Objective:This study aimed to analyze and summarize the clinicopathologic characteristics and treatment protocols of large cell lung carcinoma (LCLC). Methods:Clinicopathologic data of 83 cases with LCLC confirmed by pathology in 2012 were retrospectively reviewed. Results:Exactly 83 cases of LCLC accounted for 5.4%of lung cancer in 2012. Sixty-three cases were male and twenty were female. The average age was 60.4 years old. The average maximum diameter of the tumor was 4.6 cm. The common manifestations in imageology were peripheral type. Only four cases were correctly diagnosed by sputum exfoliocytology, biopsy of bronchofibroscope, and paracentesis before surgery. Sixty-three cases (76%) underwent surgical resection, and pulmonary lobectomy was mainly selected. Postoperative pathology diagnosis indicated that 39 cases were classic large cell carcinoma, 31 were large cell neu-roendocrine carcinoma, 2 were combined large cell neuroendocrine carcinoma, 8 were basaloid carcinoma, 2 were clear cell carcinoma, and 1 was lymphoepithelioma-like carcinoma. Each subtype of LCLC had respective characteristics of pathomorphology and immuno-histochemistry. Lymph node metastasis occurred in 62 cases (75%). Conclusion:The incidence rate of LCLC, which is a highly aggres-sive malignancy, is low. The clinical manifestation and imageology characteristics of LCLC do not have specificity, and its final diagno-sis depends on pathology diagnosis. Operation is the main treatment method. Improving the diagnosis rate of LCLC and further subdi-viding the pathological subtypes are important for a normalized comprehensive treatment of LCLC.

It is critical to regulate the senescence-associated secretory phenotype (SASP) due to its effect on promoting malignant phenotypes and limiting the efficiency of cancer therapy. In this study, we demonstrated that marchantin M (Mar-M, a naturally occurring bisbibenzyl) suppressed pro-inflammatory SASP components which were elevated in chemotherapy-resistant cells. Mar-M treatment attenuated the pro-tumorigenic effects of SASP and enhanced survival in drug-resistant mouse models. No toxicity was detected on normal fibroblast cells or in animals following this treatment. Inactivation of transcription factor EB (TFEB) and nuclear factor-B (NF-B) by Mar-M significantly accounted for its suppression on the components of SASP. Furthermore, inhibition of SASP by Mar-M contributed to a synergistic effect during co-treatment with doxorubicin to lower toxicity and enhance antitumor efficacy. Thus, chemotherapy-driven pro-inflammatory activity, seen to contribute to drug-resistance, is an important target for Mar-M. By decreasing SASP, Mar-M may be a potential approach to overcome tumor malignancy.

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.