Lung Cancer
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Lung cancer is one of the most common types of cancer. The lungs are a pair of cone-shaped organs situated inside the chest, they bring oxygen into the body and take out waste carbon dioxide. There is a strong link between smoking and lung cancer. There are two main categories of lung cancer; Small Cell Lung Cancer (SCLC) , and Non-Small Cell Lung Cancer (NSCLC). World-wide over 1 million people are diagnosed with lung cancer each year.

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Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
Non-Small Cell Lung Cancer
Small Cell Lung Cancer
Risk Factors and Prevention of Lung Cancer

Information Patients and the Public (19 links)

Information for Health Professionals / Researchers (17 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Donfut AL, Lemaitre J, Van de Walle H, et al.
Primitive pulmonary "malignant epithelioid hemangioendothelioma" versus epithelioid angiosarcoma. A case report and review of the literature.
Acta Chir Belg. 2014 Mar-Apr; 114(2):143-5 [PubMed] Related Publications
We describe the case of a 56-year-old man presenting a primary pulmonary epithelioid angiosarcoma versus malignant epithelioid hemangioendothelioma still alive, without recurrence at nearly two years after the beginning of the symptoms. The primary pulmonary angiosarcoma is extremely rare, being reported only in a handful of cases. Metastatic involvement of the lung (90%) is far more common than primary pulmonary involvement (10%). Various predisposing condition for the development of angiosarcoma have been described. Early diagnosis is not common, because of the rarity of angiosarcoma in the lung and consequent low index of suspicion. Due to the paucity of cases, there are no defined treatment regimens for this entity. However, there is a tendency for surgical intervention in all reported cases.

Borneman T, Irish T, Sidhu R, et al.
Death awareness, feelings of uncertainty, and hope in advanced lung cancer patients: can they coexist?
Int J Palliat Nurs. 2014; 20(6):271-7 [PubMed] Related Publications
Patients diagnosed with stage-IV lung cancer are forced to quickly transition from a cancer-free and perhaps healthy life to one of serious illness, uncertainty, and anticipation of a premature death. Health professionals may be too quick to label the patient as being in denial if they hope for healing. Hope may not be lost when reality is accepted. Studies have investigated what it is like to live with awareness of impending death. Using a patient case study this paper discusses the concepts of death awareness, uncertainty, and hope. The aim is to provide a deeper understanding of how these seemingly antithetical emotions can coexist to the benefit of the patient, and to provide clinicians with practical considerations for supporting patients' hope throughout their terminal illness.

Tomaszewski M, Stepien KM, Tomaszewski A
Diaphragm fibrillation--an incidental finding detected by transoesophageal echocardiography.
Acta Cardiol. 2014; 69(3):338-40 [PubMed] Related Publications
We present a case of diaphragmatic fibrillation (with a frequency of 600/min) in a patient at the early post-operative stages. In view of the decreased oxygen saturation and confusion, the patient was sedated and mechanically ventilated. His declining physical condition was partially associated with diaphragmatic fibrillation superimposed on heart failure and lung disease. The transthoracic echocardiography was technically difficult. Consequently, transoesophageal echocardiography was undertaken. This is the first case report presenting diaphragmatic fibrillation as an incidental finding on transoesophageal echocardiography.

Vanderheeren P, De Maeseneer D, De Pauw M
A patient with progressive dyspnoea and a new heart murmur.
Acta Cardiol. 2014; 69(3):322-4 [PubMed] Related Publications
A 74-year-old man was referred to the outpatient clinic of the cardiology department with progressive dyspnoea and a new heart murmur. Physical examination of the chest wall showed a hard immobile and painless sternal swelling at the level of the angulus of Ludovici. There was an increase of the velocities across the pulmonary valve (continuous Doppler) on echocardiography as a result of the RVOT and pulmonary trunk stenosis. Computed tomography (CT) of the chest revealed a mass in the anterior mediastinum which had grown through the sternum into the skin, as well as an external compression of the ascending aorta, the truncus pulmonalis and the pericardium. Anatomo-pathological examination revealed a non-small-cell lung carcinoma. PET CT showed another nodule with FDG uptake in the right kidney, suspected for metastasis, and an uptake in a right paratracheal lymph node. The tumour was staged as a cT4cN2M1b. Palliative radiochemotherapy was started. The patient had a good clinical and radiographic response, but relapsed a few months later.

Related: Non-Small Cell Lung Cancer

Zimmermann M, Mueller T, Dieplinger B, et al.
Circulating heat shock protein 27 as a biomarker for the differentiation of patients with lung cancer and healthy controls--a clinical comparison of different enzyme linked immunosorbent assays.
Clin Lab. 2014; 60(6):999-1006 [PubMed] Related Publications
BACKGROUND: Increased heat shock protein 27 (HSP27) has been described in patients with non-small cell lung cancer (NSCLC). The aim of this study was to evaluate five commercially available assays for HSP27 measurement with respect to their capabilities to differentiate NSCLC patients from healthy controls.
METHODS: We measured HSP27 serum concentrations in 40 NSCLC cases and 40 healthy controls by different assays (i.e., R&D, Enzo Life Sciences, Invitrogen, Abcam, and MyBioSource). We analyzed receiver operating characteristic plots and calculated areas under the curve (AUCs) for the five HSP27 assays with the case-control status as the classification variable.
RESULTS: The following AUCs were obtained: R&D, 0.834 (95% CI, 0.734 - 0.908); Enzo Life Sciences, 0.823 (95% CI, 0.722 - 0.899); Invitrogen, 0.780 (95% CI, 0.674 - 0.856); Abcam, 0.642 (95% CI, 0.528 - 0.747); and MyBioSource 0.523 (95% CI, 0.408 - 0.636). An explorative comparison of the AUCs revealed that the R&D, Enzo Life Sciences, and Invitrogen assays perform better than the Abcam and MyBioSource assays in the setting evaluated. Results obtained by different HSP27 assays had up to 10-fold difference of serum concentrations, and correlation coefficients of pairwise assay comparisons ranged from 0.184 - 0.938.
CONCLUSIONS: The results of our clinical method comparison study revealed that commercially available HSP27 assays are not equally useful to differentiate NSCLC patients from healthy controls. Our study suggests that certain HSP27 methods cannot be applied for diagnostic purposes in lung cancer and probably also not in other diseases.

Related: Non-Small Cell Lung Cancer

Li X, Chen S, Sun T, et al.
The transcriptional regulation of SOX2 on FOXA1 gene and its application in diagnosis of human breast and lung cancers.
Clin Lab. 2014; 60(6):909-18 [PubMed] Related Publications
BACKGROUND: Recent study demonstrated the important contribution of SOX2 to tumorigenesis and metastasis properties of various types of cancers and strongly supported the concept that SOX2 can be used as an effective marker for diagnosis and predicting prognosis of cancer patients. However, our previous RNA-Seq results from human lung cancer cell line A549 showed that some oncogenes, including FOXA1 are negatively regulated by SOX2.
METHODS: To further verify the transcriptional regulation effect of SOX2 on FOXA1 and elucidate its application in the diagnosis of human lung and breast cancer, we performed real-time RT-PCR and Western blotting to test the regulation effect of SOX2 on the expression of FOXA1 gene. OncoPrint analysis was used to reveal the alteration of SOX2 and FOXA1 genes in breast invasive carcinoma cases and lung squamous cell carcinoma cases from the Cancer Genome Atlas (TCGA) data portal. Immunohistochemistry staining was performed to test the expression of SOX2 and FOXA1 in human breast and lung carcinoma.
RESULTS: The results showed that there is an inhibitory effect of SOX2 on the expression of FOXA1 gene. In addition, these two genes are altered in 5.8% of 484 breast invasive carcinoma cases and 46.4% of 179 lung squamous cell carcinoma cases from the Cancer Genome Atlas (TCGA) data portal, which showed an increased percentage of carcinoma cases when compared with single gene alteration. Immunohistochemistry staining of SOX2 and FOXA1 in human breast and lung carcinoma further revealed the mutual complementary effect of these two proteins in the diagnosis of carcinoma.
CONCLUSIONS: Our study revealed SOX2 as a negative upstream regulator for FOXA1 gene and demonstrated SOX2 and FOXA1 as effective dual markers in improving the diagnosis efficiency for human lung and breast tumor.

Related: Breast Cancer

Abdolmohammadi A, Sears W, Rai S, et al.
Survey of primary care physicians on therapeutic approaches to lung and breast cancers.
South Med J. 2014; 107(7):437-42 [PubMed] Related Publications
BACKGROUND: Primary care physicians (PCPs) are an important part of the decision-making process in the care of patients with cancer. The survey discussed herein evaluates what percentage of academic and community PCPs recognize benefits from systemic therapy in lung and breast cancers.
METHODS: PCPs were surveyed regarding their beliefs toward systemic therapy in early- and late-stage lung and breast cancers and were asked to rate the importance of specific factors that influence their referral decisions.
RESULTS: A total of 3444 surveys were distributed, and 316 physicians (9.1%) responded: 89 academic physicians (28%) and 227 nonacademic physicians (72%). The rate of returned surveys was equal by specialty. A total of 57%, 42.1% in lung cancer and 72.6 % in breast cancer (P < 0.001) of PCPs, believe in the curative effect of systemic therapy in early stages. Sixty-six percent (58.2% in lung cancer and 75.5% in breast cancer [P < 0.001]) believe in improved disease-free survival. Although 82% believe that systemic therapy can prevent symptoms and prolong life in advanced asymptomatic disease, half (lung cancer 50.8%, breast cancer 53.1% [P = 0.5]) of the PCPs would refer symptomatic patients with advanced disease to palliative care before referral to an oncologist. The type and stage of cancer, as well as the patient's desire or reluctance to be referred to an oncologist were rated by PCPs as the most important reasons to refer patients to an oncologist (P < 0.0001).
CONCLUSIONS: Although a majority of PCPs in academia and the community acknowledge the positive effect of chemotherapy, the benefit of systemic therapy for early-stage lung cancer is less appreciated as compared with breast cancer. Patients' preferences influence PCPs significantly in the decision to refer patients to an oncologist.

Related: Breast Cancer

Mincarini M, Bagnasco D, Ferrantino MG, et al.
Multiple pulmonary nodules and unexplained fever: when the pulmonologist fails.
Int J Immunopathol Pharmacol. 2014 Apr-Jun; 27(2):309-11 [PubMed] Related Publications
We describe herein a difficult case of persistent and refractory fever, associated with multiple lung nodules, progressive respiratory failure and general deterioration. Our patient was carefully investigated for the possible causes of his symptoms, using current and advanced diagnostic procedures, either serological or by imaging. The confirmatory diagnosis of anaplastic T-cell lymphoma, was obtained only after an invasive procedure (with severe pneumothorax), although it was too late. This suggests that also very rare diseases should be considered in the presence of unexplained signs/symptoms, and that in such cases, aggressive diagnostic procedures should be applied as early as possible.

Brawley OW, Flenaugh EL
Low-dose spiral CT screening and evaluation of the solitary pulmonary nodule.
Oncology (Williston Park). 2014; 28(5):441-6 [PubMed] Related Publications
Lung cancer screening using helical low-dose computerized tomography (LDCT) increased drastically after publication of a successful well-designed prospective randomized screening study, the National Lung Screening Trial. This increase in screening has led to a significant increase in the diagnosis of solitary pulmonary nodules (SPNs). Some of these lesions are early cancers, and their removal can potentially prevent a lung cancer death. Some have the histologic appearance of a cancer but will never progress and cause harm. Some are non-neoplastic and are best observed. The number of lesions detected with LDCT is so great that algorithms are being developed for more efficient evaluation and management of SPNs. This article will discuss current tools, approaches, and concerns regarding patient care in this setting.

Related: Cancer Screening and Early Detection

Van den Borre L, Deboosere P
Asbestos in Belgium: an underestimated health risk. The evolution of mesothelioma mortality rates (1969-2009).
Int J Occup Environ Health. 2014 Apr-Jun; 20(2):134-40 [PubMed] Related Publications
BACKGROUND: Although Belgium was once a major international manufacturer of asbestos products, asbestos-related diseases in the country have remained scarcely researched.
OBJECTIVES: The aim of this study is to provide a descriptive analysis of Belgian mesothelioma mortality rates in order to improve the understanding of asbestos health hazards from an international perspective.
METHODS: Temporal and geographical analyses were performed on cause-specific mortality data (1969-2009) using quantitative demographic measures. Results were compared to recent findings on global mesothelioma deaths.
RESULTS: Belgium has one of the highest mesothelioma mortality rates in the world, following the UK, Australia, and Italy. With a progressive increase of male mesothelioma deaths in the mid-1980s, large differences in mortality rates between sexes are apparent. Mesothelioma deaths are primarily concentrated in geographic areas with proximity to former asbestos industries.
CONCLUSIONS: Asbestos mortality in Belgium has been underestimated for decades. Our findings suggest that the location of asbestos industries is correlated with rates of mesothelioma, underlining the need to avert future asbestos exposure by thorough screening of potential contaminated sites and by pursuing a global ban on asbestos.

Related: Mesothelioma

Xi S, Chuang K, Fang K, et al.
Effect of berberine on activity and mRNA expression of N-acetyltransferase in human lung cancer cell line A549.
J Tradit Chin Med. 2014; 34(3):302-8 [PubMed] Related Publications
OBJECTIVE: To study the effects of berberine on activity and mRNA expression of N-acetyltransferase in human lung cancer cell line A549.
METHODS: N-acetyltransferase antibodies were prepared. The human lung cancer A549 cells were cultivated randomly in the wells of culture plate, and divided into the control group, and berberine 0.0008, 0.008, 0.08, 0.8 and 1.6 mM treatment groups, with 3 wells for each group. 24 h later, A549 cells in each group were collected respectively, the content of N-acetyltransferase was detected by Flow cytometry, and the mRNA expression of N-acetyltransferase was observed by reverse transcription polymerase chain reaction.
RESULTS: The N-acetyltransferase content in human lung cancer A549 cells decreased with the increasing of berberine concentration, significantly lower than that in the control group (P < 0.05 or P < 0.001); and the mRNA expression of N-acetyltransferase also decreased with the increasing of berberine concentration, significantly lower in Huangliansu treatment groups (P < 0.001).
CONCLUSION: Berberine can inhibit the activity of N-acetyltransferase in human lung cancer cell line A549, and shows negative correlations of dose and time in a certain extent. The inhibited gene expression of N-acetyltransferase in human lung cancer A549 cell may probably represent one of the mechanisms for its antineoplastic effect.

Shu Q, Shen M, Wang B, et al.
Aqueous extract of Taxus chinensis (Pilger) Rehd inhibits lung carcinoma A549 cells through the epidermal growth factor receptor/mitogen-activated protein kinase pathway in vitro and in vivo.
J Tradit Chin Med. 2014; 34(3):293-301 [PubMed] Related Publications
OBJECTIVE: To explore the anticancer mechanism of aqueous extract of Taxus Chinensis (Pilger) Rehd (AETC).
METHODS: The serum pharmacological method was used to avoid interference from administration of the crude medicinal herbs. Eight purebred New Zealand rabbits were used for preparation of serum containing various concentrations of AETC. Forty-eight Balb/c-nu mice were used for in vivo experiments. The effects of serum containing AETC on the proliferation of A549 cells and expression levels of the epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) pathway-related proteins in vitro were investigated. Additionally, the effects on the growth of A549 xenografts in nude mice, and expression levels of the EGFR/MAPK pathway-related proteins in the xenografts, were investigated.
RESULTS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that the serum containing AETC significantly decreased the viability of A549 cells in a dose-dependent manner. Western blot showed that the serum containing various concentrations of AETC strongly reduced the levels of phospho-Jun N-terminal kinase (p-JNK) and phospho-extracellular signal-regulated kinasel/2 (ERK1/2) while it increased the level of p-p38. However, no significant effects on the expression levels of JNK, ERK1/2, and p38 MAPK were found. In addition, an anticancer effect from AETC was observed in vivo in the Balb/c-nu mice bearing A549 xenografts.
CONCLUSION: AETC has significant effects on the growth of A549 xenografts and on the activity of the EGFR/MAPK pathway. Therefore, AETC may be beneficial in lung carcinoma treatment.

Yanar M, Abel F, Haalck T, et al.
The microenvironment in the human lung partly determines the site of the first metastasis.
Anticancer Res. 2014; 34(7):3845-9 [PubMed] Related Publications
BACKGROUND: Due to local ventilation and perfusion differences in the pulmonary lobes, the microenvironmental influence on metastasis formation in the lung can be studied. We, therefore, investigated whether the anatomical distribution of first lung metastases follow a particular pattern.
MATERIALS AND METHODS: Thirty-three out of 273 patients with melanoma who underwent 18F-fluorodeoxyglucose positron emission tomography and computed tomography (18FDG-PET/CT) were identified as patients with detected primary pulmonary metastases. All solitary metastases were allocated to the appropriate lung segment.
RESULTS: Segment L3 had the significantly highest number of metastases (n=11; p<0.001). Overall, both upper lung lobes manifested numerously more metastases in comparison to the lower lobes (26 metastases (70%) vs. 11 metastases (30%); p<0.001).
CONCLUSION: Our results provide novel information supporting the hypothesis that pulmonary metastases occur prevalently in the upper lung segments.

Morodomi Y, Takenoyama M, Inamasu E, et al.
Non-small cell lung cancer patients with EML4-ALK fusion gene are insensitive to cytotoxic chemotherapy.
Anticancer Res. 2014; 34(7):3825-30 [PubMed] Related Publications
BACKGROUND: Although patients with the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase gene (EML4-ALK) re-arrangement and epidermal growth factor gene EGFR mutations have proven sensitive to specific inhibitors, there is currently no consensus regarding the sensitivity of non-small cell lung cancer (NSCLC) patients with such mutations to cytotoxic chemotherapy.
PATIENTS AND METHODS: The responses to first-line cytotoxic chemotherapy were retrospectively compared between advanced or postoperative recurrent patients with non-squamous NSCLC who harbor the EML4-ALK fusion gene (ALK+), EGFR mutation (EGFR+), or neither abnormality (wild-type).
RESULTS: Data for 22 ALK+, 30 EGFR+, and 60 wild-type patients were analyzed. The ALK+ group had a significantly lower response rate than the other two groups. Progression-free survival was significantly shorter in the ALK+ cohort compared to the EGFR+ (p<0.001) and wild-type cohorts (p=0.0121).
CONCLUSION: NSCLC patients with the EML4-ALK fusion gene might be relatively insensitivite to cytotoxic chemotherapy.

Related: Non-Small Cell Lung Cancer EGFR

Kobierzycki C, Pula B, Werynska B, et al.
The lack of evidence for correlation of pyruvate kinase M2 expression with tumor grade in non-small cell lung cancer.
Anticancer Res. 2014; 34(7):3811-7 [PubMed] Related Publications
BACKGROUND: Over the last years, evidence has accumulated that an increased expression of pyruvate kinase M2 isozyme (PKM2) is related to neoplastic transformation as well that its plasma concentrations might be a marker of lung cancer progression.
MATERIALS AND METHODS: In the present manuscript an immunohistochemical technique was used to detect the expression of two pyruvate kinase isoforms: PKM1 (muscle isozyme of PK) and PKM2 as well Ki-67 antigen on paraffin sections of 218 cases of non-small cell lung cancer (NSCLC) of different histological types and grades of malignancy.
RESULTS: A significant correlation between expressions of both pyruvate kinase isoforms in all NSCLC types was found (r=0.42, p<0.0001). Expression levels of PKM1 and PKM2 were independent of the histological classification of the tumor and patients' clinicopathological data.
CONCLUSIONS: PKM2 and PKM1 have no value as predictive markers of NSCLC regardless of the histological type and grade of malignancy.

Related: Non-Small Cell Lung Cancer MKI67

Muley TR, Sianidou M, Thomas M, et al.
Comparison of two ERCC1 antibodies as prognostic and predictive biomarkers for early non-small cell lung cancer.
Anticancer Res. 2014; 34(7):3707-13 [PubMed] Related Publications
AIM: Expression of excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1) was suggested to be of predictive value for selecting patients with clinical benefit from platinum-based chemotherapy.
PATIENTS AND METHODS: In order to validate the prognostic and predictive value of ERCC1, we comparatively analyzed 298 patients with non-small cell lung cancer (NSCLC) treated with and without platinum-based adjuvant chemotherapy with two different antibodies against ERCC1 (clones 8F1 and SP68).
RESULTS: We found that both antibodies have a different immunoreactivity, with SP68 showing a more distinct, predominantly nuclear staining pattern. There was no prognostic effect for patients with high compared to patients with low ERCC1 expression, regardless of the antibody applied. In contrast, patients with squamous cell carcinoma treated with adjuvant platinum-based chemotherapy who had a low ERCC1 expression had a survival benefit with respect to disease-free and overall survival. This was especially true for expression by the SP68 antibody.
CONCLUSION: Oour data point to a potential predictive value of ERCC1 expression for the selection of adjuvant platinum-based chemotherapy for patients with pulmonary squamous cell carcinomas but not for those with adenocarcinomas. With more specific antibodies in hand, this should be substantiated in subsequent clinical studies.

Related: Non-Small Cell Lung Cancer

Homa I, Sawicki M, Wojas-Krawczyk K, et al.
Rare co-existence of mutation in KRAS and ALK gene re-arrangement in an adenocarcinoma patient--a case report.
Anticancer Res. 2014; 34(7):3701-5 [PubMed] Related Publications
Anaplastic lymphoma kinase (ALK) gene re-arrangements are present in approximately 4% of patients with non-small cell lung cancer (NSCLC), mostly in non-smokers with adenocarcinoma. V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are more common in smokers. These molecular lesions were usually described as are mutually exclusive. We herein describe a rare case of co-existence of ALK and KRAS abnormalities in adenocarcinoma tumor with massive local growth (disproportionality of clinical symptoms) and rapid central nervous system (CNS) metastases spread. T3N1M0 stage tumor (size: 10×12×13 cm) in upper lobe of the right lung was diagnosed in a 56-year-old Caucasian male smoker. Adenocarcinoma of solid predominant was surgically resected with chest wall reconstruction. One month after surgery, CNS metastases were diagnosed and subsequently treated with radiotherapy. We noted an 8-month overall survival from tumor resection. In the case of comorbidity of disorders in the ALK (uncertain prognostic significance) and KRAS gene (described as unfavorable prognostic factor), these abnormalities may ultimately decide the course of the disease in the form of brain metastases.

Related: KRAS gene

Takakuwa O, Oguri T, Uemura T, et al.
ABCB1 polymorphism as a predictive biomarker for amrubicin-induced neutropenia.
Anticancer Res. 2014; 34(7):3517-22 [PubMed] Related Publications
BACKGROUND: Amrubicin is a promising therapy for lung cancer, but is associated with a high incidence of severe neutropenia. The present study assessed the utility of ABCB1 and NAD(P)H quinone oxidoreductase 1 (NQO1) polymorphism as a predictor of amrubicin-induced neutropenia.
MATERIALS AND METHODS: Fifty-four Japanese lung cancer patients who received amrubicin chemotherapy were consecutively recruited and toxicities and SNPs (MDR1; C1236T, C3435T and G2677T/A, NQO1; C609T) were evaluated.
RESULTS: The incidence of neutropenia was higher in patients treated with 40 mg/m2 of amrubicin (n=32) compared to patients treated with 35 mg/m2 of amrubicin (n=22) (53.1% vs. 22.7%). Patients who were homogenous for the wild-type allele of C3435T were at significantly higher risk of neutropenia compared to patients with other genotypes. By contrast, the C609T genotype of NQO1 was not related to neutropenia.
CONCLUSION: C3435T polymorphisms of ABCB1 might be able to predict severe amrubicin-induced neutropenia.

Ahmad M, Hahn IF, Chatterjee S
GRP78 up-regulation leads to hypersensitization to cisplatin in A549 lung cancer cells.
Anticancer Res. 2014; 34(7):3493-500 [PubMed] Related Publications
BACKGROUND: GRP78 is one of the stress proteins linked to different functions in the cell. Previous reports have shown opposing functions of GRP78 in relation to drug resistance/sensitivity. In the current study, we examined the role of GRP78 in cisplatin-treated A549 cells.
MATERIALS AND METHODS: GRP78 was over-expressed in A549 cells with 2-deoxyglucose (2-dG) or tunicamycin (TM) treatments for 48 h and subsequently exposed to cisplatin for 2 h. Viability of these cells was determined at 0, 12, 24, 36 and 48 h afterwards.
RESULTS: We showed that A549 cells are hypersensitized to cisplatin following a transient GRP78 up-regulation. This hypersensitization is caused by the activation of JNK pathway and NF-κB, leading to early onset of apoptosis.
CONCLUSION: Induction of GRP78 can be used as a potential tool to overcome drug resistance in lung cancer cells.

Related: Non-Small Cell Lung Cancer Cisplatin

Soans E, Evans SC, Cipolla C, Fernandes E
Characterizing the sphingomyelinase pathway triggered by PRIMA-1 derivatives in lung cancer cells with differing p53 status.
Anticancer Res. 2014; 34(7):3271-83 [PubMed] Related Publications
BACKGROUND/AIM: Derivatives of PRIMA-1 compound, 8a and 8b have been shown to increase cytotoxicity in lung cancer cells through sphingomyelinase pathways in IR and 8a or 8b co-treated lung cancer cells. The goal of the present study was to further elaborate the molecular mechanism of 8a- or 8b-treated lung cancer cells in order to understand their potential as anti-cancer drugs.
MATERIALS AND METHODS: Biochemical assays, western blot, flow cytometry and gene array analyses were employed to distinguish these mechanisms.
RESULTS: Herein we demonstrated that 8a and 8b cause apoptosis with S-phase arrest in lung cancer cells by activating neutral sphingomyelinase with ceramide production. 8a induces expression of TNF family genes while 8b induces p53-mediated apoptosis genes. Protein analysis shows an increased expression in caspase 8, bcl-2, bax, caspase 9 and cytochrome c.
CONCLUSION: PRIMA-1 derivatives provoke cytotoxicity in lung cancer cells mainly through the neutral sphingomyelinase-dependent apoptosis pathway.

Related: Apoptosis TP53

Rupachandra S, Sarada DV
Anti-proliferative and apoptotic properties of a peptide from the seeds of Polyalthia longifolia against human cancer cell lines.
Indian J Biochem Biophys. 2014; 51(2):127-34 [PubMed] Related Publications
The peptides produced enzymatically from various plants have shown various biological activities including cytotoxicity. Different types of cytotoxic peptides have been reported from the seeds and leaves of Violaceae, Rubiaceae and Annonaceae families. In this study, we report purification and characterization of peptide(s) showing cytotoxic activity against A549 and HeLa cancer cell lines from the seeds of Polyalthia longifolia (Annonaceae). Seed proteins of P. longifolia were extracted and hydrolyzed using trypsin. The enzyme hydrolysate was applied on to a Sephadex G10 column and eluted using Tris-HC1 buffer (pH 7.5). Two fractions F1 and F2 were obtained, of which F2 showed significant cytotoxic activity against lung (A549) cancer cells at 10 microg/mL and cervical (HeLa) cancer cell lines at 30 microg/mL, as revealed by the MTT assay. DNA fragmentation was observed in the tested cancer cell lines treated with F2 peptide at a concentration of 10microg/mL and 30 pg/mL, respectively. Further, increased number of apoptotic cells was observed in sub-G0 phase of cell cycle of A549 and HeLa cell lines, when treated with 10 microg/mL and 30 microg/mL of F2, as revealed by the flow cytometric analyses. FTIR spectrum of F2 peptide detected the presence of stretching vibrations of carboxylic acid OH residue with peak at 3420 cm-and carbonyl (C=O) groups at 1636 cm-1, respectively. RP-HPLC analysis of F2 peptide showed a single peak at a retention time of 12.8 min detected at 280 nm, depicting the purity of F2 to be more than 90%. LC-ESI-MS/MS analysis showed the average theoretical mass of F2 to be 679.8 using m/z ratios. In conclusion, the findings suggest that F2 peptide is an effective inducer of apoptosis of cancer cells, thus offers an important strategy in the development of cancer therapeutics.

Related: Apoptosis

Weeks JC, Uno H, Taback N, et al.
Interinstitutional variation in management decisions for treatment of 4 common types of cancer: A multi-institutional cohort study.
Ann Intern Med. 2014; 161(1):20-30 [PubMed] Related Publications
BACKGROUND: When clinical practice is governed by evidence-based guidelines and there is consensus about their validity, practice variation should be minimal. For areas in which evidence gaps exist, greater variation is expected.
OBJECTIVE: To systematically assess interinstitutional variation in management decisions for 4 common types of cancer.
DESIGN: Multi-institutional, observational cohort study of patients with cancer diagnosed between July 2006 through May 2011 and observed through 31 December 2011.
SETTING: 18 cancer centers participating in the formulation of treatment guidelines and systematic outcomes assessment through the National Comprehensive Cancer Network.
PATIENTS: 25 589 patients with incident breast cancer, colorectal cancer, lung cancer, or non-Hodgkin lymphoma.
MEASUREMENTS: Interinstitutional variation for 171 binary management decisions with varying levels of supporting evidence. For each decision, variation was characterized by the median absolute deviation of the center-specific proportions.
RESULTS: Interinstitutional variation was high (median absolute deviation >10%) for 35 of 171 (20%) oncology management decisions, including 9 of 22 (41%) decisions for non-Hodgkin lymphoma, 16 of 76 (21%) for breast cancer, 7 of 47 (15%) for lung cancer, and 3 of 26 (12%) for colorectal cancer. Forty-six percent of high-variance decisions involved imaging or diagnostic procedures and 37% involved choice of chemotherapy regimen. The evidence grade underpinning the 35 high-variance decisions was category 1 for 0%, 2A for 49%, and 2B/other for 51%.
LIMITATION: Physician identifiers were unavailable, and results may not generalize outside of major cancer centers.
CONCLUSION: The substantial variation in institutional practice manifest among cancer centers reveals a lack of consensus about optimal management for common clinical scenarios. For clinicians, awareness of management decisions with high variation should prompt attention to patient preferences. For health systems, high variation can be used to prioritize comparative effectiveness research, patient-provider education, or pathway development.
PRIMARY FUNDING SOURCE: National Cancer Institute and National Comprehensive Cancer Network.

Related: Breast Cancer Colorectal (Bowel) Cancer Non Hodgkin's Lymphoma

Sengupta A, Saha K, Jash D, Bandyopadhyay A
Squamous cell lung cancer producing bilateral air bronchograms on CT scan thorax.
J Assoc Physicians India. 2013; 61(11):839-41 [PubMed] Related Publications
A young lady presented with cough for three months and dyspnoea for one month along with clinical signs of bilateral consolidation of lung. On CT scan thorax there were bilateral air bronchograms with alveolar filling opacities predominantly in lower lobes. After bronchoscopy when there was presence of suspicious malignant cells on bronchoalveolar lavage fluid, transbronchial lung biopsy diagnosed the case as squamous cell lung cancer. Radiological presentation of squamous cell lung cancer as air bronchogram is not a very common phenomenon and can present a diagnostic challenge to the clinician.

Nair VS, Pritchard CC, Tewari M, Ioannidis JP
Design and Analysis for Studying microRNAs in Human Disease: A Primer on -Omic Technologies.
Am J Epidemiol. 2014; 180(2):140-52 [PubMed] Article available free on PMC after 15/07/2015 Related Publications
microRNAs (miRNAs) are fundamental to cellular biology. Although only approximately 22 bases long, miRNAs regulate complex processes in health and disease, including human cancer. Because miRNAs are highly stable in circulation when compared with several other classes of nucleic acids, they have generated intense interest as clinical biomarkers in diverse epidemiologic studies. As with other molecular biomarker fields, however, miRNA research has become beleaguered by pitfalls related to terminology and classification; procedural, assay, and study cohort heterogeneity; and methodological inconsistencies. Together, these issues have led to both false-positive and potentially false-negative miRNA associations. In this review, we summarize the biological rationale for studying miRNAs in human disease with a specific focus on circulating miRNAs, which highlight some of the most challenging topics in the field to date. Examples from lung cancer are used to illustrate the potential utility and some of the pitfalls in contemporary miRNA research. Although the field is in its infancy, several important lessons have been learned relating to cohort development, sample preparation, and statistical analysis that should be considered for future studies. The goal of this primer is to equip epidemiologists and clinical researchers with sound principles of study design and analysis when using miRNAs.

Gu F, Wacholder S, Kovalchik S, et al.
Time to smoke first morning cigarette and lung cancer in a case-control study.
J Natl Cancer Inst. 2014; 106(6):dju118 [PubMed] Article available free on PMC after 01/06/2015 Related Publications
BACKGROUND: Targeting smokers at higher lung cancer risk can improve efficiency and reduce false-positive detection in lung cancer screening. We evaluated whether time to first cigarette after waking (TTFC), a single-item measure of nicotine dependency, could improve stratification of lung cancer risk beyond standard smoking metrics (intensity, duration, and pack-years).
METHODS: In 3249 ever-smokers (n = 1812 case subjects; n = 1437 control subjects) from a population-based case-control study in Italy, we examined the association between TTFC and lung cancer using logistic regression and estimated lung cancer incidence by levels of TTFC, and intensity, duration, and pack-years using absolute risk regression. Significance tests were two-sided.
RESULTS: Compared with smokers with TTFC greater than 60 minutes, the lung cancer odds ratios for TTFC of 31 to 60 minutes, 6 to 30 minutes, and 5 or fewer minutes (by increasing dependency) were 2.57 (95% confidence interval [CI] = 2.03 to 3.26), 2.27 (95% CI = 1.79 to 2.88), and 3.50 (95% CI = 2.64 to 4.64), respectively (P trend < .0001). The average lung cancer incidence rates for smokers of 1 to 10, 11 to 20, 21 to 30 and more than 30 cigarettes per day were consistently higher among smokers with TTFC of 60 or fewer minutes vs more than 60 minutes (64.1 vs 11.7; 125.6 vs 28.6; 130.1 vs 40.7; and 260.8 vs 108.9 per 100000 person-years, respectively). The slopes of increase in lung cancer rates with smoking duration and pack-years were statistically significantly greater among smokers with higher dependency (P interaction < .001).
CONCLUSIONS: Lung cancer risk increases with shorter TTFC; this simple nicotine dependency measure increases lung cancer risk stratification beyond standard smoking measures. Assessing TTFC may improve lung cancer risk prediction and could be useful in lung cancer screening and smoking cessation programs.

Qu Y, Wu X, Yin Y, et al.
Antitumor activity of selective MEK1/2 inhibitor AZD6244 in combination with PI3K/mTOR inhibitor BEZ235 in gefitinib-resistant NSCLC xenograft models.
J Exp Clin Cancer Res. 2014; 33:52 [PubMed] Article available free on PMC after 01/06/2015 Related Publications
PURPOSE: Although the EGF receptor tyrosine kinase inhibitors (EGFR-TKI) gefitinib have shown dramatic effects against EGFR mutant lung cancer, patients become resistant by various mechanisms, including gatekeeper EGFR-T790M mutation, MET amplification, and KRAS mutation, thereafter relapsing. AZD6244 is a potent, selective, and orally available MEK1/2 inhibitor. In this study, we evaluated the therapeutic efficacy of AZD6244 alone or with BEZ235, an orally available potent inhibitor of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR), in gefitinib-resistant non-small cell lung carcinoma (NSCLC) models.
EXPERIMENTAL DESIGN: NCI-H1975 with EGFR-T790M mutation, NCI-H1993 with MET amplification and NCI-H460 with KRAS/PIK3CA mutation human NSCLC cells were subcutaneous injected into the athymic nude mice respectively. Mice were randomly assigned to treatment with AZD6244, BEZ235, AZD6244 plus BEZ235, or control for 3 weeks, then all mice were sacrificed and tumor tissues were subjected to western blot analyses and immunohistochemical staining.
RESULTS: AZD6244 could inhibit the tumor growth of NCI-H1993, but slightly inhibit the tumor growth of NCI-1975 and NCI-H460. Combining AZD6244 with BEZ235 markedly enhanced their antitumor effects and without any marked adverse events. Western blot analysis and immunohistochemical staining revealed that AZD6244 alone reduced ERK1/2 phosphorylation, angiogenesis, and tumor cell proliferation. Moreover, MEK1/2 inhibition resulted in decreased AKT phosphorylation in NCI-H1993 tumor model. BEZ235 also inhibited AKT phosphorylation as well as their downstream molecules in all three tumor models. The antiangiogenic effects were substantially enhanced when the agents were combined, which may due to the reduced expression of matrix metallopeptidase-9 in tumor tissues (MMP-9).
CONCLUSIONS: In this study, we evaluated therapy directed against MEK and PI3K/mTOR in distinct gefitinib-resistant NSCLC xenograft models. Combining AZD6244 with BEZ235 enhanced their antitumor and antiangiogenic effects. We concluded that the combination of a selective MEK inhibitor and a PI3K/mTOR inhibitor was effective in suppressing the growth of gefitinib-resistant tumors caused by EGFR T790M mutation, MET amplification, and KRAS/PIK3CA mutation. This new therapeutic strategy may be a practical approach in the treatment of these patients.

Related: Non-Small Cell Lung Cancer MKI67 Signal Transduction Gefitinib (Iressa)

Liu Y, Yang J, Ren T, et al.
The encouraging prognosis of nongestational ovarian choriocarcinoma with lung metastases.
J Reprod Med. 2014 May-Jun; 59(5-6):221-6 [PubMed] Related Publications
OBJECTIVE: To study nongestational ovarian choriocarcinoma (NGOC) with lung metastases: its early diagnosis, optimal therapeutic method, and prognosis.
STUDY DESIGN: Twelve cases of NGOC with lung metastases treated in Peking Union Medical College Hospital from 1982-2011 were analyzed retrospectively. The 12 cases included 9 pure NGOCs and 3 mixed with other germ cell tumors (mature teratoma, endodermal sinus tumor and embryonal carcinoma components, and dysgerminoma, respectively). Chemotherapy was given in all 12 cases, mainly including EMA/CO, BEP, and
RESULTS: The median age for the cases was 23.9 years. Abdominal pain was the most common symptom (7/12). Follow-up was available for 11 cases, ranging from 17-174 months (median, 86.6 months). Of those, only 1 patient died of the disease, at 42 months from the disease onset. The other patient for whom follow-up was not available gave up treatment due to chemoresistance and disease progression. An overall sustained remission had been achieved in 10 cases (83.3%).
CONCLUSION: Surgery combined with the appropriate chemotherapy regimen can improve therapeutic efficacy and survival in the treatment of NGOC with lung metastasis, even in recurrent or chemorefractory cases. Commencement of EMA/CO chemotherapy, which seems to be associated with better prognosis, should be considered as a good choice of treatment. Conservative surgery is acceptable for young patients desiring to preserve fertility.

Related: Cyclophosphamide Dactinomycin Etoposide Methotrexate Ovarian Cancer Vincristine

Umihanic S, Umihanic S, Jamakosmanovic S, et al.
Glasgow prognostic score in patients receiving chemotherapy for non-small-cell lung cancer in stages IIIb and IV.
Med Arch. 2014; 68(2):83-5 [PubMed] Related Publications
INTRODUCTION: Lung cancer is most common cause of cancer-related mortality worldwide. Non-small-cell lung carcinoma (NSCLC) is disease with very low 5-year relative survival rate. For patients with non-small cell lung cancer, roles of current treatments are to prolong survival time and to improve quality of life.
AIM: The aim of the work was to compare values of Glasgow Prognostic Score (GPS) before application of the chemotherapy medication with response to chemotherapy and toxic side effects associated with chemotherapy in patients treated with cisplatin-etopozid (PE) and cisplatin-gemcitabin (PG) in stages IIIb and IV of NSCLC. Testing role of Glasgow Prognostic Score as a possible predictor of response to therapy and toxic side effects of chemotherapeutic protocol was another aim of this work.
PATIENTS AND METHODS: This prospective study included 60 patients in stages IIIb or IV of NSCLC, with ECOG < or = 2. The patients were divided in two groups. First group contained 30 patients treated with chemotherapeutic protocol using cisplatin-etopozid (PE), and the same number of patients in the second group were treated with cisplatin-gemcitabin (PG).
RESULTS: Glasgow Prognostic Score (GPS) evaluation before the chemotherapy inclusion showed values of 1 (43.30:53.30), then 2 (40.00:36.70) and the lowest 0 (16.70:10.00) which supports the pathological values of GPS in developed lung cancer, i.e. most patients had pathological GPS value in both protocols (83.30:90.00). Monitoring of toxic side effects and response to chemotherapy was done after each cycle of treatment.
DISCUSSION: Results of this study revealed importance of GPS in selection of patients for treatment with chemotherapy. Patients with lower values of GPS treated using PE chemotherapeutic protocol had weaker response to therapy.
CONCLUSION: Coefficient of correlation for therapy response in both chemotherapeutic protocol, compared with values of GPS before treatment, were not statistically significant, therefore GPS cannot be considered as a predictor of therapeutic on chemotherapy.

Related: Non-Small Cell Lung Cancer Cisplatin Etoposide Gemcitabine

Diot Q, Marks LB, Bentzen SM, et al.
Comparison of radiation-induced normal lung tissue density changes for patients from multiple institutions receiving conventional or hypofractionated treatments.
Int J Radiat Oncol Biol Phys. 2014; 89(3):626-32 [PubMed] Related Publications
PURPOSE: To quantitatively assess changes in computed tomography (CT)-defined normal lung tissue density after conventional and hypofractionated radiation therapy (RT).
METHODS AND MATERIALS: The pre-RT and post-RT CT scans from 118 and 111 patients receiving conventional and hypofractionated RT, respectively, at 3 institutions were registered to each other and to the 3-dimensional dose distribution to quantify dose-dependent changes in normal lung tissue density. Dose-response curves (DRC) for groups of patients receiving conventional and hypofractionated RT were generated for each institution, and the frequency of density changes >80 Hounsfield Units (HU) was modeled depending on the fractionation type using a Probit model for different follow-up times.
RESULTS: For the pooled data from all institutions, there were significant differences in the DRC between the conventional and hypofractionated groups; the respective doses resulting in 50% complication risk (TD50) were 62 Gy (95% confidence interval [CI] 57-67) versus 36 Gy (CI 33-39) at <6 months, 48 Gy (CI 46-51) versus 31 Gy (CI 28-33) at 6-12 months, and 47 Gy (CI 45-49) versus 35 Gy (32-37) at >12 months. The corresponding m values (slope of the DRC) were 0.52 (CI 0.46-0.59) versus 0.31 (CI 0.28-0.34) at <6 months, 0.46 (CI 0.42-0.51) versus 0.30 (CI 0.26-0.34) at 6-12 months, and 0.45 (CI 0.42-0.50) versus 0.31 (CI 0.27-0.35) at >12 months (P<.05 for all comparisons).
CONCLUSION: Compared with conventional fractionation, hypofractionation has a lower TD50 and m value, both suggesting an increased degree of normal tissue density sensitivity with hypofractionation.

Related: Non-Small Cell Lung Cancer

Atallah S, Cho BC, Allibhai Z, et al.
Impact of pretreatment tumor growth rate on outcome of early-stage lung cancer treated with stereotactic body radiation therapy.
Int J Radiat Oncol Biol Phys. 2014; 89(3):532-8 [PubMed] Related Publications
PURPOSE: To determine the influence of pretreatment tumor growth rate on outcomes in patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT).
METHODS AND MATERIALS: A review was conducted on 160 patients with T1-T2N0M0 NSCLC treated with SBRT at single institution. The patient's demographic and clinical data, time interval (t) between diagnostic and planning computed tomography (CT), vital status, disease status, and cause of death were extracted from a prospectively kept database. Differences in gross tumor volume between diagnostic CT (GTV1) and planning CT (GTV2) were recorded, and growth rate was calculated by use of specific growth rate (SGR). Kaplan-Meier curves were constructed for overall survival (OS). Differences between groups were compared with a log-rank test. Multivariate analyses were performed by use of the Cox proportional hazard model with SGR and other relevant clinical factors. Cumulative incidence was calculated for local, regional, and distant failures by use of the competing risk approach and was compared with Gray's test.
RESULTS: The median time interval between diagnostic and planning CT was 82 days. The patients were divided into 2 groups, and the median SGR was used as a cut-off. The median survival times were 38.6 and 27.7 months for the low and high SGR groups, respectively (P=.03). Eastern Cooperative Oncology Group performance status (P=.01), sex (P=.04), SGR (P=.03), and GTV2 (P=.002) were predictive for OS in multivariable Cox regression analysis and, except sex, were similarly predictive for failure-free survival (FFS). The 3-year cumulative incidences of regional failure were 19.2% and 6.0% for the high and low SGR groups, respectively (P=.047).
CONCLUSION: High SGR was correlated with both poorer OS and FFS in patients with early-stage NSCLC treated with SBRT. If validated, this measurement may be useful in identifying patients most likely to benefit from adjuvant therapy after SBRT.

Related: Non-Small Cell Lung Cancer

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