Convenient approaches for accurate biopsy are extremely important to the diagnosis of lung cancer. We aimed to systematically review the clinical updates and development trends of approaches for biopsy, i.e., CT-guided PTNB (Percutaneous Transthoracic Needle Biopsy), ENB (Electromagnetic Navigation Bronchoscopy), EBUS-TBNA (Endobroncheal Ultrasonography-Transbronchial Needle Aspiration), mediastinoscopy and CTC (Circulating Tumor Cell). Medline and manual searches were performed. We identified the relevant studies, assessed study eligibility, evaluated methodological quality, and summarized diagnostic yields and complications regarding CT-guided PTNB (22 citations), ENB(31 citations), EBUS-TBNA(66 citations), Mediastinoscopy(15 citations) and CTC (19 citations), respectively. The overall sensitivity and specificity of CT-guided PTNB were reported to be 92.52% ± 3.14% and 97.98% ± 3.28%, respectively. The top two complications of CT-guided PTNB was pneumothorax (946/4170:22.69%) and hemorrhage (138/1949:7.08%). The detection rate of lung cancer by ENB increased gradually to 79.79% ± 15.34% with pneumothorax as the top one complication (86/1648:5.2%). Detection rate of EBUS-TBNA was 86.06% ± 9.70% with the top three complications, i.e., hemorrhage (53/8662:0.61%), pneumothorax (46/12432:0.37%) and infection (34/11250:0.30%). The detection rate of mediastinoscopy gradually increased to 92.77% ± 3.99% with .hoarseness as the refractory complication (4/2137:0.19%). Sensitivity and specificity of CTCs detection by using PCR (Polymerase Chain Reaction) were reported to be 78.81% ± 14.72% and 90.88% ± 0.53%, respectively. The biopsy approaches should be chosen considering a variety of location and situation of lesions. CT-guided PTNB is effective to reach lung parenchyma, however, diagnostic accuracy and incidence of complications may be impacted by lesion size or needle path length. ENB has an advantage for biopsy of smaller and deeper lesions in lung parenchyma. ENB plus EBUS imaging can further improve the detection rate of lesion in lung parenchyma. EBUS-TBNA is relatively safer and mediastinoscopy provides more tissue acquisition and better diagnostic yield of 4R and 7th lymph node. CTC detection can be considered for adjuvant diagnosis.

The goal of this study was to evaluate the ability of EVO to decrease cell viability and promote cell cycle arrest and apoptosis in small cell lung cancer (SCLC) cells. Lung cancer has the highest incidence and mortality rates among all cancers. Chemotherapy is the primary treatment for SCLC; however, the drugs that are currently used for SCLC are less effective than those used for non-small cell lung cancer (NSCLC). Therefore, it is necessary to develop new drugs to treat SCLC. In this study, the effects of evodiamine (EVO) on cell growth, cell cycle arrest and apoptosis were investigated in the human SCLC cell lines NCI-H446 and NCI-H1688. The results represent the first report that EVO can significantly inhibit the viability of both H446 and H1688 cells in dose- and time-dependent manners. EVO induced cell cycle arrest at G2/M phase, induced apoptosis by up-regulating the expression of caspase-12 and cytochrome C protein, and induced the expression of Bax mRNA and by down-regulating of the expression of Bcl-2 mRNA in both H446 and H1688 cells. However, there was no effect on the protein expression of caspase-8. Taken together, the inhibitory effects of EVO on the growth of H446 and H1688 cells might be attributable to G2/M arrest and subsequent apoptosis, through mitochondria-dependent and endoplasmic reticulum stress-induced pathways (intrinsic caspase-dependent pathways) but not through the death receptor-induced pathway (extrinsic caspase-dependent pathway). Our findings suggest that EVO is a promising novel and potent antitumor drug candidate for SCLC. Furthermore, the cell cycle, the mitochondria and the ER stress pathways are rational targets for the future development of an EVO delivery system to treat SCLC.

Today, it is very challenging to develop new active pharmaceutical ingredients. Developing good preparations of well-recognized natural medicines is certainly a practical and economic strategy. Low-solubility, low-permeability natural medicines (LLNMs) possess valuable advantages such as effectiveness, relative low cost and low toxicity, which is shown by the presence of popular products on the market. Understanding the in vivo metabolic and pharmacokinetic characteristics of LLNMs contributes to overcoming their associated problems, such as low absorption and low bioavailability. In this review, the structure-based metabolic reactions of LLNMs and related enzymatic systems, cellular and bodily pharmacological effects and metabolic influences, drug–drug interactions involved in metabolism and microenvironmental changes, and pharmacokinetics and dose-dependent/linear pharmacokinetic models are comprehensively evaluated. This review suggests that better pharmacological activity and pharmacokinetic behaviors may be achieved by modifying the metabolism through using nanotechnology and nanosystem in combination with the suitable administration route and dosage. It is noteworthy that novel nanosystems, such as triggered-release liposomes, nucleic acid polymer nanosystems and PEGylated dendrimers, in addition to prodrug and intestinal penetration enhancer, demonstrate encouraging performance. Insights into the metabolic and pharmacokinetic characteristics of LLNMs may help pharmacists to identify new LLNM formulations with high bioavailability and amazing efficacy and help physicians carry out LLNM-based precision medicine and individualized therapies.