• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.3
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• pp.700-704
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• 2007

In the recent, increased concern has been focused on the pharmacology and clinical utility of herbal extracts and derivatives as a drug or adjunct to chemotherapy and immunotherapy. Here we investigated the role of the extract of Anethi Fructus in the expression of inflammatory mediators, surface molecule, and related receptors in vitro. In murine macrophage RAW 264.7 cells and peritoneal macrophages of C57BL/6N mice, water extract of Anethi Fructus increased the production of secretary tumor necrosis factor (TNF)-a and Nitric oxide (NO), and the expression level of CD14, LPS co-receptor and CD86, co-stimulatory molecule compared to negative natural extract ex vivo. The water extract of Anethi Fructus increased the production of interferon (IFN)-g from splenocytes. Also, water extract of Anethi Fructus increased ConA-induced cell proliferation. These results suggest that water extract of Anethi Fructus may enhance the immune response through immune modulation of macrophage and lymphocytes.

• Journal of Breast Cancer
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• v.21 no.4
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• pp.382-390
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• 2018

Purpose: PIK3CA mutation is considered to be a possible cause for resistance to neoadjuvant chemotherapy (NAC) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We investigated the association between PIK3CA mutations and the outcome of NAC in HER2-positive breast cancers. Methods: A total of 100 HER2-positive breast cancer patients who had undergone NAC and surgery between 2004 and 2016 were examined. Mutation status was sequentially assessed in pre-NAC, post-NAC, and recurrent specimens taken from these patients. Results: PIK3CA mutations were identified in the sequential specimens of 17 patients (17.0%). These 17 patients experienced shorter disease-free survival (DFS) than the rest of the patients (58.3 months vs. 119.3 months, p=0.020); however, there was no significant difference in pathologic complete response (pCR) and overall survival (OS) (pCR, 17.6% vs. 33.7%, p=0.191; OS, 84.5 months vs. 118.0 months, p=0.984). While there was no difference in pCR between the wild-type and mutant PIK3CA groups in pre-NAC specimens (25.0% vs. 31.8%, p=0.199), PIK3CA mutations correlated with lower pCR in postNAC specimens (0.0% vs. 24.3%, p<0.001). Multivariate analysis revealed significantly worse DFS in the mutant PIK3CA group than in the wild-type group (hazard ratio, 3.540; 95% confidence interval, 1.001-12.589; p=0.050). Moreover, the DFS curves of the change of PIK3CA mutation status in sequential specimens were significantly different (p=0.016). Conclusion: PIK3CA mutation in HER2-positive breast cancer was correlated with a lower pCR rate and shorter DFS. These results suggest that PIK3CA mutation is a prognostic marker for NAC in HER2-positive breast cancer, especially in post-NAC specimens.

• Journal of Life Science
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• v.29 no.7
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• pp.824-835
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• 2019

In recent decades, oncolytic viruses (OVs) have extensively been investigated as a potential cancer drug. Oncolytic viruses have primarily the unique advantage in the fact that they can only infect and destroy cancer cells. Secondary, oncolytic viruses induce the activation of specific adaptive immunity which targets tumor-associated antigens that were hidden during the initial cancer progression. In 2015, one genetically modified oncolytic virus, talimogene laherparepvec (T-VEC), was approved by the American Food and Drug Administration (FDA) for the treatment of melanoma. Currently, various oncolytic viruses are being investigated in clinical trials as monotherapy or in combination with preexistent cancer therapies like immunotherapy, radiotherapy or chemotherapy. The efficacy of oncolytic virotherapy relies on the balance between the induced anti-tumor immunity and the anti-viral response. Despite the revolutionary outcome, the development of oncolytic viruses for the treatment of cancer faces a number of obstacles such as delivery method, neutralizing antibodies and induction of antiviral immunity due to the complexity, variability and reactivity of tumors. Intratumoral administration has been successful reducing considerably solid tumors with no notable side effects unfortunately some tumors are not accessible (brain) and require a systemic administration of the oncolytic viruses. In order to overcome these hurdles, various strategies to enhance the efficacy of oncolytic viruses have been developed which include the insertion of transgenes or combination with immune-modulatory substances.

• The Journal of the Korea Contents Association
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• v.19 no.3
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• pp.365-374
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• 2019

Unlike benign tumors, malignant tumors are capable of metastasis, easy to relapse, poor survival, and low quality of life. In Korea, here is a tendency to treat the tumors collectively according to the General Principles of Cancer Chemotherapy(GPCC) of the Health Insurance Review & Assessment Service (HIRA). But recently, companion diagnostics(CDx) is recommended rather than unilateral medication because biomarker-based molecular diagnostics is possible to predict the drug response of patients before drug treatment. Not only domestic but also overseas Food and Drug Administratio (FDA) recommends the development of the CDx system at the stage of drug development to ensure the responsiveness and safety of medicines. In this study, I focused on the necessity of CDx development direction as well as CDx development status through literature review. Furthermore I also discussed CDx types according to the molecular diagnostic technology such as immunohistochemistry (IHC), polymerase chain reaction (PCR), in situ hybridization (ISH), and next-generation sequencing (NGS) not only in the approved CDx but also in the developing one by US FDA. And I suggested the technology issue of CDx development process such as a selection of molecular diagnostics at the time of release, a clear understanding of the CDx mechanism, and a convergence of drug with CDx development. The necessity of social insurance system also was proposed for CDx development.

• Journal of Pharmacopuncture
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• v.22 no.1
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• pp.28-34
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• 2019

Background: Breast cancer is a complex, heterogeneous disease and one of the most common malignancies in women worldwide. The efficacy of chemotherapy as an important breast cancer treatment option has been severely limited because of the inherent or acquired resistance of cancer cells. The molecular chaperone heat shock protein 90 (HSP90) upregulated in response to cellular stress is required for functions such as conformational maturation, activation and stability in more than 200 client proteins, mostly of the signaling type. In this study, the expression of HSP90 isoforms including $HSP90{\alpha}$ and $HSP90{\beta}$ in breast cancer cell lines before and after treatment with doxorubicin (DOX) was assessed. Material and Methods: The cell cytotoxicity of DOX in MDA-MB-231 and MCF-7 cell lines was determined using the MTT assay. immunofluorescence and western blotting techniques were used to determine the expression of $HSP90{\beta}$ in the cell lines before and after DOX treatment. Immunofluorescence was also conducted to ascertain the expression of $HSP90{\alpha}$. Results: The MTT assay results showed that the MDA-MB-231 cells ($IC_{50}=14.521{\mu}M$) were more sensitive than the MCF-7 cells ($IC_{50}=16.3315{\mu}M$) to DOX. The immunofluorescence results indicated that the expression of $HSP90{\alpha}$ in both cell lines decreased after exposure to DOX. The western blot and immunofluorescence analyses showed that $HSP90{\beta}$ expression decreased in the MCF-7 cells but increased in the MDA-MB-231 cells after DOX treatment. Conclusion: The obtained results suggested that $HSP90{\alpha}$ and $HSP90{\beta}$ expression levels were reduced in the MCF-7 cells after exposure to DOX. In the MDA-MB-231 cells, $HSP90{\alpha}$ expression was reduced while $HSP90{\beta}$ was found to be overexpressed following DOX treatment.

• The Journal of Korean Medicine
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• v.40 no.1
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• pp.153-173
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• 2019

Objectives: This study aimed to ascertain what should be considered in the "Guideline for Clinical Trials with Herbal Medicinal Products for Lung Cancer" by analyzing the existing guidelines and clinical trials. Methods: The committee searched guidelines and clinical trials about herbal medicine for lung cancer. The searched trials were analyzed in terms of inclusion and exclusion of participants, intervention, comparator, outcomes and trial design. Then, we compared the results of our analysis with the guidelines to identify the issues we will have to consider when making the "Guideline for Clinical Trials with Herbal Medicinal Products for Lung Cancer". Several guidelines for anti-tumor agents and clinical trials with herbal medicine were searched on the national institution homepage. The search terms were as follows: 'lung neoplasm', 'herbal medicine', 'Medicine, Korean traditional', 'Medicine, Chinese Traditional' etc. Results: There was no guideline for clinical trial with herbal medicine for lung cancer. In addition, 7 articles were searched through database searching. All the participants had non-small cell lung cancer. The type of intervention was decoction. Comparators included conventional treatments such as chemotherapy. The outcome measurements used in the studies were quality of life, tumor response, and survival duration, etc. Safety was evaluated by recording adverse events and blood test. Conclusions: Findings were made by reviewing existing guidelines and comparing them with clinical trials for lung cancer and herbal medicinal products. These results will be utilized in the development of "Guideline for Clinical Trials with Herbal Medicinal Products for Lung Cancer".

• The Journal of Korean Medicine
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• v.40 no.1
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• pp.124-152
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• 2019

Objectives: This study aimed to ascertain what should be considered in the "Guideline for Clinical Trials with Herbal Medicinal Products for Colorectal Cancer" by analyzing the existing guidelines and clinical trials. Methods: The development committee searched guidelines for herbal medicinal products for colorectal cancer that have already been developed. Then, clinical trials for colorectal cancer using herbal medicine were searched. The searched trials were analyzed in terms of inclusion and exclusion of participants, intervention, comparator, outcomes and trial design. Then, we compared the results of our analysis with the regulations and guidelines of the Ministry of Food and Drug Safety in order to identify the issues we will have to consider when making the "Guideline for Clinical Trials with Herbal Medicinal Products for Colorectal Cancer". Several guidelines for anti-tumor agents and clinical trials with herbal medicinal products were searched on the national institution homepage. In addition, 12 articles were searched using a combination of the following search terms: 'colorectal neoplasms', 'herbal medicine', 'Medicine, Korean traditional', 'Medicine, Chinese Traditional', 'medicine, East Asian medicine', 'medicine, Kampo', etc. Results: The characteristics of participants were various, such as people with medical histories of surgeries or recurrent cancers or who complained of chemotherapy-induced side effects. The types of interventions were also various and included decoctions, powders, intravenous fluids, intraperitoneal injections and gargles. Comparators used included placebos and conventional treatments. The outcome measurements used in the studies were quality of life, symptom score, tumor response, and survival duration, etc. Safety was evaluated by recording adverse events. Conclusions: Findings were made by reviewing existing guidelines and comparing them with clinical trials for colorectal cancer and herbal medicinal products. These results will be utilized in the development of the "Guideline for Clinical Trials with Herbal Medicinal Products for Colorectal Cancer".

• Genomics & Informatics
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• v.20 no.3
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• pp.29.1-29.12
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• 2022

Several studies have shown associations between irinotecan toxicity and UGT1A genetic variations in colorectal and lung cancer, but only limited data are available for gastric cancer patients. We evaluated the frequencies of UGT1A polymorphisms and their relationship with clinicopathologic parameters in 382 Korean gastric cancer patients. Polymorphisms of UGT1A1*6, UGT1A1*27, UGT1A1*28, UGT1A1*60, UGT1A7*2, UGT1A7*3, and UGT1A9*22 were genotyped by direct sequencing. In 98 patients treated with irinotecan-containing regimens, toxicity and response were compared according to the genotype. The UGT1A1*6 and UGT1A9*22 genotypes showed a higher prevalence in Korean gastric cancer patients, while the prevalence of the UG1A1*28 polymorphism was lower than in normal Koreans, as has been found in other studies of Asian populations. The incidence of severe diarrhea after irinotecan-containing treatment was more common in patients with the UGT1A1*6, UGT1A7*3 and UGT1A9*22 polymorphisms than in controls. The presence of the UGT1A1*6 allele also showed a significant association with grade III-IV neutropenia. Upon haplotype and diplotype analyses, almost every patient bearing the UGT1A1*6 or UGT1A7*3 variant also had the UGT1A9*22 polymorphism, and all severe manifestations of UGT1A polymorphism-associated toxicity were related to the UGT1A9*22 polymorphism. By genotyping UGT1A9*22 polymorphisms, we could identify high-risk gastric cancer patients receiving irinotecan-containing chemotherapy, who would experience severe toxicity. When treating high-risk patients with the UGT1A9*22 polymorphism, clinicians should closely monitor them for signs of toxicity such as severe diarrhea or neutropenia.

• Radiation Oncology Journal
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• v.18 no.1
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• pp.11-16
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• 2000

Purpose :We peformed the retrospective analysis to find the outcome of external beam radiotherapy alone in advanced esophageal cancer patients. Methods and Materials : One hundred and six Patients treated with external beam radiotherapy alone between July 1990 and December 1996 were analyzed retrospectively. We limited the site of the lesions to the thoracic esophagus and cell type to the squamous cell carcinoma. Follow-up was completed in 100 patients (94$\%$) and ranged from 1 month to 92 months (median; 6 months). Results :The median age was 62 years old and male to female ratio was 104 2. Fifty-three percent was the middle thorax lesion and curative radiotherapy was peformed in 83$\%$. Mean tumor dose delivered with curative aim was 58.6 Gy (55$\~$70.8 Gy) and median duration of the radiation therapy was 53 days. The median survival of all patients was 6 months and )-year and 2-year overall survival rate was 27$\%$ and 12$\%$, respectively, Improvement of dysphagia was obtained in most patients except for 7 patients who underwent feeding gastrostomy. The complete response rate immediately after radiation therapy was 32$\%$ (34/106). The median survival and 2-year survival rate of the complete responder was 14 months and 30$\%$ respectively, while those of the nonresponder was 4 months and 0$\%$ respectively (p=0.000). The median survival and 2-year survival rate of the patients who could tolerate regular diet was 9 months and 16$\%$ while those of the patients who could not tolerate regular diet was 3 months and 0$\%$, respectively (p=0.004). The survival difference between the patients with S cm or less tumor length and those with more than 5 cm tumor length was marginally statistically significant (u=0,06). However, the survival difference according to the periesophageal invasion or mediastinal tyrnphadenopathy in the chest CT imaging study was not statistically significant in this study. In a multivariate analysis, the statistically significant covariates to the survival were complete response to radiotherapy, tumor length, and initial degree of dysphagia in a decreasing order. The complication was observed in 10 patients (9$\%$). Conclusion :The survival outcome for advanced esophageal cancer patients treated by external beam radiotherapy alone was very poor. In the treatment of these patients, the brachytherapy and chemotherapy should be added to improve the treatment outcome.

• Radiation Oncology Journal
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• v.5 no.2
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• pp.97-104
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• 1987

From January 1970 through December 1984, 15 patients with sinonasal Non-Hodgkin's lymphoma combined to the head and neck were treated by external irradiation.13 patients were stage It and 2 were stage IIE by Ann Arbor Classification. However, when using TNM system, 7 were locally advanced T3, T4 lesions. All patients had follow up from 3.7 to 16 years with the median follow-up of 8.5 years. The overall actuarial 5-year survival rates were $25\%,\;28\%$ for IE and $0\%$ for IIE. Total tumor dose varied from 40 to 68 Gy. $100\%$ complete response with a total tumor dose of more than 55 Gy and $73\%$ complete response with less than 55Gy. When the disease was staged using the TNM (AJC) system, the five-year disease free survival for T1 and T2 patients was $50\%$ as compared with $14\%$ for T3 and T4. Failure rate by stage was $33\%(2/6)$ for T1 and T2, $86\%(6/7)$ for T3 and T4, and $100\%$(2/2) for IIE. The results suggest that 1. Higher CR could be obtained with a total tuner dose of more than 55 Gy. 2. Use of TNM staging system is as important as Ann arbor in management of sinonasal NHL. 3. The addition of combination chemotherapy should be considered for T3, T4 and IIE the sinonasal Non-Hodgkin's lymphoma although the disease is limited to head and neck.