though it is neither predictive nor prognostic, serum caveolin-1 level may be a valuable diagnostic indicator in patients with gastric cancer. Key


2019 ◽  
Vol 22 (4) ◽  
pp. 232-237 ◽  
Author(s):  
Jihong An

Objective: This study aims to investigate the expression and clinical significance of Th17 cells and related factors in peripheral blood of patients with Autoimmune Hepatitis (AIH). Methods: A retrospective selection of 100 patients with AIH were included as a study group, and 100 healthy volunteers in the outpatient clinic were selected as the control group. The levels of IL- 17, IL-6, IL-21 and TNF-α in peripheral blood of all subjects were detected by enzyme-linked immunosorbent assay and the frequency of Th17 cells and Treg cells was detected by flow cytometry. Results: Results showed that the study group had higher levels of serum total bilirubin (TBil), alkaline phosphatase (ALP), γ -glutamyltranspeptidase (γ-GT), immunoglobulin G (IgG), immunoglobulin M (IgM), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than the control group, as well as higher levels of IL-17, IL-6, IL-21 and TNF-α in serum. The frequency of Th17 cells in peripheral blood was higher in the study group, while the frequency of Treg cells was lower. Also, serum IL-17, TNF-α levels and Th17 cells frequency were positively correlated with ALT and AST, whereas Treg cells frequency were negatively correlated with ALT and AST levels. Conclusion: Our finding demonstrates that Th17 cell frequency and their related factors IL-17 and TNF-α, are associated with liver damage, which might be used to monitor AIH disease severity.


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