A phase IV study to evaluate the safety of fruquintinib in Chinese patients in real-world clinical practice.

INTRODUCTION: Fruquintinib is approved in China for patients with metastatic colorectal cancer (CRC) who progressed after 2 lines of chemotherapy. This postmarketing study was conducted to evaluate the safety of fruquintinib in the Chinese population, including previously treated patients with advanced CRC and other solid tumors. METHODS: Patients in the first cycle of fruquintinib or expected to start fruquintinib within a week were enrolled. Fruquintinib was administrated according to the label or per physicians' discretion. Patient characteristics and safety information were collected at baseline, 1 month, and 6 months after consent (or 30 days after the last dose). RESULTS: Overall, 3005 patients enrolled between April 24, 2019 and September 27, 2022. All enrolled patients received at least one dose of fruquintinib. Most patients had metastases at baseline. The median age was 60 years. More than half (64.0%) of the patients started fruquintinib at 5 mg, and the median treatment exposure was 2.7 months. Nearly one-third (32.5%) of patients with CRC received fruquintinib with concomitant antineoplastic agents. Treatment-emergent adverse events (TEAEs) leading to dose modification were reported in 626 (20.8%) patients, and 469 (15.6%) patients experienced TEAEs leading to treatment discontinuation. The most common grade ≥ 3 TEAEs were hypertension (6.6%), palmar-plantar erythrodysesthesia syndrome (2.2%), and platelet count decreased (1.0%). Combination therapy did not lead to excessive toxicities. CONCLUSIONS: The safety profile of fruquintinib in the real world was generally consistent with that in clinical studies, and the incidence of TEAEs was numerically lower than known VEGF/VEGFR inhibitor-related AEs. Fruquintinib exhibited manageable safety and tolerability in Chinese patients in the real-world setting.

Triplet-drug chemotherapy combined with anti-EGFR antibody as an effective therapy for patients with initially unresectable metastatic colorectal cancer: a meta-analysis.

The meta-analysis aimed to assess the clinical efficacy of chemotherapeutic triplet-drug regimen combined with anti-EGFR antibody in patients with initially unresectable metastatic colorectal cancer (mCRC). A systematic literature search was performed in PubMed Publisher. Studies evaluating FOLFOXIRI combine with panitumumab or cetuximab as the therapy for initially unresectable mCRC were included. The primary outcome was objective response rate (ORR) and rate of R0 resections. The secondary outcomes included overall survival (OS), progression-free survival (PFS), and grades 3 or 4 adverse events. R software (version 4.0.2) and RevMan (version 5.3) were used to analyze the extracted data. The studies included were published between 2010 and 2021, involving four single-arm phase II trials and two randomized phase II trials. A total of 6 studies with 282 patients were included. The data showed a significant benefit for the FOLFOXIRI + anti-EGFR antibody arm compared with FOLFOXIRI arm (RR 1.33; 95% CI, 1.13-1.58; I2 = 0%, P < 0.05). The pooled ORR and pooled rate of R0 resection in patients who receiving FOLFOXIRI + anti-EGFR antibody were 85% (95% CI, 0.78-0.91; I2 = 58%) and 42% (95% CI, 0.32-0.53; I2 = 62%), respectively. The range of median PFS between all the six studies was 9.5-15.5 months, with weighted pooled median PFS mean 11.7 months. The range of median OS between all the four studies was 24.7-37 months, with weighted pooled median PFS mean 31.9 months. The common grades 3 and 4 adverse events were diarrhea and neutropenia. Our findings show that triplet-drug chemotherapy (FOLFOXIRI) combined with anti-EGFR antibody (panitumumab or cetuximab) represents a very effective therapeutic combination associated with a significant ORR and R0 rection rate for patients with molecularly unselected and surgically unresectable metastatic CRC.

Serplulimab, a novel anti-PD-1 antibody, in patients with microsatellite instability-high solid tumours: an open-label, single-arm, multicentre, phase II trial.

BACKGROUND: Microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) tumours have a high response rate to immunotherapy. Antitumour activity and safety of serplulimab, a novel humanised anti-PD-1 monoclonal antibody, were evaluated in this phase II study. METHODS: In this ongoing, single-arm, open-label, phase II trial, patients with previously treated unresectable or metastatic MSI-H/dMMR solid tumours received intravenous serplulimab 3 mg/kg every 2 weeks for up to 52 cycles. The primary endpoint was objective response rate (ORR) assessed by an independent radiological review committee per Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included additional efficacy measures, safety, and tolerability. RESULTS: As of 9 January 2021, 108 patients were enrolled, and 68 patients with confirmed MSI-H solid tumours were included in the main efficacy analysis population (MEAP). The median follow-up duration in the MEAP was 7.7 months, with an ORR of 38.2% (95% confidence interval, 26.7-50.8). Of the 108 patients, grade ≥3 treatment-emergent adverse events were reported in 53 (49.1%) patients; immune-related adverse events occurred in 52 (48.1%) patients. CONCLUSIONS: Serplulimab demonstrates a durable antitumour effect and a manageable safety profile in previously treated patients with MSI-H solid tumours. Serplulimab is a promising tissue-agnostic treatment for previously treated MSI-H solid tumours. TRIAL REGISTRATION: NCT03941574.

Multiplexed dynamic strain sensing system based on a fiber ring laser using a non-tunable fiber Fabry-Perot filter.

In this paper, a non-tunable fiber Fabry-Perot filter (FFPF) is configured to demodulate dynamic strain signals in a multiplexed dynamic sensing system based on a fiber ring laser. A semiconductor optical amplifier (SOA) contained in the fiber ring laser cavity enables this system to implement multiplex operation because of the inhomogeneous broadening of the SOA source. The shift of the reflective spectrum of the fiber Bragg grating caused by external dynamic strain is demodulated by the FFPF in the laser cavity, which ultimately generates an amplified output. In the experiment, the sensing system can respond to dynamic strains at ultra-high frequencies up to megahertz, and an example for detection of ultrasonic signals in water has been successfully demonstrated. A dual-channel system for multiplexing demodulation is also discussed. This system presented here has a simple structure and a low cost, which makes it attractive for dynamic strain detection in structural health monitoring.

Increased lymphocyte to monocyte ratio is associated with better prognosis in patients with newly diagnosed metastatic nasopharyngeal carcinoma receiving chemotherapy.

Inflammation has been demonstrated to be widely involved in the carcinogenesis of nasopharyngeal carcinoma (NPC). However, the prognostic significance of lymphocyte to monocyte ratio (LMR) in metastatic NPC is not fully addressed. The purpose of the study is to investigate the prognostic impact of pre-treatment absolute lymphocyte count (ALC), absolute monocyte count (AMC), and LMR on patients with newly diagnosed metastatic NPC undergoing chemotherapy. Between January 2006 and December 2010, patients with newly diagnosed metastatic NPC undergoing chemotherapy were retrospectively collected. The prognostic significance of baseline clinical features and inflammatory markers was investigated. A total of 256 patients were eligible for the study. The best cut-off value of ALC, AMC, and LMR was 2.25 × 10(9)/L, 0.35 × 10(9)/L, and 5.07, respectively. Patients in the high LMR group had a significantly longer overall survival (OS) (25.0 months [24.50-25.49]) than patients in the low LMR group (16.0 months [15.51-16.49]; p < 0.001). In addition, ALC ≥ 2.25 × 10(9)/L (HR, 0.59; 95% CI, 0.43-0.81; p = 0.001) and LMR ≥ 5.07 (HR, 0.42; 95% CI, 0.30-0.59; p < .001) remained as independent prognostic factors for superior OS, while AMC did not retained its prognostic significance in COX multivariate analysis. Pre-treatment ALC and LMR were demonstrated to be independent prognostic factors in patient with newly diagnosed metastatic NPC receiving chemotherapy. Future prospective studies are needed to validate the findings.

The functions and prognostic values of chemokine and chemokine receptors in gastric cancer.

Chemokine and chemokine receptors (CCRs) play a significant role in tumor infiltration of immune cells, tumor angiogenesis and distant metastasis. In this study, we explored the importance of CCRs in gastric cancer (GC) by analyzing the datasets from TCGA database. First, we analyzed the characteristics of the CCRs mutations. Then, we screened the differentially expressed CCRs and performed GO functional annotation and KEGG pathway analyses to explore their potential biological functions. Using multivariate Cox regression analyses, we constructed a prediction model based on four-CCRs (CCL15, CCL21, CCR3 and ACKR3) signature, and we found that the risk score of the model was an independent prognostic factor of GC. Next, a nomogram was constructed to assess the prognosis of GC patients. GSEA indicated that the high-risk group was significantly enriched in immune response and immune system process. Moreover, GSVA was employed to investigate the up- and down-regulated signaling pathways in the high- and low-risk groups. The correlation between risk score and immune-cell infiltration indicated that the four-CCRs signature might play a pivotal role in GC immune microenvironment. In conclusion, we revealed the potential molecular mechanisms of CCRs in GC and constructed a prediction model which might guide personalized treatment and prognosis for GC patients.

Long non-coding RNA (FALEC) promotes malignant behaviors of gastric cancer cells by regulating miR-203b/PIM3 axis.

Background: Existing research shows that long non-coding RNAs (lncRNAs) have important regulatory effects in gastric cancer (GC). In recent years, focally amplified lncRNA on chromosome 1 (FALEC) has been repeatedly reported to have carcinogenic effects in thyroid carcinoma, colorectal cancer, and endometrial cancer, etc. While the role and mechanism of FALEC during GC tumorigenesis remains unclear. Methods: The levels of FALEC, microRNA-203b (miR-203b), and Recombinant Pim-3 Oncogene (PIM3) were confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell autophagy, proliferation, apoptosis, migration, and invasion were estimated using western blot, transmission electron microscopy (TEM), cell counting kit-8 (CCK-8), flow cytometer, and Transwell assays. The interaction between miR-203b and FALEC or PIM3 was verified using a dual-luciferase reporter assay. Moreover, the involvement of miR-203b and PIM3 in the regulatory effects of FALEC on GC was determined with rescue experiments. Results: The results showed that FALEC and PIM3 were highly expressed, while miR-203b was lowly expressed, in GC. FALEC knockdown repressed GC cell proliferation, migration, and invasion, and promoted apoptosis and autophagy in vitro. Meanwhile, FALEC knockdown prevented growth and induced GC autophagy in vivo. This shows that FALEC upregulated PIM3 by sponging miR-203b in GC cells. Besides, FALEC induced the malignant behaviors of GC cells by regulating the miR-203b/PIM3 axis. Conclusions: The FALEC/miR-203b/PIM3 axis might be a promising therapeutic target for therapy in GC patients.

Impact of inoculation and turning for full-scale composting on core bacterial community and their co-occurrence compared by network analysis.

Window composting with inoculation or frequent turning is a superior way to improve traditional composting efficiency. However, the relationship between the innocent treatment in composting with inoculation or turning and microbial dynamics is unclear. Here, the impact of inoculation and turning for full scale composting on core bacterial community and their co-occurrence network as well as harmless level were compared by network analysis. Results showed that composts with both inoculation and turning had 46% increase of total organic carbon degradation compared to traditional composting and decreased the abundance of potential pathogens. The relative abundance of thermophilic bacteria and Galbibacter, Methylocaldum, Steroidobacter, etc. increased during composting with turning and inoculation. Luteimonas, Sphaerobacter, Turicibacter and Flavobacterium as core bacteria had significant difference between control and composting with enhanced innocent treatment efficiency. Network analysis suggested that turning increased the number of indigenous core bacteria and inoculation enhanced the interaction among key bacterial network.

Strong spring winds accelerated the recruitment and reinvasion of cyanobacteria.

The reinvasion and recruitment of overwintering cyanobacteria in sediments in spring have an important impact on cyanobacterial blooms in summer and autumn, but until now, this process has not been observed in natural water bodies. In this study, wireless sensors and automatic water sample collection systems were used to carry out continuous high-frequency monitoring of cyanobacteria and related environmental indicators in Meiliang Bay, Lake Taihu, during a northwest wind event in spring. The results showed that there were many dormant cyanobacteria seeds in the sediments of Lake Taihu. These cyanobacterial seeds were easily resuspended from sediments, allowing them to reinvade and remain in the overlying water. Simultaneously, the water temperature exceeded the recovery temperature after the northwest wind event and the available light was sufficient to allow the reinvading cyanobacteria to recruit. The circadian photosynthetic rhythm of these recruited cyanobacteria eventually led to a rapid increase in dissolved oxygen in the water body during the south wind phase to a supersaturated state, and periodic diurnal fluctuations of the water body dissolved oxygen saturation curve. This study provided direct evidence for fully understanding the annual cycle of cyanobacterial blooms.

Phase I First-in-Human Dose Escalation Study of the oral SF3B1 modulator H3B-8800 in myeloid neoplasms.

We conducted a phase I clinical trial of H3B-8800, an oral small molecule that binds Splicing Factor 3B1 (SF3B1), in patients with MDS, CMML, or AML. Among 84 enrolled patients (42 MDS, 4 CMML and 38 AML), 62 were red blood cell (RBC) transfusion dependent at study entry. Dose escalation cohorts examined two once-daily dosing regimens: schedule I (5 days on/9 days off, range of doses studied 1-40 mg, n = 65) and schedule II (21 days on/7 days off, 7-20 mg, n = 19); 27 patients received treatment for ≥180 days. The most common treatment-related, treatment-emergent adverse events included diarrhea, nausea, fatigue, and vomiting. No complete or partial responses meeting IWG criteria were observed; however, RBC transfusion free intervals >56 days were observed in nine patients who were transfusion dependent at study entry (15%). Of 15 MDS patients with missense SF3B1 mutations, five experienced RBC transfusion independence (TI). Elevated pre-treatment expression of aberrant transcripts of Transmembrane Protein 14C (TMEM14C), an SF3B1 splicing target encoding a mitochondrial porphyrin transporter, was observed in MDS patients experiencing RBC TI. In summary, H3B-8800 treatment was associated with mostly low-grade TAEs and induced RBC TI in a biomarker-defined subset of MDS.

Clinical Features and Prognostic Impact of Coexpression Modules Constructed by WGCNA for Diffuse Large B-Cell Lymphoma.

OBJECTIVE: Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive malignant tumor, accounting for 30-40% of non-Hodgkin's lymphoma. Our aim was to construct novel prognostic models of candidate genes based on clinical features. METHODS: RNA-seq and clinical data of DLBCL were retrieved from TCGA database. Coexpression modules were constructed by WGCNA. Then, we investigated the interactions between modules and clinical features. By overall survival analysis, prognostic candidate genes from modules of interest were identified. A coexpression network of prognostic candidate genes was then constructed through WGCNA. GEPIA was used to analyze the expression of a candidate gene between DLBCL and normal samples. RESULTS: 19 coexpression modules were constructed by 12813 genes from 52 DLBCL samples. The number of genes in modules ranged from 34 to 5457. We found that the purple module was significantly related with histological type (p value = 1e-04). Overall survival analysis revealed that MAFA-AS1, hsa-mir-338, and hsa-mir-891a were related with prognosis of DLBCL (p value = 0.027, 0.039, and 0.022, respectively). A coexpression network was constructed for the three prognostic genes. MAFA-AS1 was interacted with 36 genes, hsa-mir-891a was interacted with 11 genes, while no gene showed interaction with hsa-mir-338. Using GEPIA, we found that MAFA-AS1 showed low expression in DLBCL samples (p < 0.01). CONCLUSION: We constructed a coexpression module related with histological type and identified three candidate genes (MAFA-AS1, hsa-mir-338, and hsa-mir-891a) that possessed potential value as prognostic biomarkers and therapeutic targets of DLBCL.

Production of furfural and levoglucosan from typical agricultural wastes via pyrolysis coupled with hydrothermal conversion: Influence of temperature and raw materials.

The liquid product from biomass direct pyrolysis is usually complex and difficult to effectively utilize. By combining hydrothermal conversion and low-temperature pyrolysis, the hemicellulose and cellulose of biomass can be transformed into value-added furfural and levoglucosan (LG), respectively. The effects of temperature during hydrothermal treatment (160-240 °C) and subsequent pyrolysis (340-400 °C) on the production of furfural and LG were investigated by using three typical agricultural wastes, namely corn stalk, peanut shells, and rice stalk. The maximum furfural yield of 4.2% was achieved upon hydrolysis of peanut shells at 200 °C. The hydrochar produced from peanut shells presented the highest LG yield of 7.3% (based on original biomass weight) for a pyrolysis temperature of 360 °C. Under this optimal condition, the total revenue from various products of the hybrid thermochemical process was estimated at $0.362 per kilogram of peanut shells, whereas furfural and LG account for 90% of the revenue.

Shear stress activates ATOH8 via autocrine VEGF promoting glycolysis dependent-survival of colorectal cancer cells in the circulation.

BACKGROUND: Metastasis and recurrence, wherein circulating tumour cells (CTCs) play an important role, are the leading causes of death in colorectal cancer (CRC). Metastasis-initiating CTCs manage to maintain intravascular survival under anoikis, immune attack, and importantly shear stress; however, the underlying mechanisms remain poorly understood. METHODS: In view of the scarcity of CTCs in the bloodstream, suspended colorectal cancer cells were flowed into the cyclic laminar shear stress (LSS) according to previous studies. Then, we detected these suspended cells with a CK8+/CD45-/DAPI+ phenotype and named them mimic circulating tumour cells (m-CTCs) for subsequent CTCs related researches. Quantitative polymerase chain reaction, western blotting, and immunofluorescence were utilised to analyse gene expression change of m-CTCs sensitive to LSS stimulation. Additionally, we examined atonal bHLH transcription factor 8 (ATOH8) expressions in CTCs among 156 CRC patients and mice by fluorescence in situ hybridisation and flow cytometry. The pro-metabolic and pro-survival functions of ATOH8 were determined by glycolysis assay, live/dead cell vitality assay, anoikis assay, and immunohistochemistry. Further, the concrete up-and-down mechanisms of m-CTC survival promotion by ATOH8 were explored. RESULTS: The m-CTCs actively responded to LSS by triggering the expression of ATOH8, a fluid mechanosensor, with executive roles in intravascular survival and metabolism plasticity. Specifically, ATOH8 was upregulated via activation of VEGFR2/AKT signalling pathway mediated by LSS induced VEGF release. ATOH8 then transcriptionally activated HK2-mediated glycolysis, thus promoting the intravascular survival of colorectal cancer cells in the circulation. CONCLUSIONS: This study elucidates a novel mechanism that an LSS triggered VEGF-VEGFR2-AKT-ATOH8 signal axis mediates m-CTCs survival, thus providing a potential target for the prevention and treatment of hematogenous metastasis in CRC.

[Preparation and evaluation of mouse model of house dust mite-induced asthma].

OBJECTIVE: To prepare a mouse model of asthma by sensitizing and challenging with house dust mite allergen Derp and evaluate its reliability by measuring airway allergy inflammation and airway responsiveness. METHODS: Twelve C57BL/6J mice were randomly divided into two groups: control and asthma model. Mice of the asthma model group were sensitized by intraperitoneal injection of house dust mite allergen Derp on the first and tenth days of the experiment. From the 17th day, the mice were challenged by intranasal Derp, once every other day, seven times. The control group was treated with normal sodium instead of Derp. Twenty-four hours after the last challenge, airway responsiveness was evaluated. Bronchoalveolar lavage and histological examination of the lung were performed. RESULTS: Airway resistance increased and dynamic lung compliance decreased significantly in the asthma model group as compared to the control group (P<0.01). When airway resistance increased by 25% and dynamic lung compliance decreased by 15%, the required metacholine concentration in the asthma model group was significantly lower than that in the control group (P<0.01). In the bronchoalveolar lavage fluid of the asthma model group, the number of total cells, absolute number of eosinophils (EOS) and the percentage of EOS in the total cell were significantly higher than those in the control group (P<0.01). Pulmonary pathological scores in the asthma model group were significantly higher than those in the control group (P<0.01). The asthma model group showed ultrastructural changes of bronchial and pulmonary arterioles. Goblet cells, mastocyte granules, and increased mucus were observed in the lung tissues of the asthma model group. CONCLUSIONS: A mouse model of asthma was prepared by sensitizing and challenging with house dust mite allergen Derp, with the characteristics of airway allergy inflammation and airway hypersensitivity reaction.

miR-5195-3p Inhibits Proliferation and Invasion of Human Bladder Cancer Cells by Directly Targeting Oncogene KLF5.

miRNAs play a key role in the carcinogenesis of many cancers, including bladder cancer. In the current study, the role of miR-5195-3p, a quite recently discovered and poorly studied miRNA, in the proliferation and invasion of human bladder cancer cells was investigated. Our data displayed that, compared with healthy volunteers (control) and SU-HUC-1 normal human bladder epithelial cells, miR-5195-3p was sharply downregulated in bladder cancer patients and five human bladder cancer cell lines. The oligo miR-5195-3p mimic or miR-5195-3p antagomir was subsequently transfected into both T24 and BIU-87 bladder cancer cell lines. The miR-5195-3p mimic robustly increased the miR-5195-3p expression level and distinctly reduced the proliferation and invasion of T24 and BIU-87 cells. In contrast, the miR-5195-3p antagomir had an opposite effect on miR-5195-3p expression, cell proliferation, and invasion. Our data from bioinformatic and luciferase reporter gene assays identified that miR-5195-3p targeted the mRNA 3'-UTR of Krüppel-like factor 5 (KLF5), which is a proven proto-oncogene in bladder cancer. miR-5195-3p sharply reduced KLF5 expression and suppressed the expression or activation of its several downstream genes that are kinases improving cell survival or promoting cell cycle regulators, including ERK1/2, VEGFA, and cyclin D1. In conclusion, miR-5195-3p suppressed proliferation and invasion of human bladder cancer cells via suppression of KLF5.

Elevated neutrophil-to-lymphocyte ratio predicts poor outcome in patients with advanced non-small-cell lung cancer receiving first-line gefitinib or erlotinib treatment.

AIM: Elevated neutrophil-to-lymphocyte ratio (NLR) has been demonstrated to be a poor prognostic factor in multiple types of malignancies, whereas the effect of NLR on the prognosis of epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) patients treated with first-line EGFR tyrosine kinase inhibitors (TKIs) is not fully addressed. METHODS: 81 metastatic NSCLC patients harboring EGFR mutation treated with first-line EGFR TKIs were retrospectively included. The associations between baseline clinical characteristics, including NLR, and tumor response, progression and survival were investigated. RESULTS: Elevated NLR (≥3.5) was observed in 33 of 81 patients. The progression-free and overall survival of the patients with increased NLR was significantly worse than that of the patients with decreased NLR (8.20 vs 10.60 months, P < 0.001 and 17.20 vs 23.20 months, P < 0.001, respectively). Elevated NLR was confirmed to be an independent prognostic factor for worse progression-free and overall survival in Cox multivariate analysis. CONCLUSION: Elevated NLR is likely to be associated with poor outcome in EGFR-mutated advanced NSCLC patients treated with first-line EGFR TKIs.

Programmed Cell Death-1 Polymorphisms Decrease the Cancer Risk: A Meta-Analysis Involving Twelve Case-Control Studies.

Programmed cell death-1 (PD-1) plays an important inhibitory role in anti-tumor responses, so it is considered as a powerful candidate gene for individual's genetic susceptibility to cancer. Recently, some epidemiological studies have evaluated the association between PD-1 polymorphisms and cancer risk. However, the results of the studies are conflicting. Therefore, a meta-analysis was performed. We identified all studies reporting the relationship between PD-1 polymorphisms and cancers by electronically searches. According to the inclusion criteria and the quality assessment of Newcastle-Ottawa Scale (NOS), only high quality studies were included. A total of twelve relevant studies involving 5,206 cases and 5,174 controls were recruited. For PD-1.5 (rs2227981) polymorphism, significantly decreased cancer risks were obtained among overall population, Asians subgroup and population-based subgroup both in TT vs. CC and TT vs. CT+CC genetic models. In addition, a similar result was also found in T vs. C allele for overall population. However, there were no significant associations between either PD-1.9 (rs2227982) or PD-1 rs7421861 polymorphisms and cancer risks in all genetic models and alleles. For PD-1.3 (rs11568821) polymorphism, we found different cancer susceptibilities between GA vs. GG and AA vs. AG+GG genetic models, and no associations between AA vs. GG, AA+AG vs. GG genetic models or A vs. G allele and cancer risks. In general, our results firstly indicated that PD-1.5 (rs2227981) polymorphism is associated a strongly decreased risk of cancers. Additional epidemiological studies are needed to confirm our findings.

Prognostic significance of the pre-chemotherapy lymphocyte-to-monocyte ratio in patients with previously untreated metastatic colorectal cancer receiving FOLFOX chemotherapy.

BACKGROUND: As a surrogate marker of systemic inflammation, the lymphocyte-to-monocyte ratio (LMR) is an independent prognostic factor for various malignancies. This study investigated the prognostic significance of the pre-chemotherapy LMR in patients with previously untreated metastatic colorectal cancer (mCRC) receiving chemotherapy. METHODS: The present study included newly diagnosed mCRC patients treated between January 2005 and December 2013 with FOLFOX chemotherapy, specifically oxaliplatin 180 mg/m(2) on day 1, with leucovorin 400 mg/m(2) administered as a 2-hour infusion before the administration of 5-fluorouracil 400 mg/m(2) as an intravenous bolus injection, and 5-fluorouracil 2400 mg/m(2) as a 46-h infusion immediately after 5-fluorouracil bolus injection. The LMR was calculated as the absolute count of lymphocytes divided by the absolute count of monocytes. COX proportional hazards analysis was performed to evaluate the association of LMR with survival outcomes. RESULTS: A total of 488 patients were included. Patients with high pre-chemotherapy LMR experienced significant improvements in progression-free survival (PFS, 9.2 vs. 7.6 months, P < 0.001) and overall survival (OS, 19.4 vs. 16.6 months, P < 0.001) compared with patients with low pre-chemotherapy LMR. Subsequent COX multivariate analysis showed that high pre-chemotherapy LMR (≥3.11) was an independent favorable prognostic factor for PFS and OS. Additionally, patients whose LMR remained high (high-high subgroup), increased (low-high subgroup), or decreased (high-low subgroup) following chemotherapy showed better results in terms of PFS and OS than patients whose LMR remained low (low-low subgroup) after chemotherapy. CONCLUSIONS: For patients with previously untreated mCRC receiving FOLFOX chemotherapy, an elevated pre-chemotherapy LMR is an independent favorable prognostic factor for PFS and OS, and changes in the LMR before and after chemotherapy seem to predict the benefit of chemotherapy.

Hepatitis B Virus Infection Is Associated with Poor Prognosis in Patients with Advanced Non Small Cell Lung Cancer.

BACKGROUND: Hepatitis B virus (HBV) infection has been reported to be associated with inferior prognosis in hepatocellular and pancreatic carcinoma cases, but has not been studied with respect to non small cell lung cancer (NSCLC). The purpose of this study was to investigate the prognostic significance of HBV infection in advanced NSCLC patients. MATERIALS AND METHODS: A retrospective cohort of 445 advanced NSCLC patients was recruited at our hospital from January 1, 2003 until August 30, 2014. Serum HBV markers were tested by enzyme-linked immunosorbent assay. COX proportional hazards analysis was used to evaluate associations of HBV infection with overall survival (OS). RESULTS: Of 445 patients who were qualified for the study, 68 patients were positive for HBsAg, also considered as HBV infection. Patients in HBsAg negative group were found to have better OS (12.6 months [12.2-12.9]) than those in HBsAg positive group (11.30 months [10.8-11.9]; p=0.001). Furthermore, COX multivariate analysis identified HBV infection as an independent prognostic factor for OS (HR 0.740 [0.560, 0.978], p=0.034). CONCLUSIONS: Our study found that HBsAg-positive status was an independent prognostic factor for OS in patients with advanced NSCLC. Future prospective studies are required to confirm our findings.