Preoperative Serum Interleukin-6 Is a Potential Prognostic Factor for Colorectal Cancer, including Stage II Patients

Shiga, Kiyoto; Hara, Masayasu; Nagasaki, Takaya; Sato, Takafumi; Takahashi, Hiroki; Sato, Mikinori; Takeyama, Hiromitsu

doi:10.1155/2016/9701574

Cited by 26 publications

(24 citation statements)

References 24 publications

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“…Because of the use of chemical agents for carcinogenesis in the development of spontaneous tumour‐bearing mice, which might exert additional influences on hepatic CYP450s, we preferred s.c. transplanted tumour‐bearing mice in our study and further validated this mouse model from the perspective of drug metabolic enzyme kinetics considerations (Figure ). Similar to clinical reports (Baharlou et al, ; Schneider et al, ; Shiga et al, ; Yang et al, ), no significant inflammation was observed at the early stage of tumour bearing (Figure f). However, it was interesting to note that CYP3A had already been inhibited at this stage (Figure ).…”

Section: Discussionsupporting

confidence: 90%

Disrupted hepatic pentose phosphate pathway directly participates in and indirectly promotes CYP3A reduction: A new strategy for CYP3A‐mediated drug hepatotoxicity

Liu

Jin

Zhou

et al. 2020

British J Pharmacology

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Background and Purpose Hepatic CYP450s play an important role in drug‐induced hepatotoxicity. They are altered in liver diseases and in many non‐liver diseases, such as extra‐hepatic tumours. Consequently, CYP450‐mediated abnormal drug exposure increases the incidence and extent of hepatotoxicity. This risk is often underestimated because the mechanisms underlying decreases in hepatic CYP450s in extra‐hepatic tumours remain unclear. Experimental Approach We used Balb/c nude mice with s.c. transplanted 4T1, LoVo and HepG2 tumours to model extra‐hepatic tumours. Decreased levels of CYP3A were evaluated by qPCR, western blotting, and metabolic activity. LC‐Q/TOF‐MS and GC–MS were used in combination for analysing liver metabolomics. The contribution of the pentose phosphate pathway (PPP) to decreased CYP3A was assessed using menadione and silencing of glucose‐6‐phosphate dehydrogenase. Key Results CYP3A activity was inhibited at early stages of tumour growth when no significant inflammatory response was observed. The PPP was predominately disrupted at this non‐inflammatory stage. Disruption of the PPP directly inhibited CYP3A through the chk2/p53/p65 pathway at the non‐inflammatory stage, but at the later inflammatory stage, it indirectly potentiated the subsequent IL‐6‐mediated CYP3A decrease. Recovery of the PPP with menadione at the non‐inflammatory stage, reversed the decreased CYP3A. Similar reversal was obtained with the IL‐6 inhibitor, tocilizumab. Such modulation of the PPP to alleviate CYP3A‐mediated drug hepatotoxicity was validated with dasatinib in vivo. Conclusions and Implications PPP modulation at early, non‐inflammatory stages might provide a novel and distinctive approach to manage drug hepatotoxicity mediated by decreased CYP3A.

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Section: Discussionsupporting

confidence: 90%

Disrupted hepatic pentose phosphate pathway directly participates in and indirectly promotes CYP3A reduction: A new strategy for CYP3A‐mediated drug hepatotoxicity

Liu

Jin

Zhou

et al. 2020

British J Pharmacology

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“…It is assumed that adipose tissue produces different types of hormones and pro-inflammatory cytokines including IL-6, TNF-α, leptin and adiponectin, which could provide desirable micro-environmental inflammatory conditions for cancerous cells [22, 25]. Besides, it was shown that high levels of IL-23 and IL-10 in serum [29, 42] and IL-8 and IL-6 in the microenvironment are associated with progression of CRC [43–45]. Recent investigations have highlighted the role of IGF in CRC.…”

Section: Discussionmentioning

confidence: 99%

Obesity, diabetes and the risk of colorectal adenoma and cancer

et al. 2019

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BackgroundColorectal cancer (CRC) is the fourth most commonly diagnosed gastrointestinal (GI) malignancy and the third leading cause of cancer-related death worldwide. In the current case-control study, an association between diagnosis of CRC, obesity and diabetes was investigated.MethodsDemographic characteristics, colonoscopy reports, history of drug, smoking, and medical history were collected from patients referred to a colonoscopy unit. The location, size and number of the polyps were recorded during the colonoscopy. Statistically, t-test was conducted for mean comparison for the groups. Pearson’s chi-squared test (χ2) was applied to categorize variables. Five classification methods based on the important clinicopathological characteristics such as age, BMI, diabetes, family history of colon cancer was performed to predict the results of colonoscopy.ResultsOverall, 693 patients participated in this study. In the present study, 115 and 515 patients were evaluated for adenoma/adenocarcinoma and normal colonoscopy, respectively. The mean age of patients positive for adenoma or adenocarcinoma were significantly higher than the negative groups (p value < 0.001). Incidence of overweight and/or obesity (BMI > 25 kg/m2) were significantly higher in adenoma positive patients as compared to controls (49.9 and 0.9% respectively, p value = 0.04). The results also demonstrated a significant association between suffering from diabetes and having colon adenoma (OR = 1.831, 95%CI = 1.058–3.169, p value = 0.023). The experimental results of 5 classification methods on higher risk factors between colon adenoma and normal colonoscopy data were more than 82% and less than 0.42 for the percentage of classification accuracy and root mean squared error, respectively.ConclusionsIn the current study, the occurrence of obesity measured based on BMI and diabetes in the adenoma positive patient group was significantly higher than the control group although there was no notable association between obesity, diabetes and adenocarcinoma.

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“…It is assumed that adipose tissue produces different types of hormones and pro-inflammatory cytokines including IL-6, TNF-α, leptin and adiponectin, which could provide desirable micro-environmental inflammatory conditions for cancerous cells [22,25]. Besides, it was shown that high levels of IL-23 and IL-10 in serum [29,42] and IL-8 and IL-6 in the microenvironment are associated with progression of CRC [43][44][45]. Recent investigations have highlighted the role of IGF in CRC.…”

Section: Discussionmentioning

confidence: 99%

Obesity, Diabetes and the Risk of Colorectal Adenoma and Cancer

Soltani

Poursheikhani

Yassi

et al. 2019

Preprint

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Background: Colorectal cancer (CRC) is the fourth most commonly diagnosed gastrointestinal (GI) malignancy and the third leading cause of cancer-related death worldwide. In the current case-control study, an association between diagnosis of CRC, obesity and diabetes was investigated. Methods: Demographic characteristics, colonoscopy reports, history of drug, smoking, and medical history were collected from patients referred to a colonoscopy unit. The location, size and number of the polyps were recorded during the colonoscopy. Statistically, t -test was conducted for mean comparison for the groups. Pearson's chi-squared test (χ2) was applied to categorize variables. Five classification methods based on the important clinicopathological characteristics such as age, BMI, diabetes, family history of colon cancer was performed to predict the results of colonoscopy. Results: Overall, 693 patients participated in this study. In the present study, 115 and 515 patients were evaluated for adenoma/adenocarcinoma and normal colonoscopy, respectively. The mean age of patients positive for adenoma or adenocarcinoma were significantly higher than the negative groups (p value <0.001). Incidence of overweight and/or obesity (BMI> 25 kg/m2) were significantly higher in adenoma positive patients as compared to controls (49.9% and 0.9% respectively, p value= 0.04). The results also demonstrated a significant association between suffering from diabetes and having colon adenoma (OR=1.831, 95%CI=1.058–3.169, p value=0.023). The experimental results of 5 classification methods on higher risk factors between colon adenoma and normal colonoscopy data were more than 82% and less than 0.42 for the percentage of classification accuracy and root mean squared error, respectively. Conclusions: In the current study, the occurrence of obesity measured based on BMI and diabetes in the adenoma positive patient group was significantly higher than the control group although there was no notable association between obesity, diabetes and adenocarcinoma.

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Preoperative Serum Interleukin-6 Is a Potential Prognostic Factor for Colorectal Cancer, including Stage II Patients

Cited by 26 publications

References 24 publications

Disrupted hepatic pentose phosphate pathway directly participates in and indirectly promotes CYP3A reduction: A new strategy for CYP3A‐mediated drug hepatotoxicity

Disrupted hepatic pentose phosphate pathway directly participates in and indirectly promotes CYP3A reduction: A new strategy for CYP3A‐mediated drug hepatotoxicity

Obesity, diabetes and the risk of colorectal adenoma and cancer

Obesity, Diabetes and the Risk of Colorectal Adenoma and Cancer

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