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Dysregulation of PAK1 Is Associated with DNA Damage and Is of Prognostic Importance in Primary Esophageal Small Cell Carcinoma.

Gan J, Zhang Y, Ke X, Tan C, Ren H, Dong H, Jiang J, Chen S, Zhuang Y, Zhang H - Int J Mol Sci (2015)

Bottom Line: Overexpression of PAK1 was significantly associated with tumor location (p = 0.011), lymph node metastasis (p = 0.026) and patient survival (p = 0.032).We also investigated the association of PAK1 with DNA damage, a driven cause for malignancy progression. γH2AX, a DNA damage marker, was detectable in 18 of 24 (75.0%) cases, and PAK1 expression was associated with γH2AX (p = 0.027).Further studies are worth determining the potentials of PAK1 as prognostic indicator and therapeutic target for PESCC.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Centre, Shantou University Medical College, Shantou 515063, China. gjf88900406@126.com.

ABSTRACT
Primary esophageal small cell carcinoma (PESCC) is a rare, but fatal subtype of esophageal carcinoma. No effective therapeutic regimen for it. P21-activated kinase 1 (PAK1) is known to function as an integrator and an indispensable node of major growth factor signaling and the molecular therapy targeting PAK1 has been clinical in pipeline. We thus set to examine the expression and clinical impact of PAK1 in PESCC. The expression of PAK1 was detected in a semi-quantitative manner by performing immunohistochemistry. PAK1 was overexpressed in 22 of 34 PESCC tumors, but in only 2 of 18 adjacent non-cancerous tissues. Overexpression of PAK1 was significantly associated with tumor location (p = 0.011), lymph node metastasis (p = 0.026) and patient survival (p = 0.032). We also investigated the association of PAK1 with DNA damage, a driven cause for malignancy progression. γH2AX, a DNA damage marker, was detectable in 18 of 24 (75.0%) cases, and PAK1 expression was associated with γH2AX (p = 0.027). Together, PAK1 is important in metastasis and progression of PESCC. The contribution of PAK1 to clinical outcomes may be involved in its regulating DNA damage pathway. Further studies are worth determining the potentials of PAK1 as prognostic indicator and therapeutic target for PESCC.

No MeSH data available.


Related in: MedlinePlus

Representative serial sections of PESCC (Primary esophageal small cell carcinoma) immunohistochemiscal staining for PAK1: (A) negative staining; (B) weak staining; and (C) strong staining. Magnification: 400×.
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ijms-16-12035-f001: Representative serial sections of PESCC (Primary esophageal small cell carcinoma) immunohistochemiscal staining for PAK1: (A) negative staining; (B) weak staining; and (C) strong staining. Magnification: 400×.

Mentions: PAK1 protein, which is shown as brown granules in Figure 1B, Figure 1C, was mainly localized in the cytoplasm. Of the 34 PESCC samples analyzed, 22 (64.71%) were grouped as positive and 12 (35.29%) were grouped as negative (Figure 1A), based on the composite histoscore. Of the 18 adjacent non-cancerous tissues analyzed, 2 (11.11%) were grouped as positive and 16 (88.89%) were grouped as negative. Comparison of expression level of PAK1 between tumor and adjacent normal tissue showed a statistically significant increase in tumor tissues (p = 0.000, Table 1).


Dysregulation of PAK1 Is Associated with DNA Damage and Is of Prognostic Importance in Primary Esophageal Small Cell Carcinoma.

Gan J, Zhang Y, Ke X, Tan C, Ren H, Dong H, Jiang J, Chen S, Zhuang Y, Zhang H - Int J Mol Sci (2015)

Representative serial sections of PESCC (Primary esophageal small cell carcinoma) immunohistochemiscal staining for PAK1: (A) negative staining; (B) weak staining; and (C) strong staining. Magnification: 400×.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490427&req=5

ijms-16-12035-f001: Representative serial sections of PESCC (Primary esophageal small cell carcinoma) immunohistochemiscal staining for PAK1: (A) negative staining; (B) weak staining; and (C) strong staining. Magnification: 400×.
Mentions: PAK1 protein, which is shown as brown granules in Figure 1B, Figure 1C, was mainly localized in the cytoplasm. Of the 34 PESCC samples analyzed, 22 (64.71%) were grouped as positive and 12 (35.29%) were grouped as negative (Figure 1A), based on the composite histoscore. Of the 18 adjacent non-cancerous tissues analyzed, 2 (11.11%) were grouped as positive and 16 (88.89%) were grouped as negative. Comparison of expression level of PAK1 between tumor and adjacent normal tissue showed a statistically significant increase in tumor tissues (p = 0.000, Table 1).

Bottom Line: Overexpression of PAK1 was significantly associated with tumor location (p = 0.011), lymph node metastasis (p = 0.026) and patient survival (p = 0.032).We also investigated the association of PAK1 with DNA damage, a driven cause for malignancy progression. γH2AX, a DNA damage marker, was detectable in 18 of 24 (75.0%) cases, and PAK1 expression was associated with γH2AX (p = 0.027).Further studies are worth determining the potentials of PAK1 as prognostic indicator and therapeutic target for PESCC.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Centre, Shantou University Medical College, Shantou 515063, China. gjf88900406@126.com.

ABSTRACT
Primary esophageal small cell carcinoma (PESCC) is a rare, but fatal subtype of esophageal carcinoma. No effective therapeutic regimen for it. P21-activated kinase 1 (PAK1) is known to function as an integrator and an indispensable node of major growth factor signaling and the molecular therapy targeting PAK1 has been clinical in pipeline. We thus set to examine the expression and clinical impact of PAK1 in PESCC. The expression of PAK1 was detected in a semi-quantitative manner by performing immunohistochemistry. PAK1 was overexpressed in 22 of 34 PESCC tumors, but in only 2 of 18 adjacent non-cancerous tissues. Overexpression of PAK1 was significantly associated with tumor location (p = 0.011), lymph node metastasis (p = 0.026) and patient survival (p = 0.032). We also investigated the association of PAK1 with DNA damage, a driven cause for malignancy progression. γH2AX, a DNA damage marker, was detectable in 18 of 24 (75.0%) cases, and PAK1 expression was associated with γH2AX (p = 0.027). Together, PAK1 is important in metastasis and progression of PESCC. The contribution of PAK1 to clinical outcomes may be involved in its regulating DNA damage pathway. Further studies are worth determining the potentials of PAK1 as prognostic indicator and therapeutic target for PESCC.

No MeSH data available.


Related in: MedlinePlus