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Study of the clinical effect of fucoidan combined chemotherapy for advanced unresectable gastric carcinoma． 

ZHANG Hong － heng． Department of General Surgery，Baoji Central Hospital，Baoji Shaanxi 721000，China．

Gastric cancer is one of the most common digestive system malignancies, ranking fourth in the global prevalence of malignant tumors [1]. There are approximately 989,600 new cases of gastric cancer each year worldwide, of which approximately 70% occur in developing countries such as my country [2,3]. In the early stages of gastric cancer, the most effective treatment is surgery [4,5]. However, due to the lack of typical symptoms in early gastric cancer, most cases have already developed to the late stage of gastric cancer when diagnosed, often with lymph node, peritoneal or liver metastasis [6], and have lost the opportunity for surgical treatment [7,8]. Therefore, systemic chemotherapy has become the main treatment for advanced gastric cancer [9]. Chemotherapy often causes bone marrow suppression toxicity such as thrombocytopenia and leukocytopenia, and is accompanied by adverse reactions such as nausea, vomiting or liver and kidney damage [10]. In recent years, studies have found that brown algae polysaccharide has biological activities such as antiviral, antitumor, and immunity enhancement [11-13], which can reduce complications caused by chemotherapy and improve the quality of life of patients [14].This study observed the clinical efficacy and adverse reactions of fucoidan combined with FOLFOX4 chemotherapy in the treatment of advanced gastric cancer, and the results are reported as follows.

1. Information and methods
   

(1) Information

General information: 94 patients with advanced gastric cancer who came to our hospital from January 1, 2010 to August 31, 2013 were selected, including 60 males and 34 females; aged 37 to 75 years old, with an average age of 54. 2 ± 4. 23 years old. All cases were diagnosed as advanced gastric cancer through B-ultrasound, MRI imaging examination and pathological examination. Among them, 50 cases had peritoneal metastasis, 19 cases had liver metastasis, 11 cases had distant lymph node metastasis, and 14 cases had local progression. 94 patients were randomly divided into observation group and control group, 47 patients in each group. There were no significant differences in gender composition ratio, age, pathological type, etc. between the two groups of patients (P>0.05), and they were comparable. See Table 1.

Table 1: Comparison of general information between the two groups of patients

(2) Methods: Venous blood was collected from all patients before treatment to examine the CD4/CD8 ratio of T cells. The control group was treated according to the FOLFOX4 (oxaliplatin, leucovorin, and fluorouracil) regimen, namely, oxaliplatin (Qilu Pharmaceutical Co., Ltd.) 85 mg/m2, intravenous drip for 2 hours on the first day; leucovorin (Chongqing Yaoyou Pharmaceutical Co., Ltd.) 200 mg/m2, intravenous drip for 2 hours on the first and second days; fluorouracil (Yabao Pharmaceutical Group Co., Ltd.) 400 mg/m2, intravenous push on the first and second days; fluorouracil 600 mg/m2, intravenous drip for 22 hours on the first and second days.The above treatment regimen was repeated every two weeks, with 28 days as one cycle. Patients in the observation group took 150 ml/d (4.05 g) of fucoidan (Shandong Jiejing Group) orally on the basis of the treatment regimen of the control group, and continued the treatment for 4 months. The efficacy and toxic side effects of the two groups were evaluated after 4 months.

(3) Observation indexes T cell CD4/CD8 were examined in the two groups of patients after 4 months of treatment. Toxic reactions such as nausea, vomiting, liver and kidney damage in the two groups of patients during treatment were recorded. The clinical efficacy of the treatment of the two groups of patients was evaluated according to the World Health Organization (WHO) solid tumor treatment efficacy evaluation criteria. Complete remission (CR): All tumor lesions disappeared and maintained for 4 weeks; Partial remission (PR): Tumors shrank by 50% or more (but did not reach CR), maintained for 4 weeks; Stable (SD): Non-PR/PD; Progression (PD): Tumors increased by 25%, non-CR/PR/SD before the increase of lesions. Treatment efficacy (%) = (CR + PR) / total number of cases × 100%. The quality of life of patients was evaluated according to the Karnofsky score standard. After treatment, the quality of life improved: the Karnofsky score increased by ＞10 points; after treatment, the quality of life decreased: the Karnofsky score decreased by ＞10 points; after treatment, the quality of life was stable: the Karnofsky score increased or decreased by ＜10 points. The patients were followed up for 2 years, and the overall survival (OS), progression-free survival (PFS) and adverse reactions between the two groups were compared.

(4) Statistical analysis SPSS 17.0 software was used to process the experimental data. The measurement data were expressed as mean ± standard deviation (x ± s) and the t test was used; the count data were analyzed using the χ2 test. P < 0.05 was considered statistically significant.

2. Result

(1) Comparison of the effective rate of the two groups of patients: After treatment, the effective rate of the observation group (57.4%) was significantly higher than that of the control group (40.4%), and the difference was statistically significant (χ2 = 8.854, P < 0.05). See Table 2.

Table 2: Comparison of the effective rate of treatment between the two groups

(2) Comparison of long-term efficacy of treatment between the two groups of patients: After treatment, the OS and PFS of the observation group at 3 months, 6 months and 12 months were higher than those of the control group, and the difference was statistically significant (P < 0.05). See Table 3.

Table 3: Comparison of OS and PFS between the two groups of patients

(3) Comparison of quality of life between the two groups after treatment: The quality of life of 31 patients in the observation group improved compared with that before treatment, accounting for 66.0%, and the quality of life of 18 patients in the control group improved compared with that before treatment, accounting for 38.3%. The improvement of the quality of life of patients in the observation group was better than that in the control group, and the difference was statistically significant (χ2=7.366, P<0.05). See Table 4.

Table 4: Comparison of improvement in quality of life between the two groups of patients after treatment

(4) Comparison of T cell subsets between the two groups of patients before and after treatment. There was no significant difference in venous blood T cell CD4/CD8 between the two groups of patients before treatment (P>0.05); while 4 months after treatment, the T cell CD4/CD8 of the observation group CD8 was significantly higher than that in the control group, and the difference was statistically significant (P < 0. 05). See Table 5.

    Table 5: Comparison of T cell CD4/CD8 between the two groups before and after treatment

(5) Comparison of the occurrence of adverse reactions in the two groups of patients. During the treatment process, it was found that the main adverse reactions in the two groups of patients included bone marrow suppression, gastrointestinal reactions such as nausea and vomiting, and liver and kidney function damage. The incidence of adverse reactions in the observation group was significantly lower than that in the control group, and the difference was significant (χ2 = 6. 095, P < 0. 05). See Table 6.

Table 6: Comparison of adverse reactions between the two groups of patients

3. Discussion

Gastric cancer, lung cancer, liver cancer, and intestinal cancer are all high-incidence malignant tumors in my country, and the mortality rate of gastric cancer ranks second among malignant tumors in the world [15]. Studies have shown that the occurrence of gastric cancer is related to Helicobacter pylori, diet and lifestyle, and genetic factors [16, 17]. Patients with early gastric cancer often present with atrophic gastritis or intestinal metaplasia [18], but without obvious clinical symptoms. Therefore, many gastric cancers have already developed to the late stage when diagnosed, missing the best time for surgical treatment. Chemotherapy is of great significance for advanced gastric cancer that cannot be surgically removed. However, simple chemotherapy often causes serious toxic reactions to the patient's body while killing tumor cells, such as bone marrow suppression, hair loss, liver and kidney damage, decreased immunity, and gastrointestinal reactions such as nausea and vomiting, which seriously affect the patient's quality of life.

Studies have found that fucoidan from marine brown algae is an acidic heteropolysaccharide rich in sulfate groups and L-fucose. It is a water-soluble sulfated polysaccharide with a wide range of biological activities from non-mammalian sources. Its main component is L-fucose-4-sulfate, and it also includes a small amount of glucose, galactose, arabinose, mannose, uronic acid, xylose, protein and metal ions such as Na, K, Mg, and Ca. Its molecular composition and structure are relatively complex. It has antiviral, anti-tumor, immunity-enhancing, and chemotherapy complication-reducing effects [19]. Studies have shown that fucoidan has an enhancing effect on the secretion of various tumor-related cytokines, has the effect of enhancing the immune activity of cell nuclei in the body, is a good immunomodulator, and has potential application value [20]. At present, the research on fucoidan has become a hot topic and main direction in the field of natural marine drug research. Fucoidan has rich physiological activities, is natural in origin, and is safe to eat. It has a broad application prospect in the fields of health food and medicine.

This study observed the clinical efficacy of fucoidan sulfate combined with FOLFOX4 chemotherapy regimen for advanced unresectable gastric cancer. The results found that after treatment of the two groups of patients, the treatment effective rate of the observation group (57.4%) was significantly higher than that of the control group (40.4%). %); The improvement of the quality of life of the patients in the observation group was significantly better than that of the control group; 4 months after treatment, the T cell CD4/CD8 of the patients in the observation group was significantly higher than that of the control group; during the treatment process, it was found that the patients in the observation group had different

The incidence of adverse reactions was significantly lower than that of the control group; the 3-month, 6-month and 12-month progression-free survival and overall survival of the observation group were better than those of the control group, and the difference was statistically significant (P ＜ 0. 05) . This shows that fucoidan sulfate combined with chemotherapy in the treatment of unresectable advanced gastric cancer can significantly reduce the incidence of adverse reactions caused by chemotherapy, improve the patient's own immunity, improve the patient's quality of life, improve the treatment efficiency, and can significantly prolong. The overall survival and progression-free survival of patients with unresectable advanced gastric cancer are worthy of clinical promotion and application.

4. Conclusion

The combination of fucoidan and chemotherapy in the treatment of unresectable advanced gastric cancer can significantly reduce the incidence of adverse reactions caused by chemotherapy, enhance the patient's own immunity, improve the patient's quality of life, and improve the treatment efficiency, which is worthy of clinical promotion and application.

Where to buy fucoidan?

Shandong Jiejing Group is the first company that started to produce fucoidan from brown seaweed in China, Jiejing is the pioneer in the industry. Fucoidan is water soluble, it can be edible directly or keep powder into capsule for consumtion. If you are interested, feel free to contact jiejinggroup@gmail.com to buy fucoidan. 

References:

［1］ Wang Jiemin, Lin Sanren． New progress in the research and diagnosis and treatment of gastric cancer［J］． Journal of Gastroenterology and Hepatology，2012，21(1): 3－5．

［2］ Jemal A，Bray F，Center MM，et al． Global cancer statistics［J］． CA Cancer J Clin，2011，61(2): 69－90．

［3］ Zou Wenbin, Li Zhaoshen． Research progress on the incidence and mortality of gastric cancer in China［J］． Chinese Journal of Practical Internal Medicine，2014，34(4): 408－415．

［4］ Shao Wensheng． Clinical effect evaluation of minimally invasive radical mastectomy in the treatment of early gastric cancer［J］． Chinese Journal of General Surgery (Electronic Edition)，2016，(1): 27－29．

［5］ Wu CX，Zhu ZH． Diagnosis and evaluation of gastric cancer by positron emission tomography［J］． World J Gastroenterol，2014，20 ( 16) : 4574

－ 4585．

［6］ Deng JY，Liang H． Clinical significance of lymph node metastasis in gastric cancer［J］． World J Gastroenterol． 2014，20( 14) : 3967 － 3975．

［7］ Li Kehua． Clinical observation of Shenqi Fuzheng injection combined with chemotherapy in the treatment of advanced gastric cancer［J］．

Chinese Journal of Clinical Oncology and Rehabilitation，2013，20( 7) : 769 － 771．

［8］ He Guisheng，Wu Huangfu，Han Hua． Clinical effect of different capecitabine regimens in patients with advanced gastric cancer and postoperative recurrence and metastasis of gastric cancer［J］． Journal of Clinical and Experimental Medicine, 2016, 15(8): 774-777.

［9］ Bilici A． Treatment options in patients with metastatic gastric cancer: Current status and future perspectives［J］． World J Gastroenterol，

2014，20(14): 3905-3915．

［10］ Xu Judi． Effects of ginseng polysaccharide injection combined with chemotherapy on immune function and clinical efficacy in patients with advanced gastric cancer［J］． Central South Pharmacy，2015，13(3): 316-321．

［11］ Kwak JY． Fucoidan as a marine anticancer agent in preclinical development［J］．Mar Drugs，2014，12( 2) : 851 － 870．

［12］ Jin JO，Zhang W，Du JY，et al． Fucoidan can function as an adjuvant in vivo to enhance dendritic cellmaturation and function and promote antigen

－ specific T cell immuneresponses［J］． PLoS One，2014，9 ( 6 ) : e99396．

［13］ Elizondo － Gonzalez Ｒ，Cruz － Suarez LE，Ｒicque － Marie D，etal． In vitro characterization of the antiviral activity of fucoidan from Cladosiphon

okamuranus against Newcastle Disease Virus［J］． Virol J，2012，9: 307．

［14］ Ikeguchi M，Saito H，Miki Y，etal． Effect of fucoidan dietary supplement on the chemotherapy treatment of patients with unresectable advanced

gastric cancer［J］． J Cancer Ther，2015，6: 1020 － 1026．

［15］ Lee HJ，Song IC，Yun HJ，etal． CXC chemokines and chemokine receptors in gastric cancer: From basic findings towards therapeutic targe

ting［J］． World J Gastroenterol，2014，20( 7) : 1681 － 1693．

［16］ Ang TL，Fock KM． Clinical epidemiology of gastric cancer［J］． Singapore Med J，2014，55( 12) : 621 － 628．

［17］ Choi IJ． Current evidence of effects of Helicobacter pylori eradication on prevention of gastric cancer［J］． Korean J Intern Med，2013，28 ( 5) :

525 － 537．

［18］ Yoon H，Kim N． Diagnosis and management of high risk group for gastric cancer［J］． Gut Liver，2015，9( 1) : 5 － 17．

［19］ Yang Lili，Wang Peisheng，Teng Hongming，et al． Effect of oxidative stress on apoptosis of liver cancer cells induced by fucoidan［J］． Chinese Journal of Cell Biology, 2013, 35(4): 437-441．

［20］ Liu Xianli, Liu Dongying, Wang Yanqiu, et al. Study on immunomodulatory and anti-tumor activity of fucoidan ［J］． Chinese Journal of Microecology, 2010, 22(12): 1074-1076．