Journal: Journal of Clinical Laboratory Analysis

Article Title: Association between squamous cell carcinoma antigen level and EGFR mutation status in Chinese lung adenocarcinoma patients

doi: 10.1002/jcla.24613

Figure Lengend Snippet: Multivariable regression for the association between SCCAg and EGFR mutation probability

Article Snippet: The EGFR gene mutation detection kit from Shanghai Yuanqi company was used with PCR fluorescent probe method to detect the mutations on EGFR gene Exon18 (G719C, G719S), Exon19 (2235–2249del, 2236–2250del, 2236–2253del, 2239–2253del, 2239–2256del, 2240–2251del, 2240–2254del, 2240–2257del, 2237–2255 > T, 2238–2248 > GC, 2237–2252 > GCA, 2239–2251 > C, 2254–2277del, 2238‐2255del, 2240–2248del, 2239–2259del), Exon20 (V769_D770insASV, D770_N771insG, H773_V774insH), and Exon21 (L858R, L861Q).

Techniques: Mutagenesis

Journal: Journal of Clinical Laboratory Analysis

Article Title: Association between squamous cell carcinoma antigen level and EGFR mutation status in Chinese lung adenocarcinoma patients

doi: 10.1002/jcla.24613

Figure Lengend Snippet: (A) Use the generalized additive model to fit a smooth curve to the relationship between SCCAg and EGFR mutation probability (the horizontal axis is the level of SCCAg, and the vertical axis is the adjusted EGFR mutation probability; solid red line represents the fitted line between EGFR mutation probability and SCCAg; blue dotted line is 95% confidence interval; the relationship was adjusted for age, sex, smoking history, nodule type, bronchial sign, pleural indentation sign, vessel convergence sign, tumor short diameter, and clinical stage). (B) Use the generalized additive model to fit a smooth curve to the relationship between SCCAg tertile and EGFR mutation probability (the horizontal axis is SCCAg tertile, and the vertical axis is the adjusted EGFR mutation probability; black dashed line represents the fitted line between EGFR mutation probability and SCCAg tertile; the red line is the 95% confidence interval; the relationship was adjusted for age, sex, smoking history, nodule type, bronchial sign, pleural indentation sign, vessel convergence sign, tumor short diameter, and clinical stage). EGFR , epidermal growth factor receptor; SCCAg, squamous cell carcinoma antigen.

Article Snippet: The EGFR gene mutation detection kit from Shanghai Yuanqi company was used with PCR fluorescent probe method to detect the mutations on EGFR gene Exon18 (G719C, G719S), Exon19 (2235–2249del, 2236–2250del, 2236–2253del, 2239–2253del, 2239–2256del, 2240–2251del, 2240–2254del, 2240–2257del, 2237–2255 > T, 2238–2248 > GC, 2237–2252 > GCA, 2239–2251 > C, 2254–2277del, 2238‐2255del, 2240–2248del, 2239–2259del), Exon20 (V769_D770insASV, D770_N771insG, H773_V774insH), and Exon21 (L858R, L861Q).

Techniques: Mutagenesis

Journal: Journal of Clinical Laboratory Analysis

Article Title: Association between squamous cell carcinoma antigen level and EGFR mutation status in Chinese lung adenocarcinoma patients

doi: 10.1002/jcla.24613

Figure Lengend Snippet: The stratification analysis of the association between SCCAg and the probability of EGFR mutation (OR, 95% CI, p ‐value, and p for interaction were calculated; adjusted for age, sex, smoking history, nodule type, bronchial sign, pleural indentation sign, vessel convergence sign, tumor short diameter, clinical stage). EGFR , epidermal growth factor receptor; CEA, carcinoembryonic antigen; CYFRA21‐1, cytokeratin soluble fragment 19; NSE, neuron‐specific enolase; *15 cases missing; #6 cases missing

Article Snippet: The EGFR gene mutation detection kit from Shanghai Yuanqi company was used with PCR fluorescent probe method to detect the mutations on EGFR gene Exon18 (G719C, G719S), Exon19 (2235–2249del, 2236–2250del, 2236–2253del, 2239–2253del, 2239–2256del, 2240–2251del, 2240–2254del, 2240–2257del, 2237–2255 > T, 2238–2248 > GC, 2237–2252 > GCA, 2239–2251 > C, 2254–2277del, 2238‐2255del, 2240–2248del, 2239–2259del), Exon20 (V769_D770insASV, D770_N771insG, H773_V774insH), and Exon21 (L858R, L861Q).

Techniques: Mutagenesis

Journal: Annals of Oncology

Article Title: HER2 exon 20 insertions in non-small-cell lung cancer are sensitive to the irreversible pan-HER receptor tyrosine kinase inhibitor pyrotinib

doi: 10.1093/annonc/mdy542

Figure Lengend Snippet: Activity of pyrotinib in HER2-mutant patient-derived organoids. (A, B) 3D organoids in bright field (10 × 10), and H&E and IHC results of representative organoids suggested epithelial origin. (C) Sequencing results of representative organoids showed HER2 A775_G776insYVMA, indicating that the genomic characterization of this patient-derived in vitro models was identical to the parental tumor. (D) Drug response curves of the organoids treated with the dual EGFR/HER2 inhibitors (afatinib and pyrotinib, respectively) showed that the IC50 of afatinib and pyrotinib were 89.1 and 112.5 nM. Cell viability was measured by a CellTiter-Glo (Promega) Luminescent Cell Viability Assay after 72 h of treatment. (E) Cell growth curves of the organoids treated with vehicle (DMSO), afatinib (29 nM#) and pyrotinib (180 nM#) showed that compared with afatinib, pyrotinib at plasma concentration inhibited the cell growth more significantly (*P = 0.0038). #The concentrations were adopted from the in vivo plasma concentrations of the 2 drugs in previous phase I clinical studies, e.g. (Cafatinib: 21.1 ng/ml)/(MWafatinib: 718.08 g/mol)×1000 = 29 nM; (Cpyrotinib: 147 ng/ml)/(MWpyrotinib: 815.22 g/mol)×1000 = 180 nM. (F) Representative images (three repeated well) of the 3D organoids treated with vehicle (DMSO), afatinib (29 nM) and pyrotinib (180 nM) on day 16 after dosing.

Article Snippet: HER2 mutation was tested using ADx HER2 Mutation Detection Kit (Amoy Diagnostics, Xiamen, China) or NGS, and confirmed by DNA direct sequencing if needed.

Techniques: Activity Assay, Mutagenesis, Derivative Assay, Sequencing, In Vitro, Cell Viability Assay, Clinical Proteomics, Concentration Assay, In Vivo

Journal: Annals of Oncology

Article Title: HER2 exon 20 insertions in non-small-cell lung cancer are sensitive to the irreversible pan-HER receptor tyrosine kinase inhibitor pyrotinib

doi: 10.1093/annonc/mdy542

Figure Lengend Snippet: In vivo activity of pyrotinib in PDX models. (A) Tumor volume curves of the PDX models treated with vehicle, and different doses of pyrotinib. (B) Tumor volume changes among mice treated with vehicle, and different doses of pyrotinib by 24 days. (C) Body weight changes among mice treated with vehicle, and different doses of pyrotinib. (D) Tumor volume curves of the PDX models treated with vehicle, pyrotinib, afatinib and T-DM1. (E) Tumor volume changes among mice treated with vehicle, and pyrotinib, afatinib and T-DM1 by 24 days. (F) Body weight changes among mice treated with vehicle, pyrotinib, afatinib and T-DM1. (G) Concentrations in plasma and in tumor in different doses of pyrotinib treatment groups were detected on day 24 after administration. The pyrotinib concentration in the tumor of the 80 mg/kg group was not available due to a low volume of tumor tissue after 24 days of pyrotinib treatment. (H) Concentrations in plasma and in tumor of pyrotinib and afatinib treatment groups were detected on day 24 after administration. (I) IHC staining of HER2 and its downstream proteins including ERK and Akt, in vehicle and pyrotinib treatment groups. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

Article Snippet: HER2 mutation was tested using ADx HER2 Mutation Detection Kit (Amoy Diagnostics, Xiamen, China) or NGS, and confirmed by DNA direct sequencing if needed.

Techniques: In Vivo, Activity Assay, Clinical Proteomics, Concentration Assay, Immunohistochemistry

Journal: Annals of Oncology

Article Title: HER2 exon 20 insertions in non-small-cell lung cancer are sensitive to the irreversible pan-HER receptor tyrosine kinase inhibitor pyrotinib

doi: 10.1093/annonc/mdy542

Figure Lengend Snippet: PK/PD correlation of pyrotinib in PDX model. (A) Concentrations of pyrotinib in plasma and in tumor were detected at 0, 2, 6, 24 h after dosing. Pyrotinib plasma concentrations peaked at ∼2 h after dosing. Concentration of pyrotinib in tumor reached a relative maximum at 6 h, and at the same time, pHER2 was maximally inhibited. (B) Representative images of pHER2 in tumor tissues at 0, 2, 6, 24 h after pyrotinib treatment. (C, D) Western blot analyzed the proteins of HER2 and its downstream proteins including ERK and Akt in mice treated with pyrotinib (80 mg/kg) at 0, 2, 6 h after dosing. Phosphorylation of these proteins was significantly inhibited 6 h after dosing. (E, F) IHC analyzed the proteins of HER2 and its downstream proteins including ERK and Akt in mice treated with pyrotinib (80 mg/kg) at 0, 2, 6 h after dosing. Phosphorylation of these proteins was significantly inhibited 6 h after dosing. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

Article Snippet: HER2 mutation was tested using ADx HER2 Mutation Detection Kit (Amoy Diagnostics, Xiamen, China) or NGS, and confirmed by DNA direct sequencing if needed.

Techniques: Clinical Proteomics, Concentration Assay, Western Blot, Phospho-proteomics

Journal: Annals of Oncology

Article Title: HER2 exon 20 insertions in non-small-cell lung cancer are sensitive to the irreversible pan-HER receptor tyrosine kinase inhibitor pyrotinib

doi: 10.1093/annonc/mdy542

Figure Lengend Snippet: HER2-mutant lung cancer patients response to pyrotinib. (A, B) Percent best change from baseline of target lesions and progression-free survival (PFS) plots corresponding to each type of HER2 mutations. *The target lesions of this patient increased by <20% while the nontarget lesions progressed, so we evaluated this as progressive disease. (C) Distribution of HER2 mutations observed in the cohort of 15 patients. (D) Treatment time of 15 patients in this study. Prior treatment: Time from diagnosis of advanced NSCLC or relapse. ⋆, this patient had received one cycle of albumin bound-paclitaxel (100 mg i.v.gtt, D1) during postprogressive pyrotinib treatment. (E) Computed tomography (CT) scan of a 78-year-old patient with HER2-A775_G776YVMA-inserted advanced lung cancer. His lung lesions were significantly reduced after pyrotinib treatment and CT scan showed sustained tumor shrinkage. (F) CT scan of a 53-year-old patient with HER2-A775_G776YVMA-inserted advanced lung cancer. He responded to pyrotinib after disease progression on afatinib.

Article Snippet: HER2 mutation was tested using ADx HER2 Mutation Detection Kit (Amoy Diagnostics, Xiamen, China) or NGS, and confirmed by DNA direct sequencing if needed.

Techniques: Mutagenesis, Biomarker Discovery, Computed Tomography

Journal: The Clinical Respiratory Journal

Article Title: Radiological and clinical features of large consolidative‐type pulmonary invasive mucinous adenocarcinoma

doi: 10.1111/crj.13743

Figure Lengend Snippet: Pathological characteristics and genetic testing of large consolidative‐type IMA.

Article Snippet: Moreover, molecular analyses of mutations of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) were performed using a polymerase chain reaction‐based amplification refractory mutation system with the Human EGFR Gene Mutations Detection Kit (Beijing ACCB Biotech Ltd., Beijing, China).

Techniques: Mutagenesis