• Title/Summary/Keyword: Neoplasm biology

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The Clinical, Molecular, and Mechanistic Basis of RUNX1 Mutations Identified in Hematological Malignancies

  • Yokota, Asumi;Huo, Li;Lan, Fengli;Wu, Jianqiang;Huang, Gang
    • Molecules and Cells
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    • v.43 no.2
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    • pp.145-152
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    • 2020
  • RUNX1 plays an important role in the regulation of normal hematopoiesis. RUNX1 mutations are frequently found and have been intensively studied in hematological malignancies. Germline mutations in RUNX1 cause familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML). Somatic mutations of RUNX1 are observed in various types of hematological malignancies, such as AML, acute lymphoblastic leukemia (ALL), myelodysplastic syndromes (MDS), myeloproliferative neoplasm (MPN), chronic myelomonocytic leukemia (CMML), and congenital bone marrow failure (CBMF). Here, we systematically review the clinical and molecular characteristics of RUNX1 mutations, the mechanisms of pathogenesis caused by RUNX1 mutations, and potential therapeutic strategies to target RUNX1-mutated cases of hematological malignancies.

A New Paradigm to Mitigate Osteosarcoma by Regulation of MicroRNAs and Suppression of the NF-${\kappa}B$ Signaling Cascade

  • Mongre, Raj Kumar;Sodhi, Simrinder Singh;Ghosh, Mrinmoy;Kim, Jeong Hyun;Kim, Nameun;Sharma, Neelesh;Jeong, Dong Kee
    • Development and Reproduction
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    • v.18 no.4
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    • pp.197-212
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    • 2014
  • Osteosarcoma (OS) is one of the most common malignant primary bone tumors and NF-${\kappa}B$ appears to play a causative role, but the mechanisms are poorly understood. OS is one of the pleomorphic, highly metastasized and invasive neoplasm which is capable to generate osteoid, osteoclast and osteoblast matrix. Its high incidence has been reported in adolescent and children. Cell signal cascade is the pivotal functional mechanism acquired during the differentiation, proliferation, growth and survival of the cells in neoplasm including OS. The major limitation to the success of chemotherapy in OS is the development of multidrug resistance (MDR). Answers to all such queries might come from the knock-in experiments in which the combined approach of miRNAs with NF-${\kappa}B$ pathway is put into use. Abnormal miRNAs can modulate several epigenetical switching as a hallmark of number of diseases via different cell signaling. Studies on miRNAs have opened up the new avenues for both the diagnosis and treatment of cancers including OS. Collectively, through the present study an attempt has been made to establish a new systematic approach for the investigation of microRNAs, bio-physiological factors and their target pairs with NF-${\kappa}B$ to ameliorate oncogenesis with the "bridge between miRNAs and NF-${\kappa}B$". The application of NF-${\kappa}B$ inhibitors in combination with miRNAs is expected to result in a more efficient killing of the cancer stem cells and a slower or less likely recurrence of cancer.

New Insights into the Role of Endoplasmic Reticulum Stress in Breast Cancer Metastasis

  • Han, Chang-chang;Wan, Fu-sheng
    • Journal of Breast Cancer
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    • v.21 no.4
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    • pp.354-362
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    • 2018
  • Cellular stress severely disrupts endoplasmic reticulum (ER) function, leading to the abnormal accumulation of unfolded or misfolded proteins in the ER and subsequent development of endoplasmic reticulum stress (ERS). To accommodate the occurrence of ERS, cells have evolved a highly conserved, selfprotecting signal transduction pathway called the unfolded protein response. Notably, ERS signaling is involved in the development of a variety of diseases and is closely related to tumor development, particularly in breast cancer. This review discusses recent research regarding associations between ERS and tumor metastasis. The information presented here will help researchers elucidate the precise mechanisms underlying ERS-mediated tumor metastasis and provide new directions for tumor therapies.

Gonadal Abnormality and Intersexuality of Oplegnathus fasciatus (Teleostei: Oplegnathidae) Collected from the Southern Coast of Korea: A Case Report

  • Choi, Ji Sung;Shin, So Ryung;Kim, Hyeon Jin;Kim, Hyejin;Kim, Yeonghye;Lee, Jung Sick
    • Development and Reproduction
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    • v.25 no.3
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    • pp.123-131
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    • 2021
  • We report on the gonadal structure abnormality and intersexuality found from a survey regarding the reproductive potential of the rock bream, Oplegnathus fasciatus, along the southern coast of Korea. In total, 448 samples were collected for histological analysis (total length 27.5±6.8 cm; total weight 522.9±385.6 g). The sex ratio (F:M) was 1:0.46 (n=307:141), with 68.5% being females. The frequency of oocyte atresia and ovarian neoplasm in the females was 85.3% and 21.5%, respectively, and the frequency of testicular lobule and cyst deformation and testicular neoplasm in the males was 73.1% and 37.6%, respectively. The scale formation in the ovary and testis was approximately 2.0% for both sexes. The intersexuality was 42.2%, with the intersexuality among females being 49.5%, which was significantly higher than that of males (26.2%). Such findings indicate a negative impact on the reproductive output of the rock bream along the southern coast of Korea; however, a more detailed study is required to ascertain accurate causes.

Clear cell odontogenic carcinoma: a mini review

  • Kim, Young Hwan;Seo, Eun Jin;Park, Jae Kyung;Jang, Il Ho
    • International Journal of Oral Biology
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    • v.44 no.3
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    • pp.77-80
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    • 2019
  • Clear cell odontogenic carcinoma (CCOC), a very rare neoplasm located mostly in the mandible, has been regarded as a benign tumor. However, due to the accumulation of case reports, CCOC has been reclassified as a malignant entity by the World Health Organization. Patients with CCOC present with regional swelling and periodontal indications with variable pain, often remaining misdiagnosed for a long period. CCOC has slow growth but aggressive behavior, requiring radical resection. Histologic analysis revealed the monophasic, biphasic, and ameloblastic types of CCOC with clear cells and a mixed combination of polygonal and palisading cells. At the molecular level, CCOC shows the expression of cytokeratin and epithelial membrane antigen, along with markers that assign CCOC to the sarcoma family. At the genetic level, Ewing sarcoma breakpoint region 1-activating transcription factor 1 fusion is regarded as the key feature for identification. Nevertheless, the scarcity of cases and dependence on histological data delay the development of an efficient therapy. Regarding the high recurrence rate and the potential of distant metastasis, further characterization of CCOC is necessary for an early and accurate diagnosis.

Drug Discovery Platform Using Organoids (오가노이드를 활용한 약물 검색 플랫폼)

  • Ju Eun Maeng;Soon-Chan Kim;Myoung-Hyun Song;Nahyun Jeong;Ja-Lok Ku
    • Journal of Digestive Cancer Research
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    • v.10 no.2
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    • pp.82-91
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    • 2022
  • Gastrointestinal cancer accounts for one-third of the overall cancer occurrence worldwide. Pancreatic ductal adenocarcinoma (PDAC) is a type of gastrointestinal cancer that is known to be one of the most fatal among all cancer types, with a 5-year survival rate of less than 8%. Chemotherapy combined with surgical resection is its probable curative option. However, surgery is accessible for only 10-15% of patients diagnosed with PDAC. Organoids show self-organizing capacities and resemble the original tissue in terms of morphology and function. Organoids can also be cultured with high effectiveness from tumor tissues derived from each patient, making them an extremely fitting model for translational uses and improving personalized cancer medicine. Enhancing drug screening platforms is necessary to apply personalized medicinebased organoids in clinical settings.

The Inhibitory Effects of Forsythia Koreana Extracts on the Metastatic Ability of Breast Cancer Cells and Bone Resorption by Osteoclasts

  • Kim, Yu Li;Lee, Sun Kyoung;Park, Kwang-Kyun;Chung, Won-Yoon
    • Journal of Cancer Prevention
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    • v.21 no.2
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    • pp.88-94
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    • 2016
  • Background: Breast cancer is the most common malignant disease in women. The patients with advanced breast cancer develop metastasis to bone. Bone metastasis and skeletal-related events by breast cancer are frequently associated with the invasiveness of breast cancer cells and osteoclasts-mediated bone resorption. Forsythia koreana is used in oriental traditional medicine to treat asthma, atopy, and allergic diseases. The aim of this study was to evaluate the inhibitory effects of F. koreana extracts on the invasion of breast cancer cells and bone resorption by osteoclasts. Methods: Cell viability was measured by an MTT assay and the migration and invasion of MDA-MB-231 cells were detected by a Boyden chamber assay. The formation of osteoclasts and pit was detected using tartrate-resistant acid phosphatase staining and calcium phosphate-coated plates, respectively. The activities of matrix metalloproteinases (MMPs) and cathepsin K were evaluated by gelatin zymography and a cathepsin K detection kit. Results: The fruit and leaf extracts of F. koreana significantly inhibited the invasion of MDA-MB-231 cells at noncytotoxic concentrations. The fruit extract of F. koreana reduced the transforming growth factor ${\beta}1-induced$ migration, invasion and MMPs activities of MDA-MB-231 cells. In addition, the fruit, branch, and leaf extracts of F. koreana also inhibited the receptor activator of nuclear factor kappa-B ligand-induced osteoclast formation and osteoclast-mediated bone-resorbing activity by reducing the activities of MMPs and cathepsin K. Conclusions: The extracts of F. koreana may possess the potential to inhibit the breast cancer-induced bone destruction through blocking invasion of breast cancer cells, osteoclastogenesis, and the activity of mature osteoclasts.

Brain metastasis in human epidermal growth factor receptor 2-positive breast cancer: from biology to treatment

  • Koo, Taeryool;Kim, In Ah
    • Radiation Oncology Journal
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    • v.34 no.1
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    • pp.1-9
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    • 2016
  • Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents.

Mutantional analysis of tumor suppressor gene p53 in human oral squamous carcinoma cell line YD-9

  • Min, Ji-Hak;Kim, Do-Kyun;Lee, Moo-Hyung;Bae, Moon-Kyoung;Um, Kyung-Il;Kwak, Hyun-Ho;Park, Bong-Soo;Kim, Gyoo-Cheon
    • International Journal of Oral Biology
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    • v.32 no.2
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    • pp.79-84
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    • 2007
  • Oral squamous carcinoma (OSC) is the most common malignant neoplasm of the oral mucosa. Although the etiology of OSC is not fully understood, accumulated evidences indicate that the activation of proto-oncogenes and the inactivation of tumor suppressor genes underlie the disease development. An OSC cell line, YD-9 was newly established and characterized. However, the mutational analysis of p53 gene was not performed. Thus, in this study, the presence of mutation in the p53 gene was examined by amplification of exon-4 to -8 and subsequent DNA sequencing. Two point mutations were found in exon-4 and -6: A to G, resulting in amino acid change Tyr to Cys in exon-4, and C to G, resulting in amino acid change Gly to Arg in exon-6, respectively. Any mutation was not found in the exon-5, -7 and -8. The presented results would contribute to basic research to understand the biological mechanism of OSC using YD-9 cells.

Parental Age-Related Risk of Retinoblastoma in Iranian Children

  • Saremi, Leila;Imani, Saber;Rostaminia, Maryam;Nadeali, Zakiye
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2847-2850
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    • 2014
  • Background: Retinoblastoma is a rare malignant intraocular neoplasm. About 90% of cases feature a germline mutation in the RB1 gene and these will develop retinoblastoma during their early childhood. An association between mutations in germline cells and aging has been demonstrated. This suggests a higher incidence of childhood cancer including retinoblastoma among children of older parents. Materials and Methods: In the present study we aimed to determine the association of paternal and maternal age with an increased risk of retinoblastoma in a case-control study in Iranian population. The study was carried out on 240 persons who were born during 1984-2012 in Mahak and Mofid hospitals in Tehran, Iran. The statistical analysis included studying the mean age of parents and in order to know whether parental age of patients is different from parental age of control group, (t-test) compare averages test is used perfectly. By binary logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: The results of statistical analysis including the study of mean parental age by the use of (t-test) compare averages test showed a significant difference between parental ages of patients and controls. Logistic regression showed that coefficients were significant for maternal but not paternal age. Conclusions: Our findings indicate that advanced maternal age can increase the risk of retinoblastoma in offspring, but the paternal age has no significant effect.