Associations of the Fat-age-infl ammation Index with Overall Survival in Patients with Metastatic Lung Cancer

Background Metastatic lung cancer(LC)is a threat to human health.We previously proposed a fat age-inflammation(FAIN)index which showed prognostic value in patients with certain cancers.However,whether a similar association exists in patients with metastatic LC remains unknown.Methods We performed a cohort study including 1360 patients with metastatic LC from January 2013 to April 2019.The FAIN index was defined as:(triceps skinfold thickness+albumin)/[age+5×(neutrophil count/lymphocyte count)]×100%.Sex-specific cutoffs of the FAIN were determined using an optimal stratification approach.The associations of the FAIN index with the nutrition related factors,short-term outcomes and overall survival(OS)of patients were comprehensively assessed.Results The study enrolled 865 males and 495 females with a median age of 59.9 years.The continuous FAIN was significantly associated with the OS in both genders(both P<0.05).The optimal stratification-defined FAIN cutoffs were 82 for women and 60 for men.A total of 623 patients(45.8%)were categorized as having a low FAIN.A low FAIN was associated with poorer nutrition-related factors and impaired short-term outcomes including the thirty-day mortality,length of hospital stay,intensive care unit stay and cost(all P<0.05).Multivariate Cox regression analysis revealed that a lower FAIN was also associated with an increased death hazard(HR=1.428,95%CI=1.209-1.686).Conclusion This study assessed the FAIN index,which might act as a feasible tool to monitor nutrition-related factors and help develop management strategies to optimize the clinical outcomes of patients with metastatic LC.

Cancer cell membrane-coated bacterial ghosts for highly efficient paclitaxel delivery against metastatic lung cancer

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer,although it is limited by the low tumor delivery efficacy of anticancer drugs.Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect;however,excessively generated immunogenicity will cause serious inflammatory response syndrome.Here,we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts(LP@BG@CCM)by layer-by-layer encapsulation for the treatment of metastatic lung cancer.The preparation processes were simple,only involving film formation,electroporation,and pore extrusion.LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells.In the 4T1 breast cancer metastatic lung cancer mouse models,the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance,the reduced lung weight,the clear lung tissue structure,and the enhanced cancer cell apoptosis compared to its precursors.Moreover,several major immune factors were improved after administration of LP@BG@CCM,including the CD4^(+)/CD8a^(+)T cells in the spleen and the TNF-α,IFN-γ,and IL-4 in the lung.LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy,which is a promising medication for the treatment of metastatic lung cancer.

Sericin microparticles enveloped with metal-organic networks as a pulmonary targeting delivery system for intra-tracheally treating metastatic lung cancer

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer.However,systemic chemotherapy is limited by poor therapeutic efficiency and severe toxic side effects,due to the extremely low delivery efficacy and non-specificity of anticancer drugs.Herein,we report a sericin microparticles enveloped with metal-organic networks as a pulmonary delivery system for treating lung metastasis of breast cancer in an animal model.The sericin microparticles(SMPs)were prepared using water in oil(w/o)emulsification method.After doxorubicin(DOX)loading,tannic acid(TA)/ferric irons(Fe3+)based metal organic networks(MON)were coated on the particles to obtain DOX-loaded microparticles(DOX@SMPs-MON).The SMPs-MON with good biocompatibility could effectively encapsulate DOX and sustainably unload cargos in a pH-dependent manner.The DOX-loaded microparticles could be uptaken by 4T1 cells,and effectively kill the cancer cells.In vivo,DOX@SMPs-MON was deposited in the lungs and remained for over 5 days after pulmonary administration.In contrast to conventional DOX treatment that did not show significantly inhibitory effects on lung metastatic tumor,DOX@SMPs-MON markedly decreased the number and size of metastatic nodules in lungs,and the lung weight and appearance were similar to those of healthy mice.In summary,the sericin microparticles with MON wrapping might be a promising pulmonary delivery system for treating lung metastatic cancer.

Combined spatial frequency spectroscopy analysis with visible resonance Raman for optical biopsy of human brain metastases of lung cancers

The purpose of this study is to examine optical spatial frequency spectroscopy analysis(SFSA)combined with visible resonance Raman(VRR)spectroscopic method,for thefirst time,to discriminate human brain metastases of lung cancers adenocarcinoma(ADC)and squamous cell carcinoma(SCC)from normal tissues.A total of 31 label-free micrographic images of three type of brain tissues were obtained using a confocal micro-Raman spectroscopic system.VRR spectra of the corresponding samples were synchronously collected using excitation wavelength of 532 nm from the same sites of the tissues.Using SFSA method,the difference in the randomness of spatial frequency structures in the micrograph images was analyzed using Gaussian functionfitting.The standard deviations,calculated from the spatial frequencies of the micrograph images were then analyzed using support vector machine(SVM)classifier.The key VRR biomolecularfingerprints of carotenoids,tryptophan,amide II,lipids and proteins(methylene/methyl groups)were also analyzed using SVM classifier.All three types of brain tissues were identified with high accuracy in the two approaches with high correlation.The results show that SFSA–VRR can potentially be a dual-modal method to provide new criteria for identifying the three types of human brain tissues,which are on-site,real-time and label-free and may improve the accuracy of brain biopsy.

Anti-tumor effects of combined doxorubicin and siRNA for pulmonary delivery

Direct administration of drugs and genes to the lungs by pulmonary delivery offers a potential effective therapy for lung cancers.In this study,combined doxorubicin（DOX） and Bcl2 siRNA was employed for cancer therapy using polyethylenimine（PEI） as the carrier of Bcl2 siRNA.Most of the DOX and siRNA possessed high cellular uptake efficiency in B16F10 cells,which was proved by FCM and CLSM analysis.Real-time PCR showed that PEI/Bcl2 siRNA exhibited high gene silencing efficiency with 70%Bcl2 mRNA being knocked down.The combination of DOX and siRNA could enhance the cell proliferation inhibition and the cell apoptosis against B16F10 cells compared to free DOX or PEI/Bcl2 siRNA.Furthermore,the biodistribution of DOX and siRNA via pulmonary administration was studied in mice with B16F10 metastatic lung cancer.The results showed that most of the DOX and siRNA were accumulated in lungs and lasted at least for 3 days,which suggested that combined DOX and siRNA by pulmonary administration may have high anti-tumor effects for metastatic lung cancer treatment in vivo.