Qiang Lin

Bio: Qiang Lin is an academic researcher from Shanghai Jiao Tong University. The author has contributed to research in topics: Lung cancer & Cell growth. The author has an hindex of 15, co-authored 28 publications receiving 497 citations. Previous affiliations of Qiang Lin include Soochow University (Suzhou).

Multi-slice computed tomography characteristics of solitary pulmonary ground-glass nodules: Differences between malignant and benign.

Abstract: Background Ground-glass nodules (GGNs), which are possible precursors of lung cancer, attract increasing attention. Many studies have attempted to identify the characteristic imaging features of GGNs for their qualitative diagnosis; however, the comprehension of GGNs remains controversial. We performed this study to identify imaging characteristics helpful to the differential diagnosis of solitary GGNs. Methods We retrospectively evaluated 112 solitary GGNs resected from 112 patients, pathologically examined after surgical resection. Imaging features of the GGNs, such as size, shape, a solid component, lobulation, spiculation, vascular convergence sign, pleural tag, and air cavity density, were assessed. Differences between malignant and benign nodules were analyzed using binary logistic regression analysis. Results Of the 112 GGNs, 82 were malignant and 30 were benign. A solid component, vascular convergence sign, and a larger diameter were risk factors for malignancy, with a sensitivity, specificity, and accuracy of 93.9%, 60.0%, and 84.8%, respectively. Lobulation, spiculation, air cavity densities, and pleural tags were also important indicators of malignancy, with positive predictive values of 93.5%, 83.3%, 91.7%, and 87.2%, respectively. Conclusion GGNs with a solid component, vascular convergence sign, and a larger diameter are highly suggestive of malignancy. The possibility of a neoplasm should also be considered in the case of GGNs that show lobulation, spiculation, air cavity densities, or pleural tags. To obtain a comprehensive and accurate analysis of the nodules, three-dimensional reconstruction is highly recommended.

RASSF1A, APC, ESR1, ABCB1 and HOXC9, but not p16INK4A, DAPK1, PTEN and MT1G genes were frequently methylated in the stage I non-small cell lung cancer in China

Abstract: To identify the DNA methylation biomarkers for the detection of the stage I non-small cell lung cancer (NSCLC). The methylated state of p16INK4A, ESR1, HOX9, RASSF1A, DAPK1, PTEN, ABCB1, MGMT, APC and MT1G genes that have been reported frequently methylated in lung cancer was determined using methylation-specific PCR in four lung cancer cell lines, 124 cancer tissues of the stage I NSCLC and 26 non-cancerous disease tissues. The RASSF1A (53/124, 42.74%), APC (49/123, 39.52%), ESR1 (37/124, 29.84%), ABCB1 (31/124, 24.19%, MT1G (25/124, 20.16%) and HOXC9 (17/124, 13.71%) genes were more frequently methylated in the lung tissue from the stage I NSCLC than the non-cancerous lesion patients (2/26, 7.69%, P 0.05). No significant association between the methylated state of the genes and the smoking, age or the pathologic types (squamous carcinoma, adenoma and the mixed types) was found. However, p16INK4A methylation was more frequently detected in the male (23/80, 28.75%) than the female (5/44, 11.36%, P > 0.05) patients. MGMT was barely methylated: 1/67, 1.49%), while DAPK1 and PTEN were not at all methylated in the cancer groups. Methylation analysis in tissue of RASSF1A, APC, ESR1, ABCB1 and HOXC9 genes confirmed 79.8% of the existing diagnosis for the stage I NSCLC at specificity: 73.1%. The insufficiency of predicting disease onset in China, using the previously recommended targets (MGMT, DAPK1 and PTEN) in the United States reflects a potential disease disparity between these two populations. Alternatively, methylated state of this set of genes may be more specific to the late rather than the early stage of NSCLC.

Effect of chronic restraint stress on human colorectal carcinoma growth in mice.

Abstract: Stress alters immunological and neuroendocrinological functions. An increasing number of studies indicate that chronic stress can accelerate tumor growth, but its role in colorectal carcinoma (CRC) progression is not well understood. The aim of this study is to investigate the effects of chronic restraint stress (CRS) on CRC cell growth in nude mice and the possible underlying mechanisms. In this study, we showed that CRS increased the levels of plasma catecholamines including epinephrine (E) and norepinephrine (NE), and stimulated the growth of CRC cell-derived tumors in vivo. Treatment with the adrenoceptor (AR) antagonists phentolamine (PHE, α-AR antagonist) and propranolol (PRO, β-AR antagonist) significantly inhibited the CRS-enhanced CRC cell growth in nude mice. In addition, the stress hormones E and NE remarkably enhanced CRC cell proliferation and viability in culture, as well as tumor growth in vivo. These effects were antagonized by the AR antagonists PHE and PRO, indicating that the stress hormone-induced CRC cell proliferation is AR dependent. We also observed that the β-AR antagonists atenolol (ATE, β1- AR antagonist) and ICI 118,551 (ICI, β2- AR antagonist) inhibited tumor cell proliferation and decreased the stress hormone-induced phosphorylation of extracellular signal-regulated kinases-1/2 (ERK1/2) in vitro and in vivo. The ERK1/2 inhibitor U0126 also blocked the function of the stress hormone, suggesting the involvement of ERK1/2 in the tumor-promoting effect of CRS. We conclude that CRS promotes CRC xenograft tumor growth in nude mice by stimulating CRC cell proliferation through the AR signaling-dependent activation of ERK1/2.

FKBP3 Promotes Proliferation of Non-Small Cell Lung Cancer Cells through Regulating Sp1/HDAC2/p27.

Abstract: FKBP3 is a member of FK506-binding proteins (FKBPs). Little is known about the expression and functional role(s) of FKBP3 in non-small cell lung cancer (NSCLC). In the present study, we demonstrated up-regulation of FKBP3 expression, both at mRNA and protein levels, in NSCLC samples which closely correlated with poor survival in NSCLC patients. In vitro and in vivo experiments revealed that FKBP3 could promote NSCLC cell proliferation. Furthermore, knockdown of FKBP3 significantly decreased histone deacetylase 2 (HDAC2) expression and increased p27 (a cell cycle inhibitor) expression. HDAC2 modulated the acetylation of histone H3K4 by directly binding to the p27 promoter. The proliferation-promoting effect of FKBP3 was dependent on HDAC2 and inhibited by p27. Also, FKBP3 induced HDAC2 promoter activity via inhibiting the ubiquitination of transcription factor Sp1. Additionally, we identified miR-145-5p as a regulator of FKBP3. miR-145-5p overexpression suppressed cell proliferation of NSCLC cells which was abrogated by FKBP3 overexpression. Taken together, our data clearly show that FKBP3/Sp1/HDAC2/p27 control cell proliferation during NSCLC development.

Role of high expression levels of STK39 in the growth, migration and invasion of non-small cell type lung cancer cells.

Abstract: // Zhao Li 1, * , Wenzhuo Zhu 1, * , Liwen Xiong 2 , Xiaobo Yu 1 , Xi Chen 1 , Qiang Lin 1 1 Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 2 Department of Pulmonary Diseases, Shanghai Chest Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China * These authors contributed equally to this work Correspondence to: Qiang Lin, email: xklinqiang@hotmail.com Keywords: STK39, NSCLC, proliferation, metastasis Received: June 07, 2016 Accepted: July 30, 2016 Published: August 17, 2016 ABSTRACT Non-small cell type lung cancer (NSCLC) is the most common malignancy and the leading cause of cancer related mortality. In this study, serine/threonine kinase 39 (STK39) was identified as an up-regulated gene in NSCLC tissues by next-generation RNA sequencing. Although STK39 gene polymorphisms may be prognostic of overall survival in patients with early stage NSCLC, the roles of STK39 in NSCLC cancer are poorly understood. In the current study, Genome Set Enrichment Analysis (GSEA) on the RNA-seq data of NSCLC specimens indicated that cancer-related process and pathways, including metastasis, cell cycle, apoptosis and p38 pathway, were significantly correlated with STK39 expression. STK39 expression was significantly increased in NSCLC cases and its protein expression was positively correlated with the poor tumor stage, large tumor size, advanced lymphnode metastasis and poor prognosis. Down-regulation of STK39 in NSCLC cells significantly decreased cell proliferation by blocking of cell cycle and inducing apoptosis. We also found that STK39 knockdown in NSCLC cells remarkably repressed cell migration and invasion. On the contrary, overexpression of STK39 in NSCLC cells had inverse effects on cell behaviors. Taken together, STK39 acts as a tumor oncogene in NSCLC and can be a potential biomarker of carcinogenesis.

Molecular principles of metastasis: a hallmark of cancer revisited

Abstract: Metastasis is the hallmark of cancer that is responsible for the greatest number of cancer-related deaths. Yet, it remains poorly understood. The continuous evolution of cancer biology research and the emergence of new paradigms in the study of metastasis have revealed some of the molecular underpinnings of this dissemination process. The invading tumor cell, on its way to the target site, interacts with other proteins and cells. Recognition of these interactions improved the understanding of some of the biological principles of the metastatic cell that govern its mobility and plasticity. Communication with the tumor microenvironment allows invading cancer cells to overcome stromal challenges, settle, and colonize. These characteristics of cancer cells are driven by genetic and epigenetic modifications within the tumor cell itself and its microenvironment. Establishing the biological mechanisms of the metastatic process is crucial in finding open therapeutic windows for successful interventions. In this review, the authors explore the recent advancements in the field of metastasis and highlight the latest insights that contribute to shaping this hallmark of cancer.

Role of interleukin-6 in cancer progression and therapeutic resistance

Abstract: In the last several decades, the number of people dying from cancer-related deaths has not reduced significantly despite phenomenal advances in the technologies related to diagnosis and therapeutic modalities The principal cause behind limitations in the curability of this disease is the reducing sensitivity of the cancer cells towards conventional anticancer therapeutic modalities, particularly in advance stages of the disease Amongst several reasons, certain secretory factors released by the tumour cells into the microenvironment have been found to confer resistance towards chemo- and radiotherapy, besides promoting growth Interleukin-6 (IL-6), one of the major cytokines in the tumour microenvironment, is an important factor which is found at high concentrations and known to be deregulated in cancer Its overexpression has been reported in almost all types of tumours The strong association between inflammation and cancer is reflected by the high IL-6 levels in the tumour microenvironment, where it promotes tumorigenesis by regulating all hallmarks of cancer and multiple signalling pathways, including apoptosis, survival, proliferation, angiogenesis, invasiveness and metastasis, and, most importantly, the metabolism Moreover, IL-6 protects the cancer cells from therapy-induced DNA damage, oxidative stress and apoptosis by facilitating the repair and induction of countersignalling (antioxidant and anti-apoptotic/pro-survival) pathways Therefore, blocking IL-6 or inhibiting its associated signalling independently or in combination with conventional anticancer therapies could be a potential therapeutic strategy for the treatment of cancers with IL-6-dominated signalling

Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials.

Abstract: Epigenetic alternations concern heritable yet reversible changes in histone or DNA modifications that regulate gene activity beyond the underlying sequence. Epigenetic dysregulation is often linked to human disease, notably cancer. With the development of various drugs targeting epigenetic regulators, epigenetic-targeted therapy has been applied in the treatment of hematological malignancies and has exhibited viable therapeutic potential for solid tumors in preclinical and clinical trials. In this review, we summarize the aberrant functions of enzymes in DNA methylation, histone acetylation and histone methylation during tumor progression and highlight the development of inhibitors of or drugs targeted at epigenetic enzymes.

Sympathetic nervous system regulation of the tumour microenvironment

Abstract: The peripheral autonomic nervous system (ANS) is known to regulate gene expression in primary tumours and their surrounding microenvironment. Activation of the sympathetic division of the ANS in particular modulates gene expression programmes that promote metastasis of solid tumours by stimulating macrophage infiltration, inflammation, angiogenesis, epithelial-mesenchymal transition and tumour invasion, and by inhibiting cellular immune responses and programmed cell death. Haematological cancers are modulated by sympathetic nervous system (SNS) regulation of stem cell biology and haematopoietic differentiation programmes. In addition to identifying a molecular basis for physiologic stress effects on cancer, these findings have also identified new pharmacological strategies to inhibit cancer progression in vivo.

The solitary pulmonary nodule.

Abstract: This study is a clinical pathological correlation based on 887 resected pulmonary masses. Because of the nature of the study and the source of the material there is a certain amount of selection. The patients were all males, and they had all been healthy enough to have been inducted into the armed services. Only 16 of 887 had significant other pulmonary disease. While the author draws few conclusions, the monograph itself asserts some very forceful points: second primary malignancies can and do occur and may present as pulmonary nodules; pulmonary granulomas can occur in patients with history of malignancy elsewhere; benign tumors of the lung can occur in patients who have had a previous malignancy; preoperative examination with bronchoscopy, cytologic study of the sputum, and scalene node biopsy offer a very low yield of positive diagnoses in pulmonary nodules; size cannot be used as a criterion for determining malignancy; tuberculosis