Mixed鄄phenotypic acute leukemia with SET鄄NUP214 fusion gene positive and extramedullary infiltration: report of one case and review of literature / 白血病·淋巴瘤

Objective To investigate the clinical and molecular biological characteristics of mixed_phenotypic acute leukemia (MPAL) with SET_NUP214 fusion gene positive and extramedullary infiltration. Methods The clinical characteristics, diagnosis and treatment of one MPAL patient with SET_NUP214 and extramedullary infiltration who was admitted to Hebei Yanda Ludaopei Hospital in November 2017 were analyzed, and the literature was reviewed. Results The patient was diagnosed as MPAL with extramedullary infiltration. Gene detection found SET exon7_NUP214 exon17 fusion positive accompanied with PHF6, SRSF2 and NRAS mutations. After intensive chemotherapy, the patient achieved complete remission, and then received hematopoietic stem cell transplantation (HSCT), followed by early extramedullary relapse after transplantation, and achieved secondary remission after consolidation chemotherapy. Conclusions MPAL with SET_NUP214 fusion gene positive and extramedullary infiltration has a poor prognosis, and it is easy to relapse. Currently, HSCT is the best available treatment strategy for such patients.

Clinicopathologic features of atypical type A thymoma / 中华病理学杂志

Objective@#To study the clinicopathologic features, immunophenotype and differential diagnosis of atypical type A thymoma.@*Methods@#Clinicopathologic and follow-up data of three cases of atypical type A thymoma from 2004 to 2016 were reviewed. Immunohistochemical staining was performed.@*Results@#All three patients were male with average age of 59 years. Clinically, the lesions presented as anterior mediastinal masses. Grossly, the tumor ranged in size from 4 to 6 cm in greatest dimension and partially enclosed within fibrous capsule. The cut surface was homogenously fleshy, tan to brown in color, with multinodular and lobulated configurations. Cystic changes and necrosis were seen. Microscopically, the tumor was composed of plump spindle or oval-shaped cells arranged in storiform, microcystic, glandular, rosettes-like and hemangiopericytoma-like histological patterns. The tumor cells showed mild cytological atypia and mitotic activity ranged from 4 to 5/10HPF. Necrosis was present in all tumors. All tumors showed diffuse CK(AE1/AE3), CK19, p63 and vimentin expression. TdT, CK20, CD20, CD5 and CD117 were negative. The proliferative index, as measured with Ki-67, was 15.2% to 26.4%. None of the cases had recurrence or metastases during the follow-up period (9 to 27 months).@*Conclusions@#Atypical type A thymoma presents atypical features including tumor necrosis and increased mitotic activity. However, the implications of such atypical features to the biological behavior of the tumor remain to be determined.

Calpain 2-dependent IκBα degradation mediates CPT-11 secondary resistance in colorectal cancer xenografts.

CPT-11 (irinotecan), the first-line chemotherapy for advanced stage colorectal cancer, remains inactive in about half of patients (primary chemoresistance) and almost all initial responders develop secondary resistance after several courses of treatment (8 months on average). Nude mice bearing HT-29 colon cancer xenografts were treated with CPT-11 and/or an NF-κB inhibitor for two courses. We confirm that NF-κB inhibition potentiated CPT-11 anti-tumoural effect after the first course of treatment. However, tumours grew again at the end of the second course of treatment, generating resistant tumours. We observed an increase in the basal NF-κB activation in resistant tumours and in two resistant sublines, either obtained from resistant HT-29 tumours (HT-29R cells) or generated in vitro (RSN cells). The decrease of NF-κB activation in HT-29R and RSN cells by stable transfections with the super-repressor form of IκBα augmented their sensitivity to CPT-11. Comparing gene expression profiles of HT-29 and HT-29R cells, we identified the S100A10/Annexin A2 complex and calpain 2 as over-expressed potential NF-κB inducers. SiRNA silencing of calpain 2 but not of S100A10 and/or annexin A2, resulted in a decrease in NF-κB activation, an increase in cellular levels of IκBα and a partial restoration of the CPT-11 sensitivity in both HT-29R and RSN cells, suggesting that calpain 2-dependent IκBα degradation mediates CPT-11 secondary resistance. Thus, targeted therapies directed against calpain 2 may represent a novel strategy to enhance the anti-cancer efficacy of CPT-11.

The regulatory effect of endothelial cells of pulmonary arteriole on the tone of pulmonary artery / 中国病理生理杂志

The regulatory effect of endothelial cells of the rabbit pulmonary arteriole(PAECs) on the tone of pulmonary artery was studied. The conditioned medium (CM) ofPAECs, cultivated under normal and hypoxic condition for 24 hours, did not induce con-striction of pulmonary artery ring. The aqueous phase was able to induce the constriction.The constriction of pulmonary artery rings was reduced by the heated aqueous phase, but it was disappeared when the heated aqueous phase was treated with trypsin. The constric-tion caused by heated aqueous phase was stronger in hypoxic endothelial cells than innormal cells. Treatment of PAECs with indomethacin and captoril, and administration ofFPL 55712, BN 52021, chlorpheniramine and prazozin to contraction pool did not affectthe constriction of pulmonary artery rings. It was concluded that PAECs might producelong half-life lipid substances which could induce the dilatation of pulmonary artery.Hypoxia inhibted the release of long half-life aqueous heat-unstable vasoconstrictive sub-stances. but enhanced that of the heat-stable fraction which was probably a peptide.

Relation of TXA_2 and PGI_2 to the difference of hypoxic pulmonary vasoconstriction between different strains of rats / 中国病理生理杂志

TXB_2 and 6-keto-PGF_(1?) levels of arterial and venous plasma in Wistar and4 Hilltep rats were measured to investigate the roles of TXA_2 and PGI_2 in the hypoxic pulmonary vasoconstriction(HPV) and responsiveness difference of pulmonary vessels to hypoxia between different strains of rats. The results showed that PGI_2 might play an important role in maintaining the low resistance of pulmonary circulation in these two strains of rats. TXA, increased during hypoxia might partially mediate HPV in Hilltop rats, on the contrary, PGI_2 augmented during hypoxia might modulate HPV in Wistar rats. This might be the major methanism responsible for the more intensive responsiveness of pulmonary vessels to hypoxia in Hilltop than in Wistar rats.