The Clinical Importance of IL-6, IL-8, and TNF-α in Patients with Ovarian Carcinoma and Benign Cystic Lesions

Pawlik, Weronika; Pawlik, Jakub; Kozłowski, Mateusz; Łuczkowska, Karolina; Kwiatkowski, Sebastian; Kwiatkowska, Ewa; Cymbaluk‐Płoska, Aneta

doi:10.3390/diagnostics11091625

Cited by 13 publications

(8 citation statements)

References 40 publications

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“…Preclinical models are proposed to understand possible mechanistic functions that may interlink these microorganisms with local and systemic inflammation during EOC development. C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) serum markers have shown to be higher in women with malignant ovarian tumors while there is uncertainty if serum levels are associated with unique GI microbes [ 27 , 28 , 29 , 30 ]. Thus, the purpose of this research was to explore the influences of GI microbiota dysbiosis on inflammatory markers during EOC development and progression using a mouse model.…”

Section: Introductionmentioning

confidence: 99%

Influences of Gastrointestinal Microbiota Dysbiosis on Serum Proinflammatory Markers in Epithelial Ovarian Cancer Development and Progression

Mahoney

Chalise

Rahman

et al. 2022

Cancers

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GI microbiota has been implicated in producing the inflammatory tumor microenvironment of several cancers. Women with ovarian cancer often report GI-related symptoms at diagnosis although minimal is known about the possible GI bacteria that may trigger pro-tumorigenic immune responses in early EOC. The purpose of this study was to investigate the influences of GI microbiota dysbiosis on serum inflammatory markers during EOC utilizing a rodent model. This experimental design consisted of C57BL/6 mice randomly assigned to either the microbiota dysbiosis group (n = 6) or control group (n = 5). The CD7BL/6 mice assigned to the microbiota dysbiosis group were administered a mixture of broad-spectrum antibiotics (bacitracin and neomycin) for 2 weeks. Both groups were injected intraperitoneally with mouse ovarian epithelial cells that induce ovarian tumorigenesis. Levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were assessed in the serum, and the composition of the GI microbiota in fecal samples was measured using 16S rRNA gene sequencing. Overall CRP serum levels were significantly lower and TNFα levels were significantly higher in the microbiota dysbiosis group compared to the control group. The abundances of microbiota that correlated with CRP serum levels in the combined groups were genus Parabacteroides, Roseburia, and Emergencia and species Ruminococcus faecis, Parabacteroides distasonis, Roseburia Faecis, and Emergencia timonensis. This study provides evidence to support for further investigation of the GI microbial profiles in patients at risk of EOC.

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Section: Introductionmentioning

confidence: 99%

Influences of Gastrointestinal Microbiota Dysbiosis on Serum Proinflammatory Markers in Epithelial Ovarian Cancer Development and Progression

Mahoney

Chalise

Rahman

et al. 2022

Cancers

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Section: Discussionmentioning

confidence: 91%

“…IL-6 and IL-8 in particular are proinflammatory cytokines that are biomarkers of ongoing inflammation and known to negatively affect adaptive immune responses. They have been shown previously to be elevated in the sera of cancer patients (32, 33) and to modulate response to immunotherapy (34, 35). More recently they have also been found in premalignant disease, such as in individuals with cervical epithelial neoplasms (36), oral premalignant lesions (37, 38), and Barrett’s esophagus (39).…”

Section: Discussionmentioning

confidence: 96%

Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma

Schoen

Boardman

Cruz‐Correa

et al. 2022

Preprint

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Objective: Vaccines against antigens expressed on adenomas could prevent new adenoma formation. We assessed whether a MUC1 peptide vaccine produces an immune response and prevents subsequent colonic adenoma formation. Design: Multicenter, double blind, placebo-controlled randomized trial in individuals age 40-70 with diagnosis of an advanced adenoma ≤1 year from randomization. Vaccine was administered at 0, 2, and 10 weeks with a booster injection at week 53. Adenoma recurrence was assessed >1 year from randomization. The primary endpoint was vaccine immunogenicity at 12 weeks defined by anti-MUC1 ratio ≥2.0. Results: 53 participants received the MUC1 vaccine and 50 placebo. 13/52 (25%) of MUC1 vaccine recipients had a ≥2-fold increase in MUC1 IgG (range 2.9-17.3) at week 12 vs. 0/50 placebo recipients (1-sided Fisher exact P<0.0001). Of the 13 responders at week 12, 11 (84.6%) had a ≥2-fold increase in MUC1 IgG with the booster and were considered immune responders. A recurrent adenoma was observed in 31 of 47 (66.0%) in the placebo group vs. 27 of 48 (56.3%) participants in the MUC1 group (adjusted relative risk (aRR) = 0.83 [95% CI, 0.60-1.14], P=0.25). Adenoma recurrence occurred in 3/11 (27.3%) immune responders, (aRR = 0.41 [95% CI, 0.15-1.11], P=0.08). Vaccine recipients had more injection site reactions than placebo recipients, but there was no difference in serious adverse events. Conclusion: An immune response was observed only in vaccine recipients. Overall adenoma recurrence was not different than placebo, but a 38% absolute reduction in adenoma recurrence was observed in immune responders.

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“…Women diagnosed with HGSOC have consistently shown elevated circulating levels of IL-6, IL-8, and TNF-α. Clinical data have indicated that IL-6 and IL-8 are significantly amplified between benign ovarian tumors and HGSOCs [163,164]. Studies have shown that innate and activated immune cells are largely responsible for cytokine secretion.…”

Section: Cytokinesmentioning

confidence: 99%

Comparing the Secretomes of Chemorefractory and Chemoresistant Ovarian Cancer Cell Populations

Lee

Pena

Dawson

2022

Cancers

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High-grade serous ovarian cancer (HGSOC) constitutes the majority of all ovarian cancer cases and has staggering rates of both refractory and recurrent disease. While most patients respond to the initial treatment with paclitaxel and platinum-based drugs, up to 25% do not, and of the remaining that do, 75% experience disease recurrence within the subsequent two years. Intrinsic resistance in refractory cases is driven by environmental stressors like tumor hypoxia which alter the tumor microenvironment to promote cancer progression and resistance to anticancer drugs. Recurrent disease describes the acquisition of chemoresistance whereby cancer cells survive the initial exposure to chemotherapy and develop adaptations to enhance their chances of surviving subsequent treatments. Of the environmental stressors cancer cells endure, exposure to hypoxia has been identified as a potent trigger and priming agent for the development of chemoresistance. Both in the presence of the stress of hypoxia or the therapeutic stress of chemotherapy, cancer cells manage to cope and develop adaptations which prime populations to survive in future stress. One adaptation is the modification in the secretome. Chemoresistance is associated with translational reprogramming for increased protein synthesis, ribosome biogenesis, and vesicle trafficking. This leads to increased production of soluble proteins and extracellular vesicles (EVs) involved in autocrine and paracrine signaling processes. Numerous studies have demonstrated that these factors are largely altered between the secretomes of chemosensitive and chemoresistant patients. Such factors include cytokines, growth factors, EVs, and EV-encapsulated microRNAs (miRNAs), which serve to induce invasive molecular, biophysical, and chemoresistant phenotypes in neighboring normal and cancer cells. This review examines the modifications in the secretome of distinct chemoresistant ovarian cancer cell populations and specific secreted factors, which may serve as candidate biomarkers for aggressive and chemoresistant cancers.

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The Clinical Importance of IL-6, IL-8, and TNF-α in Patients with Ovarian Carcinoma and Benign Cystic Lesions

Cited by 13 publications

References 40 publications

Influences of Gastrointestinal Microbiota Dysbiosis on Serum Proinflammatory Markers in Epithelial Ovarian Cancer Development and Progression

Influences of Gastrointestinal Microbiota Dysbiosis on Serum Proinflammatory Markers in Epithelial Ovarian Cancer Development and Progression

Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma

Comparing the Secretomes of Chemorefractory and Chemoresistant Ovarian Cancer Cell Populations

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