• Molecules and Cells
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• v.42 no.11
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• pp.804-809
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• 2019

Oncogenic gain-of-function mutations are clinical biomarkers for most targeted therapies, as well as represent direct targets for drug treatment. Although loss-of-function mutations involving the tumor suppressor gene, STK11 (LKB1) are important in lung cancer progression, STK11 is not the direct target for anticancer agents. We attempted to identify cancer transcriptome signatures associated with STK11 loss-of-function mutations. Several new sensitive and specific gene expression markers (ENO3, TTC39C, LGALS3, and MAML2) were identified using two orthogonal measures, i.e., fold change and odds ratio analyses of transcriptome data from cell lines and tissue samples. Among the markers identified, the ENO3 gene over-expression was found to be the direct consequence of STK11 loss-of-function. Furthermore, the knockdown of ENO3 expression exhibited selective anticancer effect in STK11 mutant cells compared with STK11 wild type (or recovered) cells. These findings suggest that ENO3-based targeted therapy might be promising for patients with lung cancer harboring STK11 mutations.

• IMMUNE NETWORK
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• v.20 no.4
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• pp.29.1-29.20
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• 2020

The development of refractory tumor cells limits therapeutic efficacy in cancer by activating mechanisms that promote cellular proliferation, migration, invasion, metastasis, and survival. Benzimidazole anthelmintics have broad-spectrum action to remove parasites both in human and veterinary medicine. In addition to being antiparasitic agents, benzimidazole anthelmintics are known to exert anticancer activities, such as the disruption of microtubule polymerization, the induction of apoptosis, cell cycle (G2/M) arrest, anti-angiogenesis, and blockage of glucose transport. These antitumorigenic effects even extend to cancer cells resistant to approved therapies and when in combination with conventional therapeutics, enhance anticancer efficacy and hold promise as adjuvants. Above all, these anthelmintics may offer a broad, safe spectrum to treat cancer, as demonstrated by their long history of use as antiparasitic agents. The present review summarizes central literature regarding the anticancer effects of benzimidazole anthelmintics, including albendazole, parbendazole, fenbendazole, mebendazole, oxibendazole, oxfendazole, ricobendazole, and flubendazole in cancer cell lines, animal tumor models, and clinical trials. This review provides valuable information on how to improve the quality of life in patients with cancers by increasing the treatment options and decreasing side effects from conventional therapy.

• Nutrition Research and Practice
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• v.18 no.1
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• pp.62-77
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• 2024

BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer worldwide with a high recurrence rate. Oxaliplatin (OXA) resistance is one of the major reasons hindering CRC therapy. β-Carotene (BC) is a provitamin A and is known to have antioxidant and anticancer effects. However, the combined effect of OXA and BC has not been investigated. Therefore, this study investigated the anticancer effects and mechanism of the combination of OXA and BC on CRC. MATERIALS/METHODS: In the present study, the effects of the combination of OXA and BC on cell viability, cell cycle arrest, and cancer stemness were investigated using HCT116, HT29, OXA-resistant cells, and human CRC organoids. RESULTS: The combination of OXA and BC enhanced apoptosis, G₂/M phase cell cycle arrest, and inhibited cancer cell survival in human CRC resistant cells and CRC organoids without toxicity in normal organoids. Cancer stem cell marker expression and self-replicating capacity were suppressed by combined treatment with OXA and BC. Moreover, this combined treatment upregulated apoptosis and the stem cell-related JAK/STAT signaling pathway. CONCLUSIONS: Our results suggest a novel potential role of BC in reducing resistance to OXA, thereby enhances the anticancer effects of OXA. This enhancement is achieved through the regulation of cell cycle, apoptosis, and stemness in CRC.

• Oncology Letters
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• v.17 no.3
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• pp.2576-2582
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• 2019

Gestational trophoblastic disease (GTD) is an unusual disease occurring in pregnancy that originates from abnormal trophoblastic cells and comprises a group of diseases with different properties of invasion, metastasis and recurrence. The GTD group includes hydatidiform moles and gestational trophoblastic neoplasms (GTNs), with GTNs being divided into invasive moles, choriocarcinoma, placental site trophoblastic tumors and epithelioid trophoblastic tumors. The present review focuses on current effective treatments for GTD, including conventional and novel promising direct enzyme prodrug therapies (DEPTs). Conventional therapies, such as chemotherapy and hysterectomy, are currently used in a clinical setting; however, the use of diverse DEPTs, including antibody-DEPT and gene-DEPT is also being attempted to cure GTNs. In addition, gene delivery tools using genetically engineered neural stem cells (NSCs) are presently being examined for the treatment of GTNs. The tumor-tropism of NSCs by chemoattractant factors is a unique characteristic of these cells and can serve as a vehicle to deliver anticancer agents. Previous studies have demonstrated that injection with NSC-expressing suicide genes into xenograft animal models has a significant inhibitory effect on tumor growth. Stem cells can be genetically engineered to express anticancer genes, which migrate to the metastatic sites and selectively target cancer cells, and are considered to effectively target metastatic GTNs. However, the safety issue of stem cell therapy, such as tumorigenesis, remains a challenge. Novel therapies comprising a combination of conventional and novel promising treatments are anticipated to be definitive treatments for metastasized and/or recurrent patients with GTNs.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.8.1-8.15
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• 2020

Immune checkpoint blockade targeting PD-1 and PD-L1 has resulted in unprecedented clinical benefit for cancer patients. Anti-PD-1/PD-L1 therapy has become the standard treatment for diverse cancer types as monotherapy or in combination with other anticancer therapies, and its indications are expanding. However, many patients do not benefit from anti-PD-1/PD-L1 therapy due to primary and/or acquired resistance, which is a major obstacle to broadening the clinical applicability of anti-PD-1/PD-L1 therapy. In addition, hyperprogressive disease, an acceleration of tumor growth following anti-PD-1/PD-L1 therapy, has been proposed as a new response pattern associated with deleterious prognosis. Anti-PD-1/PD-L1 therapy can also cause a unique pattern of adverse events termed immune-related adverse events, sometimes leading to treatment discontinuation and fatal outcomes. Investigations have been carried out to predict and monitor treatment outcomes using peripheral blood as an alternative to tissue biopsy. This review summarizes recent studies utilizing peripheral blood immune cells to predict various outcomes in cancer patients treated with anti-PD-1/PD-L1 therapy.

• Journal of Pharmaceutical Investigation
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• v.39 no.1
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• pp.13-18
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• 2009

Docetaxel is an anticancer agent with low aqueous solubility. More extensive clinical use of this drug is somewhat delayed due to lack of appropriate delivery vehicles. An attempt was made to adopt an o/w emulsion as the drug carrier which incorporated docetaxel in the propyleneglycerol stabilized by a mixed-emulsifier system. A suitable formulation was found in this study: 10 mg/mL docetaxel, 10% (w/v) oil blend, 4% (w/v) PG, 3% (w/v) Solutol HS 15 in 2.25% (w/v) glycerol solution. The formulated emulsion has very good stability when stored at $40^{\cird}C$, and the docetaxel containment efficiency can be maintained above 95% and the mean emulsion diameter around $10{\mu}m$ for at least 3 months. The formulated emulsion is a promising carrier for docetaxel and other lipophilic drugs.

• Biomolecules & Therapeutics
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• v.31 no.5
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• pp.496-514
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• 2023

Cold atmospheric plasma (CAP), a redox modulation tool, is capable of inhibiting a wide spectrum of cancers and has thus been proposed as an emerging onco-therapy. However, with incremental successes consecutively reported on the anticancer efficacy of CAP, no consensus has been made on the types of tumours sensitive to CAP due to the different intrinsic characteristics of the cells and the heterogeneous design of CAP devices and their parameter configurations. These factors have substantially hindered the clinical use of CAP as an oncotherapy. It is thus imperative to clarify the tumour types responsive to CAP, the experimental models available for CAP-associated investigations, CAP administration strategies and the mechanisms by which CAP exerts its anticancer effects with the aim of identifying important yet less studied areas to accelerate the process of translating CAP into clinical use and fostering the field of plasma oncology.

• Physical Therapy Korea
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• v.5 no.2
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• pp.91-97
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• 1998

The purpose of this study is to introduce prosthetic discipline and ambulation training after hemipelvectomy due to osteosarcoma. Over the past years, when the malignant bone tumors occurs in the extremities amputation is not enough to prevent a part recurrence and distal transformation resulting in fatal prognosis. On the other hand, these procedures could bring about a difficulty in rehabilitation in curing patient who have had hemipelvectomy. However the recent development of chemotherapy and diagnostic facility have permitted the orthopedic surgeons to many try amputations for the treatment of the malignant bone tumors. Unfortunately, there has not been many researches on hemipelvectomy. Since there is no studies found on hemipelvectomy either. Therefore, we introduce successful procedures for rehabilitation through the ambulation training for patients who have had amputation. One of our patients, who is an eighteen years old male, has had hemipelvectomy on the eighteenth of June in 1997 after his anticancer treatment over 12 times. He has had physical therapy of prosthetic ambulation training at the department of rehabilitation medicine Yonsei University Medical Center from the fifteenth of October to December '2nd in 1997.

• Journal of Microbiology and Biotechnology
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• v.19 no.9
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• pp.1070-1076
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• 2009

Telomerase reverse transcriptase (TERT), which prolongs the replicative life span of cells, is highly upregulated in 85-90% of human cancers, whereas most normal somatic tissues in humans express limited levels of the telomerase activity. Therefore, TERT has been a potential target for anticancer therapy. Recently, we described a new approach to human cancer gene therapy, which is based on the group I intron of Tetrahymena thermophila. This ribozyme can specifically mediate RNA replacement of human TERT (hTERT) transcript with a new transcript harboring anticancer activity through a trans-splicing reaction, resulting in selective regression of hTERT-positive cancer cells. However, to validate the therapeutic potential of the ribozyme in animal models, ribozymes targeting inherent transcripts of the animal should be developed. In this study, we developed a Tetrahymena-based trans-splicing ribozyme that can specifically target and replace the mouse TERT (mTERT) RNA. This ribozyme can trigger transgene activity not only also in mTERT-expressing cells but hTERT-positive cancer cells. Importantly, the ribozyme could selectively induce activity of the suicide gene, a herpes simplex virus thymidine kinase gene, in cancer cells expressing the TERT RNA and thereby specifically hamper the survival of these cells when treated with ganciclovir. The mTERT-targeting ribozyme will be useful for evaluation of the RNA replacement approach as a cancer gene therapeutic tool in the mouse model with syngeneic tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.23-29
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• 2015

Background: Current cancer therapy mainly focuses on identifying novel targets crucial for tumorigenesis. The FoxM1 is of preference as an anticancer target, due to its significance in execution of mitosis, cell cycle progression, as well as other signal pathways leading to tumorigenesis. FoxM1 is partially regulated by oncoproteins or tumor suppressors, which are often mutated, lost, or overexpressed in human cancer. Since sustaining proliferating signaling is an important hallmark of cancer, FoxM1 is overexpressed in a series of human malignancies. Alarge-scale gene expression analysis also identified FoxM1 as a differentially-expressed gene in most solid tumors. Furthermore, overexpressed FoxM1 is correlated with the prognosis of cancer patients, as verified in a series of malignancies by Cox regression analysis. Thus, extensive studies have been conducted to explore the roles of FoxM1 in tumorigenesis, making it an attractive target for anticancer therapy. Several antitumor drugs have been reported to target or inhibit FoxM1 expression in different cancers, and down-regulation of FoxM1 also abrogates drug resistance in some cancer cell lines, highlighting a promising future for FoxM1 application in the clinic.