Cystic Lung Cancer Research Articles

Clinical Multi-features Analysis of Cystic Lung Adenocarcinoma and Construction of Invasive Risk Prediction Model

Cystic lung cancer, a special type of lung cancer, has been paid more and more attention. The most common pathological type of cystic lung cancer is adenocarcinoma. The invasiveness of cystic lung adenocarcinoma is vital for the selection of clinical treatment and prognosis. The aim of this study is to analyze the multiple clinical features of cystic lung adenocarcinoma, explore the independent risk factors of its invasiveness, and establish a risk prediction model. A total of 129 cases of cystic lung adenocarcinoma admitted to the Department of Thoracic Surgery of the First Affiliated Hospital of Nanjing Medical University from January 2021 to July 2022 were retrospectively analyzed and divided into pre-invasive group [atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA)] and invasive group [invasive adenocarcinoma (IAC)] according to pathological findings. There were 47 cases in the pre-invasive group, including 19 males and 28 females, with an average age of (51.23±14.96) years. There were 82 cases in the invasive group, including 60 males and 22 females, with an average age of (61.27±11.74) years. Multiple clinical features of the two groups were collected, including baseline data, imaging data and tumor markers. Univariate analysis, LASSO regression and multivariate Logistic regression analysis were used to screen out the independent risk factors of the invasiveness of cystic lung adenocarcinoma, and the risk prediction model was established. In univariate analysis, age, gender, smoking history, history of emphysema, neuron-specific enolase (NSE), number of cystic airspaces, lesion diameter, cystic cavity diameter, nodule diameter, solid components diameter, cyst wall nodule, smoothness of cyst wall, shape of cystic airspace, lobulation, short burr sign, pleural retraction, vascular penetration and bronchial penetration were statistically different between the pre-invasive group and invasive groups (P<0.05). The above variables were processed by LASSO regression dimensionality reduction and screened as follows: age, gender, smoking history, NSE, number of cystic airspaces, lesion diameter, cystic cavity diameter, cyst wall nodule, smoothness of cyst wall and lobulation. Then the above variables were included in multivariate Logistic regression analysis. Cyst wall nodule (P=0.035) and lobulation (P=0.001) were found to be independent risk factors for the invasiveness of cystic lung adenocarcinoma (P<0.05). The prediction model was established as follows: P=e^x/(1+e^x), x=-7.927+1.476* cyst wall nodule+2.407* lobulation, and area under the curve (AUC) was 0.950. Cyst wall nodule and lobulation are independent risk factors for the invasiveness of cystic lung adenocarcinoma, which have certain guiding significance for the prediction of the invasiveness of cystic lung adenocarcinoma.

Cystic and Cavitary Lung Cancer: Its Characteristic Features on CT and FDG-PET Scans

Background: Cystic and cavitary lung cancer (CCLC) is infrequently observed on computed tomography (CT) scans; however, its diagnosis is often overlooked or delayed. Objectives: The current study aimed to investigate the CT and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) features of CCLC. Patients and Methods: A total of 809 patients who underwent lung tumor resection were examined in this study, and the presence of cystic and cavitary lesions on CT scans was investigated. Based on the CT scans, CCLC was identified in 102 consecutive patients. The diameters of the whole nodule and the airspace portion of the lesion, morphological patterns of cystic and cavitary lesions, presence of ground glass opacity (GGO), and loculation pattern (including the presence of a septum) were evaluated. The positron emission tomography (PET) scans of CCLC were also assessed visually and semi-quantitatively. Results: A total of 104 CCLC lesions were evaluated in this study. The histological analysis indicated 85 cases of adenocarcinoma (AD) and 19 cases of squamous cell carcinoma (SCC). The morphological patterns of cystic and cavitary lesions were classified into four types. The presence of GGO, type 4 morphological pattern (a soft-tissue-density structure intermixed within clusters of a cavitary lesion), and multilocular with septum (MS) loculation pattern were significantly different according to the histological type. The maximum standardized uptake value (SUVmax) on PET scans was significantly lower in AD compared to SCC (P = 0.002). In the solid nodule part of cystic and cavitary lesions, the MS pattern was significantly more common in AD (P = 0.044). Conclusion: When cystic and cavitary lesions are observed on CT scans, the presence of GGO and the MS pattern should be considered, as it may help differentiate the histological findings.

Application of PLGA as a Biodegradable and Biocompatible Polymer for Pulmonary Delivery of Drugs

Pulmonary administration of biodegradable polymeric formulation is beneficial in the treatment of various respiratory diseases. For respiratory delivery, the polymer must be non-toxic, biodegradable, biocompatible, and stable. Poly D, L-lactic-co-glycolic acid (PLGA) is a widely used polymer for inhalable formulations because of its attractive mechanical and processing characteristics which give great opportunities to pharmaceutical industries to formulate novel inhalable products. PLGA has many pharmaceutical applications and its biocompatible nature produces non-toxic degradation products. The degradation of PLGA takes place through the non-enzymatic hydrolytic breakdown of ester bonds to produce free lactic acid and glycolic acid. The biodegradation products of PLGA are eliminated in the form of carbon dioxide (CO2) and water (H2O) by the Krebs cycle. The biocompatible properties of PLGA are investigated in various in vivo and in vitro studies. The high structural integrity of PLGA particles provides better stability, excellent drug loading, and sustained drug release. This review provides detailed information about PLGA as an inhalable grade polymer, its synthesis, advantages, physicochemical properties, biodegradability, and biocompatible characteristics. The important formulation aspects that must be considered during the manufacturing of inhalable PLGA formulations and the toxicity of PLGA in the lungs are also discussed in this paper. Additionally, a thorough overview is given on the application of PLGA as a particulate carrier in the treatment of major respiratory diseases, such as cystic fibrosis, lung cancer, tuberculosis, asthma, and pulmonary hypertension.

CHST11‐mediated microenvironment events contribute to pulmonary fibrosis and cancer progression

The Carbohydrate sulfotransferase (CHST) family is essential for Chondroitin Sulfate synthesis and is associated with cancer progression. Comparing all CHST families, we found that CHST11 has prognostic value than other families. CHST11 is related to the overall survival rate in the pan‐cancer profile, among which lung adenocarcinoma is the most significant. From pulmonary fibrosis to lung cancer, the expression of CHST11 showed a linear increase. We analyzed the CHST11 interactome, and the results indicated that CHST11 contributes to diverse canonical pathways, including immune microenvironment, fibrosis, and cancer progression. Based on the prediction results of Ingenuity Pathway Analysis (IPA), we speculate that CHST11 can secrete IL1B and IL6 signals to activate the upstream regulator IRF8. This is also the key to the fact that IRF8 has contributed to cystic fibrosis and lung cancer progression. In addition, IRF8 can also transactivate CD80 and CD86 to reform the tumor microenvironments and immune response. By reversing the CHST11‐IL6/IL1B‐IRF8‐CD80/CD86 mediated axis, we confirmed that VE821 and LY2603618 have the value of drug repurposing. Our study proves novel insight into how CHST11 contributes to cystic fibrosis and lung cancer by reprogramming the immune microenvironment.

The Multi-slice Spiral Computed Tomography (MSCT) Features of Thin-Walled Cystic Lung Cancer with Ground Glass Opacity

Background: Lung cancer is the leading cause of cancer-related mortality worldwide. Thin-walled cystic lung cancer with ground glas s opacity (GGO) is a type of lung carcinoma with specific computed tomography (CT) features. Objectives: To investigate the imaging features of multi-slice spiral computed tomography (MSCT) of GGO and to improve the imaging diagnosis of this type of lung cancer. Patients and Methods: The clinical data of 24 patients with pathologically confirmed thin-walled cystic lung cancer with GGO were retrospectively analyzed in this study. The imaging features of preoperative MSCT, including vascular convergence, burr signs, pleural depression signs, lobulation signs, thickness and uniformity of the cavity wall, partitive membranes, and position of the ground-glass cavity, were examined. The relationship between the imaging features and postoperative pathological findings of lung carcinoma were also explored. Results: Most of the lesions (75.0%) were located in the upper lobe of the lungs. The size range of the cavity was 5.8 - 28.1 mm, with a mean of 13.6 ± 7.2 mm. Fifteen patients (62.5%) had a cavity wall thickness &lt; 2 mm, 6 (25.0%) patients had a cavity wall thickness in the range of 2 - 3 mm, and 3 (12.5%) patients had a cavity wall thickness of about 3 - 4 mm. A uniform cavity wall was found in 10 (41.7%) cases, while a non-uniform cavity wall was observed in 14 (58.3%) cases. Eleven patients showed pure GGO (45.8%), while 13 patients showed mixed GGO (54.2%). Besides, nine patients (37.5%) showed lobular signs, 12 (50.0%) patients showed spicule signs, and 6 (28.6%) patients showed vascular convergence signs. Twelve patients (50.0%) had signs of pleural indentation, while 14 (66.7%) patients showed thick or thin small blood vessel opacity or fine partitive membranes. Twenty-three patients were diagnosed with lung adenocarcinoma, while one patients was diagnosed with mixed adenosquamous carcinoma. Conclusion: Thin-walled cystic lung cancer with GGO is a rare clinical phenomenon. The imaging features of this type of lung cancer on MSCT are consistent with the characteristics of lung cancers.

Cystic Primary Lung Cancer: Evolution of Computed Tomography Imaging Morphology Over Time.

Primary lung cancers associated with cystic airspaces are increasingly being recognized; however, there is a paucity of data on their natural history. We aimed to evaluate the prevalence, pathologic, and imaging characteristics of cystic lung cancer in a regional thoracic surgery center with a focus on the evolution of computed tomography morphology over time. Consecutive patients referred for potential surgical management of primary lung cancer between January 2016 and December 2018 were included. Clinical, imaging, and pathologic data were collected at the time of diagnosis and at the time of the oldest computed tomography showing the target lesion. Descriptive analysis was carried out. A total of 441 cancers in 431 patients (185 males, 246 females), median age 69.6 years (interquartile range: 62.6 to 75.3 y), were assessed. Overall, 41/441 (9.3%) primary lung cancers were cystic at the time of diagnosis. The remaining showed solid (67%), part-solid (22%), and ground-glass (2%) morphologies. Histopathology of the cystic lung cancers at diagnosis included 31/41 (76%) adenocarcinomas, 8/41 (20%) squamous cell carcinomas, 1/41 (2%) adenosquamous carcinoma, and 1/41 (2%) unspecified non-small cell lung carcinoma. Overall, 8/34 (24%) cystic cancers at the time of diagnosis developed from different morphologic subtype precursor lesions, while 8/34 (24%) cystic precursor lesions also transitioned into part-solid or solid cancers at the time of diagnosis. This study demonstrates that cystic airspaces within lung cancers are not uncommon, and may be seen transiently as cancers evolve. Increased awareness of the spectrum of cystic lung cancer morphology is important to improve diagnostic accuracy and lung cancer management.

First-time in-human study of VMD-928, an oral allosteric TrkA selective inhibitor targeting TrkA protein overexpression, in patients with solid tumors or lymphoma.

3081 Background: Tropomyosin receptor kinase A (TrkA) is a protein encoded by the NTRK1 gene. Upregulation of TrkA signal transduction pathways, which can be caused by either NTRK1 gene fusions or intact TrkA protein overexpression, are oncogenic for multiple tumor types. This is clinically validated by demonstrated efficacy of ATP-competitive pan-TrkA/B/C inhibitors, larotrectinib and entrectinib for treatment of advanced solid tumors harboring NTRK1/2/3 gene fusions. VMD-928 is the first oral small-molecule TrkA (NTRK1) selective inhibitor with differentiated allosteric (ATP non-competitive) and irreversible mechanisms of action, acting as a molecular glue which sticks two TrkA proteins together and dose-dependently inhibits TrkA functions and downstream effectors, e.g. activated ERK, a hallmark of cancer. We conducted a first time in human phase 1 trial and completed the dose escalation phase. Methods: This is an open label, Phase 1 study investigating oral VMD-928 in adults with advanced solid tumors or lymphoma. The primary objective is to assess the safety and tolerability of VMD-928 and determine the recommended phase 2 dose. Secondary objectives include characterizing the pharmacokinetics (PK) and pharmacodynamics as well as assessing antitumor activity. Results: Non-biomarker-selected patients (n = 20) were accrued to 4 dose escalation cohorts ranging from 300 mg/day to 2400 mg/day. Three patients were accrued to the 2400 mg dose level with one DLT of elevated bilirubin, AST and ALT. The trough concentrations (Ctrough, ng/mL) ranged from 5.3 to 727. The dose was de-escalated to 1200 mg per day in divided doses and fifteen heavily pretreated patients were accrued with the following tumor types: adenoid cystic carcinoma, cholangiocarcinoma, lung cancer, pancreatic cancer, parotid, and squamous cell carcinoma of head and neck. There were no DLT’s at this dose and one patient with adenoid cystic carcinoma had prolonged stable disease. Common adverse events related to therapy were dark stool (35%), elevated liver enzymes (25%, primarily at 2400 mg/day), fatigue, nausea or vomiting, and decreased appetite (20% each). Conclusions: VMD-928 was well tolerated with mainly gastrointestinal side effects. The recommended phase 2 dose (RP2D) is 600 mg twice (1200 mg) per day. The study is currently accruing in expansion cohorts to evaluate efficacy in biomarker-selected patients with tumors of TrkA protein overexpression. Tumor types with reported high TrkA protein expression including thymic carcinoma (98% with TrkA protein expression without NTRK1/2/3 gene fusions), mesothelioma (81%), squamous cell carcinoma of head and neck (80%), ovarian (80%), hepatocellular (72%), and squamous cell carcinoma of the lung (71%) are being accrued. Clinical trial information: NCT03556228.

Prevalence and Economic Burden of Respiratory Diseases in Central Asia and Russia: A Systematic Review.

Prevalence data of respiratory diseases (RDs) in Central Asia (CA) and Russia are contrasting. To inform future research needs and assist government and clinical policy on RDs, an up-to-date overview is required. We aimed to review the prevalence and economic burden of RDs in CA and Russia. PubMed and EMBASE databases were searched for studies that reported prevalence and/or economic burden of RDs (asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, interstitial lung diseases (ILD), lung cancer, pulmonary hypertension, and tuberculosis (TB)) in CA (Kyrgyzstan, Uzbekistan, Tajikistan, Kazakhstan, and Turkmenistan) and Russia. A total of 25 articles (RD prevalence: 18; economics: 7) were included. The majority (n = 12), mostly from Russia, reported on TB. TB prevalence declined over the last 20 years, to less than 100 per 100,000 across Russia and CA, yet in those, multidrug-resistant tuberculosis (MDR-TB) was alarming high (newly treated: 19–26%, previously treated: 60–70%). COPD, asthma (2–15%) and ILD (0.006%) prevalence was only reported for Russia and Kazakhstan. No studies on cystic fibrosis, lung cancer and pulmonary hypertension were found. TB costs varied between US$400 (Tajikistan) and US$900 (Russia) for drug-susceptible TB to ≥US$10,000 for MDR-TB (Russia). Non-TB data were scarce and inconsistent. Especially in CA, more research into the prevalence and burden of RDs is needed.

The mechanism of formation of thin-walled cystic lung cancer.

Thin-wall cystic lung cancer is becoming of increasing interest in the study of pulmonary medicine. Consequently, more and more different images and pathologic manifestations have been found. The purpose of this article is to find pathologic characteristics and try to explain the formation mechanism of thin-walled cystic lung cancer.Sixty-five patients with this special lung cancer were analyzed retrospectively based on the review of medical records, radiologic findings, and pathologic changes.We found 3 pathologic types: adenocarcinoma, squamous cell carcinoma, and lymphoma. There were 60 cases of adenocarcinoma, 4 cases were squamous cell carcinoma, and only 1 lymphoma. Tumor cells, pulmonary vessels, fibrous tissues, and residual bronchi are the pathologic basis of different image findings.Thin-walled cystic lung cancers are mostly adenocarcinoma, but other pathologic types can also appear, such as squamous cell carcinoma and lymphoma. We can see that a large amount of fibrous tissues were generated by tumors around the bronchus, resulting in airway stenosis and degeneration. Tumor cells also can invade the bronchial wall and cause structural damage. All these lesions are similar to 1-way valves which can cause gas accumulation in the tumor area and result in thin-walled cystic lung cancer.

CT Characteristics and Pathologic Basis of Solitary Cystic Lung Cancer.

CT Characteristics and Pathologic Basis of Solitary Cystic Lung Cancer.

CT Characteristics and Pathologic Basis of Solitary Cystic Lung Cancer.

There are increasing reports of a type of lung cancer that manifests as solitary cystic airspaces. The purpose of this case series was to identify the CT features and possible mechanisms of solitary cystic lung cancer, on the basis of CT observations and pathologic characteristics. The clinical, imaging, and pathologic data of 106 patients with solitary cystic lung cancer were collected and analyzed between January 2011 and December 2017. CT images were reviewed independently by three radiologists who were blinded to pathologic findings. Demographic data and clinical and smoking status were extracted from the medical records. The mean age was 58.8 years 6 10.6 (standard deviation) (range, 30–82 years). CT features in the 106 patients included nonuniform cystic walls in 96 (90.6%) patients, cyst septations in 62 (58.5%) patients, nodular walls in 58 (54.7%) patients, ground-glass opacity around the cyst in 53 patients (50.0%), and irregular margins in 42 (39.6%) patients. At histologic examination, the majority of cases (81 [87.1%] of 93) were adenocarcinoma.

Thin-wall cystic lung cancer: A study of 45 cases.

Thin-wall cystic lung cancer is uncommon. Consequently, there is a lack of knowledge concerning the features of this type of lung cancer, which may lead to misdiagnosis and delayed treatment. The aim of the present study is to understand the invasiveness and metastasis of thin-wall cystic lung cancer. The prognosis of this type of cancer will also be discussed. The present study attempted to determine the pathological interpretation of the imaging results. A total of 45 patients with this specific type of lung cancer were analyzed retrospectively based on the review of medical records, radiological findings, pathological changes and treatment strategies. Certain patients were also telephoned in order to learn about their recent physical conditions. Thin-wall cystic lung cancer displayed suspected malignant signs. The majority of these cases are adenocarcinoma, but certain cases of squamous cell carcinoma may also display cysts on their images. Although thin-wall cystic lung cancer is often thought to progress slowly, certain cases may progress rapidly. Distant metastasis, which is relatively rare, occurred in three cases. Cancer cells proliferate along the terminal bronchioles and destroy the lung tissues exposing the bronchial arteries and adjacent bronchi. Therefore, separation in cysts on the images was observed. In the majority of cases, the thin-wall cystic lung cancer proliferates slowly, but in a few cases it may be very aggressive.

Lung Disease and Genomics.

Research and application of genomic medicine in lung disease during the past century has clarified our understanding and focus on specific phenotypes, helping clinicians tailor treatment for individual patients. Cystic fibrosis and lung cancer have been researched extensively; specific genotypes have been instrumental in precision medicine to treat these lung diseases. Asthma and chronic obstructive pulmonary disease are more complex and heterogeneous in their pathogenesis, genotypic profile, and phenotypic expression, making treatment more difficult with increasing disease severity. This article focuses on the evolving state of the science of precision medicine in lung cancer, chronic obstructive pulmonary disease, asthma, and cystic fibrosis. The body of knowledge in lung disease is growing related to pharmacogenomics, clinical guidelines, genome editing, and approaches to genomic health that will guide clinical treatment options, reduce risk, and promote health.

Magnetic nanoparticles-based drug and gene delivery systems for the treatment of pulmonary diseases.

Magnetic nanoparticles (MNPs) have gained much attention due to their unique properties such as biocompatibility and biodegradability as well as magnetic and heat-medicated characteristics. Due to these inherent properties, MNPs have been widely used in various biomedical applications including targeted drug delivery and hyperthermia-based therapy. Hyperthermia is a promising approach for the thermal activation therapy of several diseases, including pulmonary diseases. Additionally, due to their large loading capacity and controlled release ability, several MNP-based drug delivery systems have been emerged for treatment of cystic fibrosis and lung cancer. This review provides an overview on the unique properties of MNPs and magnetic-mediated hyperthermia with emphasis on the recent biomedical applications of MNPs in treatment of both lung cancer and cystic fibrosis.

16 - Human Lung Disease-Associated Proteins Are Oxidized in Mouse Lung by Cadmium Levels Found in Human Environmental and Dietary Exposures

Cd accumulates in humans from dietary, environmental including cigarette smoke, and occupational sources, and has a twenty-year biologic half-life. Our previous studies show that environmental low dose Cd oxidizes protein redox states and stimulates inflammatory signaling and actin cytoskeleton disruption; these results suggest that Cd could impact multiple disease mechanisms. Although considerable information is available concerning effects of high dose occupational Cd exposures and cigarette smoking, little is known about the relative sensitivities of subcellular compartmental redox proteome and the effect of its disruption on lung physiology and pathophysiology at low environmental and dietary levels. In the present study lung tissues from mice exposed to low dose Cd by drinking water (3.3 mg/L, 16 weeks), compared to Cd-free drinking, were examined for redox proteomics (n=3 per group). Redox proteomics was performed by a mass spectrometry-based Isotope Coded Affinity Tag (ICAT) method to measure oxidation of cysteine residues, and pathway and network analyses were performed using MetaCore software. Results showed that 545 protein peptides of two groups were identified and redox states of all 545 were measured (mean % oxidation, control, 32.3%; Cd, 36.4%). Of these, 173 were oxidized 1.3 fold or more by Cd compared to respective protein peptides in control. The results of subcellular compartmental analysis of these 173 showed that mitochondrial proteins were relatively more susceptible to oxidation (1.8 fold) by Cd than proteins in other compartments. Pathway analysis showed that pathways for cystic fibrosis, lung cancer and asthma were associated with the 173 proteins oxidized by Cd, suggesting that exposure to environmental and diet levels of Cd could alter lung redox proteome and impact pulmonary health and diseases.

Thin-walled cystic lung cancer: an analysis of 24 cases and review of literatures

背景与目的英国学者Anderson和Pierce于1954年首先报道了表现为囊性病变的肺癌。作为少见的肺癌特殊表现类型，薄壁囊性肺癌在临床中经常被误诊。本研究旨在探讨薄壁空洞性肺癌的临床特点、影像学特点，诊断及治疗。方法自2007年3月-2013年12月，解放军总医院胸外科共收治4, 897例原发性肺癌患者，其中24例影像学表现为薄壁空洞型肺癌。我们将影像学上表现为囊性且75%以上囊壁厚度小于4 mm的肺癌定义为薄壁空洞性肺癌。回顾性总结24例病例的临床资料、病理结果及随访情况。结果薄壁空洞型肺癌在我科同期接受手术的肺癌中比例为0.49%（24/4, 897）。其中男性19例，女性5例，平均年龄56.5岁。14例无临床症状，于查体时发现。10例有呼吸道症状。24例患者中18例为腺癌（包括原位腺癌及微浸润腺癌），3例鳞癌，1例大细胞癌，1例小细胞癌，1例腺鳞癌。平均随访时间28个月，3例因肺癌死亡，其余21例未见复发。结论薄壁空洞型肺癌是肺癌少见的影像学表现类型，临床中应避免误诊。其具体形成机制并不明确，可能是肺癌形成的某一阶段。薄壁空洞型肺癌如能早期诊断，可获得较好预后。

Lung cancer presenting as thin‐walled cysts: An analysis of 15 cases and review of literature

Lung cancer presenting as cysts is a rare entity in clinical practice. Differential diagnosis is difficult in the benign-like cyst. We conducted a retrospective analysis of the clinical records of 15 patients who underwent surgery for primary lung cancer presenting as cysts (wall thickness <5 mm) in our department between 2007 and 2012. The whole group underwent postoperative follow-up. The subjects' age ranged from 18 to 80 years with a median age of 58.3 years. Eight cases presented with respiratory symptoms while seven showed abnormal shadows on a chest computed tomography without symptoms. Histological analysis showed that 10 cases were of adenocarcinoma, two of squamous cell carcinoma and one of large cell carcinoma. Two patients died at 13 and 26 months and the remaining 13 patients are alive and disease free at 3-38 months. Cystic lung cancer should be considered in the differential diagnosis of focal benign cyst. Cystic lung cancer could achieve a good outcome if early diagnosis can be obtained.

Sex Steroid Hormone Effects in Normal and Pathologic Conditions in Lung Physiology

Progesterone and estradiol participate in the regulation of many pulmonary functions, for example progesterone mediates the fall of alveolar carbon dioxide tension observed in the luteal phase of the menstrual cycle and during pregnancy in humans, when progesterone levels are high. The treatment with estradiol diminishes vasoconstriction and hypoxia. Progesterone and estradiol in addition to participating in non-pathological functions such as vasodilation and lung maturation, also have influence on pathologies as asthma, cystic diseases and cancer. Therefore this review will provide an overview of the action and effects of these hormones in lung, their mechanism of action through their intracellular receptors and their influence over asthma, cystic lung diseases and cancer.

In vivo transfection study of chitosan-DNA-FAP-B nanoparticles as a new non viral vector for gene delivery to the lung

Gene therapy targeted at the respiratory epithelium holds therapeutic potential for diseases such as cystic fibrosis and lung cancer. We recently reported that Chitosan-DNA-FAP-B nanoparticles are good candidates for targeted gene delivery to fibronectin molecules (FAP-B receptors) of lung epithelial cell membrane. In this study Chitosan-DNA-FAP-B nanoparticles were nebulized to mice using air jet nebulizer. The effect of nebulization on size, zeta potential and DNA binding ability of nanoparticles were studied. The level of gene expression in the mice lungs was evaluated. Nebulization did not affect the physicochemical properties of nanoparticles. Aerosol delivery of Chitosan-DNA-FAP-B nanoparticles resulted in 16-fold increase of gene expression in the mice lungs compared with Chitosan-DNA nanoparticles. This study suggested that Chitosan-FAP-B nanoparticle can be a promising carrier for targeted gene delivery to the lung.

Cystic fibrosis transmembrane conductance regulator gene mutation and lung cancer risk

The cystic fibrosis transmembrane conductance regulator (CFTR) holds an important role in retaining lung function, but its association with lung cancer is unclear. A case-control study was conducted to determine the possible associations of the genetic variants in the CFTR gene with lung cancer risk. Genotypes of the most common deletion ΔF508, one functional SNP, and eight tag SNPs in the CFTR gene were determined in 574 lung cancer patients and 679 controls. A logistic regression model, adjusting for known risk factors, was used to evaluate the association of each variant with lung cancer risk, as confirmation haplotype and sub-haplotype analyses were performed. ΔF508 deletion and genotypes with minor alleles in one tag SNP, rs10487372, and one functional SNP, rs213950, were inversely associated with lung cancer risk. The results of haplotype and sub-haplotype analyses were consistent with single variant analysis, all pointing to deletion ΔF508 being the key variant for significant haplotypes and sub-haplotypes. Individuals with ‘deletion-T’ (ΔF508/rs10487372) haplotype had a 68% reduced risk for lung cancer compared to common haplotype ‘no-deletion-C’ (OR = 0.32; 95% CI = 0.15–0.68; p = 0.01). Genetic variations in the CFTR gene might modulate the risk of lung cancer. This study, for the first time, provides evidence of a protective role of the CFTR deletion carrier in the etiology of lung cancer.