• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.4
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• pp.799-804
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• 2009

Kamikaekyuk-tang(KMKKT), a formula of ten Oriental herbs, was orientally designed to promote vital energy, to remove blood stasis, and to decrease inflammation for treating cancers. KMKKT and its component had potent antiandrogen and androgen receptor activities in prostate cancer and also inhibited angiogenesis induced by basic fibroblast growth factor (bFGF) in human umbilical vein endothelial cells and suppressed the tumor growth in LLC-bearing mice, and liver metastasis of colon 26-L5 cancer cells, suggesting a potent cancer preventive agent. Nevertheless, there is no safety study of KMKKT before clinical trial so far. Thus, in the current study, we investigated the toxicity about ethanol-extracted KMKKT. Male and female Spraque Dawley (SD) rats were given orally by KMKKT at 250, 500, and 1000 mg/kg for 4 weeks. Mortality, clinical signs and measured change of body weight, food consumption and water consumption were observed. In addition, we performed ophthalmologic, urinary, hematological, blood serum biochemical and histopathological examination. Any general toxicity was not found in KMKKT treated group. Also, there were no significant differences in the parameters such as body weight, food consumption and water consumption, a lot of urine and blood factor levels except WBC, MCHC and Ca level compared with control group. Although WBC and MCHC were elevated in female rats and Ca level was decreased in male rats, these were within normal ranges. Finally, we determined that maximum tolerated dose (MTD) was 1000 mg/kg and no observed adverse effect level (NOAEL) was 500 mg/kg. Taken together, these results demonstrated that KMKKT is very safe to SD rats.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1273-1276
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• 2012

Purpose: The incidence of colorectal cancer (CRC) has been increasing in Asian countries including Thailand. Double contrast barium enema (DCBE) is one of the investigation tools used in CRC screening. This study aimed to determine the incidence of colorectal neoplasm detected at screening by DCBE in Thai people. Methods: The computerized radiology database of screening DCBE in Thai adults between June 2009 and October 2011 at the Faculty of Medicine, Siriraj Hospital, was reviewed. DCBE examination performed in a surveillance program after curative CRC resection or the removal of colorectal polyps was also considered as a screening DCBE. Results: A total of 819 screening DCBEs performed during this 28-month period were analyzed. The mean age of patients was $59.8{\pm}13.6$ years. Of the total, 467 (57%) were male. A family history of CRC and a previous history of curative CRC resection or polyp removal were noted in 34 patients (4%) and 124 patients (15%), respectively. A total of 31 patients (3.8%; 95%CI = 2.7%-5.3%) were reported to have colorectal polyp or mass demonstrated on DCBE. Of these, follow-up endoscopy was performed in 20 cases (65%). According to pathological results, the incidence of advanced adenoma and CRC detected at screening DCBE was 0.7% (95%CI = 0.3%-1.6%; n=6) and 0.4% (95%CI = 0.1%-1.1%; n=3), respectively. Conclusions: The screening DCBE performed in Thai adults had a diagnostic yield of 0.7% for advanced adenoma and 0.4% for CRC.

• Archives of Pharmacal Research
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• v.25 no.3
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• pp.293-299
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• 2002

Cytotoxic and antimutagenic effects of a novel cis-$\varepsilon$-viniferin and five known stilbenes, transresveratrol, trans-$\varepsilon$-viniferin, gnetin H, suffruticosols A and B, isolated from the seeds of Paeonia lactiflora Pall. (Paeoniaceae) were determined against five different cancer cell lines, and mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Salmonella typhimurium TA100, respectively. Six stilbenes showed cytotoxic activity in a dose-dependent manner, and especially did potent cytotoxic activity against C6 (mouse glioma) cancer cell with $IC_{50}$ values ranging from 8.2 to $20.5{\;}{\mu\textrm{g}}/ml$. trans-Resveratrol showed significant cytotoxic activity against HepG2 (liver hepatoma) and HT-29 (colon) human cancer cell lines with $IC_{50}$ values of 11.8 and 25.2 g/ml, respectively. In contrast, trans-$\varepsilon$-viniferin and cis--viniferin, and gnetin H exhibited marked cytotoxic activity against Hela (cervicse) and MCF-7 (breast) human cancer cell lines with $IC_{50}$ values of 20.4, 21.5, and $12.9{\;}{\mu\textrm{g}}/ml$, respectively. However, suffruticosol A and B had less cytotoxic effect against all cancer cells except C6. Meanwhile, six stilbenes exerted antimutagenic activity in a dose-dependent fashion. Of them, trans-resveratrol exhibited the strongest antimutagenic effect against MNNG with $IC_{50}$ value of $27.0{\;}{\mu\textrm{g}}/plate$, while other five resveratrol oligomers also did moderate antimutagenic activity with $IC_{50}$ values ranging from 31.7 to $35.2{\;}{\mu\textrm{g}}/plate$.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1947-1959
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• 2016

Background: Colorectal cancer (CRC) is a major cause of morbidity and mortality, being the second most common type of cancer worldwide in both men and women. It accounts yearly for approximately 9% of all new cases of cancers. Furthermore, the current chemotherapeutic regimens seem unsatisfactory, so that exploration of novel therapeutic modalities is needed. The present study was undertaken to investigate the inhibitory effects of a crude alkaloid extract (CAERS) of a medicinal herb, Rhazya stricta, on proliferation of CRC HCT116 cells and to elucidate mechanisms of action. To achieve these aims, we utilized MTT, comet, DNA laddering and gene reporter assays, along with Western blot and RT-PCR analyses. Results: We found that CAERS inhibited cell proliferation and induced apoptotic cell death in HCT116 cells. Hallmarks of morphological and biochemical signs of apoptosis were clearly evident. CAERS down-regulated DNA-binding and transcriptional activities of NF-${\kappa}B$ and AP-1 proteins, while up-regulating expression of the Nrf-2 protein. It also down-regulated expression levels of the ERK MAPK, Bcl-2, cyclin D1, CDK-4, survivin and VEGF and up-regulated levels of Bax, caspase-3/7 and -9, p53, p21, Nrf-2. Markedly, it promoted mRNA expression levels of cytoprotective genes including the hemeoxygenase-1, NAD(P)H quinine oxidoreductase 1 and UDP-glucuronyltransferase. Conclusions: These findings indicate that CAERS exerts antiproliferative action on CRC cells through induction of apoptotic mechanisms, and suggest CAERS could be a promising agent for studying and developing novel chemotherapeutic agents aimed at novel molecular targets for the treatment of CRC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1767-1770
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• 2012

Background: The Asia Pacific consensus for colorectal cancer (CRC) recommends that screening programs should begin by the age of 50. However, there have been reports about increasing incidence of CRC at a younger age (i.e. early-onset CRC). Little is known about the features of early-onset CRC in the Vietnamese population. Aim: To describe the clinical, endoscopic and pathological characteristics of early-onset CRC in Vietnamese. Method: A prospective, cross-sectional study was conducted at the University Medical Center from March 2009 to March 2011. All patients with definite pathological diagnosis of CRC were recruited. The early-onset CRC group were analyzed in comparison with the late-onset (i.e. ${\geq}$ 50-year-old) CRC group. Results: The rate of early-onset CRC was 28% (112/400) with a male-to-female ratio of 1.3. Some 22.3% (25/112) of the patients only experienced abdominal pain and/or change in bowel habit without alarming symptoms, 42.9% (48/112) considering their symptoms intermittent. The rate of familial history of CRC in early-onset group was significantly higher that of the late-onset group (21.4% versus 7.6%, p<0.001). The distribution of CRC lesions in rectum, distal and proximal colon were 51.8% (58/112), 26.8% (30/112) and 21.4% (24/112), respectively; which was not different from that in the late-onset group (${\chi}2$, p = 0.29). The rates for poorly differentiated tumors were also not significantly different between the two groups: 12.4% (14/112) versus 8.3% (24/288) (${\chi}2$, p = 0.25). Conclusion: A high proportion of CRC in Viet Nam appear at an earlier age than that recommended for screening by the Asia Pacific consensus. Family history was a risk factor of early-onset CRC. Diagnosis of early-onset CRC needs more attention because of the lack of alarming symptoms and their intermittent patterns as described by the patients.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.987-991
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• 2013

Aim: To study anti-tumor effects of exosomes from class II transactivator (CIITA) gene transfected CT26 cells. Methods: In this study, we established an MHC class II molecule-expressing murine colon cancer cell line (CT26-CIITA) by transduction of the CIITA gene. Immune effects in vitro and tumor protective results in vivo were tested and monitored. Results: Exosomes from CT26-CIITA cells were found to contain a high level of MHC class II protein. When loaded on dendritic cells (DCs), exosomes from CT26-CIITA cells significantly increased expression of MHC class II molecules, CD86 and CD80, as compared to exosomes from CT26 cells. In vitro assays using co-culture of immunized splenocytes and exosome-loaded DCs demonstrated that CIITA-Exo enhanced splenocyte proliferation and IFN-${\gamma}$ production of CD4+T cells, while inhibiting IL-10 secretion. In addition, compared to exosomes from CT26 cells, CT26-CIITA-derived exosomes induced higher TNF-${\alpha}$ and IL-12 mRNA levels. A mouse tumour preventive model showed that CT26-CIITA derived exosomes significantly inhibited tumour growth in a dose-dependent manner and significantly prolonged the survival time of tumour-bearing mice. Conclusion: Our findings indicate that CT26-CIITA-released exosomes are more efficient to induce anti-tumour immune responses, suggesting a potential role of MHC class II-containing tumour exosomes as cancer vaccine candidates.

• Natural Product Sciences
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• v.15 no.1
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• pp.1-7
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• 2009

This study was performed to investigate the cell growth inhibitory effect of tissue cultured root of wild Panax ginseng C.A. Mayer (tcwPG). The human stomach carcinoma cell line, MKN 74, was incubated with 70% EtOH extract of tcwPG or Panax ginseng C.A. Mayer (PG) for 24 hrs. tcwPG inhibited cell growth at a concentration of $250{\mu}g/ml$. However, Panax ginseng extract did not inhibit cell growth at the same concentration. We also tested the ethyl acetate and $H_2O$ fractions of tcwPG. The inhibitory effect of the ethyl acetate fraction on cell proliferation in MKN 74 cells was more potent than that of the crude extract, and the inhibitory effect of the $H_2O$ fraction was less than that of the ethyl acetate fraction. When we separated tcwPG into polar and non-polar saponin fractions and then measured cell growth inhibition, the non-polar saponin in tcwPG exhibited cytotoxicity. To compare the effects of tcwPG on various cancer cell lines, we measured cytotoxicity in MKN 74 (stomach cancer cell line), SW 620 (colon cancer cell line) and PC 3 (prostate cancer cell line). All three cell lines showed cell growth inhibition, and the cell growth inhibitory effects were not quite different in the various cell lines. The non-polar saponins of tcwPG arrested PC 3 cells at G1-phase as did Panax ginseng.

• Journal of Gastric Cancer
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• v.6 no.4
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• pp.291-294
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• 2006

F-18 FDG-PET/CT could be used to evaluate the surveillance of recurrent stomach cancer, but some cases reported as false-positives. The authors found an activated charcoal granuloma from intraperitoneal chemotherapy by using a curative resection and mitomycin C for stomach cancer. A mass behind the right colon that showed on CT 6 months after an operation in a 46-year-old male patient had no progression in size, but 36 months after the operation, an increase was seen on F-18 FDG-PET/CT, and a metastatic tumor was suspected. The tumor was resected by an explorative laparotomy and was diagnosed as being an activated charcoal granuloma based on the histologic finding. Based on this case, we should be reminded of the possibility of a false-positive on analysis of F-18 FDG-PET/CT caused by an activated charcoal granuloma in a patient who has intraperitoneal chemotherapy.

• Journal of Gastric Cancer
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• v.16 no.2
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• pp.85-92
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• 2016

Purpose: PIK3CA is often mutated in a variety of malignancies, including colon, gastric, ovary, breast, and brain tumors. We investigated PIK3CA expression in gastric cancer and explored the relationships between the PIK3CA expression level and clinicopathological features as well as survival of the patients. Materials and Methods: We examined PIK3CA expression in a tissue microarray of 178 gastric adenocarcinomas by immunohistochemistry and reviewed patients' medical records. Results: In our study, 112 of the 178 gastric cancer patients displayed positive PIK3CA expression. Overexpression of PIK3CA was correlated with low grade differentiation (P=0.001), frequent lymphatic invasion (P=0.032), and high T stage (P=0.040). Patients with positive PIK3CA staining were more likely to display worse overall survival rate than those with negative PIK3CA staining, as determined by Kaplan-Meier survival analysis with log-rank test (P=0.047) and a univariate analysis using the Cox proportional hazard model (hazard ratio=1.832, P=0.051). Conclusions: Elevated PIK3CA expression was significantly correlated with tumor invasiveness, tumor phenotypes, and poor patient survival.

• Journal of Radiation Industry
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• v.5 no.1
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• pp.35-39
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• 2011

This study was investigated the effect of tumor cell cytotoxicity of gamma irradiated Chaga mushroom extract (CME). CME was prepared by hot water extraction at $70^{\circ}C$ for 4 hours and lyophilized. $Ten\;mg\;ml^{-1}$ of lyophilized CME powder was dissolved with deionized water and then irradiated at the doses of 10, 50, 100, and 150kGy by cobalt 60 gamma irradiator. The gamma-irradiated and non-irradiated CME were treated into the cancer cell, including human stomach cancer and human colon cancer. Cytotoxicity against the cancer cell was increased in gamma-irradiated CME and antioxidant activity was also increased in gamma-irradiated CME, as irradiation dose increased. Therefore, it was considered that gamma irradiation was effective method for improvement of the cancer cell cytotoxicity and antioxidant activity of Chaga mushroom extract.