Sabtu, 16 Juni 2012

my First Articel review






ACTIVITY OF GEMCITABINE BY EMODIN AGAINST
PANCREATIC CANCER
Via Hayati1,  Endang Darmawan2
1Pharmacist Program, Pharmacy Graduate Program2, Faculty of Pharmacy, Ahmad Dahlan University, Yogyakarta, Indonesia

Abstract
Objective
This review article aims to determine efektiftas emodin when combined with gemcitabine for pancreatic-cancer.
Methode
The presentation all results and discussion based on a review journal that carried out from various sources journals: Pubmed, NIH, IJO (Journal of the Institute of Oncology), and google scholar of 2003-2011. Then carried out compiling some journals resulting in a complete journal.
Results
Based on in vitro assays, preclinical, and human data, emodin combination with gemcitabine may enhance gemcitabine activity and reduced side effects as anticancer gemcitabine. Emodin in vitro to inhibit the growth, suppress cell migration and invasion and induces apoptosis SW 1990 cancer cells by inhibiting the growth of BxPC-3 cells. On the decline in preclinical testing regulation on Bcl / Bax and an increase in the release of mitochondrial citokrom C leads to increased apoptosis and decreased tumor volume and weight of the combination gemcitabine + emodin. While the human data, emodin used in conjunction with gemcitabine may reduce the side effects of gemcitabine with a decline in the number of VEGF and CA19-9 in the treated group (emodin + Gemcitabine) is significantly higher than control group (gemcitabinea) P <0.05.
Conclusion
Use of emodin which together with gemcitabine may enhance the activity gemcitebine and reduce side effects. So it can be recommended as a treatment alternative in the treatment of pancreatic cancer.

Keyword :  Pancreatic cancer, emodin, gemcitabine, combination.

1.    INTRODUCTION
Cancer is one of the leading causes of death in the United States, caused by uncontrolled division of abnormal cells (BKEdwards et al, 2010). Pancreatic cancer is the fourth leading cause of death, PCAN (Pancreatic Cancer Action Network) in 2011 in the United Bunch of approximately 44 030 people diagnosed with pancreatic cancer and 37 660 died of the disease (PCAN, 2011). SEER (Surveillance Epidemiology and Result) estimated 43 920 (22 090 men and 21 830 women) diagnosed with pancreatic cancer and 37,390 will die of pancreatic cancer in 2012, this (Howlader N et al, 2012). Pancreatic cancer is known as the "silent disease" because in the early stages of pancreatic cancer almost have symptoms. We must be wary of pancreatic cancer because pancreatic cancer is a rare type of cancer but it is quite dangerous and quite vicious, because pancreatic cancer can only be detected when it is already at an advanced stage.
Treatment used is ionizing radiation, surgery and chemotherapy the tumor tissue. However, current methods of cancer pegobatan mnyebabkan severe systemic side effects. Gemcitabine is the standard drug treatment of advanced pancreatic cancer, gemcitabine but have side effects, toxicity and drug resistance is large. For that reason, much research focuses on alternative medicine based padaekstrak plants. The use of drugs alternatives, especially when used together with conventional medicine of anticancer therapy. May serve to reduce side effects, increasing the absorption of drugs and strengthen the immune system konvensioanal body to fight cancer (MS Goldstein, 2003).
Emodin is an anthraquinone. In Pharmacology has shown anticancer effects in several human cancers. Liu et al (2011) in his study suggests that emodin may inhibit cancer cell growth and induce apoptosis of cancer cells. Emodin has antipoliferatif and antimetastatik activity in cancer cells both in vitro and in vivo.
This study aims to determine the activity of gemcitabine after combined with emodin, expected by the study could be used as a reference for anticancer therapy.

2.    METHODE
The presentation all results and discussion based on literature study using PICO and journals from various sources: Pubmed, NIH, IJO (Journal of the Institute of Oncology), and google scholar of 2003-2011. Then do the compiling some journals that produces a complete journal.
3.    RESULTS AND DISCUSSION
RESULTS
The results obtained by searches made 5 journals including the journal of research in vitro, preclinical and clinical trials. Effect of emodin Data science journal Gemcitabine As Anticancer Activity Against shown in Table 1.
No
Research
Methode
Actifity
Referensi
1
In vitro
-    Tunel Assay,
-    Imunohitochrmistry
-    Western bolt
Emodin enhance the antitumor effects of gemcitabine.
Chen H et al, 2011
Cell Kit-8 Assay and  BxPC-3 Cell
Emodin inhibits the growth of BxPC-3 cells and work synergistically against gemcitabine.

Zeng Yong et al, 2011

Emodin combined with gemcitabine induced a higher percentage of growth inhibition and apoptosis in both pancreatic cancer cell lines compared to gemcitabine alone.
Liu et al, 2011
2.
Praklinik
Model xenograft sel
Emodin and gemcitabine combination resulted in increased apoptosis of cancer cells.
Weitian et al, 2010
3.
Human Data

The use of a combination of emodin and gemcitabine in pancreatic cancer patients can reduce side effects.
Wang et al, 2011
Table 1. Effect Of Emodin On Activity Of Gemcitabine Againts Pancreatic Cancer

DISCUSSION
Based on research that has been done, emodin shown to increase the effectiveness of gemcitabine. Emodin in vitro to inhibit the growth, suppress cell migration and invasion of SW 1990. Test showed emodine western downregulated CD34, NF-kappaB, and MMP-9 in SW 1990 cells. 1990 SW Tues merupkan found in tumor cells (Liu et al, 2010). Chen et al study (2010) showed that emodin can induce tumor cell apoptosis with a decrease in Bcl-2/Bax regulation and increase the release of citokrom C (CytC). Meanwhile, when combined with gemcitabine then emodin can enhance the antitumor efficacy of gemcitabine as even at low doses, thereby reducing the toxicity effects of gemcitabine. Zeng et al (2011) in his research revealed that emodin significantly inhibited cell growth of BxPC-3, and work synergistically with gemcitabine in inhibiting tumor cell proliferase BxPC-3. Synergism of action can be achieved due to the induction of apoptosis in pancreatic cancer cells.
The experimental results showed that emodin diindukis cells (40μmol / L) for 24, 48 and 72 hours had survival rates 79. 39%, 46. 35%, and 45. 44%, whereas the survival rate of BxPC-3 cells for 72 h at E & G is only 26. 62%, this indicates a significant difference between gemecitabine induced cells alone (42.78%) and emodin alone (47.18%). Ratio of early apoptotic cells BxPC-3 induced emodin (40μmol / L) for 24 hours and gemecitabine (20 mol / L) was 4.70% + / - 1.54% and 11.20% + / - 1.41% , while the ratio of early apoptosis of BxPC-3 cells induced E & G was 20.60% + / -3.23%, the data showed significant differences from that induced by emodin or gemecitabine alone (P <0.05).
Preclinical trials conducted Weitian et al (2010), in athymic mice using xenograft models of SW 1990 cells are injected IP (intraperitonial) with different groups, namely the N (sodium chloride 0.9%), group E (40 mg emodin / kg), group G (gemcitabine 125 mg / kg) and E + G (emodin 40 mg / kg and gemcitabine 80 mg / kg). The results obtained after 1 week of injection was a significant decrease in tumor volume and the average tumor weight of the average G + E combination group than the other treatment groups. Tunel test showed the combination of E + G group had a greater apoptosis than the other groups. Immunohistochemical analysis (IHC) and Western blot (WB) shows cytochrome C in cytoplasm and Bax protein in the combination E + G upregulated while Bcl decreased regulation as compared with other groups, in other words there is a decrease in the regulation of Bcl / Bax and an increase in the release citokrom C from the mitochondria that lead to increased apoptosis.
Wang et al (2011) in his research on the safety of the combination of gemcitabine by emodin capsules of pancreatic cancer patients showed emodin capsules can reduce the burden of cancer patients. Data supporting these studies, reductions in VEGF and CA19-9 in the treated group (emodin + Gemcitabine) is significantly higher than control group (gemcitabinea) P <0.05. Incidence of bleeding and gastrointestinal disorders due to drug side effects in the treated group was significantly lower than control kselompok. The response rate in cancer inhibition does not occur significant differences between the treatment and control groups.

4.    CONCLUSION
Based on the review journal that has been done can be concluded that emodin affects the activity of gemcitabine. Use of emodin in combination with gemcitabine may enhance the activity of gemcitabine in the treatment of pancreatic cancer, and can reduce side effects caused by gemcitabine.
5.    RECOMMENDED
Emodin and gemcitabine combination can be used as a therapeutic alternative for the treatment of pancreatic cancer.


REFERENCES
B. K. Edwards, E. Ward, B. A. Kohler et al., “Annual report to the nation on the status of cancer, 1975–2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates,” Cancer, vol. 116, no. 3, pp. 544–573, 2010. View at Publisher · View at Google Scholar · View at PubMed

PCAN. 2011. Pancreatic Cancer Incidence And Death Rate On The Rise As Overall Cancer Death Rates Continue To Decline. http://www.pancan.org/section_about/news_press_center/2011_press_releases/06_17_11_pr.php
Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Altekruse SF, Kosary CL, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations), National Cancer Institute. Bethesda, MD http://seer.cancer.gov/csr/1975_2009_pops09/, based on November 2011 SEER data submission, posted to the SEER web site, 2012.
M. S. Goldstein, “Complementary and alternative medicine: its emerging role in oncology,” Journal of Psychosocial Oncology, vol. 21, no. 2, pp. 1–21, 2003. View at Publisher · View at Google Scholar · View at Scopus
Liu A, et al. 2011. Antiproliferative and antimetastatic effects of emodin on human pancreatic cancer. Department of Surgery, The Second Affiliated Hospital of Wenzhou Medical College, No. 109, West Xue-yuan Road, Wenzhou 325027, PR China. ( www.pubmed.com )
Chen H, et al. 2011. Enhanced effect of gemcitabine by emodin against pancreatic cancer in vivo via cytochrome C-regulated apoptosis. Department of Surgery, The Second Affiliated Hospital of Wenzhou Medical College, No. 109, West Xue-yuan Road, Wenzhou 325027, PR China.   www.pubmed.com

Zeng Y, Liu A, Tong HF. 2011. Effect of emodin combined gemcitabine on the growth and apoptosis of pancreatic cancer cell line BxPC-3 in vitro. The Second Affiliated Hospital of Wenzhou Medical College, Zhejiang. http://en.cnki.com.cn/Article_en/CJFDTOTAL-ZZXJ201104044.htm
Weitian Wei et al. 2010. Emodin Enhances antitumor effect of gemcitabine in model WS1990 cell xenograft on athymic mouse. Departement of surgery, 2nd Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China.  Oncology report. http://www.spandidos-publications.com/or/25/5/1253 
WANG Fusheng,JIANG Guozheng,WU Zhouhuan. 2011. Efficacy of Gemcitabine Combined With Emodin Capsule for Patients with Pancreatic Cancer. Department of Surgery,The Affiliated Hospital of Jinhua Medical College Jinhua 321000 China. http://en.cnki.com.cn/Article_en/CJFDTOTAL-JJYX201104014.htm

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