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The survival benefit of icotinib (an oral epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor) in patients with advanced lung cancer has been confirmed in several studies. This study (ICAPE) evaluated the efficacy of icotinib as adjuvant therapy for patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma. Patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma were enrolled in the multicenter, open-label, single-arm, phase II study. Eligible patients received oral icotinib 125 mg thrice daily for 1.5 years after complete surgical resection. The primary endpoint was disease-free survival (DFS). Between March 2014 and January 2018, 79 patients were enrolled. The median follow-up time was 39.7 months with a median DFS and overall survival (OS) of 41.4 months (95% CI: 33.6-51.8) and 67.0 months (95% CI: 21.2-not reached [NR]), respectively. The 1-year, 3-year, and 5-year OS rates were 100%, 83.3%, and 61.7%, respectively. No significant difference was found in the median DFS between patients with Bcl-2 interacting mediator of cell death (BIM) mutant-type and wild-type (NR vs. 41.7 months; p = 0.75). No significant difference was found in the median DFS according to EGFR mutation types. Icotinib as adjuvant therapy demonstrated a favorable survival benefit in patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma, indicating that icotinib might be a promising treatment option for this patient population. The optimal adjuvant duration of icotinib is still not clear and needs more incoming data to answer., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Multiple morphological abnormalities of the sperm flagella (MMAF) is a rare disease that causes primary infertility. However, the genetic causes for approximately half of MMAF cases are unknown. Whole exome sequencing analysis of the 27 patients with MMAF identified several CFAP44 mutations (3 homozygous: c.2935_2944del: p.D979*, c.T1769A: p.L590Q, c.2005_2006del: p.M669Vfs*13; and putative compound heterozygous: c.G3262A: p.G1088S and c.C1718A: p.P573H.) and CFAP43 acceptor splice-site deletion (c.3661-2A>-) mutations in 5 and 1 patients, respectively. Real-time quantitative polymerase chain reaction assays also demonstrated that CFAP44 expression was very weak in patient (P)1 and P3, and CFAP43 expression was lower in P6 than in the control. Immunofluorescence analysis of CFAP43 showed lower CFAP43 protein expression levels in P6 than in the normal control. This study demonstrated that biallelic mutations in CFAP44 and CFAP43 cause MMAF. These results provide researchers with a new insight to understand the genetic etiology of MMAF and to identify new loci for genetic counselling of MMAF.

3,3'-Diindolylmethane (DIM) has been investigated as a potential anti-cancer chemopreventive agent in many preclinical and clinical studies. In this study, we sought to characterize the pharmacokinetics of DIM and to build a pharmacokinetic (PK) and pharmacodynamic (PD) model of the DIM-induced gene expression of phase II drug metabolizing enzymes (DME), which potentially links DIM's molecular effects to its in vivo chemopreventive efficacy. DIM (10 mg/kg) was administered intravenously (i.v.) to male Sprague-Dawley rats and blood samples were collected at selected time points for 48 h. The plasma concentration of DIM was determined using a validated HPLC method. The mRNA expression of NQO1, GSTP1 and UGT1A1 in blood lymphocytes was measured using quantitative PCR. An indirect response model was employed to relate the concentration of DIM to the expression of the genes NQO1, GSTP1 and UGT1A1, which were chosen as PD markers for DIM. After i.v. administration, the plasma concentration of DIM declined quickly, and the expression of target genes increased significantly, peaking at 1-2 h and then returning to basal levels after 24 h. The parameters in the PK-PD model were estimated. The PK-PD model aptly described the time delay and magnitude of gene expression induced by DIM. Our results indicate that DIM is effective at inducing various phase II DME, which are capable of detoxify carcinogens. This PK-PD modeling approach provides a framework for evaluating the acute effects of DIM or other similar drugs in clinical trials.

A novel algorithm, four-way self-weighted alternating normalized residue fitting (SWANRF), which is an extension of its three-way form, for the decomposition of quadrilinear data with new weight factors, was proposed and applied to the quantitative analysis of serotonin contents in plasma samples. It was observed that the third-order calibration could not only retain a "second-order advantage" and but also obtain other advantages. The introduction of a fourth mode can relieve the serious problem of collinearity, which seems to be one of the "third-order advantages". The proposed algorithm shows great potential as a promising alternative for the third-order calibration of a four-way data array by contrasting with four-way parallel factor analysis (four-way PARAFAC). Furthermore, both algorithms mentioned above were utilized to analyze the 5-hydroxytryptamine (serotonin) contents in plasma samples by obtaining four-way array (excitation-emission-pH-sample) data, and produced satisfactory results. The serotonin contents in plasma samples obtained by using four-way SWANRF and four-way PARAFAC were 0.324 ± 0.005 and 0.348 ± 0.006 nmol mL(-1), respectively.