ASAP3 upregulation contributes to colorectal carcinogenesis and indicates poor survival outcome

Summary

The function and clinical implication of ArfGAP With SH3 Domain, Ankyrin Repeat And PH Domain 3 (ASAP3) in colorectal cancer (CRC) remains undefined. In the present study, we showed that the expression level of ASAP3 was dramatically increased in CRC and its upregulation was associated with American Joint Committee on Cancer (AJCC) stage (P<0.001) and poor prognosis (P=0.0022). The combination of AJCC stage and ASAP3 expression improved the prediction of survival in CRC patients. Suppression of ASAP3 inhibited cell proliferation by inducing G1-phase arrest without influencing apoptosis. ASAP3 promoted growth of colon tumors in mice with colitis. ASAP3 accelerated cell invasion and migration in vitro. Increased ASAP3 was associated with activation of the NF-κB canonical pathway in CRC. Upregulation of ASAP3 increased the phosphorylation and nuclear translocation of p65 NF-κB subunit. Mechanistically, ASAP3 interact with NEMO and could reduce the polyubiquitinylation of NEMO. Overall, ASAP3 might regulate NF-κB via binding to NEMO. ASAP3 acts as an oncogene in colonic cancer and could be a potential biomarker of colon carcinogenesis.

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DYRK2 is a suppressor and potential prognostic marker for liver metastasis of colorectal cancer

Summary

Colorectal cancer is a common cancer and a leading cause of cancer-related death worldwide. The liver is a dominant metastatic site for patients with colorectal cancer. Molecular mechanisms that allow colorectal cancer cells to form liver metastases are largely unknown. Activation of epithelial-mesenchymal-transition (EMT) is the key step for metastasis of cancer cells. We have recently demonstrated in breast cancer and ovarian serous adenocarcinoma that dual-specificity tyrosine-regulated kinase 2 (DYRK2) controls EMT. The aim of this study is to clarify whether DYRK2 regulates liver metastases of colorectal cancer. We demonstrated that the ability of cell invasion and migration was abrogated in DYRK2-overexpressing cells. In an in vivo xenograft model, liver metastatic lesions were markedly diminished by an ectopic expression of DYRK2. Furthermore, we found that patients whose liver metastases expressed low DYRK2 levels had significantly worse overall and disease-free survival. Given the findings that DYRK2 regulates cancer cell metastasis, we concluded that the expression status of DYRK2 could be a predictive marker for liver metastases of colorectal cancer.

This article is protected by copyright. All rights reserved.

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ASAP3 upregulation contributes to colorectal carcinogenesis and indicates poor survival outcome

Summary

The function and clinical implication of ArfGAP With SH3 Domain, Ankyrin Repeat And PH Domain 3 (ASAP3) in colorectal cancer (CRC) remains undefined. In the present study, we showed that the expression level of ASAP3 was dramatically increased in CRC and its upregulation was associated with American Joint Committee on Cancer (AJCC) stage (P<0.001) and poor prognosis (P=0.0022). The combination of AJCC stage and ASAP3 expression improved the prediction of survival in CRC patients. Suppression of ASAP3 inhibited cell proliferation by inducing G1-phase arrest without influencing apoptosis. ASAP3 promoted growth of colon tumors in mice with colitis. ASAP3 accelerated cell invasion and migration in vitro. Increased ASAP3 was associated with activation of the NF-κB canonical pathway in CRC. Upregulation of ASAP3 increased the phosphorylation and nuclear translocation of p65 NF-κB subunit. Mechanistically, ASAP3 interact with NEMO and could reduce the polyubiquitinylation of NEMO. Overall, ASAP3 might regulate NF-κB via binding to NEMO. ASAP3 acts as an oncogene in colonic cancer and could be a potential biomarker of colon carcinogenesis.

This article is protected by copyright. All rights reserved.

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DYRK2 is a suppressor and potential prognostic marker for liver metastasis of colorectal cancer

Summary

Colorectal cancer is a common cancer and a leading cause of cancer-related death worldwide. The liver is a dominant metastatic site for patients with colorectal cancer. Molecular mechanisms that allow colorectal cancer cells to form liver metastases are largely unknown. Activation of epithelial-mesenchymal-transition (EMT) is the key step for metastasis of cancer cells. We have recently demonstrated in breast cancer and ovarian serous adenocarcinoma that dual-specificity tyrosine-regulated kinase 2 (DYRK2) controls EMT. The aim of this study is to clarify whether DYRK2 regulates liver metastases of colorectal cancer. We demonstrated that the ability of cell invasion and migration was abrogated in DYRK2-overexpressing cells. In an in vivo xenograft model, liver metastatic lesions were markedly diminished by an ectopic expression of DYRK2. Furthermore, we found that patients whose liver metastases expressed low DYRK2 levels had significantly worse overall and disease-free survival. Given the findings that DYRK2 regulates cancer cell metastasis, we concluded that the expression status of DYRK2 could be a predictive marker for liver metastases of colorectal cancer.

This article is protected by copyright. All rights reserved.

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Dietary inflammatory index and non-Hodgkin lymphoma risk in an Italian case–control study

Abstract

Background

While dietary factors have been shown to play an important etiologic role in non-Hodgkin lymphoma (NHL), little is known about the association between inflammatory properties of diet and NHL risk.

Methods

We explored the association between the dietary inflammatory index (DII) and NHL risk in a multicenter Italian case–control study conducted between 1999 and 2014. Cases were 536 subjects with incident, histologically confirmed NHL from three areas in Italy. Controls were 984 subjects admitted to the same network of hospitals as the cases for acute, nonmalignant conditions, unrelated to diet. DII scores were computed based on 30 nutrients and food items assessed using a reproducible and validated 78-item food-frequency questionnaire. Odds ratios (ORs) were estimated through logistic regression models adjusting for age, total energy intake, and other recognized confounding factors.

Results

Subjects in the highest quartile of DII scores (i.e., with the most pro-inflammatory diets) had a higher risk of NHL compared with subjects in the lowest quartile (i.e., with the most anti-inflammatory diets) (OR_Quartile4vs1 1.61, 95% confidence interval CI 1.07–2.43; p-trend = 0.01). Stratified analyses produced stronger associations between DII and NHL among males (OR_Quartile4vs1 2.14; 95% CI 1.25–3.67) with significant heterogeneity (p value = 0.02); when analyzed by histologic subtype, a significant association was observed with diffuse large B-cell lymphoma (OR_Quartile4vs1 1.84; 95% CI 1.09–3.10).

Conclusion

A pro-inflammatory diet, as indicated by higher DII scores, is associated with elevated odds of NHL, especially among males.

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Dietary inflammatory index and non-Hodgkin lymphoma risk in an Italian case–control study

Abstract

Background

While dietary factors have been shown to play an important etiologic role in non-Hodgkin lymphoma (NHL), little is known about the association between inflammatory properties of diet and NHL risk.

Methods

We explored the association between the dietary inflammatory index (DII) and NHL risk in a multicenter Italian case–control study conducted between 1999 and 2014. Cases were 536 subjects with incident, histologically confirmed NHL from three areas in Italy. Controls were 984 subjects admitted to the same network of hospitals as the cases for acute, nonmalignant conditions, unrelated to diet. DII scores were computed based on 30 nutrients and food items assessed using a reproducible and validated 78-item food-frequency questionnaire. Odds ratios (ORs) were estimated through logistic regression models adjusting for age, total energy intake, and other recognized confounding factors.

Results

Subjects in the highest quartile of DII scores (i.e., with the most pro-inflammatory diets) had a higher risk of NHL compared with subjects in the lowest quartile (i.e., with the most anti-inflammatory diets) (OR_Quartile4vs1 1.61, 95% confidence interval CI 1.07–2.43; p-trend = 0.01). Stratified analyses produced stronger associations between DII and NHL among males (OR_Quartile4vs1 2.14; 95% CI 1.25–3.67) with significant heterogeneity (p value = 0.02); when analyzed by histologic subtype, a significant association was observed with diffuse large B-cell lymphoma (OR_Quartile4vs1 1.84; 95% CI 1.09–3.10).

Conclusion

A pro-inflammatory diet, as indicated by higher DII scores, is associated with elevated odds of NHL, especially among males.

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Ventilator Management of Bronchopleural Fistula Secondary to Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia in a Pregnant Patient with Systemic Lupus Erythematosus

Managing mechanical ventilation in patient with bronchopleural fistula with coexisting acute respiratory distress syndrome is a challenging situation for the intensivist. We are reporting a case of a pregnant patient with systemic lupus erythematosus on immunosuppressive medications who developed methicillin-resistant Staphylococcus aureus necrotizing pneumonia complicated by bronchopleural fistula and acute respiratory distress syndrome.

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