• Korean Journal of Psychosomatic Medicine
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• v.29 no.2
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• pp.77-85
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• 2021

Breast cancer is the most prevalent oncological disease among women. Various psychosocial distress is common at the diagnosis, treatment, and posttreatment phase of breast cancer. For the treatment of breast cancer, not only medical treatment but also psychosomatic integrative care will be needed. Patients with breast cancer may lead to increased vulnerability to stress, adjustment disorder, anxiety disorder, and depressive disorder, and these psychiatric diseases and conditions are associated with recurrence or exacerbation of breast cancer. Psychosocial treatment of anxiety and depression could increase the quality of life of patients and decrease the recurrence and progression of breast cancer. In this article, we reviewed 5 clinical breast cancer survivorship guidelines focused on psychosomatic integrative care including psychosocial treatment and alternative treatment for psychosocial distress. Because 5 treatment guidelines were using various definitions of evidence, we confirmed evidence of various psychosocial treatments for patients with breast cancer based on the definition of evidence by the US Preventive Service Task Force (USPSTF) guideline. We also reviewed the effect size of psychosocial treatment for anxiety, depression, mood, and quality of life in patients with breast cancer. This article discusses the barrier to the delivery of psychosomatic integrative care and suggests integrative care planning for breast cancer. Multi-disciplinary teams, patient's needs assessment, information technology support, patient and caregiver engagement, planned periodic monitoring of psychosocial distress by a psychosomatic specialist or consultation-liaison psychiatrist are recommended as key features of a psychosomatic integrated care plan.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.237-246
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• 2004

Purpose: To investigate the effects of radiation dose-escalation on the treatment outcome, complications and the other prognostic variables for glioblastoma patients treated with 3D-conformal radiotherapy (3D-CRT). Materials and Methods: Between Jan 1997 and July 2002, a total of 75 patients with histologically proven diagnosis of glioblastoma were analyzed. The patients who had a Karnofsky Performance Score (KPS) of 60 or higher, and received at least 50 Gy of radiation to the tumor bed were eligible. All the patients were divided into two arms; Arm 1, the high-dose group was enrolled prospectively, and Arm 2, the low-dose group served as a retrospective control. Arm 1 patients received $63\~70$ Gy (Median 66 Gy, fraction size $1.8\~2$ Gy) with 3D-conformal radiotherapy, and Arm 2 received 59.4 Gy or less (Median 59.4 Gy, fraction size 1.8 Gy) with 2D-conventional radiotherapy. The Gross Tumor Volume (GTV) was defined by the surgical margin and the residual gross tumor on a contrast enhanced MRI. Surrounding edema was not included in the Clinical Target Volume (CTV) in Arm 1, so as to reduce the risk of late radiation associated complications; whereas as in Arm 2 it was included. The overall survival and progression free survival times were calculated from the date of surgery using the Kaplan-Meier method. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicities were evaluated using the Radiation Therapy Oncology Group neurotoxicity scores. Results: During the relatively short follow up period of 14 months, the median overall survival and progression free survival times were $15{\pm}1.65$ and $11{\pm}0.95$ months, respectively. The was a significantly longer survival time for the Arm 1 patients compared to those in Arm 2 (p=0.028). For Arm 1 patients, the median survival and progression free survival times were $21{\pm}5.03$ and $12{\pm}1.59$ months, respectively, while for Arm 2 patients they were $14{\pm}0.94$ and $10{\pm}1.63$ months, respectively. Especially in terms of the 2-year survival rate, the high-dose group showed a much better survival time than the low-dose group; $44.7\%$ versus $19.2\%$. Upon univariate analyses, age, performance status, location of tumor, extent of surgery, tumor volume and radiation dose group were significant factors for survival. Multivariate analyses confirmed that the impact of radiation dose on survival was independent of age, performance status, extent of surgery and target volume. During the follow-up period, complications related directly with radiation, such as radionecrosis, has not been identified. Conclusion: Using 3D-conformal radiotherapy, which is able to reduce the radiation dose to normal tissues compared to 2D-conventional treatment, up to 70 Gy of radiation could be delivered to the GTV without significant toxicity. As an approach to intensify local treatment, the radiation dose escalation through 3D-CRT can be expected to increase the overall and progression free survival times for patients with glioblastomas.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.5 no.1
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• pp.47-60
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• 1999

Traditional oriental medicines have been used for treatment of various kinds of human cancers for long times and some of them proven to be effective clinically. However, the pharmacological actions and mechanisms related to cancer treatment are generally unknown. In an effort to clarify the action mechanisms of several oriental medicines used for cancer treatments, we planned this experimental procedures. We selected Cordyceps sinensis (冬蟲下草), Punellae Herba (夏枯草), Rehmanniae Radix (熟地黃), Paeoniae Radix (白芍藥), Oldenlandiae Herba (白花蛇舌草), Partulaceae Herba (馬齒? ), Scdopendra subspinipes mutilans (蜈蚣), Mylabris Phalerara (班蟄), Phellinus igniarius(桑黃), Ganodermae Lignum(靈芝) for evaluation, which have been used for patients of gastric cancers. The twenty grams of medicines were boiled in 100ml of water for 1 hour and filtered with $0.2\;{\mu}m$ pore-sized filter unit to remove insoluble particles. Initially we evaluated the effects oriental medicines on growth inhibition in stomach cancer cells. The gastric cancer cell line, AGS, was cultured in RPMI 1640 supplemented with l0% heat-inactivated fetal bovine serum and treated with $10{\mu}l$ oriental medicines per 1ml of medium up to 48 hours. The specimens were subjected to MTT assay for evaluation of growth inhibition. We found mat Mylabris phalerata (班蟄) markedly suppressed the growth of cancer cells as shown in results. Next, we checked the effects of oriental medicines on cancer on cell cycles and apptosis. Mylabrls phalerata (班蟄) inhibited cell cycle progression of cancer cells a compared with control cells and cells treated with other medicines. In addition, Mylabri phalerata (班蟄) induced apoptosis in 30-40% of stomch cancer cells within 24 hours. Other oriental medicines used for this experiments did not show apoptosis-inducing effects on cancer cells. Finally, we determined the expression levels of genes associated with cell cycle and apoptosis. The expressions of Bcl-2 and bcl-XL were downregulated by the treatment of Mylabris phalerata (班蟄). However, the expression levels of genes related to cell cycles were not altered significantly. In conclusion, we found that Mylabris phalerata (班蟄) has in vivo gowth-inhibiting and apptosis-inducing effects on stomach cancer cells. However, we think that at least animal experiments are necessay for evduations.

• Tuberculosis and Respiratory Diseases
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• v.75 no.1
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• pp.9-17
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• 2013

Background: In cancer cells, autophagy is generally induced as a pro-survival mechanism in response to treatment-associated genotoxic and metabolic stress. Thus, concurrent autophagy inhibition can be expected to have a synergistic effect with chemotherapy on cancer cell death. Monensin, a polyether antibiotic, is known as an autophagy inhibitor, which interferes with the fusion of autophagosome and lysosome. There have been a few reports of its effect in combination with anticancer drugs. We performed this study to investigate whether erlotinib, an epidermal growth factor receptor inhibitor, or rapamycin, an mammalian target of rapamycin (mTOR) inhibitor, is effective in combination therapy with monensin in non-small cell lung cancer cells. Methods: NCI-H1299 cells were treated with rapamycin or erlotinib, with or without monensin pretreatment, and then subjected to growth inhibition assay, apoptosis analysis by flow cytometry, and cell cycle analysis on the basis of the DNA contents histogram. Finally, a Western blot analysis was done to examine the changes of proteins related to apoptosis and cell cycle control. Results: Monensin synergistically increases growth inhibition and apoptosis induced by rapamycin or erlotinib. The number of cells in the sub-$G_1$ phase increases noticeably after the combination treatment. Increase of proapoptotic proteins, including bax, cleaved caspase 3, and cleaved poly(ADP-ribose) polymerase, and decrease of anti-apoptotic proteins, bcl-2 and bcl-xL, are augmented by the combination treatment with monensin. The promoters of cell cycle progression, notch3 and skp2, decrease and p21, a cyclin-dependent kinase inhibitor, accumulates within the cell during this process. Conclusion: Our findings suggest that concurrent autophagy inhibition could have a role in lung cancer treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6359-6364
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• 2015

Background: Preclinical studies have shown that the combination of an aromatase inhibitor (AI) and capecitabine in estrogen receptor (ER)- positive cell lines enhance antitumor efficacy. This retrospective analysis of a group of patients with metastatic breast cancer (MBC) evaluated the efficacy and safety of combined AI with capecitabine. Materials and Methods: Patients with hormone receptor-positive metastatic breast cancer treated between 1st January 2005 and 31st December 2010 with a combination of capecitabine and AI were evaluated and outcomes were compared with those of women treated with capecitabine in conventional dose or AI as a monotherapy. Results: Of 72 patients evaluated, 31 received the combination treatment, 22 AI and 19 capecitabine. The combination was used in 20 patients as first-line and 11 as second-line treatment. Mean age was 46.2 years with a range of 28-72 years. At the time of progression, 97% had a performance status of <2 and 55% had visceral disease. No significant difference was observed between the three groups according to clinical and pathological features. Mean follow up was 38 months with a range of 16-66 months. The median PFS of first-line treatment was significantly better for the combination (PFS 21 months vs 8.0 months for capecitabine and 15.0 months for AI). For second-line treatment, the PFS was longer in the combination compared with capecitabine and Al groups (18 months vs. 5.0 months vs. 11.0 months, respectively). Median 2 year and 5 year survival did not show any significant differences among combination and monotherapy groups. The most common adverse events for the combination group were grade 1 and 2 hand-for syndrome (69%), grade 1 fatigue (64%) and grade 1 diarrhoea (29%). Three grade 3 hand-foot syndrome events were reported. Conclusions: Combination treatment with capecitabine and AI used as a first line or second line treatment was safe with much lowered toxicity. Prospective randomized clinical trials should evaluate the use of combination therapy in advanced breast cancer to confirm these findings.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6015-6020
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• 2014

Background: Isolation and characterization of circulating tumor cells (CTCs) in patients suffering from a variety of different cancers have become hot biomarker topics. In this study, we evaluated the prognostic value of CTCs in pancreatic cancer. Materials and Methods: Initial literature was identified using Medline and EMBASE. The primary data were hazard ratios (HRs) with 95% confidence intervals (CIs) of survival outcomes, including overall survival (OS) and progression free survival/recurrence free survival (PFS/RFS). Results: A total of 9 eligible studies were included in this meta-analysis, published between 2002 and 2013. The estimated pooled HR and 95%CI for OS for all studies was 1.64 (95%CI 1.39-1.94, p<0.00001) and the pooled HR and 95%CI for RFS/DFS was 2.36 (95%CI 1.41-3.96, p<0.00001). The HRs and 95%CIs for OS and RFS/DFS in patients before treatment were 1.93 (95%CI 1.26-2.96, p=0.003) and 1.82 (95%CI 1.22-2.72, p=0.003), respectively. In patients receiving treatment, the HRs and 95%CI for OS and RFS/DFS were 1.37 (95%CI 1.00-1.86, p=0.05) and 1.89 (95%CI 1.01-3.51, p=0.05), respectively. Moreover, the pooled HR and 95%CI for OS in the post-treatment group was 2.20 (95%CI 0.80-6.02, p=0.13) and the pooled HR for RFS/DFS was 8.36 (95%CI 3.22-21.67, p<0.0001). Conclusions: The meta-analysis provided strong evidence supporting the proposition that CTCs detected in peripheral blood have a fine predictive role in pancreatic patients especially on the time point of post-treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3471-3476
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• 2014

Background: Aberrant expression of the microRNA-29 family is associated with tumorigenesis and cancer progression. As transport carriers, tumor-derived exosomes are released into the extracellular space and regulate multiple functions of target cells. Thus, we assessed the possibility that exosomes could transport microRNA-29c as a carrier and correlations between microRNA-29c and apoptosis of bladder cancer cells. Materials and Methods: A total of 28 cancer and adjacent tissues were examined by immunohistochemistry to detect BCL-2 and MCL-1 expression. Disease was Ta-T1 in 12 patients, T2-T4 in 16, grade 1 in 8, 2 in 8 and 3 in 12. The expression of microRNA-29c in cancer tissues was detected by quantitative reverse transcriptase PCR (QRT-PCR). An adenovirus containing microRNA-29c was used to infect the BIU-87 human bladder cancer cell line. MicroRNA-29c in exosomes was measured by QRT-PCR. After BIU-87 cells were induced by exosomes-derived microRNA-29c, QRT-PCR was used to detect the level of microRNA-29c. Apoptosis was examined by flow cytometry and BCL-2 and MCL-1 mRNA expressions were assessed by reverse transcription-polymerase chain reaction. Western blotting was used to determine the protein expression of BCL-2 and MCL-1. Results: The expressions of BCL-2 and MCL-1 protein were remarkably increased in bladder carcinoma (p<0.05), but was found mainly in the basal and suprabasal layers in adjacent tissues. The expression of microRNA-29c in cancer tissues was negatively correlated with the BCL-2 and MCL-1. The expression level of microRNA-29c in exosomes and BIU-87 cells from the experiment group was higher than that in control groups (p<0.05). Exosome-derived microRNA-29c induced apoptosis (p<0.01). Although only BCL-2 was reduced at the mRNA level, both BCL-2 and MCL-1 were reduced at the protein level. Conclusions: Human bladder cancer cells infected by microRNA-29c adenovirus can transport microRNA-29c via exosomes. Moreover, exosome-derived microRNA29c induces apoptosis in bladder cancer cells by down-regulating BCL-2 and MCL-1.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.275-278
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• 2016

The membrane epithelial mucin MUC1 is expressed at the luminal surface of most simple epithelial cells, but expression is greatly increased in most breast cancers. The aims of present study were to investigate expression of the MUC1 gene and interactive affects in metastases. Whole cell RNA isolation from 50 sentinel lymph nodes (SNLs) of breast cancer patients was performed using reverse transcription and real-time PCR. All patients were diagnosed with breast cancer and without metastasis, confirmed by IHC staining. The evaluation of tumor and normal samples for expression of MUC1 gene, the results were 49.1% non-expressive and 45.3% expression (Student t, p = 0.03). Also in comparison of normal breast tissue and breast cancer SLN for MUC1 gene, MUC1 negative SLNs were 75.0% (18 samples) and MUC1 positive samples were 25.0% (6 samples). Over-expression of MUC1 gene may offer a target for therapy related to progression and metastasis in women with breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2935-2940
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• 2016

Breast cancer is the most frequent type of cancer diagnosed among women worldwide and also in Thailand. Estrogen and estrogen receptors exert important roles in its genesis and progression. Several cytokines have been reported to be involved in the microenvironment that promotes distant metastasis via modulation of immune and inflammatory responses to tumor cells. Estrogen receptor genetic polymorphisms and several cytokines have been reported to be associated with breast cancer susceptibility and aggressiveness. To investigate roles of genetic polymorphisms in estrogen receptor alpha (ESR1) and interleukin 6 (IL6), breast cancer patients and control subjects were recruited from the Division of Head, Neck and Breast Surgery (Siriraj Hospital, Bangkok, Thailand). Polymorphisms in ESR1 (rs3798577) and IL6 (rs1800795 and rs1800797) were evaluated by real-time PCR in 391 breast cancer patients and 79 healthy controls. Associations between genetic polymorphisms and clinicopathological data were determined. There was no association between genetic polymorphisms and breast cancer susceptibility. However the ESR1 rs3798577 CT genotype was associated with presence of lymphovascular invasion (OR=2.07, 95%CI 1.20-3.56, p=0.009) when compared to the TT genotype. IL6 rs1800795 CC genotype was associated with presence of extranodal extension (OR= 2.30, 95%CI 1.23-4.31, p=0.009) when compared to the GG genotype. Survival analysis showed that IL6 rs1800797 AG or AA genotypes were associated with lower disease-free survival. These findings indicate that polymorphisms in ESR1 and IL6 contribute to aggressiveness of breast cancer and may be used to identify high risk patients.

• Journal of Life Science
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• v.31 no.12
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• pp.1057-1065
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• 2021

Alterations in mitochondrial DNA (mtDNA) copy numbers have been reported in patients with stomach cancer and suggested to play a role in gastric carcinogenesis or gastric cancer progression. However, changes in the levels of mitochondrial proteins or mtDNA-encoded oxidative phosphorylation (OXPHOS) proteins in gastric cancer remain unclear. In this study, we investigated mtDNA contents, mitochondrial protein levels, and mtDNA-encoded OXPHOS protein levels in gastric cancer tissues and cell lines. We correlated mtDNA copy numbers with clinicopathologic features of the gastric cancer samples used in this study and used quantitative PCR to analyze the mtDNA copy numbers of the gastric cancer tissues and cell lines. Western blot analysis was used for assessing the amounts of mitochondrial proteins and mtDNA-encoded OXPHOS proteins. Among the 27 gastric cancer samples, 22 showed a reduction in mtDNA copy numbers. The mtDNA content was increased in the other five samples relative to that in normal matched gastric tissues. Mitochondrial protein and OXPHOS protein levels were reduced in some gastric cancer tissues. However, mitochondrial protein and OXPHOS protein levels in gastric cancer cell lines were not always in line with their mtDNA contents. The mtDNA copy numbers were reduced in five gastric cancer cell lines tested in this study. In summary, this study reports a common reduction in mtDNA contents in gastric carcinoma tissues and cell lines, pointing to the possible involvement of mtDNA content alterations in tumorigenesis of the stomach.