• BMB Reports
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• v.51 no.4
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• pp.174-181
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• 2018

A number of genes have been therapeutically targeted to relieve cancer, but cancer relapse is still a growing issue. The concept that the surrounding tumor environment is critical for the progression of cancer may foster an answer to the issue of cancer malignancy. Runt domain transcription factors (RUNX1, 2, and 3) are evolutionarily conserved and have been intensively studied for their roles in normal development and pathological conditions. During tumor growth, a hypoxic microenvironment and infiltration of the tumor by immune cells are common phenomena. In this review, we briefly introduce the consequences of hypoxia and immune cell infiltration into the tumor microenvironment with a focus on RUNX3 as a critical regulator. Furthermore, based on our current knowledge of the functional role of RUNX3 in hypoxia and immune cell maintenance, a probable therapeutic intervention is suggested for the effective management of tumor growth and malignancy.

• Journal of Acupuncture Research
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• v.22 no.2
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• pp.211-217
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• 2005

Objectives : Terminal stage cancer patient from primary hepatocellular carcinoma metastasized into lungs was administered with cultivated wild ginseng herbal acupuncture for 5 months and observed progression. Methods : Cultivated wild ginseng herbal acupuncture was administered 5 times a week at about 150cc dosage per week. Dynamic CT was taken and interpreted at a university hospital. Results : Above patient was diagnosed with hepatocellular carcinoma and received one procedure of lobectomy and three procedures of TACE, but because of metastasis, chance of improvement was very obscure. Intensive treatment of cultivated wild ginseng herbal acupuncture five times a week for five months in association with moxibustion was done on the patient. Near elimination of the cancer cells metastasized into lungs were confirmed in terms of radiological impression through dynamic CT. Conclusion: From the results obtained in this study, cultivated wild ginseng herbal acupuncture can be an effective measure against terminal stage cancer. But this is a single case study and lack of extensive follow-up must be compensated by further researches.

• Journal of Gastric Cancer
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• v.16 no.1
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• pp.1-7
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• 2016

Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is one of the four subtypes of gastric carcinoma (GC), as defined by the novel classification recently proposed by The Cancer Genome Atlas. EBVaGC has several clinicopathological features such as longer survival and higher frequency of lymphoepithelioma-like carcinoma (LELC) and carcinoma with Crohn's disease-like lymphoid reaction that distinguish it from EBV-negative GC. The intensity and pattern of host cellular immune response in GC have been found to significantly correlate with the prognosis of patients with GC, suggesting that immune reaction and tumor microenvironment have critical roles in the progression of GC, and in particular, EBVaGC. Here, we reviewed the cellular and molecular mechanisms underlying prominent immune reactions in patients with EBVaGC. In EBVaGC, deregulation of the expression of immune response-related genes promotes marked intra-or peritumoral immune cell infiltration. The expression of programmed death receptor-ligand 1 is known to be increased in EBVaGC, and therefore, it has been proposed as a favorable prognostic factor for patients with EBVaGC, albeit some data supporting this claim are controversial. Overall, the underlying mechanisms and clinical significance of the host cellular immune response in patients with EBVaGC have not been thoroughly elucidated. Therefore, further research is necessary to better understand the role of tumor microenvironment in EBVaGC.

• Genomics & Informatics
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• v.11 no.4
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• pp.164-173
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• 2013

Genomic instability, which occurs through both genetic mechanisms (underlying inheritable phenotypic variations caused by DNA sequence-dependent alterations, such as mutation, deletion, insertion, inversion, translocation, and chromosomal aneuploidy) and epigenomic aberrations (underlying inheritable phenotypic variations caused by DNA sequence-independent alterations caused by a change of chromatin structure, such as DNA methylation and histone modifications), is known to promote tumorigenesis and tumor progression. Mechanisms involve both genomic instability and epigenomic aberrations that lose or gain the function of genes that impinge on tumor suppression/prevention or oncogenesis. Growing evidence points to an epigenome-wide disruption that involves large-scale DNA hypomethylation but specific hyper-methylation of tumor suppressor genes, large blocks of aberrant histone modifications, and abnormal miRNA expression profile. Emerging molecular details regarding the modulation of these epigenetic events in cancer are used to illustrate the alterations of epigenetic molecules, and their consequent malfunctions could contribute to cancer biology. More recently, intriguing evidence supporting that genetic and epigenetic mechanisms are not separate events in cancer has been emerging; they intertwine and take advantage of each other during tumorigenesis. In addition, we discuss the collusion between epigenetics and genetics mediated by heterochromatin protein 1, a major component of heterochromatin, in order to maintain genome integrity.

• Journal of Microbiology and Biotechnology
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• v.17 no.5
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• pp.840-846
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• 2007

Human prostate-specific antigen(PSA), a 33 kDa serine protease with comprehensive homology to glandular kallikrein, is secreted from prostatic tissue into the seminal fluid and enters into the circulation. The level of PSA increases in the serum of patients with prostatic cancer and hence is widely employed as a marker of the disease status. In particular, an enzymatically active PSA that is a form cleaved at the N-terminal seven-amino-acids prosequence, APLILSR, of proPSA may play an important roll in the progression of prostate cancer. Thus, the presence of the active form would selectively discriminate the cancer from benign prostatic hyperplasia. In this study, we developed a convenient purification method for the acquisition of active PSA and proPSA. Recombinant proPSA and active PSA were expressed directly in Escherichia coli, easily and efficiently isolated from inclusion bodies, refolded, and purified. Moreover, the enzymatic activity of the recombinant active PSA was confirmed as serine protease using chromogenic chymotrypsin substrate. This purified active PSA could be further applied to scrutinize the biological or conformational characteristics of the protein and to develop specific diagnostic and/or therapeutic agents against prostate cancer.

• Molecules and Cells
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• v.43 no.2
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• pp.198-202
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• 2020

Comprehensive inhibition of RUNX1, RUNX2, and RUNX3 led to marked cell suppression compared with inhibition of RUNX1 alone, clarifying that the RUNX family members are important for proliferation and maintenance of diverse cancers, and "cluster regulation of RUNX (CROX)" is a very effective strategy to suppress cancer cells. Recent studies reported by us and other groups suggested that wild-type RUNX1 is needed for survival and proliferation of certain types of leukemia, lung cancer, gastric cancer, etc. and for their one of metastatic target sites such as born marrow endothelial niche, suggesting that RUNX1 often functions oncogenic manners in cancer cells. In this review, we describe the significance and paradoxical requirement of RUNX1 tumor suppressor in leukemia and even solid cancers based on recent our findings such as "genetic compensation of RUNX family transcription factors (the compensation mechanism for the total level of RUNX family protein expression)", "RUNX1 inhibition-induced inhibitory effects on leukemia cells and on solid cancers through p53 activation", and "autonomous feedback loop of RUNX1-p53-CBFB in acute myeloid leukemia cells". Taken together, these findings identify a crucial role for the RUNX cluster in the maintenance and progression of cancers and suggest that modulation of the RUNX cluster using the pyrrole-imidazole polyamide gene-switch technology is a potential novel therapeutic approach to control cancers.

• Biomolecules & Therapeutics
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• v.29 no.6
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• pp.667-677
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• 2021

The elevated expression of the hyaluronan-mediated motility receptor (HMMR) is known to be highly associated with tumor progression in prostate cancer, but the molecular mechanisms underlying the regulation of HMMR expression remain unclear. Here, we report that mammalian target of rapamycin (mTOR) is a key regulator of HMMR expression, for which its kinase activity is required. Pharmacological inhibitors of mTOR, such as rapamycin and Torin2, markedly suppressed the mRNA level as well as the protein level of HMMR in LNCaP and PC-3 cells. Our data demonstrate that such regulation occurs at the transcription level. HMMR promoter reporter assays revealed that the transcription factor SRF is responsible for the mTOR-mediated transcriptional regulation of HMMR gene. Consistently, the suppression of HMMR expression by Torin2 was noticeably reversed by the overexpression of SRF. Moreover, our findings suggest that the SRF binding sites responsible for the transcriptional regulation of HMMR through the mTOR-SRF axis are located in HMMR promoter sequences carrying the first intron, downstream of the translational start site. Furthermore, the upregulation of HMMR by DHT was abolished by stimulation with rapamycin, prior to DHT treatment, suggesting that mTOR activity is required for the induction of HMMR expression by androgen. Collectively, our study provides new mechanistic insights into the role of mTOR/SRF/AR signaling in HMMR regulation in prostate cancer cells.

• The Journal of Korean Medicine
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• v.39 no.4
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• pp.171-176
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• 2018

Background: Small cell lung cancer (SCLC) tends to grow more rapidly and spread much faster than non-small cell lung cancer (NSCLC). A concurrent combination of chemotherapy and thoracic radiotherapy is suggested as the standard conventional treatment, but it is more challenging for elderly patients having pulmonary and cardiovascular comorbidities. Case presentation: Here we present a case of an 80-year-old male, current smoker diagnosed with SCLC in limited stage T3N0M0 (36mm right upper lobe, satellite nodule) in Dec, 2015. The standard concurrent chemoradiotherapy was not available for his comorbidities, which included chronic obstructive pulmonary disease (COPD) and angina pectoris. Furthermore, he and his family refused the recommended chemotherapy or radiotherapy exclusively. Alternatively, he received various non-conventional treatments including local radiofrequency hyperthermia, mistletoe, and Traditional Korean medicine including acupuncture, moxibustion and herbs since Jan. 2016. Despite the progression in primary tumor size, there have been no other distant relapse so far, and the patient has been in stable condition ever since. Conclusion: We suggest that a combination of various alternative treatments could be a candidate for elderly patients intolerable to conventional cytotoxic treatments.

• Molecules and Cells
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• v.46 no.3
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• pp.176-186
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• 2023

The oxidative balance of a cell is maintained by the Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway. This cytoprotective pathway detoxifies reactive oxygen species and xenobiotics. The role of the KEAP1/NRF2 pathway as pro-tumorigenic or anti-tumorigenic throughout stages of carcinogenesis (including initiation, promotion, progression, and metastasis) is complex. This mini review focuses on key studies describing how the KEAP1/NRF2 pathway affects cancer at different phases. The data compiled suggest that the roles of KEAP1/NRF2 in cancer are highly dependent on context; specifically, the model used (carcinogen-induced vs genetic), the tumor type, and the stage of cancer. Moreover, emerging data suggests that KEAP1/NRF2 is also important for regulating the tumor microenvironment and how its effects are amplified either by epigenetics or in response to co-occurring mutations. Further elucidation of the complexity of this pathway is needed in order to develop novel pharmacological tools and drugs to improve patient outcomes.

• Journal of Gastric Cancer
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• v.8 no.1
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• pp.40-46
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• 2008

Purpose: We wanted to evaluate the efficacy and toxicity of modified FOLFOX-6 chemotherapy for treating recurrent or inoperable gastric cancer patients. Materials and Methods: From April 2006 to August 2007, 35 patients with recurrent gastric cancer after curative resection and 43 patients with inoperable gastric cancer underwent chemotherapy, and the results were retrospectively investigated. Results: 78 patients were assessable for response and toxicity, and they underwent an average of 7.1 cycles of chemotherapy. The response was evaluated according to the RECIST criteria. 11 partial responses (14.1%), 35 cases of stable disease (44.9%), and 32 cases of progressive disease (41%) were observed. The median time to progression was 6 months, and the average overall survival was 13 months. CTCAE grade 1 or 2 anemia (52.6%) was the most prevalent toxicity. Other common toxicities included thrombocytopenia (17.9%) and peripheral neuropathy (30.8%). There were 13 changes in the chemotherapy regimen to S1-cisplatin due to disease progression, but only an average of 1.76 cycles of S1-cisplatin were delivered due to severe toxicities and poor compliance. Conclusion: Acceptable efficacy and toxicity were seen as 59% of the patients showed non-progression, and no grade 3 or 4 toxicities were observed. In conclusion, the modified FOLFOX-6 chemotherapy is considered to be the proper 1st-line choice as a palliative treatment for recurrent or inoperable gastric cancer patients.