Advanced Lung Adenocarcinoma with EGFR 19-del Mutation Transformed into SCC after EGFR-tyrosine Kinase inhibitors Treatment:A Case report

BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)significantly improve the survival of patients with Epidermal growth factor receptor(EGFR)sensitive mutations in non-small cell lung cancer(NSCLC).CASE SUMMARY A 67-year-old female patient in advanced lung adenocarcinoma suffered from drug resistance after EGFR-TKIs treatment.Secondary pathological tissue biopsy confirmed squamous cell carcinoma(SCC)transformation.Patients inevitably encountered drug resistance issues after receiving EGFR-TKIs treatment for a certain period of time,while EGFR-TKIs can significantly improve the survival of patients with EGFR-sensitive mutations in NSCLC.Notably,EGFR-TKIs resistance includes primary and acquired.Pathological transformation is one of the mechanisms of acquired resistance in EGFR-TKIs,with SCC transformation being relatively rare.Our results provide more detailed results of the patient’s diagnosis and treatment process on SCC transformation after EGFR-TKIs treatment for lung adenocarcinoma.CONCLUSION Squamous cell carcinoma transformation is one of the acquired resistance mechanisms of EGFR-TKIs in advanced lung adenocarcinoma with EGFR mutations.

Advanced lung adenocarcinoma with EGFR 19-del mutation transforms into squamous cell carcinoma after EGFR tyrosine kinase inhibitor treatment

In this editorial we comment on the article by Ji et al.We focus specifically on the EGFR tyrosine kinase inhibitor(EGFR-TKI)treatment and the development of drug resistance to EGFR-TKIs.

Lung carcinoma with spindle and/or giant cell： a clinicopathological analysis of 17 cases

Objective： Lung carcinoma with spindle and （or） giant cell （LCSG） is a rare epithelial malignant tumor. The aim of our study is to investigate the clinicopathological and prognostic characteristics of 17 cases of LCSGs. Methods： Among 421 patients underwent resection of lung carcinomas, 17 cases of LCSG were studied for clinical, gross and histological parameters. Follow-up information was obtained and analyzed to clarify prognostically significant parameters. Results： The LCSG patients consisted of 15 males and 2 females, with the age ranging from 45 to 78 years （median, 58 years）; 5 cases of stage Ⅰ, 3 of stage Ⅱ, 9 of stage Ⅲ by pathological TNM staging; 2 cases of exclusively spindle cell carcinoma, 5 cases of lung carcinoma with spindle cell, 10 cases of lung carcinoma with giant-cell carcinoma. Cough, chest distress, or chest pain were the most common presenting symptoms, occurring in 15 patients （88.2%）. Of 5 patients in stage Ⅰ, 4 were alive and free of relapse for more than 5 years. The difference in survival was statistically significant between LCSG and squamous cell carcinoma patients （median survival, 36 vs. 61 months; P = 0.027）. Lymph node metastasis and carcinoma with giant cell were the hazardous factors impacting postoperative prognosis of LCSG patients. Conclusion： LCSG patients in early stage may have an optimistic outcome. Lung carcinomas with giant cell displayed multiple cell components in histopathology, and poor outcome due to more lymph node involved.

Molecular features of gastroenteropancreatic neuroendocrine carcinoma: A comparative analysis with lung neuroendocrine carcinoma and digestive adenocarcinomas

Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes.Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas.Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.

Diagnostic Value of GDF10 for the Tumorigenesis and Immune Infiltration in Lung Squamous Cell Carcinoma

Objective:Lung squamous cell carcinoma(LUSC)is associated with a low survival rate.Evidence suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and progression.However,a comprehensive analysis of their role in LUSC is lacking.Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC.Methods:The“R/Limma”package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC,using data from TCGA,GTEx,and GEO databases.Concurrently,the“survminer”packages were employed to investigate their prognostic value and correlation with clinical features in LUSC.The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis(WGCNA).LASSO analysis was conducted to construct a prognostic risk model for LUSC.Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC.Furthermore,based on the tumor immune estimation resource database and tumor-immune system interaction database,the role of the core gene in the tumor microenvironment of LUSC was explored.Results:GDF10 had a significant correlation only with the pathological T stage of LUSC,and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC.A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes(HRASLS,HIST1H2BH,FLRT3,CHEK2,and ALPL)for LUSC.GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression.Conclusion:GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.

Influence of blood glucose fluctuations on chemotherapy efficacy and safety in type 2 diabetes mellitus patients complicated with lung carcinoma

BACKGROUND Patients with type 2 diabetes mellitus(T2DM)have large fluctuations in blood glucose(BG),abnormal metabolic function and low immunity to varying degrees,which increases the risk of malignant tumor diseases and affects the efficacy of tumor chemotherapy.Controlling hyperglycemia may have important therapeutic implications for cancer patients.AIM To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma(LC).METHODS The clinical data of 60 T2DM+LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively analyzed.All patients underwent chemotherapy and were grouped as a control group(CG;normal BG fluctuation with a mean fluctuation<3.9 mmol/L)and an observation group(OG;high BG fluctuation with a mean fluctuation≥3.9 mmol/L)based on their BG fluctuations,with 30 cases each.BGrelated indices,tumor markers,serum inflammatory cytokines and adverse reactions were comparatively analyzed.Pearson correlation analysis was performed to analyze the correlation between BG fluctuations and tumor markers.RESULTS The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG,together with markedly higher mean amplitude of glycemic excursions(MAGE),mean of daily differences,largest amplitude of glycemic excursions and standard deviation of blood glucose(P<0.05).In addition,the OG exhibited evidently higher levels of carbohydrate antigen 19-9,carbohydrate antigen 125,carcinoembryonic antigen,neuron-specific enolase,cytokeratin 19,tumor necrosis factor-α,interleukin-6,and highsensitivity C-reactive protein than the CG(P<0.05).Pearson analysis revealed a positive association of MAGE with serum tumor markers.The incidence of adverse reactions was significantly higher in the OG than in the CG(P<0.05).CONCLUSION The greater the BG fluctuation in LC patients after chemotherapy,the more unfavorable the therapeutic effect of chemotherapy;the higher the level of tumor markers and inflammatory cytokines,the more adverse reactions the patient experiences.

Combined gastroscopic and laparoscopic resection of gastric metastatic adenosquamous carcinoma from lung: A case report

BACKGROUND Primary lung cancer is the leading cause of cancer-related death worldwide.Common metastatic sites include the brain,liver,bones,and adrenal glands.However,gastric metastases from lung cancer are rare.This case may be the first report of a combined gastroscopic and laparoscopic resection for gastric metasta-tic adenosquamous carcinoma(ASC).CASE SUMMARY We report a case of gastric metastasis from lung cancer.The patient was a 61-year-old Han Chinese female who first attended our hospital complaining of a per-sistent cough,leading to the diagnosis of advanced-stage lung adenocarcinoma.After more than four years of chemotherapy,the patient began to experience epi-gastric pain.Endoscopy was performed,and pathological examination of biopsy specimens confirmed that the gastric lesion was a metastasis from lung cancer.The lesion was successfully resected by combined gastroscopy and laparoscopy.Histopathological examination of the resected gastric specimen revealed ASC.CONCLUSION Gastric metastases from lung cancer are rare.Endoscopy,histological and immunohistochemical staining are useful for diagnosing metastatic lesions.Surgical management may provide extended survival in appropriately selected patients.

Clinical Observation on Treatment of NonParvicellular Carcinoma of the Lung with Jin Fu Kang Oral Liquid

Jin Fu Kang Oral Liquid ([symbol: see text]), made of traditional Chinese drugs for supplementing qi and nourishing yin, was developed according to the common symptoms in lung carcinoma with deficiency of both qi and yin. Of the 96 cases in the Jin Fu Kang group, 1 case got complete remission (CR) after treatment, 8 cases partial remission (PR), 52 cases no change (NC), PR + NC covering 63.5%. Of the 52 cases in the group of Jin Fu Kang plus chemotherapy, 11 cases got PR after treatment, 26 cases NC, PR + NC covering 71.2%. Of the 25 cases in the chemotherapy group, 4 cases got PR after treatment, 11 cases NC, PR + NC covering 60.0%. The results show that the therapeutic effectiveness in the Jin Fu Kang group and the group of Jin Fu Kang plus chemotherapy was better than that in the chemotherapy group. The one-year survival rate and the two-year survival rate after treatment in the Jin Fu Kang group were 67.3% and 67.3% respectively; 66.7% and 66.7% in the group of Jin Fu Kang plus chemotherapy; and 40.3% and 0.0% in the chemotherapy group. The improvement of clinical symptoms, increase of body weight and improvement of health situation (KPS marks) after treatment in both the Jin Fu Kang group and the group of Jin Fu Kang plus chemotherapy were better than that in the chemotherapy group. Some indicators of immunology and hemogram after treatment were greatly improved in the Jin Fu Kang group, worse in the chemotherapy group, but no obvious improvement in the group of Jin Fu Kang plus chemotherapy.

Synchronous multiple lung cancers with hilar lymph node metastasis of small cell carcinoma:A case report

BACKGROUND Synchronous multiple lung cancers are rare and refer to the simultaneous presence of two or more primary lung tumors,which present significant challenges in terms of diagnosis and treatment.CASE SUMMARY We report a case of multiple synchronous lung cancers with hilar lymph node metastasis of small cell carcinoma of unknown origin in a 73-year-old man.Transbronchial lung biopsy revealed squamous cell carcinoma.Although enlargement of lymph node 12u was detected,no distant metastases were observed.The patient was preoperatively diagnosed with T1cN0M0 and underwent thoracoscopic right upper lobectomy with nodal dissection(ND2a).Based on histopathological findings,the primary lesion was squamous cell carcinoma.A microinvasive adenocarcinoma was also observed on the cranial side of the primary lesion.Tumors were detected in two resected lymph nodes(#12u and#11s).Both tumors were pathologically diagnosed as small cell carcinomas.The primary lesion of the small cell carcinoma could not be identified even by whole-body imaging;however,chemotherapy was initiated for hilar lymph node metastasis of the small cell carcinoma of unknown origin.CONCLUSION Multiple synchronous lung cancers can be accompanied by hilar lymph node metastasis of small cell carcinomas of unknown origin.

Comparative analysis of lung cancer with features of bronchioloalveolar carcinoma and other types of adenocarcinoma

Objective: The aim of this study was to investigate the clinicopathologic and prognostic factors of the partial subtypes of lung adenocarcinoma, including pure bronchioloalveolar carcinoma (BAC), adenocarcinoma (AC) with BAC component and AC without BAC component. Methods: One hundred and six adenocarcinoma specimens which were followed up completely for 3 years, were obtained from 106 patients (45 men and 61 women) who underwent surgical resection for pathologically confirmed pulmonary adenocarcinoma in the Cancer Hospital of Tianjin Medical University, from June 2004 to December 2005. According to the recent 2004 World Health Organization (WHO) pathological classification criteria of lung cancer, lung adenocarcinomas were divided into three subgroups: pure BAC, AC with BAC component and AC without BAC component. The clinical data were retrospectively analyzed based on statistical methods. All data were analyzed using SPSS statistics software and Kaplan-Meier survival curves were constructed, meanwhile, we conducted a Log-rank test. Results: The statistical analysis showed that no significant association was found among the three groups in gender and age; however, smoke index, tumor size, N stage, TNM stage, postoperative recurrence and metastasis had a statistically significant correlation among three groups (P < 0.01). The 3-year survival rates of the three groups were 96.4%, 61.0% and 40.5% respectively, which had a statistically significant difference. And the 3-year survival rate was significantly higher in the patients with pure BAC than in the patients with other types of lung adenocarcinomas (P < 0.01). In contrast to the other two groups (pure BAC and AC with BAC component), we found the evidence that the 3-year prognosis of lung adenocarcinoma without BAC component was worse than the two formers. Conclusion: The three groups (pure BAC, AC with BAC component and AC without BAC component) have their own distinct clinicopathologic features respectively and completely different clinical prognosis. The strict distinction of the subtypes of lung adenocarcinoma can provide more reliable basis for scientific and comprehensive clinical treatment and contribute to assess the clinical prognosis effectively.

Effect of Bcl-2 Antisense Oligodeoxynucleotides on Human Lung Carcinoma Transplanted Subcutaneously in Nude Mice

Objective： To investigate the inhibitory effects of the Bcl-2 antisense oligodeoxynucleotides （ASODN） on tumor formation and growth of human lung carcinoma transplanted subcutaneously in nude mice. Methods： Human NCI-H460 cells treated with Bcl-2 ASODN or nonesense oligodeoxynucleotide （NSODN） and untreated NCI-H460 cells were respectively implanted subcutaneously into nude mice. When the diameters of tumor were above 0.5 cm after untreated NCI-H460 cells injection, the mice bearing tumor were randomly divided into three groups： saline control group, Bcl-2 ASODN group, NSODN group. ODN was directly injected into the tumor body for 3 weeks. The weight and volume of subcutaneous tumors were measured, and the morphology of tumor cells was observed. Results： The tumorigenic ability of the treated NCI-H460 cells by Bcl-2 ASODN was reduced. The mean time at which tumor can be detected was prolonged up to 12.6 days （P〈0.01）. The maximum tumor growth inhibitory rate was 87.5%. In therapeutic efficacy, growth of tumor was significantly inhibited in Bcl-2 ASODN group as compared with that in NSODN group, saline-treated group （P〈0.01）. The NSODN control was ineffective. In comparison with NSODN-treated, saline-treated mice, those treated with Bcl-2 ASODN showed a significant decrease in median weight of subcutaneous tumors （P〈0.01）. The growth inhibitory rate was 71.0% in ASODN group. Conclusion： Bcl-2 ASODN could inhibit tumor formation and tumor growth in nude mice.

Impact of Preoperative Serum Tumor Markers in Patients with Lung Squamous Cell Carcinoma

Background: Several previous researchers have investigated the prognostic value of serum tumor markers, especially carcinoembryonic antigen (CEA). Only a limited number of studies reported the usefulness of serum tumor markers for lung squamous cell carcinoma (SQ). We aimed to examine the significance of serum tumor markers for lung SQ. Methods: Eighty-five lung SQ patients who underwent surgery and followed more than 5-year were included. The ratios of 5-year survivors to all patients in groups with several clinicopathologic factors, including tumor markers, were compared. We also compared the clinicopathologic factors between central type and peripheral type SQ. Results: The majority of patients were male gender and current/ former smokers. Age, pN status, cytokeratin-19 fragment (CYFRA 21-1), squamous cell carcinoma antigen (SCC), and comorbid interstitial pneumonia (IP) were associated with the ratio of 5-year survivors significantly. When patients were compared based on tumor location, high p-stage and CYFRA 21-1 were related to central type SQ. Conclusion: Both SCC and CYFRA 21-1 appeared to be useful prognostic markers for patients with lung SQ. Furthermore, CYFRA 21-1 was related to central type SQ.

Analysis of Gene Expression Profile in Lung Adenosquamous Carcinoma Using cDNA Microarray

Gene expression profile of the lung adenosquamous carcinoma was characterized by using cDNA microarray chip containing 4 096 human genes. Among target genes, 508 differentially expressed genes were identified in adenosquamous carcinoma of the lung, 232 genes were overexpressed and 276 genes were underexpressed. Among them, 92 genes are cell signals transduction genes, 34 genes are proto-oncogenes and tumor suppressor genes or cell cycle related genes or cell apoptosis related genes, 29 genes are cell skeleton genes, 28 genes are DNA synthesis, repair and recombination genes, 12 genes are DNA binding and transcription genes. These genes may be associated with the occurence and development of adenosquamous carinome of the lung. Key words lung carcinoma - adenosquamous carcinoma - microarray - gene expression profile CLC number R 734.2 Foundation item: Supported by the National Natural Science Foundation of China (39870305)Biography: YANG Fei(1972-), female, Ph. D candidate, research direction: etiology and pathogenesis of lung cancer.

EGFR mutation identifies distant squamous cell carcinoma as metastasis from lung adenocarcinoma

Lung cancer metastasis is typically determined by histologic similarity between distant and primary lesions. Herein, we present a 70-year-old Japanese woman with an adenocarcinoma in her lung and a squamous cell carcinoma in her femur; both tumors had an identical epidermal growth factor receptor mutation, G719 S. This indicated that both tumors had a common origin, despite their histologic dissimilarity. The tumor in the femur was thus identified genetically as a lung cancer metastasis. This case suggests that genetic analysis can determine whether a distant lesion is a lung cancermetastasis, particularly when the histology differs from that of the primary lesion.

Chronic urticaria associated with lung adenocarcinoma—a paraneoplastic manifestation:A case report and literature review

BACKGROUND Urticaria is one of the most common causes of emergency room visits.It is defined as an acute inflammatory dermatosis,characterized by localized degranulation of mast cells,with consequent dermal microvascular and formation of edematous and pruritic plaques called hives.Urticaria affects the skin and tissues of the superficial mucosa.Sometimes it is accompanied by angioedema,which is characterized by deeper edema of the dermis and subcutaneous cellular tissue known as the urticarial-angioedema syndrome.About 15%-25%of the general population has suffered at least one type of urticaria at some point during their lifetime and hyperpermeability estimated at 7.6%-16%and has experienced acute urticaria that is usually self-limited and spontaneously resolves without requiring medical attention.CASE SUMMARY We present the case of a young male patient who was referred to our department with a clinical picture of 4 mo of pruritus associated with hives of variable sizes,irregular borders,with interlesional confluence,that were non-painful,without involvement of the palms and soles of the feet but with a tendency to progression in a generalized manner.He had multiple emergency room visits and poor response to antihistamines and systemic corticosteroids.Imaging studies demonstrated nodules in the lower lingula segment,at the level of the greater fissure and in the anterior contour of the left anterior basal segment associated with parahiliar adenopathies in the absence of findings suggestive of infectious or autoimmune etiology.Segmental lobectomy was performed by thoracoscopy with resection of a lung nodule in the lingula and biopsy of the para-aortic mediastinal ganglion.The histopathological report showed the presence of poorly differentiated invasive adenocarcinoma with a solid morphological and acinar pattern with immunohistochemical description of lung tissue that expresses strong positive and diffuse reaction for thyroid transcription factor 1(TTF-1)with negativity to P40 for a histopathological diagnosis of malignant epithelial neoplasia with expression of infiltrating adenocarcinoma.Spontaneous chronic urticaria is considered possibly secondary to lung adenocarcinoma.CONCLUSION Chronic spontaneous urticaria is considered a paraneoplastic dermatosis with a controversial association in the literature.In the presented case,a young patient presented with chronic refractory urticaria and after an exhaustive clinical work-up was found to have a diagnosis of poorly differentiated lung adenocarcinoma with high expression of TTF-1.According to the Curth criteria,the urticaria presented by the patient is related to the oncological diagnosis.In addition,the high expression of TTF-1 documented in this case could be acting as an autoantigen that would cause chronic spontaneous urticaria.Further research evaluating a causal relationship between the TFF-1 protein and urticaria in lung cancer is needed.

Primary pulmonary lymphoepithelioma-like carcinoma misdiagnosed as lung squamous cell carcinoma:A case report

BACKGROUND Primary pulmonary lymphoepithelioma-like carcinoma(PPLELC)is an uncommon subtype of squamous cell carcinoma(SCC)of the lung,closely associated with Epstein-Barr virus(EBV)infection.The pathological features of PPLELC closely resemble those of SCC,which makes it prone to misdiagnosis.Surgical intervention constitutes the primary treatment approach for PPLELC.CASE SUMMARY This report describes a 44-year-old woman who was hospitalized for 1 mo due to left chest pain.Computed tomography revealed a mass shadow in the anterior basal segment of the left lower lobe,and a subsequent needle biopsy suggested SCC.The patient underwent radical tumor resection in the lower left lobe of the lung,and postoperative pathological examination indicated lymphoepithelial carcinoma,and the test for EBV encoded small RNA was positive.Following surgery,the patient was scheduled to receive four cycles of adjuvant chemotherapy,using the paclitaxel+carboplatin regimen,but the patient refused further treatment.CONCLUSION PPLELC is an exceptionally rare subtype of lung SCC and is prone to misdiagnosis.

Relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma

Objective:To study the relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma.Methods:A total of 297 patients from July 2009 to May 2013 were chosen as objects.EGFR gene mutation were detected with fluorescence quantitative PCR.Relevance of EGFR gene mutation with clinical and pathological features was analyzed,and the prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was compared.Results:In 297 patients.136(45.79%) showed EGFR gene mutation.EGFR gene mutation had no significant relevance with age.gender,smoking history,family history of cancer and clinical stage(P>0.05);there was significant relevance between EGFR gene mutation and blood type,pathologic types,differentiation and diameter of cancer(P<0.05).The difference between prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was statistical significance(P<0.05).Conclusions:EGFR gene mutation has significant relevance with pathological features,the prognosis of EGFRmutant-paticnts is better than that of EGFR- wide type-patients.

Inhibitory Effect of MiR-449b on Cancer Cell Growth and Invasion through LGR4 in Non-Small-Cell Lung Carcinoma

Non-small-cell lung carcinoma （NSCLC） is one of the most frequently diagnosed malignancies worldwide. Previous studies have shown that microRNA-449b （miR-449b） functions as a tumor suppressor in many cancers. However, the role of miR- 449b in NSCLC is still unknown. In the present study, miR-449b was significantly down- regulated in NSCLC samples and cell lines. Bioinformatics analysis revealed that 3＇-UTR region of leucine rich repeat containing G protein-coupled receptor 4 （LGR4） mRNA had putative complementary sequences to miR-449b, which was further confirmed by the luciferase assay. Western blotting showed that restoration of miR-449b in NSCLC cells decreased the expression of LGR4. Interestingly, over-expression of miR-449b inhibited growth and invasion of NSCLC cells in vitro. Furthermore, ectopic expression of LGR4 reversed miR-449b-suppressed proliferation and invasion of NSCLC cells. Therefore, the data of the present study demonstrate that miR-449b inhibits tumor cell growth and invasion by targeting LGR4 in NSCLC.

Concomitant lung metastasis in patients with advanced hepatocellular carcinoma

AIM:To investigate the clinical features and prognostic factors of advanced hepatocellular carcinoma (HCC)patients presenting with lung metastasis at initial diagnosis. METHODS:Between 2001 and 2010,we recruited 76 consecutive HCC patients initially presenting with lung metastasis,without co-existing metastasis from other sites.These patients were divided into three groups:untreated group(n=22),single treatment group(n= 19),and combined treatment group(n=35). RESULTS:Metastasis of bilateral lung lobes was common and noted in 35 patients(46.1%),and most of patients(59/76,77.6%)presented with multiple lung metastatic nodules.Nineteen patients(25.0%) received single-method treatment,including hepatectomy in 4,transcatheter arterial chemoembolization in 6,radiotherapy in 5,and oral sorafenib in 4.Thirty-five patients(46.1%)received combined treatment modalities.The overall median survival of the all patients was 8.7±0.6 mo;4.1±0.3,6.3±2.5 and 18.6±3.9 mo, respectively in the untreated group,single treatment group and combined treatment group,respectively, with a significant difference(log-rank test,P<0.001). Multivariate analysis revealed that Child-Pugh score, the absence or presence of portal vein tumor thrombus,and treatment modality were three independent prognostic factors affecting survival of patients with advanced HCC and concomitant lung metastasis. CONCLUSION:Combined treatment modalities tend to result in a better survival as compared with the conservative treatment or single treatment modality for HCC patients initially presenting with lung metastasis.

Mechanism of miR-21 via Wnt/β-catenin signaling pathway in human A549 lung cancer cells and Lewis lung carcinoma in mice

Objective:To study the mechanism of effect of miR-21 via Wnt/ β-catenin signaling pathway in human A549 lung cancer cells and Lewis lung carcinoma in mice.Methods:The effect of miR-21 on A549 cells were detected by MTT method.MiR-21 expression levels were overexpressed or inhibited in A549 cells by transfecting with miR-21 mimics or inhibitors.Correlation among key molecules(Wnt1,β-catenin.CyclinD1 and miR-21) of mRNA and protein levels in Wnt/β-catenin signaling pathway were studied by Real-time PCR and Western blot hybridization assay.Invasive ability of A549 cells was determined via Transwell chamber cell invasion assay;the role of miR-21 in A549 cells was explored via the Wnt/β-catenin signaling pathway.A Lewis lung carcinoma animal model was established to detect miR-21 expressions in tumor animals and controlled animal tissues,and verify expression changes of the above moleculesin the Wnt / β-catenin signaling pathway was determined in the animal level.Results:MTT assay results showed that miR-21 overexpression could markedly enhance cell absorbance value;that is,miR-21 could increase the ability proliferation of A549 cells.β-catenin and CyclinD1 expression levels were significantly higher in miR-21 mimic transfected cells(P<0.05),and Wnt 1 gene had no significant change.Wnt 1,β-catenin and CyclinD1 gene expression showed no significant change when miR-21 expression was suppressed,compared with controls.After cells were transfected with miR-21 mimics,cell invasion assay revealed that the perforated cells was significantly higher than the perforated cells in the control group(P<0.01).Lewis lung assay revealed that miR-21 expression levels in the Lewis lung carcinoma were significantly higher;and at the same time.Wnt1,β-catenin and CyclinD1 gene expression levels were significantly increased,compared to controls.Conclusions:In A549 human lung cancer cells and Lewis lung carcinoma in mice,key molecules β-catenin and CyclinD1 of miR-21 expressions and the Wnt/ β-catenin signaling pathway are positively correlated.