• Title/Summary/Keyword: cancer initiation

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Anticancer Activity of Atractylodes lancea (Thunb.) DC in a Hamster Model and Application of PET-CT for Early Detection and Monitoring Progression of Cholangiocarcinoma

  • Plengsuriyakarn, Tullayakorn;Matsuda, Naoki;Karbwang, Juntra;Viyanant, Vithoon;Hirayama, Kenji;Na-Bangchang, Kesara
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6279-6284
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    • 2015
  • Opisthorchis viverrini (OV)-induced cholangiocarcinoma (CCA) is an important cancer in the Great Mekong region, particularly in Thailand. Limitations of treatment options and the lack of an effective diagnostic tool for early detection of CCA are major concerns for the control of this type of cancer. The aim of the study was to investigate anti-CCA activity of the ethanolic extract of Atractylodes lancea (Thunb.) DC., and the applicability of positron emission tomography-computed tomography (PET-CT) as a tool for detection and monitoring the progression of CCA in Opisthorchis viverrini (OV)/dimethylnitrosamine (DMN)-induced CCA hamsters. Male Syrian hamsters were used for toxicity tests and anti-CCA activity evaluation. Development of CCA was induced by initial feeding of 50 metacercariae of OV, followed by drinking water containing 12.5 ppm of DMN in hamsters. The ethanolic extract of A. lancea (Thunb.) DC. was administered orally for 30 days. PET-CT was performed every 4 weeks after initiation of CCA using 18F-fluorodeoxyglucose ($^{18}F-FDG$). Results from the present study suggest that the ethanolic extract of A. lancea (Thunb.) DC. rhizome exhibited promising anti-CCA activity and safety profile in the OV/DMN-induced hamster model. To successfully apply PET-CT as a tool for early detection of tumor development and progression, modification of radiolabeling approach is required to improve its specificity for CCA cells.

Outcome of the Gynecologic Oncology Patients Surveillance Network Program

  • Suprasert, Prapaporn;Suwansirikul, Songkiat;Charoenkwan, Kittipat;Cheewakriangkrai, Chalong;Suwansirikul, Songkiat
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.4901-4903
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    • 2015
  • The gynecologic oncology patients surveillance network program was conducted with the collaboration of 5 provincial hospitals located in the north of Thailand (Chiang Rai, Lamphun Nan, Phayao and Phrae). The aim was to identify ways of reducing the burden and the cost to the gynecologic cancer patients who needed to travel to the tertiary care hospital for follow up. The clinical data of each patient was transferred to the provincial hospital by the internet via the website www.gogcmu.or.th. All the general gynecologists who participated in this project attended the training course set up for the program. From January 2011 to February 2014, 854 patients who were willing to have their next follow-up at the network hospitals close to their home were enrolled this project. Almost of them were residents in Chiang Rai province and the most common disease was cervical cancer. After the project had been running for 1 year, 604 of the enrolled patients and 21 health-care personnel who had participated in this project were interviewed to assess its success. Some 85.3% of the patients and 100% of the health-care personnel were satisfied with this project. However, 60 patients had withdrawn, the most common reason being the lack of confidence in the follow up at the local provincial hospital. In conclusion, it is possible to initiate a gynecologic oncology patients' surveillance network program and the initiation could reduce the problems associated with and the cost the patients incurred as they journeyed to the tertiary care hospital.

Purple Rice Extract Supplemented Diet Reduces DMH-Induced Aberrant Crypt Foci in the Rat Colon by Inhibition of Bacterial β-Glucuronidase

  • Summart, Ratasark;Chewonarin, Teera
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.749-755
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    • 2014
  • Background: Purple rice has become a natural product of interest which is widely used for health promotion. This study investigated the preventive effect of purple rice extract (PRE) mixed diet on DMH initiation of colon carcinogenesis. Materials and Methods: Rats were fed with PRE mixed diet one week before injection of DMH (40 mg/kg of body weight once a week for 2 weeks). They were killed 12 hrs after a second DMH injection to measure the level of $O^6$-methylguanine and xenobiotic metabolizing enzyme activities. Results: In rats that received PRE, guanine methylation was reduced in the colonic mucosa, but not in the liver, whereas PRE did not affect xenobiotic conjugation, with reference to glutathione-S-transferase or UDP-glucuronyl transferase. After 5 weeks, rats that received PRE with DMH injection had fewer ACF in the colon than those treated with DMH alone. Interestingly, a PRE mixed diet inhibited the activity of bacterial ${\beta}$-glucuronidase in rat feces, a critical enzyme for free methylazoxymethanol (MAM) release in the rat colon. These results indicated that purple rice extract inhibited ${\beta}$-glucuronidase activity in the colonic lumen, causing a reduction of MAM-induced colonic mucosa DNA methylation, leaded to decelerated formation of aberrant crypt foci in the rat colon. Conclusions: The supplemented purple rice extract might thus prevent colon carcinogenesis by the alteration of the colonic environment, and thus could be further developed for neutraceutical products for colon cancer prevention.

The experimental study of oral care for early radiation therapy in the head and neck cancer patients (두경부 악성종양 환자에서 조기 방사선치료를 위한 구강관리법에 대한 실험적 연구)

  • Moon, Won-Kyu;Cha, In-Ho;Kim, Hyung-Jun;Jung, Young-Soo;Lee, Chun-Ui;Lee, Jong-Young;Ryu, Mi-Heon;Yoo, Jae-Ha
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.37 no.3
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    • pp.169-175
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    • 2011
  • Background: Teeth requiring extraction before radiotherapy in head & neck cancer patients should be removed as long as possible before the initiation of radiation therapy. Conventionally, a minimum 2-week waiting primary healing period is recommended. Although the above 2-week period is ideal, it was not uncommon for the radiotherapist and cancer patient to feel an urgent need to process with radiotherapy despite the need for dental care. Therefore, alternative approaches for early radiotherapy, including conservative endodontic treatment and a 1-week waiting primary healing period after dental extraction at the time of radiotherapy, were considered and applied based on the experimental study Materials and Methods: Eighteen dogs were processed for histopathologic wound healing. The effect of the primary endodontic treatment and extraction before early radiotherapy was examined. Results: No specific complication, such as, post-extraction wound infection, radiation osteitis and osteoradionecrosis, were encountered despite the early radiotherapy. Conclusion: Based on the experimental study, a minimum 1-week waiting primary healing period for oral care before radiotherapy is suitable for the early radiotherapy in head and neck cancer patients.

Chemopreventive Effects of Elm Tree Root Extract on Colonic Aberrant Crypt Foci Induced by 1,2-Dimethylhydrazine in F344 Rats

  • Kwon, Hyun-Jung;Kim, Tae-Myoung;Ryu, Jae-Myun;Son, Seung-Hwan;Hong, Jin-Tae;Jeong, Heon-Sang;Kang, Jin-Seok;Ahn, Ji-Yun;Kim, Sung-Ran;Ha, Tae-Youl;Kim, Dae-Joong
    • Preventive Nutrition and Food Science
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    • v.13 no.3
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    • pp.157-165
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    • 2008
  • Cancer-preventive effects of ethanol extract of elm tree root (EEE) were investigated. In the in vitro cytotoxicity assay, colon cancer cells were incubated with a chloroform fraction of EEE (CF-EEE). CF-EEE significantly inhibited the proliferation of cells and induced apoptotic cell death in a dose-dependent manner. For the assessment of chemopreventive efficacy in vivo, male F344 rats were fed with EEE (0.5 or 1%) in diet for 8 weeks, and were subcutaneously injected with 1,2-dimethylhydrazine (DMH) to induce colonic aberrant crypt foci (ACF). EEE (0.5 and 1%) significantly decreased both the numbers of AC (1191.1/colon) and ACF (529.3/colon) induced by DMH. In addition, in the Western blot analysis on the colonic mucosa, administration of EEE triggered expression of caspase-3, a key factor of an apoptotic cascade. These results suggest that extract of elm tree root may have potential chemopreventive principles that lead to apoptosis of cancer cells, and thereby suppress colorectal carcinogenesis during the initiation stage.

Nutritional Status Indicators Affecting the Tolerability of Postoperative Chemotherapy After Total Gastrectomy in Patients With Gastric Cancer

  • Toyota, Kazuhiro;Mori, Masayuki;Hirahara, Satoshi;Yoshioka, Shoko;Kubota, Haruna;Yano, Raita;Kobayashi, Hironori;Hashimoto, Yasushi;Sakashita, Yoshihiro;Yokoyama, Yujiro;Murakami, Yoshiaki;Miyamoto, Katsunari
    • Journal of Gastric Cancer
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    • v.22 no.1
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    • pp.56-66
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    • 2022
  • Purpose: Nutritional problems after gastrectomy affect continuation of postoperative chemotherapy. There have been no studies limited to total gastrectomy, which is particularly prone to nutritional problems. In this study, we aimed to investigate the factors that predict the continuation of postoperative chemotherapy. Materials and Methods: We included 101 patients who underwent curative total gastrectomy and postoperative chemotherapy at Hiroshima Memorial Hospital. The effects of 37 factors, including perioperative inflammatory, nutritional, and tumor status, on the persistence of postoperative chemotherapy were analyzed. Results: In univariate analysis of preoperative factors, age, carbohydrate antigen 19-9, platelet-to-neutrophil ratio, Onodera's prognostic nutritional index (PNI), controlling nutritional status score, and nutritional risk screening (NRS-2002) score were significantly associated with the duration of postoperative chemotherapy. In multivariate analysis of preoperative factors, age (≥74 years) was an independent factor for a shorter duration of postoperative chemotherapy (hazard ratio [HR], 5.24; 95% confidence interval [CI], 2.19-12.96; P<0.01). In univariate analysis of factors before postoperative chemotherapy, intraoperative blood loss, perioperative weight loss rate, postoperative performance status, PNI, albumin-to-bilirubin index, and NRS-2002 score were significantly associated with the duration of postoperative chemotherapy. In multivariate analysis of factors before postoperative therapy, age (≥74 years) (HR, 5.75; 95% CI, 1.90-19.49; P<0.01) and PNI (<39) (HR, 3.29; 95% CI, 1.26-8.56; P=0.02) were independent factors for a shorter duration of postoperative chemotherapy. Conclusions: Age and PNI are useful predictors of postoperative chemotherapy intolerance after total gastrectomy and may determine the treatment strategy and timing of chemotherapy initiation.

HS-146, a novel phosphoinositide 3-kinase α inhibitor, induces the apoptosis and inhibits the metastatic ability of human breast cancer cells

  • Ok Hyeon Kim;Ju-Hee Lee;Shinmee Mah;Sung Yun Park;Sungwoo Hong;Soon-Sun Hong
    • International Journal of Oncology
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    • v.56 no.6
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    • pp.1509-1520
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    • 2020
  • The phosphoinositide 3-kinase (PI3K) signaling pathway plays an important role in human cancer as it regulates critical cellular functions, such as survival, proliferation and metabolism. In the present study, a novel PI3Kα inhibitor (HS-146) was synthesized and its anticancer effects on MCF-7, MDA-MB-231, SKBR3 and BT-474 human breast cancer cell lines were confirmed. HS-146 was found to be most effective in inhibiting the proliferation of MCF-7 cells and in inducing cell cycle arrest in the G0/G1 phase by downregulating cyclin D1, cyclin E, cyclin-dependent kinase (Cdk)2 and Cdk4, and upregulating p21Waf1/Cip1 protein levels in this cell line. The induction of apoptosis by HS-146 was confirmed by DAPI staining and western blot analysis. Cell shrinkage and nuclear condensation, which are typical morphological markers of apoptosis, were increased by HS-146 in the MCF-7 cells in a concentration-dependent manner, and HS-146 also increased the protein expression levels of cleaved poly(ADP-ribose) polymerase (PARP) and decreased the protein expression levels of Mcl-1 and caspase-7. In addition, HS-146 effectively decreased the phosphorylation levels of downstream PI3K effectors, such as Akt, mammalian target of rapamycin (mTOR), glycogen synthase kinase 3β (GSK3β), p70S6K1 and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). Hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) expression were also suppressed by HS-146 under hypoxic conditions, and HS-146 inhibited the migration and invasion of MCF-7 cells in a concentration-dependent manner. On the whole, the findings of the present study suggest that HS-146, a novel PI3Kα inhibitor, may be an effective novel therapeutic candidate that suppresses breast cancer proliferation and metastasis by inhibiting the PI3K/Akt/mTOR pathway.

A Case of Metastatic Pancreatic Cancer Treated with FOLFIRINOX as Second-Line Chemotherapy after Gemcitabine Failure (FOLFIRINOX 병합요법을 통한 이차 항암화학요법으로 완전 관해를 획득한 진행성 췌장암 증례)

  • Jae Min Lee;Kwang Hyun Chung;Jin Myung Park;Sang Hyub Lee;Ji Kon Ryu;Yong-Tae Kim
    • Journal of Digestive Cancer Research
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    • v.2 no.1
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    • pp.28-31
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    • 2014
  • Pancreatic cancer is a highly aggressive cancer with poor prognosis. Although, gemcitabine is the current standard regimen as first-line chemotherapy for advanced pancreatic cancer, effective regimens of second-line chemotherapy after gemcitabine failure have not been established yet. We report a case of gemcitabine refractory pancreatic cancer treated with second-line chemotherapy with FOLFIRINOX regimen. A 57-year-old-woman visited our hospital for pancreatic body mass detected by computed tomography (CT). The patient underwent distal pancreatectomy and splenectomy and the pathologic results after surgery demonstrated adenocarcinoma. Follow-up was performed after surgery and CT and positron emission tomography (PET) 4 months after surgery revealed multiple hepatic metastases. The patient underwent first-line chemotherapy with gemcitabine and erlotinib for recurred pancreatic cancer. However, CT after 7 cycles of the chemotherapy showed the progression of multiple hepatic metastases and switch to second-line chemotherapy with FOLFIRINOX was initiated. CT after 16 cycles of the FOLFIRINOX showed the complete remission of multiple hepatic metastases. The patient was admitted for infective endocarditis with septic pneumonia 17 months after the initiation of FOLFIRINOX. However, the patients died from the progression of septic embolism and acute respiratory distress syndrome.

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Chemopreventive Efficacy of Moringa oleifera Pods Against 7, 12-Dimethylbenz[a]anthracene Induced Hepatic Carcinogenesis in Mice

  • Sharma, Veena;Paliwal, Ritu;Janmeda, Pracheta;Sharma, Shatruhan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2563-2569
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    • 2012
  • Oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage in a variety of liver disorders. Hence there is a great demand for the development of agents with potent antioxidant effect. The aim of the present investigation is to evaluate the efficacy of Moringa oleifera as a hepatoprotective and an antioxidant against 7, 12-dimethylbenz[a]anthracene induced hepatocellular damage. Single oral administration of DMBA (15 mg/kg) to mice resulted in significantly (p<0.001) depleted levels of xenobiotic enzymes like, cytochrome P450 and b5. DMBA induced oxidative stress was confirmed by decreased levels of reduced glutathione (GSH) and glutathione-S-transferase (GST) in the liver tissue. The status of hepatic aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) which is indicative of hepatocellular damage were also found to be decreased in DMBA administered mice. Pretreatment with the Moringa oleifera (200 and 400 mg/kg) orally for 14 days significantly reversed the DMBA induced alterations in the liver tissue and offered almost complete protection. The results from the present study indicate that Moringa oleifera exhibits good hepatoprotective and antioxidant potential against DMBA induced hepatocellular damage in mice that might be due to decreased free radical generation.

Cleistocalyx nervosum Extract Ameliorates Chemical-Induced Oxidative Stress in Early Stages of Rat Hepatocarcinogenesis

  • Taya, Sirinya;Punvittayagul, Charatda;Inboot, Wanida;Fukushima, Shoji;Wongpoomchai, Rawiwan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2825-2830
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    • 2014
  • Purpose: To study the effect of Cleistocalyx nervosum extract (CE) on diethylnitrosamine (DEN) and phenobarbital (PB) induced oxidative stress in early stages of rat hepatocarcinogenesis. Materials and Methods: Male Wistar rats were divided into 4 groups, with Group 1 as a negative control and Group 2 was a positive control receiving DEN injections once a week and PB in drinking water for 6 weeks. Two weeks before DEN initiation and PB treatment, Groups 3 and 4, were fed with 500 and 1000 mg/kg of CEs, respectively, for 8 weeks. Results: A number of GST-P-positive foci, preneoplastic lesions, in the liver were markedly increased in carcinogen administered rats, but was comparatively decreased in rats treated with 1000 mg/kg of CE. The CE reduced malondialdehyde in serum and in the livers of rats treated with DEN and PB. Moreover, CE significantly increased the activities of glutathione peroxidase and catalase in rat liver. Conclusions: CE appeared to exert its chemopreventive effects by modulating antioxidant status during DEN and PB induced early stages of hepatocarcinogenesis in rats.