Objective To investigate the effect of knockdown PRTN3 on polarization phenotype and anti-tumor function of macrophages in breast cancer.Methods A mouse monocyte/macrophage cell line(RAW264.7)with knockdown of PRTN3 was constructed.The mRNA and protein levels of PRTN3 were detected by RT-qPCR and flow cytometry.Macrophages were co-cultured with tumor cells,and the polarization phenotypes of macrophages were detected by flow cytometry,and the mRNA levels of polarization and cytokines related genes were detected by RT-qPCR.The tumor phagocytosis and tumor killing ability of macrophages were determined by in vitro phagocytosis assay and tumor killing assay.The effect of macrophages with PRTN3 knockdown on tumor progression and metasta-sis was compared in an orthotopic transplantation model of mouse breast cancer.Results The mRNA and protein levels of PRTN3 in the RAW264.7 cell line with stable knockdown of PRTN3 were significantly decreased(P＜0.01).Knockdown of PRTN3 in RAW264.7 cells upregulated the expression of M1 phenotype-related genes(CD80,CD86,iNOS,IL-1β,IL-6 and TNF-α)(P＜0.05).After macrophages co-culture with tumor cells,macrophages with knockdown of PRTN3 upregulated the expression of M1 phenotype-related genes(CD80,CD86,iNOS,IL-1β,IL-6 and TNF-α)(P＜0.01).Knockdown of PRTN3 enhanced the phagocyto-sis(P＜0.05)and tumor killing ability(P＜0.05)of macrophages in vitro.Adoptive transfusion of PRTN3-knockdown macrophages into tumor-bearing mice inhibited the growth of in situ breast cancer and reduced lung metastasis(P＜0.05).Conclusions PRTN3 regulates phenotypic polarization of macrophages,and knockdown of PRTN3 enhances the anti-tumor function of macrophages.

OBJECTIVETo formulate a novel histological typing and grading-rated system for colorectal cancer (CRC) for evaluating the biological behavior of CRC and prognosis.

METHODSAccording to the highly heterogeneous histological features, WHO classification and histological differentiation criteria, and other biological behavior parameters of CRC, a novel histological typing and grading-scale system for CRC was designed. The histological typing and corresponding grading-scale of CRC was defined as the following: (1) No mucin-producing adenocarcinoma, including tubular adenocarcinoma, sieve-like acne adenocarcinoma, medullary carcinoma, serrated adenocarcinoma and micropapillary carcinoma, etc. (1-3 points); (2) Mucin-producing adenocarcinoma, including mucinous adenocarcinoma and signet ring cell carcinoma (3-4 points); (3) Squamous cell carcinoma (1-3 points); (4) Neuroendocrine tumors, including neuroendocrine tumors, neuroendocrine carcinoma (1-4 points); (5) The special type of CRC, including clear cell carcinoma, spindle cell carcinoma, etc. (4-points); (6) Undifferentiated carcinoma (5 points). The pathology report form was formatted based on the major histological type with the secondary histological type. The final total score of CRC was defined as the sum of the corresponding grading scores for different histological types. The total score of a single-structure CRC was defined as the corresponding grading score multiplied by 2. A total of 666 patients with advanced CRC were pathologically reviewed and analyzed to assess the correlation of the histological typing and grading scores with TNM staging and lymph node metastasis.

RESULTSThe results showed a significant correlation of the histological grading-scale and TNM staging and lymph node metastasis (P<0.05). The scores of CRC histological grading-scale increased synchronously with the TNM staging and lymph node metastasis rate.

CONCLUSIONThe novel histological grading system allows objective evaluation of the biological behaviors and prognosis of CRC for determining individualized postoperative treatment. This system still needs further revision and updates based on evidence from prospective, multi-centered, large-scale trials.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; methods ; Neoplasm Staging ; Prognosis ; Prospective Studies ; Young Adult

Objective To formulate a novel histological typing and grading-rated system for colorectal cancer (CRC) for evaluating the biological behavior of CRC and prognosis. Methods According to the highly heterogeneous histological features, WHO classification and histological differentiation criteria, and other biological behavior parameters of CRC, a novel histological typing and grading-scale system for CRC was designed. The histological typing and corresponding grading-scale of CRC was defined as the following:(1) No mucin-producing adenocarcinoma, including tubular adenocarcinoma, sieve-like acne adenocarcinoma, medullary carcinoma, serrated adenocarcinoma and micropapillary carcinoma, etc. (1-3 points); (2) Mucin-producing adenocarcinoma, including mucinous adenocarcinoma and signet ring cell carcinoma (3-4 points); (3) Squamous cell carcinoma (1- 3 points); (4) Neuroendocrine tumors, including neuroendocrine tumors, neuroendocrine carcinoma (1-4 points);(5) The special type of CRC, including clear cell carcinoma, spindle cell carcinoma, etc. (4-points);(6) Undifferentiated carcinoma (5 points). The pathology report form was formated based on the major histological type with the secondary histological type. The final total score of CRC was defined as the sum of the corresponding grading scores for different histological types. The total score of a single-structure CRC was defined as the corresponding grading score multiplied by 2. A total of 666 patients with advanced CRC were pathologically reviewed and analyzed to assess the correlation of the histological typing and grading scores with TNM staging and lymph node metastasis. Results The results showed a significant correlation of the histological grading-scale and TNM staging and lymph node metastasis (P<0.05). The scores of CRC histological grading-scale increased synchronously with the TNM staging and lymph node metastasis rate. Conclusion The novel histological grading system allows objective evaluation of the biological behaviors and prognosis of CRC for determining individualized postoperative treatment. This system still needs further revision and updates based on evidence from prospective, multi-centered, large-scale trials.

Objective To formulate a novel histological typing and grading-rated system for colorectal cancer (CRC) for evaluating the biological behavior of CRC and prognosis. Methods According to the highly heterogeneous histological features, WHO classification and histological differentiation criteria, and other biological behavior parameters of CRC, a novel histological typing and grading-scale system for CRC was designed. The histological typing and corresponding grading-scale of CRC was defined as the following:(1) No mucin-producing adenocarcinoma, including tubular adenocarcinoma, sieve-like acne adenocarcinoma, medullary carcinoma, serrated adenocarcinoma and micropapillary carcinoma, etc. (1-3 points); (2) Mucin-producing adenocarcinoma, including mucinous adenocarcinoma and signet ring cell carcinoma (3-4 points); (3) Squamous cell carcinoma (1- 3 points); (4) Neuroendocrine tumors, including neuroendocrine tumors, neuroendocrine carcinoma (1-4 points);(5) The special type of CRC, including clear cell carcinoma, spindle cell carcinoma, etc. (4-points);(6) Undifferentiated carcinoma (5 points). The pathology report form was formated based on the major histological type with the secondary histological type. The final total score of CRC was defined as the sum of the corresponding grading scores for different histological types. The total score of a single-structure CRC was defined as the corresponding grading score multiplied by 2. A total of 666 patients with advanced CRC were pathologically reviewed and analyzed to assess the correlation of the histological typing and grading scores with TNM staging and lymph node metastasis. Results The results showed a significant correlation of the histological grading-scale and TNM staging and lymph node metastasis (P<0.05). The scores of CRC histological grading-scale increased synchronously with the TNM staging and lymph node metastasis rate. Conclusion The novel histological grading system allows objective evaluation of the biological behaviors and prognosis of CRC for determining individualized postoperative treatment. This system still needs further revision and updates based on evidence from prospective, multi-centered, large-scale trials.