Search

Background: Non-small cell lung cancer (NSCLC) remains at the forefront of new cancer cases, and there is an urgent need to find new treatments or improve the efficacy of existing therapies. In addition to the application in the field of cerebrovascular diseases, recent studies have revealed that tanshinone IIA (Tan IIA) has anticancer activity in a variety of cancers., Purpose: To investigate the potential anticancer mechanism of Tan IIA and its impact on immunotherapy in NSCLC., Methods: Cytotoxicity and colony formation assays were used to detect the Tan IIA inhibitory effect on NSCLC cells. This research clarified the mechanisms of Tan IIA in anti-tumor and programmed death-ligand 1 (PD-L1) regulation by using flow cytometry, transient transfection, western blotting and immunohistochemistry (IHC) methods. Besides, IHC was also used to analyze the nuclear factor of activated T cells 1 (NFAT2) expression in NSCLC clinical samples. Two animal models including xenograft mouse model and Lewis lung cancer model were used for evaluating tumor suppressive efficacy of Tan IIA. We also tested the efficacy of Tan IIA combined with programmed cell death protein 1 (PD-1) inhibitors in Lewis lung cancer model., Results: Tan IIA exhibited good NSCLC inhibitory effect which was accompanied by endoplasmic reticulum (ER) stress response and increasing Ca 2+ levels. Moreover, Tan IIA could suppress the NFAT2/ Myc proto oncogene protein (c-Myc) signaling, and it also was able to control the Jun Proto-Oncogene(c-Jun)/PD-L1 axis in NSCLC cells through the c-Jun N-terminal kinase (JNK) pathway. High NFAT2 levels were potential factors for poor prognosis in NSCLC patients. Finally, animal experiments data showed a stronger immune activation phenotype, when we performed treatment of Tan IIA combined with PD-1 monoclonal antibody., Conclusion: The findings of our research suggested a novel mechanism for Tan IIA to inhibit NSCLC, which could exert anti-cancer effects through the JNK/NFAT2/c-Myc pathway. Furthermore, Tan IIA could regulate tumor PD-L1 levels and has the potential to improve the efficacy of PD-1 inhibitors., Competing Interests: Declaration of competing interest All authors declare that they have no financial conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier GmbH.)

Background: Chronic diseases such as tumors and autoimmune disorders are closely linked to metabolism and immunity and require conflicting treatment methods. AMPK can regulate cell growth and inflammation through energy metabolism. Sinomenine is a compound extracted from the traditional Chinese herb sinomenium acutum (Thunb.) Rehd. et Wils. It has been used to treat NSCLC (non-small-cell lung cancer) and RA (rheumatoid arthritis) in some studies, but with limited understanding of its mechanisms., Objective: This study aims to examine the inhibitory effect of sinomenine hydrochloride (SH) on NSCLC and RA and to understand the underlying joint mechanisms., Results: The results indicate that SH has a cytotoxic effect specifically on tumor cells, but not on normal cells. SH was found to induce cell apoptosis by activating the AMPK-mTOR pathway. Additionally, in autoimmune disease cell models, SH was shown to reduce the growth of RA-FLS cells by inhibiting the phosphorylation of AMPK, while having no effect on normal macrophages. Moreover, in vivo studies also showed that SH could reduce the production of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 and slow the development of adjuvant arthritis in rats. Furthermore, SH was found to significantly suppress tumor growth in a tumor xenograft experiment in mice., Conclusions: This study provides new insights into the treatment of tumors and autoimmune diseases by demonstrating that SH can selectively inhibit the growth of NSCLC cells and the progression of RA through activation of the AMPK pathway., Competing Interests: Declaration of Competing Interests Run Ze Li, Xiao Xiang Guan, Xuan Run Wang, Wei-Qian Bao, Li-Rong Lian, Seong Wang Choi, Fang Yuan Zhang, Pei-Yu Yan, Elaine Lai Han Leung, Hu-Dan Pan and Liang Liu declare that they have no conflict of interest or financial conflicts to disclose., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Nearly half of all Asian non-small cell lung cancer (NSCLC) patients harbour epidermal growth factor receptor (EGFR) mutations, and first-generation EGFR tyrosine kinase inhibitors (TKIs) are one of the first-line treatments that have improved the outcomes of these patients. Unfortunately, 20% of these patients can not benefit from the treatment. The basis of this primary resistance is poorly understood. Therefore, overcoming EGFR-TKI primary resistance and maintaining the efficacy of TKIs has become a key issue. β-Elemene, a sesquiterpene compound extracted from Curcuma aromatica Salisb. (wenyujing), has shown potent antitumor effects. In this research, we found that β-elemene combined with erlotinib enhanced the cytotoxicity of erlotinib to primary EGFR-TKI-resistant NSCLC cells with EGFR mutations and that ferroptosis was involved in the antitumor effect of the combination treatment. We found that lncRNA H19 was significantly downregulated in primary EGFR-TKI-resistant NSCLC cell lines and was upregulated by the combination treatment. Overexpression or knockdown of H19 conferred sensitivity or resistance to erlotinib, respectively, in both in vitro and in vivo studies. The high level of H19 enhanced the cytotoxicity of erlotinib by inducing ferroptosis. In conclusion, our data showed that β-elemene combined with erlotinib could enhance sensitivity to EGFR-TKIs through induction of ferroptosis via H19 in primary EGFR-TKI-resistant lung cancer, providing a promising strategy to overcome EGFR-TKI resistance in NSCLC patients., Competing Interests: Declarations of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Despite recent advances in diagnosis and therapeutic strategies, treatment of non-small-cell lung cancer (NSCLC) remains unsatisfactory in terms of prognosis. Andrographolide (AD), a principal active component of Andrographis paniculata (Burm.f.) Nees, exerts anti-cancer therapeutic properties. AD has been used for centuries in China for clinical treatment of viral infections. However, the pharmacological biology of AD in NSCLC remains unknown. In this study, AD regulated autophagy and PD-L1 expression in NSCLC. Molecular dynamics simulations indicated that AD bound directly to signal transducer and activator of transcription-3 (STAT3) with high affinity. Proteomics analysis indicated that AD reduced the expression of tumour PD-L1 in NSCLC by suppressing JAK2/STAT3 signalling. AD modulated the P62-dependent selective autophagic degradation of PD-L1 by inhibiting STAT3 phosphorylation. In vivo study revealed that AD suppressed tumour growth in H1975 xenograft mice and Lewis lung carcinoma cell models, and better efficacy was obtained at higher concentrations. AD prolonged the survival time of the mice and enhanced the treatment efficacy of anti-PD-1 mAb immunotherapy by stimulating CD8 + T cell infiltration and function. This work elucidated the specific mechanism by which AD inhibited NSCLC. Treatment with the combination of AD and anti-PD-1 mAb immunotherapy could be a potential strategy for patients with NSCLC., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Currently, the identification of accurate biomarkers for the diagnosis of patients with early-stage lung cancer remains difficult. Fortunately, metabolomics technology can be used to improve the detection of plasma metabolic biomarkers for lung cancer. In a previous study, we successfully utilised machine learning methods to identify significant metabolic markers for early-stage lung cancer diagnosis. However, a related research platform for the investigation of tumour metabolism and drug efficacy is still lacking., Hypothesis/purpose: A novel methodology for the comprehensive evaluation of the internal tumour-metabolic profile and drug evaluation needs to be established., Methods: The optimal location for tumour cell inoculation was identified in mouse chest for the non-traumatic orthotopic lung cancer mouse model. Microcomputed tomography (micro-CT) was applied to monitor lung tumour growth. Proscillaridin A (P.A) and cisplatin (CDDP) were utilised to verify the anti-lung cancer efficacy of the platform. The top five clinically valid biomarkers, including proline, L-kynurenine, spermidine, taurine and palmitoyl-L-carnitine, were selected as the evaluation indices to obtain a suitable lung cancer mouse model for clinical metabolomics research by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)., Results: The platform was successfully established, achieving 100% tumour development rate and 0% surgery mortality. P.A and CDDP had significant anti-lung cancer efficacy in the platform. Compared with the control group, four biomarkers in the orthotopic model and two biomarkers in the metastatic model had significantly higher abundance. Principal component analysis (PCA) showed a significant separation between the orthotopic/metastatic model and the control/subcutaneous/KRAS transgenic model. The platform was mainly involved in arginine and proline metabolism, tryptophan metabolism, and taurine and hypotaurine metabolism., Conclusion: This study is the first to simulate clinical metabolomics by comparing the metabolic phenotype of plasma in different lung cancer mouse models. We found that the orthotopic model was the most suitable for tumour metabolism. Furthermore, the anti-tumour drug efficacy was verified in the platform. The platform can very well match the clinical reality, providing better lung cancer diagnosis and securing more precise evidence for drug evaluation in the future., (Copyright © 2021. Published by Elsevier GmbH.)

Background: Lung cancer has become the principal cause of cancer-related deaths. Emodin is a Chinese herb-derived compound extracted from the roots of Rheum officinale that exhibits numerous pharmacological characteristics. Secretory phospholipase A2-IIa (sPLA2-IIa) is overexpressed in cancers and plays an important role in cancer development., Purpose: This study aims to investigate the anti-tumor mechanism of emodin in non-small-cell lung cancer (NSCLC)., Methods: MTT assay was applied to detect the sensitivity of emodin to NSCLC cell line. Flow cytometry was used to examine the effect of emodin on cell cycle distribution and evaluate ROS level and apoptosis. Western blot analysis was utilised to examine the expression levels of sPLA2-IIa, PKM2, and AMPK and its downstream pathways induced by emodin. Enzyme inhibition assay was applied to investigate the inhibitory effect of emodin on sPLA2-IIa. The anticancer effect of emodin was also detected using an in vivo model., Results: Emodin significantly inhibited NSCLC proliferation in vivo and in vitro and was relatively less cytotoxic to normal lung cell lines. Most importantly, emodin inhibited the proliferation of KRAS mutant cell lines by decreasing the expression of sPLA2-IIa and NF-κB pathways. Emodin also inhibited mTOR and AKT and activated the AMPK pathway. Furthermore, emodin induced apoptosis, increased the reactive oxygen species (ROS) level, and arrested the cell cycle., Conclusion: Emodin exhibited a novel anti-tumor mechanism of inhibiting the proliferation of KRAS mutant cell lines by decreasing the expression levels of sPLA2-IIa and NF-κB pathways. Hence, emodin can potentially serve as a therapeutic target in NSCLC., (Copyright © 2021. Published by Elsevier GmbH.)

Upregulated expression of immune checkpoint molecules correlates with exhausted phenotype and impaired function of cytotoxic T cells to evade host immunity. By disrupting the interaction of PD-L1 and PD1, immune checkpoint inhibitors can restore immune system function against cancer cells. Growing evidence have demonstrated apigenin and luteolin, which are flavonoids abundant in common fruits and vegetables, can suppress growth and induce apoptosis of multiple types of cancer cells with their potent anti-inflammatory, antioxidant and anticancer properties. In this study, the effects and underlying mechanisms of luteolin, apigenin, and anti-PD-1 antibody combined with luteolin or apigenin on the PD-L1 expression and anti-tumorigenesis in KRAS-mutant lung cancer were investigated. Luteolin and apigenin significantly inhibited lung cancer cell growth, induced cell apoptosis, and down-regulated the IFN-γ-induced PD-L1 expression by suppressing the phosphorylation of STAT3. Both luteolin and apigenin showed potent anti-cancer activities in the H358 xenograft and Lewis lung carcinoma model in vivo, and the treatment with monoclonal PD1 antibody enhanced the infiltration of T cells into tumor tissues. Apigenin exhibited anti-tumor activity in Genetically engineered KRASLA2 mice. In conclusion, both apigenin and luteolin significantly suppressed lung cancer with KRAS mutant proliferation, and down-regulated the IFN-γ induced PD-L1 expression. Treatment with the combination of PD-1 blockade and apigenin/luteolin has a synergistic effect and might be a prospective therapeutic strategy for NSCLC with KRAS-mutant., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Currently, conventional methods of treating non-small cell lung cancer (NSCLC) have many disadvantages. An alternative effective therapy with minimal adverse reactions is urgently needed. Weijing decoction (WJD), which is a classic ancient Chinese herbal prescription, has been used successfully to treat pulmonary system diseases containing lung cancer in the clinic. However, the key active component and target of Weijing decoction are still unexplored. Therefore, for the first time, our study aims to investigate the pharmacological treatment mechanism of Weijing decoction in treating NSCLC via an integrated model of network pharmacology, metabolomics and biological methods. Network pharmacology results conjectured that Tricin is a main bioactive component in this formula which targets PRKCA to suppress cancer cell growth. Metabolomics analysis demonstrated that sphingosine-1-phosphate, which is regulated by sphingosine kinase 1 and sphingosine kinase 2, is a differential metabolite in plasma between the WJD-treated group and the control group, participating in the sphingolipid signaling. In vitro experiments demonstrated that Tricin had vital effects on the proliferation, pro-apoptosis, migration and colony formation of Lewis lung carcinoma cells. Through a series of validation assays, Tricin inhibited the tumor growth mainly by suppressing PRKCA/SPHK/S1P signaling and antiapoptotic signaling. On the other hand, Weijing formula could inhibit the tumor growth and prolong the survival time. A high dosage of Tricin was much more potent in animal experiments. In conclusion, we confirmed that Weijing formula and its primary active compound Tricin are promising alternative treatments for NSCLC patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Non-small cell lung cancer (NSCLC) is one of the most frequently diagnosed cancers and the leading causes of cancer death worldwide. Therefore, new therapeutic agents are urgently needed to improve patient outcomes. Plumbagin (PLB), a natural sesquiterpene present in many Chinese herbal medicines, has been reported for its anti-cancer activity in various cancer cells. In this study, the effects and underlying mechanisms of PLB on the tumorigenesis of NSCLC were investigated. PLB dose-dependently inhibited the growth of NSCLC cell lines. PLB promoted ROS production, activated the endoplasmic reticulum (ER) stress pathway, and induced cell apoptosis, accompanied by the decreased expression level of ADP-ribosylation factor 1 (ARF1) in NSCLC cancer cells, and those effects of PLB could be reversed by the pretreatment with N-acetyl-L-cysteine (NAC). More importantly, the calcium chelator (BM) significantly reversed PLB-induced cell apoptosis. Furthermore, PLB significantly inhibited the growth of both H1975 xenograft and LLC1 tumors and exhibited antitumor activity by enhancing the number and the effector function of CD8 + T cells in KRASLA2 mice model and the LLC1 xenograft. Our findings suggest that PLB exerts potent antitumor activity against NSCLC in vitro and in vivo through ARF1 downregulation and induction of antitumor immune response, indicating that PLB is a new novel therapeutic candidate for the treatment of patients with NSCLC., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To explore the role of CT scan for the diagnosis of lung metastasis in stage Ⅲ gestational trophoblastic neoplasia (GTN) . Methods: To figure out the role of CT scan for lung metastasis in GTN initial diagnosis, treatment and follow-up, 93 GTN patients with lung metastasis from January, 2015 to December, 2016 were retrospectively analyzed in Obstetrics and Gynecology Hospital of Fudan University. Results: (1) Among 93 GTN patients with lung metastasis, 70 patients with the International Federation of Gynecology and Obstetrics (FIGO) score ≤6 were defined as low risk GTN and 23 patients score score ≥7 were defined as high risk GTN. Forty nine patients had negative chest X-ray findings and 39 cases with pulmonary lesions were identified both by chest X-ray compared to CT scan. Five cases were excluded due to no consensus could make for the results of chest X-ray. The true positive rate of chest X-ray for lung metastasis were 41% (29/70) in low risk GTN and 43% (10/23) in high risk GTN patients without statistical difference (χ(2)=0.090, P= 0.925) . For those patients with positive chest CT scan and negative chest X-ray finding, pulmonary lesions in 32 (65%, 32/49) cases were blocked by heart, chest wall or diaphragm in chest X-ray. Seventeen (35%,17/49) patients with lung lesions less than 5 mm had negative chest X-ray results due to the lower sensitivity compared to CT scan. (2) In 88 patients with stage Ⅲ, 78 patients had successful initial treatment, but 4 of them were recurrence in twelve months follow-up. Ten patients were chemotherapy resistance for the initial treatment. The initial chemotherapy remission rate in low risk GTN patients was higher than that in high risk ones (χ(2)=4.911, P= 0.027) . In 49 cases with negative chest X-ray, there was no correlation with the rate of remission,chemotherapy resistance and recurrence in stage Ⅲ patients ( P> 0.05) . (3) For those patients who had poorly response to initial chemotherapy, the diameters of lesions in lung were unchanged or increased during the treatment, form (5.1±4.1) mm to (7.4±2.8) mm. The pulmonary lesions were continuously shrunk from (7.8±5.3) mm to (4.7±4.4) mm for those patients with complete and partial remission including the recurrent GTN patients ( Z=- 2.713, P= 0.007) . Conclusions: Patients with GTN in stage Ⅲ have down staging if only use chest X-ray for imaging at the initial diagnosis. Chest CT scan is recommended for primary imaging evaluation of FIGO staging in qualified medical organization. For those patients with persistent abnormal serum hCG level and negative chest X-ray, chest CT scan is strongly recommended to identify the persist or resistant lung lesions and follow up.

Objective: MicroRNAs are critical regulators in tumorigenesis. This study is aimed at investigating the function of miR-202 in the proliferation of human lung cancer cells., Patients and Methods: Lung cancer tissues and paired adjacent normal tissues were collected from 20 patients; the expression of miR-202 was tested by Realtime PCR; cell proliferation and cell cycle distribution were determined by CCK-8 assay and flow cytometry, respectively; apoptosis was determined by TUNEL assay and Western blot analysis of cleaved-PARP; the relationship between miR-202 and cyclin D1 mRNA 3'UTR was determined by luciferase activity assay., Results: MiR-202 was significantly reduced in lung cancer tissues compared with the adjacent normal tissues. Overexpression of miR-202 inhibited cell proliferation and induced a G0/G1 cell cycle arrest and apoptosis. Luciferase activity assay and Western blot analysis together showed that miR-202 can bind to the 3'UTR of cyclin D1 mRNA directly and inhibits cyclin D1 expression at the protein level. In addition, restoration of cyclin D1 expression partially abolished cell cycle arrest and apoptosis induced by miR-202., Conclusions: MiR-202 is constantly downregulated in lung cancer and functions as a tumor suppressive gene via targeting cyclin D1. Modulating the level of miR-202 may be a novel therapeutic method for lung cancer.

Objectives: Previous epidemiological studies had limited power to investigate the joint effects of individual environmental risk factors and familial susceptibility to lung cancer. This study aimed to address this shortcoming., Methods: We recruited 345 never smoking lung cancer cases and 828 community referents. We developed a collective environmental exposure index by assigning a value of 1 to subjects at high risks regarding environmental risk factors and 0 otherwise, and then summed over using weights equivalent to the excess odds ratio. Potential additive and multiplicative interactions between environmental exposure index and family cancer history were examined., Results: Compared with "low environmental exposure and without family cancer history", the odds ratio was 6.80 (95% confidence interval = 3.31-13.98) for males who had high environmental exposures but without family cancer history, whereas it increased to 30.61 (95% confidence interval = 9.38-99.87) if they also had a positive family history. The corresponding associations became weaker in never smoking females. No multiplicative interaction was observed for both genders and an additive interaction was restricted among males., Conclusions: This study developed a novel environmental exposure index that offers sufficient interest deserving further studies on the interactions between environmental exposures and familial susceptibility to lung cancer risk.

Slug protein is a key regulator of epithelial-mesenchymal transition, but its expression in cancer is less well studied. To evaluate the expression of slug, E-cadherin and vimentin in adenocarcinoma cells from malignant pleural effusions, we analyzed 121 malignant pleural fluid specimens. Twenty-eight nonmalignant pleural fluid specimens were analyzed as control. Besides clinical cytological diagnosis tests, immunofluorescence, immunocytochemistry and Western blotting methods were used. Results showed strong membrane staining of E-cadherin in adenocarcinoma cells from pleural fluid. Slug mainly showed nucleus staining. Cytoplasma positive of vimentin was found in adenocarcinoma cells isolated from pleural fluid. Slug, E-cadherin and vimentin expression was found in 43/121 (36%), 87/121 (72%) and 102/121 (84%) cases, respectively. Our data showed elevated levels of slug were accompanied by down regulation of E-cadherin and the expression of vimentin in adenocarcinoma cells. In addition, there was no relationship between slug expression and patient's age or gender or tumor site. Hyperplasia epithelium cells from nonmalignant pleural fluid were uniformly negative for E-cadherin and slug. In conclusion, the results demonstrated the inverse expression of slug and E-cadherin in the majority of malignant pleural fluid cases compared with nonmalignant pleural fluid. The slug protein may be helpful to access the prognosis of patients with pleural fluid., (Copyright © 2011 Wiley Periodicals, Inc.)

Objectives: To examine pulmonary tuberculosis (PTB) infection and lung cancer mortality among workers with asbestosis in Hong Kong., Study Design: Historical cohort study., Methods: All 124 male incident cases of asbestosis registered at the Pneumoconiosis Clinic of the Tuberculosis and Chest Service of the Department of Health between 1981 and 2008 were recruited and followed-up until 2008 to ascertain vital status and underlying causes of death. Standardized mortality ratios (SMRs) were calculated using the person-year method. Axelson's indirect method was used to adjust for the potential confounding effect of cigarette smoking., Results: Forty-five patients (36.29%) had a history of PTB at the time of asbestosis diagnosis. The SMR of lung cancer was 5.22 [95% confidence interval (CI) 1.08-15.25] for subjects with a history of PTB, and this was reduced to 2.35 (95% CI 0.49-6.85) after indirect adjustment for smoking. Among asbestosis workers without a history of PTB, the SMR after indirect adjustment for smoking was 4.25 (95% CI 1.55-9.25) and 5.92 (95% CI 1.92-13.79) for those with comorbidities and those without comorbidities, respectively. Compared with other workers, those with a history of PTB had the highest all-cause SMR (6.73, 95% CI 4.55-9.63) and very high mortality due to heart diseases., Conclusions: This historical cohort study revealed that the prevalence of PTB infection was high among workers with asbestosis in Hong Kong. An excess risk of lung cancer mortality was observed among workers with a history of PTB, but the risk was lower than that seen among workers without a history of PTB. These interesting findings need to be confirmed by future studies., (Copyright © 2012 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Objectives: To investigate the mortality pattern among a cohort of workers with asbestosis in Hong Kong, with special emphases on mesothelioma and lung cancer., Methods: All 124 male workers with confirmed asbestosis in Hong Kong during 1981-2008 were followed up to December 31, 2008 to ascertain the vital status and causes of death. Standardized mortality ratio (SMR) for each underlying cause of death was calculated by using person-year method. Axelson's indirect method was applied to adjust for the potential confounding effect of cigarette smoking., Results: A total of 86 deaths were observed after 432.8 person-years of observations. The SMR for overall mortality (6.06, 95% CI: 4.90-7.51) increased significantly. The elevated risk of deaths from all cancers (7.53, 95% CI: 5.38-10.25) was mainly resulted from a significantly excess risk from lung cancer (SMR=7.91, 95% CI: 4.32-13.29, 14 deaths) and mesothelioma (SMR=6013.63, 95% CI: 3505.95-9621.81, 17 deaths). The SMR for lung cancer retained statistically significant after adjustment of smoking. An increased smoking adjusted SMR was also suggested for all heart diseases (2.32, 95% CI: 0.93-4.79, 7 deaths) and acute myocardial infarction (3.10, 95% CI: 0.84-7.94, 4 deaths), though the statistical significance was borderline. We found a positive association with net years of exposure to asbestos for mesothelioma and lung cancer., Conclusions: Our study provided further evidence on the carcinogenesis of asbestos/asbestosis with the risk of deaths from lung cancer and mesothelioma. This study also provided a preliminary support for a possible link between asbestosis and heart disease, but power is limited., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: We aimed to fill in the gap of knowledge on the lung cancer burden resulting from occupational exposures among Chinese men through a population-based case-referent study., Methods: Detailed information on lifestyle and full occupational histories of 1,208 male lung cancer incident cases and 1,069 age-matched male community referents were obtained through interviews during 2004-2006. The associations between lung cancer risk and exposures to specific or group of agents that were confirmed or suspected occupational carcinogens were analyzed., Results: After adjustment of smoking and other potential confounding factors, significant odds ratio of lung cancer was observed for workers employed in major industrial divisions of "construction" (1.37, 95% CI: 1.00-1.89) and "financing, insurance, real estate, and business services" (0.48, 95% CI: 0.23-0.97), as well as in the occupational groups of "bricklayers, carpenters, and other construction workers" (1.49, 95% CI: 1.07-2.06). Significantly elevated odds ratios were found for occupational exposures to silica dust (1.75, 95% CI: 1.16-2.62), welding fumes (1.74, 95% CI: 1.13-2.68), diesel exhaust (2.18, 95% CI: 1.23-3.84), and man-made mineral fibers (7.45, 95% CI: 1.63-34.00), while a significantly reduced risk (OR = 0.67, 95% CI: 0.47-0.95) was linked to cotton dust. The population attributable fraction of lung cancer was 3.2% (95% CI: 0.1-7.3%) for construction workers and 9.5% (95% CI: 4.8-15.1%) for the four significant specific exposures., Conclusions: Our study indicates that previous exposure to occupational carcinogens remains an important determinant of lung cancer burden for Hong Kong Chinese men. However, results obtained from this study should be confirmed by future analyses based on job exposure matrix.

We aimed to examine the effect of alcohol consumption on lung cancer risk stratified by smoking, and to explore whether the impact of alcohol was modified by familial susceptibility to cancer. We recruited 1208 male lung cancer incident cases and 1069 community referents during 2004-2006 and collected their lifetime history of alcohol consumption, cigarette smoking, and family cancer history. Unconditional multivariate logistic regression analysis was performed to estimate the adjusted odds ratio (OR). We tested multiplicative-scale interaction between exposures of interest and examined the additive-scale interaction using synergy index. A moderate association between frequent alcohol consumption and lung cancer was observed among men who had family cancer history (OR = 4.22, 95%CI: 2.46-7.23) after adjustment of smoking and other confounders, while the alcohol effect among men without family history was weak (OR = 1.24, 95%CI: 0.95-1.63) and it became no excess in the never smokers. We observed a consistent synergistic effect between alcohol drinking and family cancer history for all lung cancers and the adenocarcinoma, while there was no multiplicative-scale interaction between the exposures of interest (likelihood ratio test for interaction, p>0.05). Our study revealed a possible synergistic effect between alcohol consumption and familial susceptibility for lung cancer risk; however, this observed possible association needs to be confirmed by future larger analytic studies with more never smoking cases.

Background: Burning incense generates large amounts of air pollutants, many of which are confirmed or suspected human lung carcinogens., Objectives: We conducted a population-based case-referent study to examine the effect of incense smoke exposure on lung cancer risk among Chinese males and explored the joint effect of cigarette smoking and exposure to residential radon., Methods: We recruited 1,208 male lung cancer incident cases and 1,069 community referents from 2004 to 2006 and estimated their lifetime exposures to incense smoke and other residential indoor air pollutants based on self-reported information collected during interviews. We performed unconditional multivariable logistic regression analysis to estimate the odds ratio (OR) for lung cancer associated with exposure to incense smoke after adjusting for possible confounders. We conducted stratified analyses by smoking status and exposures to incense burning and residential radon and explored the potential additive-scale interactions., Results: We observed an association between incense exposure and lung cancer that was limited primarily to smokers. Cigarette smoking and high cumulative incense exposure at home appeared to have a synergistic effect on lung cancer (compared with never-smokers who never used incense, the OR for lung cancer for smokers who used incense ≥ 60 day-years = 5.00; 95% confidence interval: 3.34, 7.51). Power was limited, but we also found preliminary evidence suggesting that radon exposure may increase risk among smokers using incense., Conclusion: Our study suggests that exposure to incense smoke in the home may increase the risk of lung cancer among smokers and that exposure to radon may further increase risk.

Background: Few epidemiological studies have explored the associations between occupational exposures and lung cancer in lifelong nonsmoking men., Methods: We obtained lifetime occupational history and other relevant information for 132 newly diagnosed lung cancer cases among nonsmoking Chinese men and 536 nonsmoking community referents. Unconditional multiple logistic regression analysis was performed to estimate the odds ratio (OR) of lung cancer for specific occupational exposures., Results: Significantly increased lung cancer risk was found for nonsmoking workers occupationally exposed to silica dust (OR=2.58, 95% confidence interval (CI): 1.11, 6.01), diesel exhaust (OR=3.47, 95% CI: 1.08, 11.14), spray painting (OR=2.81, 95% CI: 1.14, 6.93), and nonspray painting work (OR=2.36, 95% CI: 1.04, 5.37). Silica dust exposure was associated with a significantly increased risk of adenocarcinoma (OR=2.91, 95% CI: 1.10, 7.68). We observed a positive gradient of all lung cancers and of adenocarcinoma with duration of employment for workers exposed to silica dust and spray painting., Conclusion: This study found an increased risk of lung cancer among nonsmoking Chinese men occupationally exposed to silica dust, diesel exhaust, and painting work.

To identify etiological connections of lung cancer in Chinese women in Hong Kong, who are among the highest in lung cancer incidence and mortality, we conducted a case-control study, in which 279 female lung cancer cases and 322 controls were selected and frequency matched. A variety of information, including dietary habits, occupational history, smoking, domestic environmental exposures, and family history of cancer was collected, and their associations with lung cancer were analyzed with logistic analysis approach. In addition to positive associations with exposures to cooking emissions and to radon at home, smoking and family cancer history, we observed that increasing consumption of meat was linked to a higher risk, whereas consumptions of vegetables had a strong protective effect against lung cancer. Moderate consumption of coffee appeared to be beneficial against the disease. Those never employed and domestic helpers were at a higher risk. The results indicated that environmental exposures, risky personal behaviors, or lifestyle, as well as family cancer aggregation are among important contributors to the high incidence of lung cancer in Hong Kong females.

Chinese women in Hong Kong have among the highest incidence and mortality of lung cancer in the world, in spite of a low prevalence of smoking. We carried out this population-based case-control study to evaluate the associations of previous lung disease and family cancer history with the occurrence of lung cancer among them. We selected 212 cases that were newly diagnosed with primary lung cancer, and randomly sampled 292 controls from the community, frequency matched by age group. All the cases and controls were lifetime nonsmokers. We estimated the main effects of preexisting asthma, pulmonary tuberculosis, pneumonia, chronic bronchitis, and family lung/all cancer history, using unconditional logistic regression, accounting for various potential risk factors and confounders. All of the previous lung diseases, except chronic bronchitis, were related to an elevated risk for lung cancer, and the association with asthma was significant. Those who had more than one previous lung disease tended to be at higher risk than those with only one of them. Positive family history of any cancer was associated with over 2-fold risk than negative family history. The joint effect of positive history of previous pulmonary diseases and positive family cancer history appeared to be additive, indicating the two factors acted independently. The results support an etiological link of preexisting lung disease and family cancer history to the risk of lung cancer.

Background: Malignant mesothelioma has a long latency period and more commonly found in those exposed to amphibole than chrysotile asbestos., Method: A 35 years old asbestos worker in an asbestos textile plant in Chongqing, China, developed mesothelioma after only 4 years of employment. He was born and bred in a company residence of an asbestos plant and manually spun asbestos thread during school age. In the plant, not amphibole but only chrysotile has been used., Results: Diagnosis of malignant mesothelioma was confirmed by comprehensive approaches including gross appearance, histology, histochemistry, and immunocytochemistry. In the lung and tumor tissues, huge number of tremolite with exceptional chrysotile was observed despite the reverse proportion in the work environment., Discussion: Residential exposure and home spinning of asbestos seemed contributed to the early development of mesothelioma in this subject. Although only chrysotile was used and contamination of tremolite was low in the work environment, chrysotile seemed to be cleared leaving tremolite remain in the tissue., Conclusion: Chrysotile with little contamination of tremolite can lead to early development of malignant mesothelioma when heavily exposed from childhood at a company residence with household exposure. There can be several mechanisms for tremolite to remain in the lung tissue, far exceeding chrysotile in number.

Background: We conducted this case-control study to evaluate smoking effect on lung cancer conditional on the level of exposure to cooking emissions and to explore whether there is a joint effect of these two risk factors., Subjects and Methods: We selected 279 newly diagnosed primary lung cancer cases and 322 community controls from Hong Kong females, frequency matched by age group, and collected relevant data. We applied logistic regression to estimate lung cancer risk related to smoking and cooking fume exposure, expressed as total cooking dish-years, while adjusting for various potential confounding factors., Results: Current smoking was associated with four-fold increased risk, and ex-smoking with two-fold risk, which was not much influenced by cooking dish-years. No increased risk was observed in environmental tobacco smoking. Increasing intakes of yellow/orange vegetables and multivitamins were significant protective factors in all models. In the analysis of joint effect, the combination of smoking and cooking dish-years tended to have a greater risk than exposure to cooking fumes alone. There was a dose-response gradient with total dish-years in nonsmokers, but not in smokers. Smoking was more strongly associated with nonadenocarcinoma, whereas exposure to cooking fumes appeared to be related to both adenocarcinoma and nonadenocarcinoma., Conclusion: We confirmed the important roles of smoking and cooking emissions in lung cancer risk among the women. These two major risk factors appeared to act independently.

When study on epidemiological causation is carried out, logistic regression has been commonly used to estimate the independent effects of risk factors, as well as to examine possible interactions among individual risk factor by adding one or more product terms to the regression model. In logistic or Cox's regression model, the regression coefficient of the product term estimates the interaction on a multiplicative scale while statistical significance indicates the departure from multiplicativity. Rothman argues that when biologic interaction is examined, we need to focus on interaction as departure from additivity rather than departure from multiplicativity. He presents three indices to measure interaction on an additive scale or departure from additivity, using logarithmic models such as logistic or Cox's regression model. In this paper, we use data from a case-control study of female lung cancer in Hong Kong to calculate the regression coefficients and covariance matrix of logistic model in SPSS. We then introduce an Excel spreadsheet set up by Tomas Andersson to calculate the indices of interaction on an additive scale and the corresponding confidence intervals. The results can be used as reference by epidemiologists to assess the biologic interaction between factors. The proposed method is convenient and the Excel spreadsheet is available online for free.

The issue of whether exposure to chrysotile asbestos alone, without contamination from amphibole asbestos, causes lung cancer and mesothelioma was investigated in a 25-year longitudinal study (1972-1996) in Chongqin, China. The study cohort comprised 515 male asbestos plant workers exposed to chrysotile only; the control cohort included 650 non-dust-exposed workers. The results of analysis in which the proportional hazards model was used indicated that mortality due to all causes, all cancers, and lung cancer was related to asbestos exposure; the relative risks, adjusted for age and smoking, were 2.9, 4.3, and 6.6, respectively. Fiber concentrations in the raw material section and the textile section of the plant were 7.6 and 4.5 fibers/ml, respectively. Because of differences between the study and control plants, the authors also compared various sections of the asbestos plant that had different levels of dust exposure. The adjusted relative risk of lung cancer was 8.1 for workers exposed to high versus low levels of asbestos. Two cases of malignant mesothelioma, one pleural and the other peritoneal, were found in the asbestos cohort. These results suggest that heavy exposure to pure chrysotile asbestos alone, with negligible amphibole contamination, can cause lung cancer and malignant mesothelioma in exposed workers.