Effects of airborne pollen on allergic rhinitis and asthma across different age groups in Beijing, China.

In the context of global warming and rapid urbanization, pollen has become a significant public health concern for Chinese citizens. However, there is a paucity of epidemiological research on the impact of pollen on allergen-linked diseases, such as allergic rhinitis and asthma, in China. Using data from the Beijing Chaoyang Hospital between 2013 and 2019, which included allergic rhinitis and asthma incidence, meteorological records, and air pollution data, we employed a Generalized Additive Model (GAM) to examine the relationship between overall and type-specific pollen concentrations in relation to varying population exposures. We found that increased overall pollen concentrations significantly increased the risks of allergic rhinitis and asthma in diverse populations. Notably, the risk of allergic rhinitis was higher than that of asthma at equivalent pollen concentrations. Seasonal trends indicated that spring pollen peaks, primarily from trees, were associated with a lower risk of both allergic rhinitis and asthma than autumn peaks, predominantly from weeds. This study underscores the importance of identifying pollen species that pose heightened risks to different demographic groups across seasons, thereby providing targeted interventions for public health agencies.

NDFIP1 limits cellular TAZ accumulation via exosomal sorting to inhibit NSCLC proliferation

NDFIP1 has been previously reported as a tumor suppressor in multiple solid tumors, but the function of NDFIP1 in NSCLC and the underlying mechanism are still unknown. Besides, the WW domain containing proteins can be recognized by NDFIP1, resulted in the loading of the target proteins into exosomes. However, whether WW domain-containing transcription regulator 1 (WWTR1, also known as TAZ) can be packaged into exosomes by NDFIP1 and if so, whether the release of this oncogenic protein via exosomes has an effect on tumor development has not been investigated to any extent. Here, we first found that NDFIP1 was low expressed in NSCLC samples and cell lines, which is associated with shorter OS. Then, we confirmed the interaction between TAZ and NDFIP1, and the existence of TAZ in exosomes, which requires NDFIP1. Critically, knockout of NDFIP1 led to TAZ accumulation with no change in its mRNA level and degradation rate. And the cellular TAZ level could be altered by exosome secretion. Furthermore, NDFIP1 inhibited proliferation in vitro and in vivo, and silencing TAZ eliminated the increase of proliferation caused by NDFIP1 knockout. Moreover, TAZ was negatively correlated with NDFIP1 in subcutaneous xenograft model and clinical samples, and the serum exosomal TAZ level was lower in NSCLC patients. In summary, our data uncover a new tumor suppressor, NDFIP1 in NSCLC, and a new exosome-related regulatory mechanism of TAZ.

Desuccinylation of pyruvate kinase M2 by SIRT5 contributes to antioxidant response and tumor growth.

Tumor cells trends to express high level of pyruvate kinase M2 (PKM2). The inhibition of PKM2 activity is needed for antioxidant response by diverting glucose flux into the pentose phosphate pathway and thus generating sufficient reducing potential. Here we report that PKM2 is succinylated at lysine 498 (K498) and succinylation increases its activity. SIRT5 binds to, desuccinylates and inhibits PKM2 activity. Increased level of reactive oxygen species (ROS) decreases both the succinylation and activity of PKM2 by increasing its binding to SIRT5. Substitution of endogenous PKM2 with a succinylation mimetic mutant K498E decreases cellular NADPH production and inhibits cell proliferation and tumor growth. Moreover, inhibition of SIRT5 suppresses tumor cell proliferation through desuccinylation of PKM2 K498. These results reveal a new mechanism of PKM2 modification, a new function of SIRT5 in response to oxidative stress which stimulates cell proliferation and tumor growth, and also a potential target for clinical cancer research.

Inhibition effects of gefitinib on non-small cell lung cancer cell lines in vitro / 肿瘤研究与临床

Objective To explore the mechanism of gefitinib in the treatment of non-small cell lung cancer (NSCLC) cell lines in vitro. Methods The effects of the gefitinib in five human NSCLC cell lines (A549, SPC-A-1, H460, H1229, 95D) were studied. The inhibition of cell proliferation in each group were measured by CCK8;The status of apoptosis cells were observed using flow cytometry after PI marked;invasion of lung cancer cell inhibited by gefitinib were assessed by transwell technique;The drug was detected by western blot on the proliferation-related signaling protein. Results The proliferation and invasive capacity of NSCLC cells were inhibited by gefitinib (P < 0.05). In gefitinib group, the apoptosis rates of A549 [(9.6±0.73) %]and SPC-A-1[(14.3±1.12) %]were higher than that of control group[(3.1±0.29) %](t =11.16,P =0.001;t =4.726, P =0.009). Expression of p-AKT, p-EGFR, p-MAPK protein levels were significantly down regulated in A549 cells when gefitinib was given after 72 hours (t =6.656, P =0.003;t =16.441, P =0.0001;t =3.736, P =0.020). Conclusion Gefitinib can inhibit the proliferation and invasion of lung cancer cell, also can induce apoptosis in vitro and most likely to contribute to the inhibition of key enzymes in EGFR signaling transduction pathway.

New hot spots on biomarkers for non-small cell lung cancer / 肿瘤研究与临床

As a hot topic, biomarkers can provide reliable evidence for the individualized treatment of non-small cell lung cancer. With the further study of molecular biology and development of new drugs,biomarkers have shown a broad prospect in clinical application. Combining with the research in recent years,this review describes the progress in biomarkers for non-small-cell lung cancer.

Advance on targeted therapy for the treatment of non-small cell lung cancer / 肿瘤研究与临床

Recent progress in molecular biology has enabled us to better understand the molecular mechanism underlying pathogenesis of human malignancy including lung cancer, the advent of therapies based on mechanisms that target critical molecular pathways of tumors has evoked considerable interest. The therapeutic index is high, and optimally effective treatment can be achieved at a dose below the maximal tolerated dose,giving us a better understanding of the human lung cancer. This review focuses on the advance of targeted therapy for the first-line, second-line treatment or the maintenance treatment of non-small cell lung cancer.

Study of sequential erlotinib and chemotherapy as first-line treatment for advanced non-small-cell lung cancer / 肿瘤研究与临床

Objective To observe the short-term efficacy and safety of sequential administration of erlotinib and chemotherapy in unselected, chemonaive patients with advanced non-small-cell lung cancer (NSCLC). Methods Previously-untreated patients (n=23) with stage Ⅲ_B/Ⅳ NSCLC and ECOG PS of 0/1 received erlotinib (150 mg/d) on days 15-28 of a 4-week cycle that included gemcitabine (1250 mg/m~2, days 1 and 8), and either cisplatin (75 mg/m~2, day 1) or carboplatin (AUC=5, day 1). The primary end points were tumor response rate and safety. Results 23 patients received a total of 95 cycles of treatment, and all were evaluable for efficacy and toxicity. The overall response rate was 30.4%, 0 case achieved complete responses (CR), 7 cases (30.4%) achieved partial responses (PR), 14 cases (60.9 %) achieved stable disease (SD), 2 cases (8.7 %) achieved progression disease (PD). The disease control rate was 91.3 %. The sequential administration of erlotinib following gemcitabine/platinum chemotherapy was well tolerated. The major grade 3 treatment-related adverse events were eutropenia (13.4%), rash (8.7%), nausea (8.7%) and thrombocytopenia (8.7%). No treatment-related interstitial lung disease. Conclusion equential administration of erlotinib following gemcitabine/platinum chemotherapy was effective, and the toxicity was tolerable. This treatment strategy warrants further investigation.

Docetaxel for 15 patients with paclitaxel-resistant advanced non-small cell lung cancer / 肿瘤研究与临床

Objective To determine the efficacy and toxicity of docetaxel in patients with paclitaxel-resistant advanced non-small cell lung cancer (NSCLC). Methods The clinical data from 15 patients with NSCLC who were admitted in the Shanghai Chest Hospital from January 2005 to May 2008 were retrospectively analyzed. The effects and toxicities of the second-line treatment were assessed. The progression-free survival time(PFS) and overall survival time(OS) were analyzed. Results The disease control rate was 66.7 %, with a progression-free survival time of 6 months, and a overall survival time of 17.3 months. The 1-year survival rate was 63.3 %. The toxic effects were as expected. Conclusion The doeetaxel-based agent is active in patients with paelitaxel-resistant advanced NSCLC.

The value of sequential, alternating and consolidation chemotherapy in advanced non-small-cell lung cancer / 肿瘤研究与临床

A platinum-based doublet with a third-generation agent represents the standard first-line treatment for advanced non-small cell lung cancer patients with good performance status (PS). Traditional chemotherapy provides response rates of 20 %-40 % and a median survival of 8-10 months. In an attempt to improve its outcome, alternative schedules have been proposed, namely sequential, alternating, and maintenance therapy. Sequential chemotherapy with a platinum-based doublet followed by a single agent is feasible in patients with good PS; The use of sequential single agents is an option for elderly and frail patients unsuitable for a platinum-based combination. Based on trials published so far, it is unlikely that an alternating chemotherapy strategy will be proved superior to standard chemotherapy in patients with good PS.Consolidation chemotherapy may provide additional benefit for patients achieving disease control after standard first-line chemotherapy.

New developments in advanced non-small cell lung cancer / 中国癌症杂志

For advanced lung cancer,multimodality treatment is the main stream.Patients with locally advanced disease may have long-term survival rate with radiation therapy combined with chemotherapy.Patients with advanced metastatic disease may achieve improved survival and palliation of symptoms with chemotherapy.Here we reviewed the recent development in treatment for advanced non-small cell lung cancer.

Targeted therapy of lung cancer-data from Asia / 中国癌症杂志

3 months. Female gender, adenocarcinoma history, non-smoking history, good PS and the presence of multiple lung metastases are associated with improved responsiveness to Gefitinib. Reflecting the results of previous clinical trials, the reports indicate that Gefitinib is generally well tolerated by Asian patients. The incidence of interstitial lung disease appears to be higher in Japanese than non-Japanese patients, although the reason for this is not clear. Recent findings regarding Erlotinib and other targeted therapy among Asian patients are discussed.