Types Of Human Lung Cancer Research Articles

Syphilis mimetic nanoparticles for cuproptosis-based synergistic cancer therapy via reprogramming copper metabolism

Small cell lung cancer (SCLC) is one of the most devastating type of human lung cancer and has a high propensity to metastasize into the brain. Cuproptosis recently has been defined as a copper dependent cell death, offers a new lens to develop the novel copper-based nanostructure inducing cuproptosis for suppressing tumor growth and metastasis. Here, we report a syphilis mimetic TP0751-peptide decorated stem cell membrane-coated copper-based metal organic framework (Cu-MOF) nanodelivery system for SCLC brain metastasis. The Cu-MOF is employed as nanocarrier to support siRNA with high loading efficiency, and its pH sensitivity facilitates endosomal disruption upon cellular uptake. Furthermore, the cell membrane coating Cu-MOF presents a good biocompatibility, high BBB transcytosis, and specific uptake by tumor cells within the brain. In vitro and in vivo trials have shown that TP-M−Cu−MOF/siATP7a exhibited high silencing efficiency against target gene, specifically blocked copper trafficking, increased copper intake, triggered cuproptosis, and improved therapeutic efficacy in SCLC brain metastasis tumor-bearing mice. Overall, the biomimetic nanodelivery platform presented here further offers a promising way of orchestrating gene therapy to target copper-dependent signalling for reprogramming copper metabolism and cuproptosis-based synergistic therapy in mice bearing brain metastases.

Verbascum chinense L. leaf aqueous extract green-synthesized nanoparticles: Its performance in the treatment of several types of human lung cancers

In recent years, scientists have tried to increase organic chemistry productions for the treatment of many cancers such as the lung cancers. In this regard, gold nanoparticles have a special place. Furthermore, one of the therapeutic properties of Verbascum chinense L. is increasing the physiological potentials of the body against several cancers. In the present study, gold nanoparticles were prepared and synthesized in aqueous medium using V. chinense leaf extract. We assessed the anti-human lung cancers potentials of these nanoparticles against well-differentiated bronchogenic adenocarcinoma, moderately differentiated adenocarcinoma of the lung, and poorly differentiated adenocarcinoma of the lung cell lines. AuNPs were characterized and analyzed by common nanotechnology techniques including FT-IR and UV–Vis. Spectroscopy, Field Emission-Scanning Electron Microscopy, and Transmission Electron Microscopy. In the FT-IR test, the presence of many antioxidant compounds with related bonds caused the excellent condition for reducing of gold in the gold nanoparticles. In UV–Vis, the clear peak in the wavelength of 542 nm indicated the formation of gold nanoparticles. We assessed the anti-human lung cancers potentials of these nanoparticles against well-differentiated bronchogenic adenocarcinoma, moderately differentiated adenocarcinoma of the lung, and poorly differentiated adenocarcinoma of the lung cell lines. AuNPs had excellent anti-human lung cancer effects dose-dependently against HLC-1, LC-2/ad, and PC-14 cell lines. The best result of anti-human lung cancer activities of AuNPs against above cell lines was observed in the case of the PC-14 cell line. In conclusion, the synthesized AuNPs showed significant anti-human lung cancer properties against well-differentiated bronchogenic adenocarcinoma, moderately differentiated adenocarcinoma of the lung, and poorly differentiated adenocarcinoma of the lung cell lines in a dose depended on manner. After confirming in the in vivo and clinical trials, AuNPs can be administrated in human for the treatment of humans’ lung cancers especially well-differentiated bronchogenic adenocarcinoma, moderately differentiated adenocarcinoma of the lung, and poorly differentiated adenocarcinoma of the lung.

Introducing a modern chemotherapeutic drug formulated by iron nanoparticles for the treatment of human lung cancer

In the present study, iron nanoparticles were green-synthesized using the aqueous extract of Alhagi maurorum leaf aqueous extract. The synthesized FeNPs were characterized by analytical techniques including EDX, FE-SEM, XRD, UV–vis and FT-IR. The anti-human lung cancer activity of FeNPs was evaluated using MTT assay. The nanoparticles were formed in a spherical shape in the average size of 60.11 nm. In the cellular and molecular part of the recent study, the treated cells with FeNPs were assessed by MTT assay for 48 h about the cytotoxicity and anti-human lung cancer properties on normal (HUVEC) and lung cancer cell lines i.e. HLC-1 and PC-14. The viability of malignant lung cell line reduced dose-dependently in the presence of FeNPs. The IC50 of FeNPs was 195 and 181 µg/mL against HLC-1 and PC-14 cell lines, respectively. In the antioxidant test, the IC50 of FeNPs and BHT against DPPH free radicals was 214 and 62 µg/mL, respectively. After the clinical study, iron nanoparticles containing A. maurorum leaf aqueous extract may be used to formulate a new chemotherapeutic drug or supplement to treat several types of human lung cancer.

Antioxidant, cytotoxicity, and anti-human lung cancer properties of Linum usitatissimum seed aqueous extract in in vitro conditions: a pre-clinical trial study

IntroductionLinum usitatissimum seed or flax seed is known as a potential candidate as a remedy to treat various diseases in many traditional medicines around the world. In the current study, the antioxidant, cytotoxicity, and anti-human lung cancer properties of Linum usitatissimum seed were investigated in in vitro conditions.Material and methodsAntioxidant activity of the plant was analyzed using radical scavenging activity and ferrous ion chelating assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to evaluate anti-lung cancer properties of the plant.ResultsThe plant extract scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) as a free radical with an IC50 of 34.2 ±0.9 µg/ml. The plant was also found to be rich in phenolic compounds with 294.8 ±2.3 mg GAE/g for total phenolic content. Cell viability of Linum usitatissimum seed was very low against lung poorly differentiated adenocarcinoma (PC-14), lung moderately differentiated adenocarcinoma (LC-2/ad), and lung well-differentiated bronchogenic adenocarcinoma (HLC-1) cell lines without any cytotoxicity towards the normal cell line. The best anti-human lung cancer properties of Linum usitatissimum seed against the above cell lines were observed in the case of the PC-14 cell line. According to the above findings, Linum usitatissimum seed may be administered for the treatment of several types of human lung cancer in humans. According to the results, the IC50 values of plant extract against lung poorly differentiated adenocarcinoma (PC-14), lung moderately differentiated adenocarcinoma (LC-2/ad), and lung well-differentiated bronchogenic adenocarcinoma (HLC-1) cell lines were found to be 392, 483, and 564 µg/ml, respectively.ConclusionsIt appears the recent formulation can be used as a novel chemotherapeutic supplement in humans.

Long non-coding RNA ENST00000500843 is downregulated and promotes chemoresistance to paclitaxel in lung adenocarcinoma.

Adenocarcinoma is one of the most common pathological types of human lung cancer and has the highest incidence and mortality rates worldwide. Resistance to paclitaxel (PTX), the standard chemotherapy agent for treatment of lung adenocarcinoma, is a major clinical obstacle. Sensitive markers are urgently required for the diagnosis and characterization of lung cancer, as well as to manage drug resistance. Previous studies have described the activity of long non-coding RNAs (lncRNAs) in human lung cancer and chemotherapy resistance. In previous studies, lncRNA ENST00000500843 was identified to be downregulated in PTX-resistant A549 human lung cancer cells. However, the roles of this lncRNA in the development of lung adenocarcinoma and its mechanism in PTX resistance, to the best of our knowledge, have not been described. In the present study, 56 pairs of lung adenocarcinoma and normal adjacent tissue samples were collected. Reverse transcription-quantitative PCR revealed that the expression levels of lncRNA ENST00000500843 were lower in lung adenocarcinoma tissues and PTX-resistant A549 cells when compared with normal adjacent tissues and A549 cells. Decreased expression levels of lncRNA ENST00000500843 in lung adenocarcinoma tissues were associated with tumor diameter, the degree of pathological differentiation and metastasis of lymph nodes. Additionally, patients with low expression levels of ENST00000500843 exhibited poorer overall survival and progression-free survival rates. Furthermore, the present study demonstrated that knockdown of lncRNA ENST00000500843 with small interfering RNA decreased the likelihood of apoptosis in A549 cells and promoted resistance to PTX. This indicated that lncRNA ENST00000500843 may be a useful diagnostic marker of lung cancer and a good prognostic marker for resistance to treatment with PTX.

PTEN inhibits non-small cell lung cancer cell growth by promoting G0/G1 arrest and cell apoptosis.

Non-small cell lung cancer (NSCLC) is a major type of human lung cancer and the primary cause of cancer-associated cases of mortality worldwide. Phosphatase and tensin homolog (PTEN) is a potent tumor suppressor gene in various human cancer types. The aim of the current study was to explore the role of PTEN and its associated regulatory mechanisms in NSCLC. Firstly, the expression of PTEN was detected using western blotting in a variety of NSCLC cell lines. The results revealed that compared with normal control cells, PTEN levels were significantly decreased in NSCLC cell lines (P<0.01). Short hairpin (sh)RNAs specific to PTEN were also used to knockdown endogenous PTEN in NSCLC cells. The results indicated that cell viability was significantly increased in PTEN-knockdown cells compared with those transfected with negative control shRNA (P<0.01). Conversely, overexpression of PTEN in A549 and SK-MES-1 cells significantly decreased the optical density of NSCLC cells (P<0.01). Flow cytometry was used to investigate the cell cycle; the results revealed that PTEN knockdown significantly increased the percentage of cells at G0/G1 phase (P<0.01) and decreased the number of cells at S phase (P<0.01). The molecular mechanism was further explored using western blotting and the results demonstrated that PTEN overexpression increased the levels of cleaved caspase-3 (P<0.01). These results suggest that PTEN may be a potential target gene for gene therapy in patients with NSCLCs.

Spleen tyrosine kinase SYK(L) interacts with YY1 and coordinately suppresses SNAI2 transcription in lung cancer cells.

Spleen tyrosine kinase (SYK) is a nonreceptor tyrosine kinase with dual properties of an oncoprotein and an oncosuppressor in distinctive cell types. In solid cancers, two isoforms SYK(L) and SYK(S) of SYK were recently identified due to its alternative mRNA splicing. However, the cellular activity and the biological significance of the long isoform of SYK, SYK(L), is still not well defined in human lung cancers. Here, we describe an interaction between SYK(L) and the ubiquitously expressed transcription regulator Yin Yang 1 (YY1) in the nucleus, which suppresses the epithelial-to-mesenchymal transition (EMT) by inactivating SNAI2 (coding transcription factor SLUG) transcription. ChIP indicated that endogenous SYK(L) interacts directly with a YY1 binding cis-regulatory element in the SNAI2 promoter. Importantly, knockdown of YY1 activates SYK(L)-dependent EMT suppression in human lung cancer H1155 cells. We also found that the protein level of SYK(L) is markedly upregulated in various types of human lung cancers, and its nuclear localization is strongly correlated with clinical benefits of lung adenocarcinomas. Collectively, our data reveal a SYK(L)-dependent transcriptional regulation of EMT through SLUG as a potential biomarker for lung cancer aggressiveness.

SH2B1 promotes NSCLC cell proliferation through PI3K/Akt/mTOR signaling cascade

BackgroundNon-small cell lung cancer (NSCLC), the most prevalent type of human lung cancer, is characterized by many molecular abnormalities. SH2B1, a member of the SH2-domain containing family, have recently been shown to act as tumor activators in multiple cancers. The objective of this study was to investigate the role SH2B1 and the underlying molecular mechanism in NSCLC.MethodsCell functional analysis and cell line-derived xenograft model were performed to determine SH2B1 potential roles on NSCLC cell proliferation in vitro and in vivo. In vitro assays were performed to identify signal molecular mechanisms. Subsequently, 104 patients with NSCLC undergoing primary surgical resection were recruited to evaluated expression of SH2B1 and Akt/mTOR signaling markers by immunohistochemical staining to determine their clinicopathologic significance.ResultsModulation of SH2B1 expression levels had distinct effects on cell proliferation, cell cycle and apoptosis in the NSCLC cell lines A549 and H1299. At the molecular level, overexpression of SH2B1 resulted in the upregulation of the Akt/mTOR markers, p-Akt and p-mTOR, and downregulation of PTEN to promote NSCLC cell proliferation, while silencing SH2B1 had the opposite effect. In human NSCLC specimens, SH2B1 expression levels were positively associated with Akt/mTOR signaling pathway markers.ConclusionsThe SH2B1/Akt/mTOR/PTEN axis is required for regulating NSCLC cell proliferation and might prove to be a promising strategy for restraining tumor progression in NSCLC patients.

Targeting cysteine-rich angiogenic inducer-61 by antibody immunotherapy suppresses growth and migration of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the most frequent type of human lung cancer; lung cancer is responsible for the highest rates of cancer-associated mortality in the world. Cysteine-rich angiogenic inducer-61 (CYR-61) has been identified as a tumorigenesis-, development- and metastasis-related gene, and is reported to enhance proliferation, migration and invasion through hepatocyte growth factor (HGF)-induced scattering and the metastasis-inducing HGF/Met signaling pathway in tumor cells and xenograft models. CYR-61 is a protein that promotes human lung cancer cell metastasis and is closely related to the patient's prognosis in NSCLC. The purpose of the present study was to investigate whether CYR-61 may serve as a dual potential target for gene therapy of human NSCLC. In the present study, an antibody targeted against CYR-61 (anti-CYR-61) was constructed and the therapeutic effects and underlying mechanism of this antibody in NSCLC cells and mice with NSCLC was investigated. It was observed that NSCLC cell viability, migration and invasion were inhibited while cell apoptosis was induced by the neutralization of CYR-61 protein by anti-CYR-61. Western blotting demonstrated that extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) expression levels in NSCLC cells were decreased following treatment with anti-CYR-61. In addition, it was observed that inhibition of NSCLC cell viability was achieved by the suppression of the epithelial-mesenchymal transition signaling pathway. ERK and AKT phosphorylation levels were downregulated in NSCLC cells and tumors following anti-CYR-61 treatment. Analysis of a murine model indicated that tumor growth was inhibited and tumor metastasis was significantly suppressed (P<0.01) following anti-CYR-61 treatment for CYR-61. In conclusion, CYR-61 may serve as a potential target for gene therapy for the treatment of human NSCLC.

SH2B1 promotes epithelial-mesenchymal transition through the IRS1/β-catenin signaling axis in lung adenocarcinoma.

Lung adenocarcinoma (LADC), the most prevalent type of human lung cancer, is characterized by many molecular abnormalities. SH2B1, a member of the SH2‐domain containing family, have recently been shown to act as tumor activators in multiple cancers, including LADC. However, the mechanisms underlying SH2B1 overexpression are not completely understood. Here, we reported that SH2B1 expression levels were significantly upregulated and positively associated with EMT markers and poor patient survival in LADC specimens. Modulation of SH2B1 levels had distinct effects on cell proliferation, cell cycle, migration, invasion, and morphology in A549 and H1299 cells in vitro and in vivo. At the molecular level, overexpression of SH2B1 resulted in the upregulation of the EMT markers, especially induced β‐catenin accumulation and activated β‐catenin signaling to promote LADC cell proliferation and metastasis, while silencing SH2B1 had the opposite effect. Furthermore, ectopic expression of SH2B1 in H1299 cells increased IRS1 expression level. Reduced expression of IRS1 considerably inhibited H1299 cell proliferation, migration, and invasion which were driven by SH2B1 overexpression. Collectively, these results provide unequivocal evidence to establish that SH2B1‐IRS1‐β‐catenin axis is required for promoting EMT, and might prove to be a promising strategy for restraining tumor progression in LADC patients.

IKKα inactivation promotes Kras-initiated lung adenocarcinoma development through disrupting major redox regulatory pathways

Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are two distinct and predominant types of human lung cancer. IκB kinase α (IKKα) has been shown to suppress lung SCC development, but its role in ADC is unknown. We found inactivating mutations and homologous or hemizygous deletions in the CHUK locus, which encodes IKKα, in human lung ADCs. The CHUK deletions significantly reduced the survival time of patients with lung ADCs harboring KRAS mutations. In mice, lung-specific Ikkα ablation (IkkαΔLu ) induces spontaneous ADCs and promotes KrasG12D-initiated ADC development, accompanied by increased cell proliferation, decreased cell senescence, and reactive oxygen species (ROS) accumulation. IKKα deletion up-regulates NOX2 and down-regulates NRF2, leading to ROS accumulation and blockade of cell senescence induction, which together accelerate ADC development. Pharmacologic inhibition of NADPH oxidase or ROS impairs KrasG12D-mediated ADC development in IkkαΔLu mice. Therefore, IKKα modulates lung ADC development by controlling redox regulatory pathways. This study demonstrates that IKKα functions as a suppressor of lung ADC in human and mice through a unique mechanism that regulates tumor cell-associated ROS metabolism.

Expression of Rab1A is upregulated in human lung cancer and associated with tumor size and T stage.

Rab1A expression is associated with malignant phenotypes in several human tumors; however, the role of Rab1A in lung cancer is still unclear. In this study, we attempted to establish the role of Rab1A in major human lung cancer subtypes. Rab1A expression in different histological types of human lung cancer was analyzed in lung cancer tissues with paired adjacent noncancerous tissues and a large panel of lung cancer cell lines. The effect of Rab1A expression on multiple cancer-associated signaling pathways was also examined. The results demonstrated that Rab1A was significantly overexpressed in the different histological types of lung cancer as compared to non-cancerous tissues, and Rab1A expression was correlated with tumor volume and stage. In a large panel of lung cancer cell lines, high Rab1A expression was observed as compared to a normal lung/bronchus epithelial cell line. However, Rab1A protein levels were not correlated with mTORC1 (P-S6K1), mTORC2 (P-AKT), MEK (P-ERK), JNK (P-c-Jun) or p38MAPK (P-MK2) signaling. Rab1A knockdown had no effect on mTOR signaling or cell growth. These data suggested that Rab1A may be involved in the pathogenesis of human lung cancer in an mTOR- and MAPK-independent manner.

Cellular immunotherapy as maintenance therapy prolongs the survival of the patients with small cell lung cancer in extensive stage

BackgroundSmall cell lung cancer (SCLC) is the most devastating type of human lung cancer. Patients usually present with disseminated disease to many organs (extensive stage). This study was to investigate the efficacy and safety of cellular immunotherapy (CIT) with autologous natural killer (NK), γδT, and cytokine-induced killer (CIK) cells as maintenance therapy for extensive-stage SCLC (ES-SCLC) patients. MethodsA pilot prospective cohort study was conducted with ES-SCLC patients who had responded to initial chemotherapy. Patients received either CIT as maintenance therapy (CIT group), or no treatment (control group). Progression-free survival (PFS), overall survival (OS), and adverse effects were compared. ResultsForty-nine patients were recruited in this study, with 19 patients in the CIT group and 30 patients in the control group. The patient characteristics of the 2 groups were comparable except for age, as patients in the CIT group were older than those in the control group (P < 0.05). PFS in the CIT group was superior to the control group (5 vs. 3.1 months, P = 0.020; HR, 0.489, 95% CI, 0.264–0.909, P = 0.024). OS of the CIT group was also longer than that of the control group (13.3 vs. 8.2 months, P = 0.044; HR, 0.528, 95% CI, 0.280–0.996, P = 0.048, respectively). No significant adverse reactions occurred in patients undergoing CIT. ConclusionsCIT maintenance therapy in ES-SCLC prolonged survival with only minimal side effects. Integrating CIT into the current treatment may be a novel strategy for ES-SCLC patients, although further multi-center randomized trials are needed.

MicroRNA-498 is downregulated in non-small cell lung cancer and correlates with tumor progression.

Non-small cell lung cancer (NSCLC) is the most common type of human lung cancer, with highly aggressive, lethal malignancy and microRNAs have already been proven to be associated with NSCLC tumorigenesis. In this study, we sought to determine the expression, the clinical value and its role in NSCLC tumor progression. Clinical NSCLC tissues and common cell lines were collected. Real-time PCR was performed to quantify the miR-498 expression. In addition, the association of miR-498 expression with clinical pathological factors and prognosis was statistically analyzed. Furthermore, cell proliferation was measured after miR-498 was overexpressed transiently in cells. We found that miR-498 was significantly decreased in NSCLC tumors as well as cell lines, when compared with their separated controls. Decreased miR-498 expression was associated with sex, tumor type and tumor size. Functionally, ectopic expression of miR-498 in A549 and H661 cells inhibited cell proliferation. Our data indicated that miR-498 is downregulated and correlated with tumor progression, which might be a putitive therapeutic target in NSCLC treatment.

Cellular immunotherapy as maintenance therapy and overall survival in patients with small cell lung cancer in extensive stage.

e14007 Background: Small cell lung cancer (SCLC) is the most devastating type of human lung cancer. These patients usually present with disseminated disease to many organs (extensive stage). Their ...

Heparanase expression and localization in different types of human lung cancer

BackgroundHeparanase is the only known mammalian glycosidase capable of cleaving heparan sulfate chains. The expression of this enzyme has been associated with tumor development because of its ability to degrade extracellular matrix and promote cell invasion. MethodsWe analyzed heparanase expression in lung cancer samples to understand lung tumor progression and malignancy. Of the samples from 37 patients, there were 14 adenocarcinomas, 13 squamous cell carcinomas, 5 large cell carcinomas, and 5 small cell carcinomas. Immunohistochemistry was performed to ascertain the expression and localization of heparanase. ResultsAll of the tumor types expressed heparanase, which was predominantly localized within the cytoplasm and nucleus. Significant enzyme expression was also observed in cells within the tumor microenvironment, such as fibroblasts, epithelial cells, and inflammatory cells. Adenocarcinomas exhibited the strongest heparanase staining intensity and the most widespread heparanase distribution. Squamous cell carcinomas, large cell carcinomas, and small cell carcinomas had a similar subcellular distribution of heparanase to adenocarcinomas but the distribution was less widespread. Heparanase expression tended to correlate with tumor node metastasis (TNM) staging in non-small cell lung carcinoma. ConclusionIn this study, we showed that heparanase was localized to the cytoplasm and nucleus of tumor cells and to cells within the microenvironment in different types of lung cancer. This enzyme exhibited a differential distribution based on the type of lung tumor.General significanceElucidating the heparanase expression patterns in different types of lung cancer increased our understanding of the crucial role of heparanase in lung cancer biology. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.

Airway basal cells of healthy smokers express an embryonic stem cell signature relevant to lung cancer

Activation of the human embryonic stem cell (hESC) signature genes has been observed in various epithelial cancers. In this study, we found that the hESC signature is selectively induced in the airway basal stem/progenitor cell population of healthy smokers (BC-S), with a pattern similar to that activated in all major types of human lung cancer. We further identified a subset of 6 BC-S hESC genes, whose coherent overexpression in lung adenocarcinoma (AdCa) was associated with reduced lung function, poorer differentiation grade, more advanced tumor stage, remarkably shorter survival, and higher frequency of TP53 mutations. BC-S shared with hESC and a considerable subset of lung carcinomas a common TP53 inactivation molecular pattern which strongly correlated with the BC-S hESC gene expression. These data provide transcriptome-based evidence that smoking-induced reprogramming of airway BC toward the hESC-like phenotype might represent a common early molecular event in the development of aggressive lung carcinomas in humans.

Abstract 1481: Srx-Prx IV axis is required for human lung cancer cell maintenance, migration, and invasion

Abstract Sulfiredoxin (Srx) is a novel antioxidant protein that has been shown to reduce the hyper oxidized Peroxiredoxins (Prxs). Our previous study has demonstrated that Srx is required for tumor promoter induced cell transformation and is highly expressed in certain types of human skin cancers (Wei et al PNAS 2008). In this study, our goal is to further examine the expression of Srx in a broad range of human tumors and to explore its functional significance and molecular mechanisms in human cancer development. We found that Srx is highly expressed in several types of human lung cancers and its level is correlated with cancer malignancy and metastasis. Using human lung cancer A549 cell in culture, we found that knockdown of Srx significantly reduces anchorage independent growth in soft agar, cell migration in a wound-healing assay and cell invasiveness in a matrigel invasion assay. In an effort to discover downstream mediators of Srx-signaling pathway, we used affinity-based pull down and mass spectrometry methods to identify proteins that interact with Srx. To our surprise, Prx IV was found to be the most abundant protein that interacts with Srx in at least three different cell lines and the preferential interaction occurs independently of its expression levels. To characterize the Srx-Prx IV interaction, bacterial expressed recombinant Srx, Prx I, II, III and IV were individually purified. In an in vitro binding assay using Surface Plasmon Resonance technique, we confirmed that purified Srx has a much higher binding affinity to Prx IV than to Prx I, II or III. With a lentiviral based shRNA technology, each individual Prx was specifically knocked down in A549 cells. The phenotypic changes of these cells were compared to the Srx knockdown cells. We found that knockdown of Prx IV, but not other Prxs, was sufficient to recapitulate the attenuation of tumor phenotype and progression of Srx knockdown cells. In addition, we also confirmed that Prx IV undergoes rapid hyperoxidation in the presence of oxidative stress and is preferentially reduced by Srx in A549 cells. Overall our data indicate that Srx is highly expressed in human lung cancers and Srx-Prx IV axis is critical for human lung cancer cell maintenance, migration and invasion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1481.

Immunohistochemical analysis of CYP2A13 in various types of human lung cancers

Human CYP2A13, which is expressed in the respiratory tract, is the most efficient enzyme for the metabolic activation of tobacco-specific nitrosamines such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The relevance of CYP2A13 in carcinogenicity and toxicity in the respiratory tract has been suggested, but the expression of CYP2A13 protein in lung cancer tissues remains to be determined. We first prepared a mouse monoclonal antibody against human CYP2A13. The antibody showed no cross reactivity with the other CYP isoforms including CYP2A6. Using the specific antibody, we performed immunohistochemical analysis for human lung carcinomas. In adenocarcinomas (n = 15), all specimens were positive for the staining and five samples showed strong staining. In squamous cell carcinomas (n = 15) and large cell carcinomas (n = 15), each 14 samples were positive for the staining and two and three samples showed strong staining, respectively. In small cell carcinoma samples (n = 15), eight samples were negative for the staining and five samples showed weak or moderate staining. In conclusion, we first found that the expression of CYP2A13 was markedly increased in non-small cell lung carcinomas. The high expression might be associated with the tumor development and progression in non-small cell lung carcinomas.

Immunohistochemical analysis of CYP2A13 in various types of human lung cancers

Immunohistochemical analysis of CYP2A13 in various types of human lung cancers