Fusion variations of neurotrophic receptor tyrosine kinase (NTRK) are oncogenic drivers in various solid tumors such as breast cancer, salivary gland carcinoma, infant fibrosarcoma, etc. Gene rearrangements involving NTRK1/2/3 lead to constitutive activation of the tropomyosin receptor kinase (TRK) domain, and the expressed fusion proteins drive tumor growth and survival. NTRK fusions are estimated to occur at a frequency of approximately 0.1% to 1% in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations are prevalent in NSCLC, but the frequency of EGFR G719A mutation is relatively low (about 2%), and EGFR mutations are typically mutually exclusive with NTRK fusion variants. The study presented the first documented case of lung adenocarcinoma harboring both EGFR G719A mutation and LMNA-NTRK1 fusion. A review of the literature was conducted to elucidate the role of NTRK fusion mutations in NSCLC and their relationship with EGFR mutations, aiming to enhance the understanding of NTRK fusion mutations in NSCLC.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung ; ErbB Receptors/genetics* ; Lamin Type A/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Receptor, trkA/metabolism*

Purpose To investigate the relationship between molecular phenotype of ductal carcinoma in situ ( DCIS) and that of inva-sive ductal carcinoma ( IDC) of the breast. Methods Immunohistochemical method was used to detect ER, PR, HER-2 and CK5 ex-pression in 165 cases of breast cancer, with DCIS and IDC existed in every one of the samples. Results In the 165 cases of breast cancer, the ER, PR, HER-2 and CK5 expression of IDC was positively correlated with that of DCIS, respectively. To evaluate IDC phenotype, the number of basal phenotype was 18 (10. 9%), HER-2-overexpression 20 (12. 1%), luminal A 102 (61. 8%), lumin-al B 20 (12. 1%), null phenotype 6 (3. 6%);to evaluate DCIS phenotype, the number of basal phenotype was 19 (11. 5%), HER-2-overexpression 20 (12. 1%), luminal A 104 (63%), luminal B 17 (10. 3%), null phenotype 5 (3%). 157 cases (95. 2%) of IDC had the same phenotype with DICS, but the rest 8 cases (4. 8%) not, three cases of luminal A DCIS transformed into one HER-2-overexpression and two null phenotype IDC, three of HER-2-overexpression DCIS transformed into luminal B IDC, one null pheno-type DCIS transformed into one luminal A IDC, and one basal phenotype DCIS transformed to HER-2-overexpression IDC. Conclusion Most of IDC have the same phenotype with DCIS, but there exist small part of DCIS which could transform into other phenotype IDC.

To investigate the therapeutic effect and influence of quercetin and allopurinol on the function of liver and kidney in hyperuricemic rats, male SD rats were administered with the drugs by oral gavage once a day for seven consecutive days throughout the experiment. On the fifth day, the animal model of hyperuricemia was set up by hypoxanthine intraperitoneal injection. The serum was used for assaying the uric acid(UA), alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBIL), direct bilirubin(DBIL), β2-microglobulin(β2-MG), serum cystatin C(Cys-C), urea nitrogen(Urea)and serum creatinine(Cr)with colorimetry, continuous monitoring, chemical oxidation and enzyme-linked immunosorbent assay. The results showed that quercetin had no effect on the uric acid levels of serum, and that allopurinol reduced uric acid levels in rats significantly(P< 0. 01). The serum levels of AST and ALT in rats substantially decreased compared with normal control group(P< 0. 01), while no significant differences were found in TBIL, and DBIL. Compared with normal control group, β2-MG and Cys-C levels were significantly increased in the other five groups(P< 0. 01), serum levels of Urea and Cr were significantly higher in the allopurinol group compared to the normal control group(P< 0. 01). Modeling and administration group showed mild histopathological changes in rat kidney. The results clearly demonstrated that quercetin had no effect on the uric acid levels of serum, and allopurinol lowered uric acid significantly. There was no significant effect on the function of liver by modeling and administration, however, there was potential impaiment of renal function after modeling. Quercetin did not exhibit a protective effect on renal injury and administration with allopurinol increased kidney damage.

Purpose To investigate the expression and significance of androgen receptor (AR) in breast carcinoma with different ER and PR status.Methods Immunohistochemical method was used to detect AR, ER and PR expression in 173 cases of breast carcinoma, and all the cases were grouped according to: (1) AR status: AR~- positive subgroup and AR~- negative subgroup, (2) ER status: En subgroup (negative for both ER and PR), Ep subgroup (positive for ER and/or PR), (3)AR, ER and PR status: En-AR~+ subgroup (AR~- positive cases of En subgroup), En-AR~- subgroup (AR~-negative cases of En subgroup), Ep-AR~+ subgroup (AR~- positive cases of Ep subgroup), and Ep-AR~- subgroup (AR~-negative cases of Ep subgroup).En-AR~- subgroup also was called negativE-for-all subgroup, and the rest three subgroups were called partly-or-completely positive subgroup (positive for at least one of the three markers), and then, the groups were compared with clinicopathological features.Results The positive rate of AR was 62.8% (54/86) in Ep subgroup and 37.9%(33/87) in En subgroup, and there was significant difference between them (P=0.001).Compared to AR~-negative subgroup, AR~-positive subgroup had smaller tumor size, less mitosis count and lower grade(P<0.05).Compared to the other three subgroups, En-AR~- subgroup had more mitosis count and higher grade (P<0.01).In En subgroup,AR~- positive cases had less mitosis count and lower grade (P<0.05), and in Ep subgroup,AR~- positive cases had higher stage(P=0.000), but no significant difference were found among partly or completely positive subgroups.Conclusions The expression of AR may play a different role in breast carcinoma with different ER and PR status, because it indicates good prognosis in negative for both ER and PR subgroup, but bad in ER and/or PR positive subgroup. When choosing a personalized therapy, all the combinations of hormone receptor status should be considered for the patients.