• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3577-3581
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• 2012

Small cell lung cancer (SCLC) is characterized by a short cell doubling time, rapid progression and early occurrence of blood-borne and lymph metastasis. The malignancy is the highest of all lung cancer types. Although SCLC has a relatively good initial response to chemotherapy as well as radiotherapy, relapse or disease progression may occur quickly after the initial treatment. Drug resistance, especially multi-drug resistance, is the most important cause of failure of SCLC chemotherapy. This article provides a brief update of research on mechanisms of drug resistance in SCLC and reversal strategies.

• Development and Reproduction
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• v.27 no.1
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• pp.1-7
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• 2023

Small-cell lung cancer (SCLC) continues to be the deadliest of all lung cancer types. Its high mortality is largely attributed to the unchangeable development of resistance to standard chemo/radiotherapies, which have remained invariable for the past 30 years, underlining the need for new therapeutic approaches. Recent studies of SCLC genome revealed a large number of somatic alterations and identified remarkable heterogeneity of the frequent mutations except for the loss of both RB and P53 tumor suppressor genes (TSGs). Identifying the somatic alterations scattered throughout the SCLC genome will help to define the underlying mechanism of the disease and pave the way for the discovery of therapeutic vulnerabilities associated with genomic alterations. The new technique made it possible to determine the underlying mechanism for the discovery of therapeutic targets. To these ends, the techniques have been focused on understanding the molecular determinants of SCLC.

• Tuberculosis and Respiratory Diseases
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• v.48 no.1
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• pp.72-77
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• 2000

A proper pathologic diagnosis of small cell lung cancer(SCLC) is essential for the application of aggressive treatment modalities. However, various authors have suggested several subtypes of SCLC based on morphological features. Among them, the incidence of small cell lung cancer(SCLC) combined with squamous cell and/or adenocarcinoma, represents less than 1% to 3% of all SCLC tumors. Because of the rarity of SCLC combined with squamous cell and/or adenocarcinoma, very little is known about its clinical characteristics and response to therapy. We report a case of SCLC combined with squamous cell and adenocarcinoma in a 68 year old male who experienced pneumonectomy of the left lung.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.6
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• pp.229-234
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• 2022

Lung cancer is the leading cause of cancer-related deaths worldwide. Indigo Naturalis (IN) is a dark blue powder obtained by processing leaves or stems of indigo plants, its anticancer effects have been reported in several studies. However, the pharmacological mechanism of IN in small cell lung cancer (SCLC) is not elucidated. In this study, to investigate the anticancer efficacy of IN for SCLC, we presented potential active ingredients, SCLC-related targets, and pharmacological mechanisms of IN that are expected to have anticancer activity for SCLC using a network pharmacological analysis. The phytochemical compounds of IN have been collected through TCMSP, SymMap, or HPLC documents. The active ingredients of IN such as indirubin, indican, isatin, and tryptanthrin were selected through ADME parameters or literature investigations for each compound. Using the Compounds, Disease-Target associations Databases, 124 common targets of IN and SCLC were obtained. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment analysis was carried out. GO biological processes are associated with response to xenobiotic stimulus, positive regulation of protein phosphorylation, regulation of mitotic cell cycle, and regulation of apoptotic signaling pathway. KEGG disease pathways included Gastric cancer, Bladder cancer, SCLC, and Melanoma. The main anticancer targets of the IN for SCLC were analyzed in 14 targets, including BCL2, MYC, and TP53. In conclusion, the results of this study based on the network pharmacology of IN can provide important data for the effective prevention and treatment of SCLC.

• Biomolecules & Therapeutics
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• v.12 no.2
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• pp.92-100
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• 2004

Effect of the depletion or oxidation of GSH on mitomycin c (MMC)-induced mitochondrial damage and cell death was assessed in small cell lung cancer (SCLC) cells. MMC induced cell death and the decrease in the GSH contents in SCLC cells, which were inhibited by z-LEHD.fmk (a cell permeable inhibitor of caspase-9), z-DQMD.fmk (a cell permeable inhibitor of caspase-3) and thiol compound, N-acetylcysteine. MMC caused nuclear damage, release of cytochrome c and activation of caspase-3, which were reduced by N-acetylcysteine. The depletion of GSH due to L-butionine-sulfoximine enhanced the MMC-induced cell death and formation of reactive oxygen species in SCLC cells, whereas the oxidation of GSH due to diamide or $NH_2Cl$ did not affect cytotoxicity of MMC. The results show that MMC may cause cell death in SCLC cells by inducing mitochondrial dysfunction, leading to activation of caspase-9 and -3. The MMC-induced change in the mitochondrial membrane permeability, followed by cell death, in SCLC cells may be significantly enhanced by the depletion of GSH. In contrast, the oxidation of GSH may not affect cytotoxicity of MMC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8429-8433
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• 2014

Circulating tumor cells (CTCs) are believed to be particularly important and a reliable marker of malignancy. However, the prognostic significance of CTCs detected in patients with small cell lung cancer (SCLC) is still unclear. We therefore aimed to assess the prognostic relevance of CTCs using a meta-analysis. We searched PubMed for relevant studies and statistical analyses were conducted to calculate the hazard ratio (HR) and 95% confidence intervals (CIs) using fixed or random-effect models according to the heterogeneity of included studies. A total of 7 papers covering 440 SCLC patients were combined in the final analysis. The meta-analysis revealed that CTCs were significantly associated with shorter overall survival (HR=1.9; 95%CI: 1.19-3.04; Z=2.67; P<0.0001) and progression-free survival (HR=2.6; 95%CI: 1.9-3.54; Z=6.04; P<0.0001). The results thus suggest that the presence of CTCs indicates a poor prognosis in patients with SCLC. Further well-designed prospective studies are required to explore the clinical applications of CTCs in SCLC.

• Journal of Chest Surgery
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• v.50 no.3
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• pp.153-162
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• 2017

Background: The mesenchymal-epithelial transition factor (MET) receptor can be overexpressed in solid tumors, including small cell lung cancer (SCLC). However, the molecular mechanism regulating MET stability and turnover in SCLC remains undefined. One potential mechanism of MET regulation involves the C-terminus of Hsp70-interacting protein (CHIP), which targets heat shock protein 90-interacting proteins for ubiquitination and proteasomal degradation. In the present study, we investigated the functional effects of CHIP expression on MET regulation and the control of SCLC cell apoptosis and invasion. Methods: To evaluate the expression of CHIP and c-Met, which is a protein that in humans is encoded by the MET gene (the MET proto-oncogene), we examined the expression pattern of c-Met and CHIP in SCLC cell lines by western blotting. To investigate whether CHIP overexpression reduced cell proliferation and invasive activity in SCLC cell lines, we transfected cells with CHIP and performed a cell viability assay and cellular apoptosis assays. Results: We found an inverse relationship between the expression of CHIP and MET in SCLC cell lines (n=5). CHIP destabilized the endogenous MET receptor in SCLC cell lines, indicating an essential role for CHIP in the regulation of MET degradation. In addition, CHIP inhibited MET-dependent pathways, and invasion, cell growth, and apoptosis were reduced by CHIP overexpression in SCLC cell lines. Conclusion: C HIP is capable of regulating SCLC cell apoptosis and invasion by inhibiting MET-mediated cytoskeletal and cell survival pathways in NCI-H69 cells. CHIP suppresses MET-dependent signaling, and regulates MET-mediated SCLC motility.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.453-456
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• 2013

Introduction: Lung cancer, the leading cause of cancer deaths, is divided into 2 main classes based on its biology, therapy and prognosis: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Many cases are at an advanced stage at diagnosis, which is a major obstacle to improving outcomes. It is important to define the high risk group patients for early diagnosis and chance of cure. Blood group antigens are chemical components on erythrocyte membranes but they are also expressed on a variety of epithelial cells. Links between ABO blood groups with benign or malignant diseases, such as gastric and pancreas cancers, have been observed for a long time. In this study, we aimed to investigate any possible relationship between lung cancer histological subtypes and ABO-Rh blood groups. Materials and Methods: The files of 307 pathologically confirmed lung cancer patients were reviewed retrospectively. Cases with a serologically determined blood group and Rh factor were included and those with a history of another primary cancer were excluded, leaving a total of 221. The distribution of blood groups of the lung cancer patients were compared with the distribution of blood groups of healthy donors admitted to the Turkish Red Crescent Blood Service in our city in the year 2012. Results: There was no significant difference between patients with lung cancer of either type and the control group in terms of distribution of ABO blood groups and Rh factor (p: 0.073). There was also no relationship with non small cell cancer histological subtypes. Conclusions: In this study, we found no relationship between the ABO-Rhesus blood groups and NSCLC and SCLC groups. To our knowledge this is the first analysis of ABO blood groups in SCLC patients.

• Toxicological Research
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• v.18 no.4
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• pp.411-416
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• 2002

Apoptosis, or programmed cell death, is a genetically regulated pathway that is altered in many cancers. Overexpression of bcl-2 leads to resistance to apoptosis and promotes tumorigenesis. To determine the effect of bcl-2 antisense treatment in human lung cancer cell lines, a 20 mer full phosphorothioate oligonucleotide (ODN) targeted at the coding region of the bcl-2 mRNA was synthesized. Western blot analyses were used to examine bcl-2 protein level in five human non-small cell lung cancer (NSCLC) cell lines (NCI-H226, SK-MES-1 NCI-H358, NCI-H522 and NCI-Hl 299) and four human small cell lung cancer (SCLC) cell lines (NCI-H69, NCI-H4l7, HCC-2108 and SW2). Three out of five NSCLC (NCI-H226, SK-MES-1 and NCI-Hl 299) and all of SCLC cell lines expressed Bcl-2 protein. Treatment of these cell with antisense ODN for 48 hours reduced their viability and Bcl-2 protein level. As a conclusion, bcl-2 antisense treatment appears reduction of the Bcl-2 protein levels and cytotoxic effect including apoptosis in human lung cancer cell lines.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2873-2877
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• 2012

Objective: To determine STAT3, P-STAT3, and VEGF-C expression levels in small cell lung cancers (SCLCs), and discuss their role and clinical significance in SCLC development. Method: Immunohistochemical methods were applied to 128 cases of SCLC and 40 cases of adjacent normal tissue. Results: The expression levels of STAT3, P-STAT3, and VEGF-C were higher in SCLC than in normal tissue (P<0.05). Pairwise comparisons showed positive correlations with lymph node metastasis, clinical stage, and tumor size (P<0.05). The expression levels were also related with the overall survival rates. Conclusion: STAT3 and VEGF-C play important roles in the development of SCLC, and might be expected to become new targets for SCLC treatment.