Assessing the impact of dust events on the Holiday Climate Index in the Taklimakan Desert region.

As a significant sector within the tourism industry, desert tourism has developed rapidly in recent years, contributing significantly to local economic development. On the other hand, desert tourism is constantly influenced by the desert climate, characterized by high temperatures, aridity, and dust events. This study examines and analyzes the impact of dust events on the Holiday Climate Index (HCI) using an improved methodology. It incorporates comprehensive meteorological data including temperature, relative humidity, cloud cover, precipitation, wind speed and dust events of Tazhong, located in the heart of the Taklimakan Desert. The results indicate that the maximum mean monthly HCI dips from an ideal level (91) to a very good level (73), the minimum dips from good level (66) to a marginal level (47), and the annual comfortable days (HCI ≥ 80) decrease from 180.5 to 95.3 after considering the impacts of dust events. The corrective HCI indicates that autumn, especially October, offers relatively comfortable climatic conditions for tourism, with the mean monthly comfortable days reach 20.1. These findings can better guide desert tourism activities and also demonstrate that the impact of dust weather on tourism activities cannot be ignored.

DDX4 enhances antiviral activity of type I interferon by disrupting interaction of USP7/SOCS1 and promoting degradation of SOCS1.

DEAD-box helicase (DDX) family members play differential roles in regulating innate antiviral immune response. However, the physiological roles played by DDX4 in antiviral innate immunity remain unclear. In this study, we unveiled that DDX4 acts as a positive regulatory molecule of Type-I interferon (IFN-I)-mediated antiviral activity. Our findings demonstrate that IFN-I upregulates DDX4 protein levels, and subsequently, overexpression of DDX4 enhances the IFN-I-mediated signaling pathway. This creates a positive feedback loop that amplifies the antiviral response. DDX4 was found to bind with deubiquitinase ubiquitin-specific protease 7 (USP7), leading to the disruption of the interaction between USP7 and suppressor of cytokine signaling 1 (SOCS1) and the subsequent degradation of SOCS1. This process enhances the antiviral function of IFN-I. Our findings provide new insights into the regulatory role of DDX4 in the IFN-I response.IMPORTANCEDDX4, identified as a putative RNA helicase that modulates RNA secondary structure through RNA binding, is primarily acknowledged for its role in regulating mRNA translation within the germline. Nevertheless, the extent of DDX4's involvement in the antiviral innate immune response remains largely unexplored. This study presents evidence of a previously unrecognized positive feedback loop between DDX4 and the antiviral response, suggesting that disruption of this loop may serve as a novel mechanism for viral evasion. Furthermore, our findings elucidate a positive regulatory mechanism by which the DDX4/USP7/SOCS1 axis mediates the antiviral activity of Type-I interferon, which provides new insight into strategies for improving the efficacy of IFN-based antiviral therapy.

Construction of Diversified Penta-Spiro-Heterocyclic and Fused-Heterocyclic Frameworks with Potent Antitumor Activity.

Invited for the cover of this issue are Xuewu Liang, Hong Liu and co-workers at the Shanghai Institute of Materia Medica and Shenyang Pharmaceutical University. The image depicts how a rhodium-catalyzed methodology leads to novel penta-spiro/fused-heterocyclic frameworks with potent antitumor activity through C-H activation/[4+1] and [4+2] annulation cascades. Read the full text of the article at 10.1002/chem. 202301553.

The glycoside hydrolase gene family profile and microbial function of Debaryomyces hansenii Y4 during South-road dark tea fermentation.

Microbes are crucial to the quality formation of Sichuan South-road Dark Tea (SSDT) during pile-fermentation, but their mechanism of action has not yet been elucidated. Here, the glycoside hydrolase (GH) gene family and microbial function of Debaryomyces hansenii Y4 during solid-state fermentation were analyzed, and the results showed that many GH genes being distributed in comparatively abundant GH17, GH18, GH76, GH31, GH47, and GH2 were discovered in D. hansenii. They encoded beta-galactosidase, alpha-D-galactoside galactohydrolase, alpha-xylosidase, mannosidase, etc., and most of the GHs were located in the exocellular space and participated in the degradation of polysaccharides and oligosaccharides. D. hansenii Y4 could develop the mellow mouthfeel and "reddish brown" factors of SSDT via increasing the levels of water extracts, soluble sugars and amino acids but decreasing the tea polyphenols and caffeine levels, combined with altering the levels of thearubiins and brown index. It may facilitate the isomerization between epicatechin gallate and catechin gallate. Moreover, the expression levels of DEHA2G24860g (Beta-galactosidase gene) and DEHA2G08602g (Mannan endo-1,6-alpha-mannosidase DFG5 gene) were sharply up-regulated in fermentative anaphase, and they were significantly and negatively correlated with epicatechin content, especially, the expression of DEHA2G08602g was significantly and negatively correlated with catechin gallate level. It was hypothesized that D. hansenii Y4 is likely to be an important functional microbe targeting carbohydrate destruction and catechin transformation during SSDT pile-fermentation, with DEHA2G08602g as a key thermotolerant functional gene.

Construction of Diversified Penta-Spiro-Heterocyclic and Fused-Heterocyclic Frameworks with Potent Antitumor Activity.

Multiple-spiro/fused-heterocyclic frameworks containing indazolone are structurally unique and represent a class of potentially dominant skeletons. In this work, we successfully fulfilled Rh(III)-catalyst mediated substrate- and pH- controlled strategies to construct four novel types of complicated penta-spiro/fused-heterocyclic frameworks via C-H activation/[4+1] and [4+2] annulation cascades. This method had mild reaction conditions, a broad scope of substrates, moderate to good yields, and valuable applications, which could realize for the first time the generation of the novel di-spiro-heterocyclic and multiple fused-heterocyclic products with unique structures. More importantly, novel spiro[cyclohexane-indazolo[1,2-a]indazole] scaffold constructed by this method exhibited potent antitumor activity against a variety of refractory solid tumors and hematological malignancies in vitro. Overall, our work provided new insights into the construction of complex and diverse multiple spiro/fused-heterocyclic systems and offered novel valuable lead compounds for the discovery of antitumor drugs.

High-Voltage Solid-State Lithium Metal Batteries with Stable Anodic and Cathodic Interfaces by a Laminated Solid Polymer Electrolyte.

Solid polymer electrolyte (SPE) is quite an attractive candidate for constructing high-voltage Li metal batteries (LMBs) with high energy density and excellent safety. However, sim ultaneous achievement of high-voltage stability against the cathode and good compatibility with the Li anode remains challenging for the current SPE technology. Herein, a dual-layered solid electrolyte (DLSE) consisting of an oxidation-resistant poly(acrylonitrile) (PAN) layer facing a high-potential cathode and a reduction-compatible poly(vinylidene fluoride) (PVDF) layer incorporated by Li6.4La3Zr1.4Ta0.6O12 (LLZTO) nanoparticles and an ionic liquid plasticizer in contact with a Li anode was fabricated. The uniquely designed DLSE holds favorable overall properties in ionic conductivity, Li+ transference number, and mechanical strength. Moreover, the combined advantages of two polymer electrolyte layers greatly address the interface issues on both the cathode and anode. Consequently, the high-voltage LMBs employing the DLSE exhibit excellent room-temperature performances including high rate capacity and long cycle life.

Comparing the environmental impacts of nuclear and renewable energy in top 10 nuclear-generating countries: evidence from STIRPAT model.

The purpose of this study is to assess the impact of nuclear energy and renewable energy on CO2 emissions in major top 10 nuclear-generating countries based on the Stochastic Impacts by Regression on Population, Affluence, and Technology (STIRPAT) model from 1993 to 2018. For comparison, the impact of renewable energy on emissions is also examined. For robust checking, four models would be used. The cross-sectional dependence (CD) test reveals the existence of CD in the panel data. Stationary tests indicate the selected variables have no unit root in 1st difference, and cointegration tests confirm the time series data in four multivariable models are long-run cointegrating relationship in each model. Fully modified ordinary least squares (FMOLS) and augmented mean group (AMG) are employed to estimate the long-run coefficients of independent variables, which reveals the positive impacts of variables on emissions. One percent increase in population, economic growth, carbon intensity, and nuclear or renewable energy consumption can lead to 0.984 ~ 1.060%, 1.001 ~ 1.012%, 1.000 ~ 1.011%, 0.009 ~ 0.011%, or 0.003 ~ 0.005% increase in emissions, respectively. Dumitrescu-Hurlin (DH) panel Granger causality test reveals that the causalities between the variables are mixed. Finally, some implications are proposed, such as limiting population quantity and improving the population quality, implementing a green economy, and developing safe nuclear and renewable energy.

Discovery of Novel Imidazo[4,5-c]quinoline Derivatives to Treat Inflammatory Bowel Disease (IBD) by Inhibiting Multiple Proinflammatory Signaling Pathways and Restoring Intestinal Homeostasis.

As a complex pathogenesis driven by immune inflammatory factors and intestinal microbiota, the treatment of inflammatory bowel disease (IBD) may rely on the comprehensive regulation of these important pathogenic factors to reach a favorable therapeutic effect. In the current study, we discovered a series of imidazo[4,5-c]quinoline derivatives that potently and simultaneously inhibited two primary proinflammatory signaling pathways JAK/STAT and NF-κB. Especially, lead compound 8l showed potent inhibitory activities against interferon-stimulated genes (IC50: 3.3 nM) and NF-κB pathways (IC50: 150.7 nM) and decreased the release of various proinflammatory factors at the nanomolar level, including IL-6, IL-8, IL-1ß, TNF-α, IL-12, and IFN-γ. In vivo, 8l produced a strong anti-inflammatory activity in both dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute enteritis models and restored the structural composition of gut microbiota. Collectively, this study provided valuable lead compounds for the treatment of IBD and revealed the great anti-inflammatory potential of the simultaneous suppression of JAK/STAT and NF-κB signals.

Microbial Community Analysis in Sichuan South-road Dark Tea Piled Center at Pile-Fermentation Metaphase and Insight Into Organoleptic Quality Development Mediated by Aspergillus niger M10.

Microbes are critical in the Sichuan South-road Dark Tea (SSDT) organoleptic quality development during pile-fermentation. Piled tea center at fermenting metaphase is crucial for the conversion of its quality components. In this study, we investigated the microbial community of piled SSDT center below the stacked tea surface of 15 cm (SSDTB), 50 cm (SSDTX), and 85 cm (SSDTH) on the second turning time of pile-fermentation, respectively. Results showed that SSDTH and SSDTB had a higher similarity in the microbial community. Pantoea (36.8%), Klebsiella (67.7%), and Aspergillus (35.3%) were the most abundant in SSDTH, SSDTB, and SSDTX, respectively. We found 895 species were common among all samples, but 86, 293, and 36 species were unique to SSDTB, SSDTX, and SSDTH, respectively. Aspergillus niger showed high co-occurrence and was positively correlated with numerous microbes in SSDT samples, and Aspergillus niger M10 isolated from SSDTX was excellent at enhancing soluble sugar (SS), amino acids (AAs), theaflavin (TF), and thearubigins (TR) contents, while decreasing catechin (Cat), tea polyphenols (TPs)/AA, Caf/SS, Cat/SS, TPs/SS, and (TPs + Caf)/SS levels in AM10 post-fermentation, as compared with the control. Moreover, it also produced a noticeable difference in the CIELab parameters in dried, liquor, and infused tea colors between AM10 and control during fermentation. When it was further inoculated on differential mediums, we detected glycoside hydrolases, namely, ß-glucosidase, mannosidase, pectinase, cellulase, amylase, and α-galactosidase being secreted by Aspergillus niger M10. Taken together, SSDXT presented a more unique microbial community. Aspergillus niger M10 probably improved the sweet and mellow taste, and the yellow brightness and red color of SSDT during fermentation. It also provided new insights into the microbial profile and organoleptic quality development mechanism of SSDT during pile-fermentation.

Discovery of Novel Pyrrolo[2,3-d]pyrimidine-based Derivatives as Potent JAK/HDAC Dual Inhibitors for the Treatment of Refractory Solid Tumors.

It remains a big challenge to develop HDAC inhibitors effective for solid tumors. Previous studies have suggested that the feedback activation of JAK-STAT3 pathway represents a key mechanism leading to resistance to HDAC inhibitors in breast cancer, suggesting the therapeutic promise of JAK/HDAC dual inhibitors. In this work, we discovered a series of pyrrolo[2,3-d]pyrimidine-based derivatives as potent JAK and HDAC dual inhibitors. Especially, compounds 15d and 15h potently inhibited JAK1/2/3 and HDAC1/6 and displayed antiproliferative and proapoptotic activities in triple-negative breast cancer cell lines. Besides, compounds 15d and 15h also diminished the activation of LIFR-JAK-STAT signaling triggered by tumor-associated fibroblasts, which suggests that these compounds could potentially overcome the drug resistance caused by the tumor microenvironment. More importantly, compound 15d effectively inhibited the tumor growth in MDA-MB-231 xenograft tumor model. Overall, this work provides valuable leads and novel antitumor mechanisms for the treatment of the SAHA-resistant triple-negative breast cancers.

Identification of Novel Fused Heteroaromatics-Based MALT1 Inhibitors by High-Throughput Screening to Treat B Cell Lymphoma.

Development of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) inhibitors is of great value and significance in the treatment of neoplastic disorders and inflammatory and autoimmune diseases. However, there is a lack of effective MALT1 inhibitors in clinic. Herein, a novel class of potent 5-oxo-1-thioxo-4,5-dihydro-1H-thiazolo[3,4-a]quinazoline-based MALT1 inhibitors and their covalent derivatives were first identified and designed through high-throughput screening. We demonstrated that compounds 15c, 15e, and 20c effectively inhibited the MALT1 protease and displayed selective cytotoxicity to activated B cell-like diffuse large B cell lymphoma with low single-digit micromolar potency. Furthermore, compound 20c specifically repressed NF-κB signaling and induced cell apoptosis in MALT1-dependent TMD8 cells in a dose-dependent manner. More importantly, 20c showed good pharmacokinetic properties and antitumor efficacy with no significant toxicity in the TMD8 xenograft tumor model. Collectively, this study provides valuable lead compounds of MALT1 inhibitors for further structural optimization and antitumor mechanism study.

In silico production of relative correction factor for the quantitative analysis of multi-components by single marker method.

INTRODUCTION: Traditional methods to derive experimentally-generated relative correction factors (RCFs) for the quantitative analysis of herbal multi-components by single marker (QAMS) method require reference standards and multiple validations with different instruments and columns, which hampers high throughput implementation. OBJECTIVES: To effectively reduce the application amounts of raw material and provide higher and more stable accuracy, this study aimed to develop a method to computationally generate RCFs of herbal components. MATERIALS AND METHODS: This strategy included the published data collection, calibration curves screening, computer algorithm-based RCFs generation and accuracy validation. RESULTS: Using the in silico approach, we have successfully produced 133 RCFs for the multi-component quantitative analysis of 63 widely used herbs. CONCLUSION: Compared with conventional RCFs, this in silico method would be a low cost and highly efficient way to produce practical RCFs for the QAMS method.

Aggregate and disaggregate analysis on energy consumption and economic growth nexus in China.

This study examines the relationship between energy consumption and economic growth based on three models in China covering the period of 1982-2015. From the Ng-Perron (NP) and Zivot-Andrews (ZA) unit root test, each variable has no unit root in the first difference. Based on Johansen multivariable co-integration test and autoregressive distributed lag (ARDL) bounds test, the co-integrating relationship existed between selected variables. Moreover, dynamic ordinary least squares (DOLS), fully modified ordinary least squares (FMOLS), and ARDL estimates are used to estimate the coefficients of each variable, which presents that any increasing of each kinds of energy sources can increase China's economic growth in the long term. Additionally, the vector error correction model (VECM) Granger causality test based on three models is investigated. Some implications based on the empirical results are given.

[Clinical Characteristics of Lung Cancer with Pancreatic Metastases].

BACKGROUND: Lacking of typical symptoms, more than 70% of patients with lung cancer are diagnosed as advanced-stage disease. Patients suffer from solid organs metastasis with different clinical features and prognosis. With development of new technology, more and more lung cancer patients are diagnosed with pancreatic metastasis. The aim of this study was to investigate clinicopathologic and survival difference by retrospective analysis among lung cancer patients with pancreatic metastases. METHODS: Of the patients with lung cancer diagnosed by pathology and thorough staging evaluation and treated at Beijing Cancer Hospital with long follow-up during July 1996 and June 2017, 35 cases had pancreatic metastases. RESULTS: There were 28 cases diagnosed as small cell lung cancer, 3 cases diagnosed as adenocarcinoma and 4 cases diagnosed as squamous cell carcinoma. There were 15 cases with pancreatic metastases in head of pancreas and 20 cases in body and tail of pancreas, 23 cases presented with isolated metastasis and 12 cases with multiple metastases. Pathological type was prognostic factor for lung cancer patients with pancreatic metastases. CONCLUSIONS: Pancreatic metastases represents an uncommon site of extrathoracic spread of disease for part of patients with advanced lung cancer. Lung cancer with pancreatic metastases should be treated by combined therapy, especially by systemic chemotherapy. Pathological type was prognostic factor for lung cancer patients with pancreatic metastases.
.

Does trade openness affect CO2 emissions: evidence from ten newly industrialized countries?

This paper examines whether the hypothetical environmental Kuznet curve (EKC) exists or not and investigates how trade openness affects CO2 emissions, together with real GDP and total primary energy consumption. The study sample comprises ten newly industrialized countries (NICs-10) from 1971 to 2013. The results support the existence of hypothetical EKC and indicate that trade openness negatively and significantly affects emissions, while real GDP and energy do positive effects of emissions. Moreover, the empirical results of short-run causalities indicate feedback hypothetical linkage of real GDP and trade, unidirectional linkages from energy to emissions, and from trade to energy. The error correction terms (ECTs) reveal in the long run, feedback linkages of emissions, real GDP, and trade openness, while energy Granger causes emissions, real GDP, and trade, respectively. The study recommendations are that our policymakers should encourage and expand the trade openness in these countries, not only to restrain CO2 emissions but also to boost their growth.

Patients harboring epidermal growth factor receptor (EGFR) double mutations had a lower objective response rate than those with a single mutation in non-small cell lung cancer when treated with EGFR-tyrosine kinase inhibitors.

BACKGROUND: Multiple prospective studies have demonstrated that epidermal growth factor receptor (EGFR) exon 19 and exon 21 mutations are the most powerful predictive biomarkers of response to EGFR tyrosine kinase inhibitors (TKIs) in advanced non-small-cell lung cancer (NSCLC). However, there are few studies focused on patients with double mutations compared with a single mutation. METHODS: We retrospectively screened 1,525 samples of Chinese patients with advanced NSCLC who underwent EGFR mutation detections in tumor tissues at Peking University Cancer Hospital between February 2006 and March 2011. Thirty-two cases harboring double mutations were included in this study. The Kaplan-Meier univariate analysis for prognostic factors of survival was applied. RESULTS: Patients with double mutations accounted for 2.1% (32/1525) of the overall tested samples. Double mutations were more common in female, adenocarcinoma, non-smokers, Eastern Cooperative Oncology Group (ECOG0)-1 and stage IV patients. Twenty-one patients with double mutations were treated with EGFR-TKIs. The objective response rate (ORR) was 23.8%, and the disease control rate (DCR) was 76.2%. In the first-line therapy, the ORR was 16.7%, and the DCR was 66.7%. In univariate analysis, gender, smoking-status, TKI type and TKI response were correlated with progression-free survival, and patients with ECOG 0-1 had longer overall survival. CONCLUSIONS: Patients with double mutations had a low objective response rate when treated with EGFR-TKIs compared with single EGFR exon 19 or exon 21 mutations.

Down-regulation of c-fos by shRNA sensitizes adriamycin-resistant MCF-7/ADR cells to chemotherapeutic agents via P-glycoprotein inhibition and apoptosis augmentation.

Multidrug resistance (MDR) is a major hurdle in the treatment of cancer. Research indicated that the main mechanisms of most cancers included so-called "pump" (P-glycoprotein, P-gp) and "non-pump" (apoptosis) resistance. Identification of novel signaling molecules associated with both P-gp and apoptosis will facilitate the development of more effective strategies to overcome MDR in tumor cells. Since the proto-oncogene c-fos has been implicated in cell adaptation to environmental changes, we analyzed its role in mediating "pump" and "non-pump" resistance in MCF-7/ADR, an adriamycin (ADR)-selected human breast cancer cell line with the MDR phenotype. Elevated expression of c-fos in MCF-7/ADR cells and induction of c-fos by ADR in the parental drug-sensitive MCF-7 cells suggested a link between c-fos and MDR phenotype. Down-regulation of c-fos expression via shRNA resulted in sensitization of MCF-7/ADR cells to chemotherapeutic agents, including both P-gp and non-P-gp substrates. Further results proved that c-fos down-regulation in MCF-7/ADR cells resulted in decreased P-gp expression and activity, enhanced apoptosis, and altered expression of apoptosis-associated proteins (i.e., Bax, Bcl-2, p53, and PUMA). All above facts indicate that c-fos is involved in both P-gp- and anti-apoptosis-mediated MDR of MCF-7/ADR cells. Based on these results, we propose that c-fos may represent a potential molecular target for resistant cancer therapy, and suppressing c-fos gene expression may therefore be an effective means to temper breast cancer cell's MDR to cytotoxic chemotherapy.

Phase III, randomized, open-label, first-line study in Asia of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer: evaluation of patients recruited from mainland China.

AIM: In the IRESSA Pan-Asia Study (IPASS), 1217 patients in East Asia with pulmonary adenocarcinoma who were never-smokers or ex/light-smokers received first-line gefitinib (250 mg/day) or carboplatin/paclitaxel (area under the curve 5/6; 200 mg/m(2) ). Efficacy analyses were pre-planned in patients in China. METHODS: In China, 372 patients (30.6% of the overall group) were randomized. The primary end-point was progression-free survival (PFS). Secondary end-points were overall survival (OS), objective response rate (ORR), health-related quality of life (HRQoL), symptom improvement, safety and tolerability. RESULTS: For patients in China, PFS did not significantly differ from the overall IPASS population (interaction test P= 0.427). PFS was numerically longer (hazard ratio [HR] 0.79; 95% CI 0.62-1.01; P= 0.065; median PFS 6.8 months for both treatments) and ORR significantly higher (ORR 44.6 vs 29.8%; odds ratio 1.88; 95% CI 1.22-2.89; P= 0.004) for gefitinib than carboplatin/paclitaxel. OS (mature data) was similar for both treatments (HR 0.92; 95% CI 0.73-1.17; P= 0.511; median OS gefitinib 18.1 months vs 18.3 months carboplatin/paclitaxel). HRQoL improvement rates favored gefitinib; symptom improvement rates were similar for both treatments. Gefitinib had a more favorable tolerability profile than carboplatin/paclitaxel. Efficacy by epidermal growth factor receptor biomarker status (exploratory analyses) was difficult to interpret due to low patient numbers with known biomarker status. CONCLUSION: For the Chinese subgroup of IPASS, gefitinib demonstrated improved PFS and ORR, similar OS, higher HRQoL, similar symptom improvement rates and a more favorable tolerability profile than carboplatin/paclitaxel, generally consistent with the overall IPASS population.

[A study on the long-term non-small cell lung cancer survivors in the Expand Access Program of gefitinib in China].

BACKGROUND AND OBJECTIVE: The Expand Access Program (EAP) of Iressa(gefitinib, ZD1839) in China was initiated in 2001 with the aim of providing gefitinib to non-small cell lung cancer (NSCLC) patients who failed to respond to standard treatment or who could not tolerate chemotherapy. The primary objective was to describe the quality of life (QoL), tumor control status, drug safety, and clinical/genomic features of active long-term survivors enrolled in the EAP. The secondary objective was to determine the clinical characteristics of long-term survivors in the EAP program. METHODS: In this descriptive observational study, data were collected based on epidemiological research methods. The data of patients who were actively participating in the EAP and still undergoing gefitinib treatment were collected in a cross-sectional manner to reflect the current status of each patient. Meanwhile, the data of patients who had been on gefitinib treatment for more than three years and had already been terminated from the EAP or those who were fast progressors were collected retrospectively. RESULTS: A total of 934 patients were screened in the EAP database. Among these patients, 25 were active long-term survivors still enrolled in the EAP and 34 were long-term survivors who had been terminated from the program. These 59 patients were enrolled in 15 different centers in China, and the remaining 875 patients were fast progressors. The median scores for the Functional Assessment of Cancer Therapy-Lung (FACT-L), Trial Outcome Index (TOI), and Lung Cancer Subscale (LCS) of the 25 long-term survivors were 64.5, 37 and 12.5, respectively. The performance status 0-1 accounted for 91.6% of the data observed during the cross-sectional survey. For active long-term survivors, the objective response rate was 37.5%, the disease control rate was 87.5%, and the median duration of response time was almost 68 months. In the long-term survivor group, no serious and new adverse events were reported. Patients who were aged under 65 years (68.5%), affected with adenocarcinoma (81.4%), female (55.9%), or had never smoked (71%) accounted for majority of the long-term survivors. The percentage of females was significantly higher in the long-term survivor group than in the fast progressor group (P=0.02). Three tissue samples were collected from each of the 24 active long-term survivors, and one patient was found to be positive of EGFR mutation. Twenty-two blood samples were also collected, and one patient tested positive for EGFR mutation. The Ki67 protein expression was also tested in three tissue samples, and two of these were found positive for Ki67 protein expression, with a response duration time of over 73 months. CONCLUSIONS: A 250 mg dose of gefitinib offers good QoL and is safe for advanced NSCLC long-term survivors even after more than three years of treatment. According to the evaluation of the current tumor control statuses of patients, gefitinib demonstrates good efficacy in these active long-term survivors.

A novel indirubin derivative PHII-7 potentiates adriamycin cytotoxicity via inhibiting P-glycoprotein expression in human breast cancer MCF-7/ADR cells.

Multidrug resistance (MDR) is a major impediment to the effective chemotherapy of many human malignancies, and novel MDR reversal agents are desirable for combination therapy to reduce MDR, enhance anti-tumor activity and reduce side effects. Overexpression of P-glycoprotein (P-gp) is the most prevalent cause of MDR in cancer tissues, and resistance to apoptosis is a common characteristic for the multidrug resistant cancer cells. Our group has synthesized a novel potent anti-tumor indirubin derivative, PHII-7. In this study, MCF-7/ADR cells, an adriamycin (ADR)-selected human breast tumor cell line with the MDR phenotype, were used to investigate the anticancer properties of this novel indirubin derivative. Cytotoxicity and apoptosis assays showed that PHII-7 significantly inhibited cell growth, induced apoptosis, potentiated ADR cytotoxicity and restored chemotherapy sensitivity in the MDR cancer cells. Further studies indicated that by down-regulation of P-gp expression, PHII-7 partially inhibited P-gp efflux pump function and increased intracellular accumulation of Rhodamine 123, a P-gp substrate. These results provide a biochemical basis for possible clinical application of PHII-7 alone or in combination with conventional antineoplastic agents in the treatment MDR tumors.