Therapeutic efficacy of gefitinib and erlotinib in patients with advanced lung adenosquamous carcinoma

Background: Adenosquamous carcinoma (ASC) of the lung is a rare subtype of nonsmall-cell lung cancer (NSCLC). To date, the efficacious targeted therapy for advanced ASC remains unclear and the epidermal growth factor receptor (EGFR) mutation rate is not well known. Methods: We retrospectively reviewed clinical information of patients with ASC who were treated with gefitinib or erlotinib at Zhejiang Cancer Hospital between January 2007 and December 2011. Survival analysis was evaluated by the Kaplan-Meier method. EGFR mutations were assessed in part using direct sequencing methods. Results: In total, 49 patients with a median age of 57 years were used in this study. Thirteen patients achieved a partial response and 19 had disease stabilization. The objective response rate was 26.5%, and the disease control rate was 65.3%. The median progression-free survival and overall survival were 4.3 and 17.6 months, respectively. In 21 patients with adequate specimens for molecular analysis, 7 (33.3%) had EGFR mutations (4 with deletions within exon 19 and 3 with L858R messenger mutation in exon 21). EGFR mutations were significantly more frequent in women (4/9, 44.4%) than men (3/12, 25%), never-smokers (6/15, 40%), and smokers (1/6, 16.7%). Conclusion: EGFR-tyrosine kinase inhibitor (TKI) is an effective treatment for ASC. The frequency of EGFR mutation and clinical characteristics of the EGFR mutants in ASC are similar to those of Asian patients with adenocarcinoma

Advances of Molecular Subtype and Targeted Therapy of Lung Cancer

The discovery of multiple molecular mechanisms underlying the development, progression, and prognosis of lung cancer, has created new opportunities for targeted therapy. Each subtype is associated with molecular tests that define the subtype and drugs that may have potential therapeutic effect on lung cancer. In 2004, mutations in the epidermal growth factor receptor (epidermal growth factor receptor, EGFR) gene were discovered in non-small cell lung cancers (NSCLC), especially in adenocarcinomas. And they are strongly associated with sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Moreover, in 2007 the existence of the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene was discovered in NSCLC, and the same as EGFR-TKIs, ALK inhibitors are being found to be highly effective in lung cancers. At present, multiple molecular subtype of lung cancer and relevant targeted drugs are undering study. Here, we review the remarkable progress in molecular subtype of lung cancer and the related targeted therapy

Neuroprotective effects of bone marrow Sca-1+ cells against age-related retinal degeneration in OPTN E50K mice

Abstract Glaucoma is characterized by retinal ganglion cell (RGC) death, the underlying mechanisms of which are still largely unknown. An E50K mutation in the Optineurin (OPTN) gene is a leading cause of normal-tension glaucoma (NTG), which directly affects RGCs in the absence of high intraocular pressure and causes severe glaucomatous symptoms in patients. Bone marrow (BM) stem cells have been demonstrated to play a key role in regenerating damaged tissue during ageing and disease through their trophic effects and homing capability. Here, we separated BM stem cells into Sca-1+ and Sca-1- cells and transplanted them into lethally irradiated aged OPTN E50K mice to generate Sca-1+ and Sca-1− chimaeras, respectively. After 3 months of BM repopulation, we investigated whether Sca-1+ cells maximized the regenerative effects in the retinas of NTG model mice with the OPTN E50K mutation. We found that the OPTN E50K mutation aggravated age-related deficiency of neurotrophic factors in both retinas and BM during NTG development, leading to retinal degeneration and BM dysfunction. Sca-1+ cells from young healthy mice had greater paracrine trophic effects than Sca-1− cells and Sca-1+ cells from young OPTN E50K mice. In addition, Sca-1+ chimaeras demonstrated better visual functions than Sca-1− chimaeras and untreated OPTN E50K mice. More Sca-1+ cells than Sca-1− cells were recruited to repair damaged retinas and reverse visual impairment in NTG resulting from high expression levels of neurotrophic factors. These findings indicated that the Sca-1+ cells from young, healthy mice may have exhibited an enhanced ability to repair retinal degeneration in NTG because of their excellent neurotrophic capability

The composition and function of the soil microbial community and its driving factors before and after cultivation of Panax ginseng in farmland of different ages

Changes in the microbial community are considered important factors affecting the yield and quality of ginseng cultivated in farmland, while the characteristics of the change in the microbial community of the soil before and after cultivation of ginseng in farmland are not well understood. Here, we aimed to fill this research gap by comparing the differences in soil nutrients and microbial communities between continuously cultivated ginseng soils for 1-, 2-, 3- and 5-year-old ginseng soils and corresponding uncultivated ginseng soils. The soil properties (pH, total soil organic carbon (TOC) content and total nitrogen (TN) content) of aged ginseng soil (3- and 5-year-old) were significantly reduced compared with those of the control soil after ginseng was cultivated in farmland. With the exception of 2-year-old ginseng, soil bacterial richness and diversity were higher in different ages of cultivated ginseng soils than in the control soil, while fungal diversity decreased in aged ginseng soil and increased in young ginseng soil (1- and 2-year-old). Ascomycota and Basidiomycota showed a consistent increasing/decreasing trend in cultivated ginseng soils of all ages compared to the control. In addition, ginseng cultivation resulted in a substantial decrease in the complexity of soil bacterial networks but a slight decrease in the complexity of fungal networks. The results from the linear discriminant size effect (LEfSe) analysis showed that beneficial microorganisms were biomarkers of the young ginseng soil, including Nitrosospira, Cephalotrichum and Humicola, while harmful microorganisms were biomarkers of aged ginseng, such as Plectosphaerella, Cladosporium and Alternaria. PICRUSt2 analysis revealed that the increase in the incidence of ginseng disease with continuous cultivation time may be related to the decreases in amino acid synthesis and physiological metabolism and the increase in fungal saprophytes. Soil pH was the most common and best predictor of bacterial and fungal community structure, followed by TOC and ammonium nitrogen (NH4+-N) contents. Meanwhile, the decreased of soil pH, TOC and AK may be the driving factors for the growth of ginseng soil pathogens. Overall, this study revealed the changing ginseng rhizosphere soil microbial community at different continuous cultivation times, provided a theoretical basis for ginseng cultivation, and promoted the development of medicinal plants such as ginseng