• International Journal of Advanced Culture Technology
• /
• v.6 no.4
• /
• pp.275-283
• /
• 2018

Cancer show distinct pattern of gene expression when it is compared to normal. This difference results malignant characteristic of cancer. Many cancer drugs are targeting this difference so that it can selectively kill cancer cells. One of the recent demand for personalized treating cancer is retrieving normal tissue from a patient so that the gene expression difference between cancer and normal be assessed. However, in most clinical situation it is hard to retrieve normal tissue from a patient. This is because biopsy of normal tissues may cause damage to the organ function or a risk of infection or side effect what a patient to take. Thus, there is a challenge to estimate normal cell's gene expression where cancers are originated from without taking additional biopsy. In this paper, we propose in-silico based prediction of normal cell's gene expression from gene expression data of a tumor sample. We call this challenge as reverting the cancer into normal. We divided this challenge into two parts. The first part is making a generator that is able to fool a pretrained discriminator. Pretrained discriminator is from the training of public data (9,601 cancers, 7,240 normals) which shows 0.997 of accuracy to discriminate if a given gene expression pattern is cancer or normal. Deceiving this pretrained discriminator means our method is capable of generating very normal-like gene expression data. The second part of the challenge is to address whether generated normal is similar to true reverse form of the input cancer data. We used, cycle-consistent adversarial networks to approach our challenges, since this network is capable of translating one domain to the other while maintaining original domain's feature and at the same time adding the new domain's feature. We evaluated that, if we put cancer data into a cycle-consistent adversarial network, it could retain most of the information from the input (cancer) and at the same time change the data into normal. We also evaluated if this generated gene expression of normal tissue would be the biological reverse form of the gene expression of cancer used as an input.

• Molecules and Cells
• /
• v.45 no.6
• /
• pp.388-402
• /
• 2022

Malignant meningiomas often show invasive growth that makes complete tumor resection challenging, and they are more prone to recur after radical resection. Invasive meningioma associated transcript 1 (IMAT1) is a long noncoding RNA located on Homo sapiens chromosome 17 that was identified by our team based on absolute expression differences in invasive and non-invasive meningiomas. Our studies indicated that IMAT1 was highly expressed in invasive meningiomas compared with non-invasive meningiomas. In vitro studies showed that IMAT1 promoted meningioma cell invasion through the inactivation of the Krüppel-like factor 4 (KLF4)/hsa-miR22-3p/Snai1 pathway by acting as a sponge for hsa-miR22-3p, and IMAT1 knockdown effectively restored the tumor suppressive properties of KLF4 by preserving its tumor suppressor pathway. In vivo experiments confirmed that IMAT1 silencing could significantly inhibit the growth of subcutaneous tumors and prolong the survival period of tumor-bearing mice. Our findings demonstrated that the high expression of IMAT1 is the inherent reason for the loss of the tumor suppressive properties of KLF4 during meningioma progression. Therefore, we believe that IMAT1 may be a potential biological marker and treatment target for meningiomas.

• BMB Reports
• /
• v.55 no.12
• /
• pp.615-620
• /
• 2022

The murine leukemia virus-based semi-retroviral replicating vectors (MuLV-based sRRV) had been developed to improve safety and transgene capacity for cancer gene therapy. However, despite the apparent advantages of the sRRV, improvements in the in vivo transduction efficiency are still required to deliver therapeutic genes efficiently for clinical use. In this study, we established a gibbon ape leukemia virus (GaLV) envelope-pseudotyped semi-replication-competent retrovirus vector system (spRRV) which is composed of two transcomplementing replication-defective retroviral vectors termed MuLV-Gag-Pol and GaLV-Env. We found that the spRRV shows considerable improvement in efficiencies of gene transfer and spreading in both human glioblastoma cells and pre-established human glioblastoma mouse model compared with an sRRV system. When treated with ganciclovir after intratumoral injection of each vector system into pre-established U-87 MG glioblastomas, the group of mice injected with spRRV expressing the herpes simplex virus type 1-thymidine kinase (HSV1-tk) gene showed a survival rate of 100% for more than 150 days, but all control groups of mice (HSV1-tk/PBS-treated and GFP/GCV-treated groups) died within 45 days after tumor injection. In conclusion, these findings sug-gest that intratumoral delivery of the HSV1-tk gene by the spRRV system is worthy of development in clinical trials for the treatment of malignant solid tumors.

• Journal of Digestive Cancer Research
• /
• v.6 no.1
• /
• pp.40-44
• /
• 2018

A 77-year-old man presented with abdominal discomfort and was diagnosed as Borrmann type 3 advanced gastric cancer with multiple lymph node metastases. An abdominal computed tomography (CT) and positron emission tomography-computed tomography (PET-CT) showed AGC, clinical stage IIIC (T4aN3M0). We started neo-adjuvant chemotherapy with FOLFOX (5-fluorouracil (5-FU))+Leucovorin+Oxaliplatin). After 3 cycles of FOLFOX chemotherapy, follow-up endoscopy showed remarkable improvement. Primary lesion and metastatic lymph nodes decreased size on follow up computed tomography (CT). The patient underwent radical total gastrectomy with esophagojejunostomy and histopathology revealed no remnant malignant cells at previous primary cancer lesion. The patient has currently completed his 3 cycle of adjuvant chemotherapy without recurrence. After an abdominal CT response assessment, further course of therapy will be decided.

• Advances in nano research
• /
• v.15 no.5
• /
• pp.451-466
• /
• 2023

Gastrointestinal cancer (GC) is a prevalent malignant tumor of the digestive system that poses a severe health risk to humans. Due to the specific organ structure of the gastrointestinal system, both endoscopic and MRI diagnoses of GIC have limited sensitivity. The primary factors influencing curative efficacy in GIC patients are drug inefficacy and high recurrence rates in surgical and pharmacological therapy. Due to its unique optical features, good biocompatibility, surface effects, and small size effects, nanotechnology is a developing and advanced area of study for the detection and treatment of cancer. Because of its deep location and complex surgery, diagnosing and treating gastrointestinal cancer is very difficult. The early diagnosis and urgent treatment of gastrointestinal illness are enabled by nanotechnology. As diagnostic and therapeutic tools, nanoparticles directly target tumor cells, allowing their detection and removal. XGBoost was used as a classification method known for achieving numerous winning solutions in data analysis competitions, to capture nonlinear relations among many input variables and outcomes using the boosting approach to machine learning. The research sample included 300 GC patients, comprising 190 males (72.2% of the sample) and 110 women (27.8%). Using convolutional neural networks (CNN) and artificial neural networks (ANN)-EXtreme Gradient Boosting (XGBoost), the patients mean± SD age was 50.42 ± 13.06. High-risk behaviors (P = 0.070), age at diagnosis (P = 0.037), distant metastasis (P = 0.004), and tumor stage (P = 0.015) were shown to have a statistically significant link with GC patient survival. AUC was 0.92, sensitivity was 81.5%, specificity was 90.5%, and accuracy was 84.7 when analyzing stomach picture.

• Tuberculosis and Respiratory Diseases
• /
• v.40 no.2
• /
• pp.177-184
• /
• 1993

Background: Accurate staging of bronchogenic carcinoma is important in determining resectability and metastasis of tumor to the subcarinal nodes is generally believed to indicate poor prognosis. The technique of Transbronchial needle aspiration (TBNA) has offered a safe & effective way to asscess mediastinal lymph node involvement in the staging of lung cancer. We performed TBNA in patients who were suspected lung cancer to evaluate the clinical usefulness of the TBNA. Method: TBNA of the subcarinal lymph node was performed at the time of initial diagnostic bronchoscopy in 60 patients with suspected lung cancer, and 42 cases of histologically proved bronchogenic cancer were analized. Results: The frequency of adequate samples by transbronchial needle aspiration (TBNA) was 81% and the positive rate of malignant cells by TBNA was 14.7%. There were no differences in positive rates by tumor cell types. In patients with thickened carina on bronchoscopy, the TBNA was positive in 33.3% as compared to 5.3% of normal carina on bronchoscopy, and the difference was statistically significant (p<0.05). In patients with enlarged subcarinal lymph node on chest CT, the positive rate of malignant cells (50.0%) was higher than that of normal sized subcarinal lymph node on chest CT (4.8%) (p<0.01). There were no specific complications in the TBNA procedure. Conclusion: TBNA is a relatively safe procedure and it offers the possibility of avoiding the cost and morbidity of surgical staging in patients especially whose carina is thickened on bronchoscopy and whose subcarinal LN was enlarged on chest CT.

• Tuberculosis and Respiratory Diseases
• /
• v.62 no.5
• /
• pp.427-431
• /
• 2007

The bronchus-asociated lymphoid tissue(BALT) lymphoma is a low-grade primary malignant lymphoma that originates from bronchus associated lymphoid tissue. A 67-year-old woman was admitted for evaluation of cough, sputum, rhinorrhea which had persisted for one month. Physical examination showed decreased breathing sound on the left upper lung field. High resolution chest computed tomography demonstrated consolidation which showed air-bronchogram and surrounding ground glass opacity in left upper lobe. These findings implicated inactive tuberculosis, organizing pneumonia, or bronchiolo-alveolar carcinoma. The histologic findings from percutaneous needle aspiration biopsy revealed aggregated atypical small lymphoid cells with lymphoepithelial lesions. With immunohistochemical staining, the atypical lymphoid cells reacted positively with CD 20 antibody and negatively with CD 3 antibody. Thus, we could diagnosed her as a patient with BALT lymphoma. After left upper lobectomy, she has been well without recurrence of the disease for 14 months. In this country of Republic of Korea, it was the 1st case of BALT lymphoma surgically treated when histological diagnosis had been done. Based on this case, we wanted to demonstrate the importance of early histological diagnosis and treatment of BALT lymphoma.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.23
• /
• pp.10255-10262
• /
• 2015

High risk human papillomavirus (HR-HPV) E2 proteins play roles in transcriptional regulation and are commonly functionally disrupted when the HPV genome integrates into host chromosomes. Some 15-40% of cancer cases, however, contain an intact E2 gene or episomal HPV. In these cases, polymorphism of the E2 gene might be involved. This study aimed to determine polymorphisms of the E2 gene in episomal HPV16 detected in high grade squamous intraepithelial lesions and squamous cell carcinomas and altered functions compared to the E2 prototype. The E2 gene was amplified and sequenced. Two expression vectors containing E2 gene polymorphisms were constructed and transfected in SiHa and C33A cells, then E6 gene as well as Il-10 and TNF-${\alpha}$ expression was determined by quantitative RT-PCR. Expression vectors and reporter vectors containing the HPV16 long control region (LCR) were co-transfected and transcriptional activity was determined. The results showed that a total of 32 nucleotides and 23 amino acids were changed in all 20 cases of study, found in the transactivation (TA) domain, hinge (H) region and DNA binding (DB) domain with 14, 5 and 13 nucleotide positions. They mostly caused amino acid change. The expressing vectors containing different E2 gene polymorphisms showed E6 mRNA suppression, TNF-${\alpha}$ mRNA suppression and IL-10 induction but no statistically significant differences when compared to the E2 prototype. Moreover, promoter activity in HPV16 LCR was not affected by E2 protein with different gene polymorphisms, in contrast to nucleotide variations in LCR that showed an effect on transcription activity. These results demonstrated that E2 gene polymorphisms of episomal HPV16 did not affect transcriptional regulation and suggested that nucleotide variation as well as epigenetic modification of the LCR might play a role in inducing malignant transformation of cells containing episomal HPV16.

• Journal of Korean Neurosurgical Society
• /
• v.29 no.6
• /
• pp.731-737
• /
• 2000

Objective : Growth factor receptors on the tumor cells are known to be expressed highly allowing the tumor cells to bind growth factors to stimulate cellular division. Immunotoxin therapy is one of the novel approaches to the primary malignant brain tumor, and expression of cell-surface receptor is essential for the immunotoxin to have specific anti-tumor activity. Despite promising cytotoxic activity of immunotoxin, tumor responses are not curative on clinical trials, and additional studies are needed regarding various factors influencing the efficacy of the immunotoxin. The purpose of this study is to detect the expression of various growth factor receptors on brain tumor cell lines which are going to be used in these studies. Materials and Methods : The authors detected transferrin receptor(TR), insulin-like growth factor-1 receptor(IGF-1R), and interleukin-4 receptor(IL-4R) on medulloblastoma cell line(Daoy) and glioblastoma cell lines(U373 MG and T98 G) by flow cytometric analysis. Results : TR was expressed on Daoy, U373 MG, and T98 G. IGF-1R was expressed on Daoy and U373 MG, but not on T98 G. IL-4R was expressed on all cell lines tested. Conclusion : The transferrin and interleukin-4 receptors might be good targets for immunotoxin therapy. The results should be considered in additional in vitro and in vivo studies regarding immunotoxin and in establishing the proper treatment model of the immunotoxin therapy including selection of the adequate immunotoxin.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.26 no.4
• /
• pp.355-362
• /
• 2000

Neoplastic growth is characterized by alterations of oncogenes and antioncogenes. The interaction between activated oncogenes and functional deletion of antioncogene appears to be the driving force directing normal cells to uncontrolled growth resulting in tumor. In addition to those genes mentioned, other genes controlling the entry of cells into the cell cycle have recently been implicated in cancer development. The overexpression of the cyclin D1 gene, which has been mapped to 11q13, either by gene rearrangement or amplification has been noted in various malignant tumors. The product of the cyclin D1 gene forms a complex with cyclin-dependent protein kinases(CDK4) that governs a key transition in the cell cycle. The relationships between the overexpression of cyclin D1 assessed by immunihistochemistry and the amplification of the cyclin D1 gene by differential polymerase chain reaction(DPCR) using primers for dopamin D2 receptor gene in 13 cases of squamous cell carcinomas of the oral cavity have been studied. The semiquantitative assay of cyclin D1 amplification has been made by cyclin D1/dopamin D2 receptor(CD/DR) ratio. The results were as follows; 1. In the normal tissue and the tumor, the CD/DR ratios were 0.82 and 1.36 respectively. This implicates 1.65-fold amplification of cyclin D1 gene in tumor compared to that in normal tissue. 2. The tumor tissue which showed overexpression of cyclin D1 by immunohistochemistry revealed 2-fold amplification of cyclin D1 compared to the normal tissue. 3. The tumor tissue which showed mild expression of cyclin D1 by immunihistochemistry revealed 1.7-fold amplification of cyclin D compared to the normal tissue. 4. The cyclin D1 was overexpressed in the tumor tissue at the rate of 38%. Above results suggest that cyclin D1 has close correlation with the development of carcinoma in the oral cavity. But further studies were needed to elucidate the carcinogeneic mechanisms by comparative studies among cyclin D1, pRb and p53.