EXTRACT cytotoxic effects of Kombucha tea on cancer cell line WiDr KOLON

ABSTRACT: Background: Kombucha is a fermented tea beverage that has long been known to people of the world especially East Asia. Kombucha tea fermentation process produces a variety of important compounds such as polyphenols, glucoronic acid, lactic acid, amino acids, antibiotics, and various vitamins and mineral such as vitamin B complex, vitamin C, and folic acid. Kombucha tea is beneficial for health trustworthy and can cure various diseases such as cancer but not a lot of research on this subject . Objectives: The purpose of this study was to study the cytotoxic activity of kombucha tea extract on colon cancer cells WiDr and to find out the fifty percent Inhibition Concentration (IC50) Method: This was a true experimental study. Kombucha tea extract is made by fermenting tea for 12 days and then concentrated using a rotary evaporator. Cytotoxic activity of kombucha tea extract was analyzed with MTT methods using 5-FU as control. The absorbance values were measured using ELISA reader (λ = 550 nm). The absorbance values were then calculated the percentage of inhibition and analyzed using probit analysis to obtain the IC50 values. Result: Kombucha tea extracts have cytotoxic effects on colon cancer cells WiDr with IC50 values of 28667,435 ug/ml, whereas the positive control 5 flourorasil have IC50 value of 78,995 ug/ml. Conclusion: Kombucha tea extracts have a lower cytotoxic effect when compared with 5-FU.

ON ACID synergistic effect Ursolic cytotoxic activity of doxorubicin IN BREAST CANCER CELLS MCF-7

ABSTRACT: Breast cancer is one of the most deadly cancers. The main priority of breast cancer treatment is the use of chemotheraupetic agents, especially doxorubicin. However, breast cancer treatment using doxorubicin has potency to generate cardiotoxicity and cancer cell resistance. An approach recently developed to overcome side effects of doxorubicin is to used of combined chemotheraupetic agent (cochemotherapeutic agent), i.e. ursolic acid. The aim of this research is to develop the potency of ursolic acid as cochemotherapeutic agent by observing the cytotoxic effect and cell cycle modulation on MCF-7 breast cancer cell lines. The determination of the cytotoxic activity of ursolic acid and doxorubicin and the combination of them was done using MTT assay to obtain the value of IC50 and CI (Combination Index). The profile of cell cycle is observed using flowcytometry and analyzed using Modfit LT 3.0 program. Ursolic acid had cytotoxic effect on MCF-7 breast cancer cell with IC50 of 37 μM. The combination ursolic acid ½ IC50 (19 μM) and doxorubicin ¼ IC50 (87,5 nM), 1/3 IC50 (116,7 nM), and ½ IC50 (175 nM); and combination ursolic acid 7/9 IC50 (28 μM) and doxorubicin with all of concentration performed synergistic effects on MCF-7 viability with CI value from 0,61 to 0,83. The analysis on the cycle of the single treated cell against ursolic acid showed accumulation in G1 phase, while the single treated on doxorubicin showed accumulation in G2 phase. The combination of ursolic acid and doxorubicin showed accumulation on MCF-7 cell cycle in G1 phase and induce apoptosis as well. Thus, ursolic acid has potential to be developed as a cochemotheraupetic agent in combination with doxorubicin.

THRESHOLD VALUE METHOD DENSITY mammography, estradiol, AND ESTROGEN RECEPTORS 1 polymorphisms as predictors BREAST CANCER

ABSTRACT: Background: Breast cancer is the leading cause of women cancer mortality and the morbidity in worldwide as well as in Indonesia. The incidence rate continuously increases each year therefore breast cancer emerges as one of major health problems, therefore breast cancer emerges as one of major health problems. Despite of the fact that the detailed mechanism of breast carcinogenesis is not yet fully understood, estrogen is believed to play an important role in the development and progression of breast cancer by inducing cell proliferation and generating genotoxic metabolites. Estradiol is the main estrogen species produced in women and estrogen receptor α, encoded by ESR 1 gene, is the main estrogen receptor. The mixed results on success of anti-estrogen therapy are believed, in one hand, due to polymorphisms of the ESR 1. Mammographic densities reflect the differences in the number of stromal, epithelial, and fat tissue. In general, mammographic densities are equivalent to the cell proliferation, which is thought to be affected by estrogen. Women with higher mammographic density have greater risk to suffer from breast cancer. Objectives: To determine the role of mammographic density, estradiol level, and ESR1 polymorphisms as predictors of estrogenic factors associated breast cancer risk in Javanese ethnic population in Indonesia, and to create a model for calculating breast cancer risk using the percentage of mammographic densities that subsequently can be used as a reference for prevention as well as intervention to reduce breast cancer risk. Methods: We performed an observational study; data were collected prospectively using a cohort study design. Subjects were women who came to oncologic clinic for mammographic screening, with either high or low breast density. Subjects were then grouped into two, with and without breast cancer. The data were analyzed using relative risk and multivariate logistic regression. Results: There were 120 subjects. Sixty subjects were diagnosed as breast cancer based on triple tests. Among breast cancer patients, the largest age group was 40- 49 year-old (36.7%). Invasive ductal carcinoma is the most common type of breast cancer (80%) in our cohort. Fifteen breast cancer patients (25%) had a negative ER/PR/HER2/neu, known as triple negative cases. Subjects with percentage mammographic density (PMD) >50% had a greater relative risk for developing breast cancer by 1.55 times (95% CI, 1.066 to 2.270), compared to subjects with PMD <50%. Subjects with PMD 25-34% had a relative risk 1.67 (95% CI, 0.47 to 5.89). Women with PMD 35-49%, 50-64% and >65% had relative risk of 3.4 (95% CI, 1.16 to 9.97), 3.43 (95% CI, 31.19 to 9.88) and 3.45 (95% CI, 1.174 to 10.14%) times, respectively, compared to PMD <25%. The highest quartile of estradiol’s level did not have significant association with breast cancer risk compare with the lowest. CT and TT genotypes of ESR1 PvuII had a relative risk 1.9104 (95% CI, 0.9594 to 3.803) and 3.36 (95% CI, 1.729 to 6.526) times, respectively, compared to CC genotype. AG genotypes of ESR1 XbaI had relative risk 2.6800 (95% CI, 0.7273 to 9.88151) times than the GG genotype, whereas AA had relative risk 3.6393 (95% CI 1.01667 to 13.1050) times. By incorporating 6 factors i.e. : PMD, ESR1 PvuII polymorphisms, BMI, family history, age and menopausal status, we were able to develop a new breast cancer risk model known as GAMA DEJAVU (Gadjah Mada Mammographic Density Java ESR1 Pvu II ) that might be suitable for Javanese population although confirmation using larger data sets is warranted. Conclusion: Mammographic density is a novel independent risk factor for breast cancer. Polymorphisms of ESR1 PvuII and ESR1 XbaI are also a predictor for breast cancer with allele T/A proportion domination, concordant with the proportion of Asian women. Estradiol levels do not have a significant association with breast cancer risk. GAMA DEJAVU, the model of breast cancer risk calculation in Javanese ethnic population in Indonesia was developed by incorporating these results.

CANCER PATIENT COPING IN THE FACE OF DEATH

ABSTRACT: Cancer is a disease that become a big threat in Indonesia. Indonesia has a big number for cancer patients. Most of the cancer patients get detected at late stadium. At the late stadium, cancer is rarely be healed, in another words, at the late stadium cancer patients are force to face the possibility that the end of their life is getting close. Cancer patient experiences many kinds of psychological disorder, regarding their terminal condition. Every cancer patient has different way to deal with the psychological disorder, and different acceptance according to terminal condition. The objective of this study was to gather information or opinion about the dinamyc of coping used by cancer patient to deal with dying. A qualitative study were applied in this study involving two cancer patients in terminal condition. Interview and observation were held as data collection. Content analyze method were held as data analyze. The result of this research was that the two subjects used different type of coping to deal with their condition. The first subject used emotional focused coping, denial as his coping. The second subject used emotional focused coping, the religion coping, and also the problem focused coping, by not wanting to give up and will keep on try to do the medication process the best that he could.

LACTIC ACID BACTERIA AND THE ROLE OF INDIGENOUS DAIRY FERMENTATION KERANDANG (Canavalia virosa): CHANGES AND ACTIVITIES oligosaccharides and antioxidant isoflavones

ABSTRACT: Canavalia virosa plants are classified as legumes. This plant can be found in Africa, South America, Australia, India, and Asia (Philiphina and Indonesia). Canavalia virosa plants are able to grow on a nutrient-poor soil and dryness resistant. In the dry season, these plants survive to grow in the sand land. This plant grows to spread, produce pods and seed. In Indonesia, especially in Yogyakarta, Canavalia virosa plants are often found on the sand land in Kulonprogo and Bantul Regency. Surrounding communities are call this plant as a kerandang, can be utilized the flowers and young pods of this plant can be utilized as vegetable and old seeds can be utilized as raw material for tempeh and tofu. Lactic acid bacteria have been used in fermented of nuts milk. The use of lactic acid bacteria in fermented foods provide benefits, i.e. can improve product safety, improve the nutritional value and providing specific flavor in fermented products. The main objective of this study was to know the role of indigenous lactic acid bacteria in kerandang milk fermentation, so that increase the functional value of lactic fermented of kerandang milk (free oligosaccharides and contain of isoflavone aglycones with high antioxidant activity and anticancer). More specific the aims of this study were 1) to know bio-diversity of indigenous lactic acid bacteria from Indonesia indigenous fermented food based on 16S rRNA gene sequences, 2) to choose the indigenous lactic acid bacteria isolated from Indonesian indigenous fermented food based on β-glucosidase activity and can hydrolyze raffinose and isoflavones, 3) to conducted the pretreatment optimization of kerandang seed as raw material for kerandang milk, 4) to study the oligosaccharides and isoflavones changes during fermentation of kerandang milk by indigenous lactic acid bacteria and 5) to evaluate the anticancer activity of crude extract isoflavones from kerandang milk fermented by indigenous lactic acid bacteria. This study consist of four steps : The first steps was identification of indigenous lactic acid bacteria based on 16S rRNA gene sequences, the second step was selection of indigenous lactic acid bacteria that produce β-glucosidase and have β-glucosidase activity, the third was optimize of pretreatment of kerandang seed as raw material for kerandang milk and the four step was fermentation of kerandang milk using indigenous lactic acid bacteria. The results showed that indigenous lactic acid bacteria are classified to the genus Lactobacillus and Pediococcus. Sixteen strains are classified to the L. plantarum-pentosus and L. plantarum species, one strain is classified to the L. paracasei subsp. paracasei species and one strain is classified to the P. pentosaceus species with similarity values above 99%. Five strains of Lactobacillus have higher β-glucosidase activity than the other strains, namely L. plantarum-pentosus T14; L. plantarum-pentosus T20; L. plantarum T33; L. plantarum-pentosus T35 and L. plantarum T32. Fifth strains of indigenous lactic acid bacteria are able to hydrolyze or transform the 100% raffinose in media MRS-raffinose 1% to sucrose, glucose, fructose and galactose. In addition, β- glucosidase from the five strains are also able to hydrolyze the β glycosidic bond in isoflavone glucosides to isoflavone aglycones, so that increase isoflavone aglycone and increased antioxidant activity. Soaking beans for 3 hr is the best way to soften the seed and reduce the HCN content as much as 41.04% before kerandang milk processing. During fermentation of kerandang milk by L. plantarum-pentosus T14 and L. plantarum-pentosus T35, consist oligosaccharides changes, particularly raffinose. In line, consist the isoflavones glucosides change into aglycones and increase the antioxidant activity of kerandang milk. The hydrolyze ability of raffinose and isoflavone by L. plantarum-pentosus T14 better than L. plantarum-pentosus T35. In line, the increase of isoflavone aglycone, so increase antioxidant activity and have positively correlated with coefisient correlation above 0.9%. Methanol extract isoflavones of kerandang milk fermented by L. plantarum-pentosus T14 and L. plantarum-pentosus T35 showed anticancer activity against Colon 26 cancer cells. Thus, kerandang milk fermented by indigenous lactic acid bacteria have functional value.

ANALYSIS micronucleus cytogenetic buccal mucosa CANCER PATIENTS IN THE HEAD AND NECK AREA AFTER RADIATION THERAPY (Studies in General Hospital Dr. Sardjito, Yogyakarta)

ABSTRACT: Radiation therapy plays an important role in the treatment ofhead and neck cancer. The purpose of this therapy is to kill cancer cells as many as possible by increasing ionization in the involved area. The oral of head and neck cancer patients has a high risk to radiation therapy because this therapy could damage the normal cell. The damage that might be happen such as the formation of micronucleus in the basal layer of epithelial buccal mucosa. The aim of this study was to determine the influence of radiation therapy in head and neck cancer patients to frequency of micronucleus. This study was conducted on 20 patients of head and neck cancer at RSUP Dr. Sardjito, Yogyakarta. They were divided into 2 groups, group I was performed by 10 patients who have not receivedradiation therapy and group II, as many as 10 patients receivedradiation therapy10 Gy within one week. The buccal ephitelial cells werecollected with a cytobrush and stained with Feulgen Fast-Green. The frequency of micronucleus was counted per 1000 cells using light microscope. The data were analyzed using independent t-test and one-way ANOVA. The results showed a significant difference inmicronucleus frequency between 2 groups. It is concluded that there was a significant increase in micronucleus frequency of ephitelial buccal mucosa cellsin head and neck cancer patients after receiving radiation therapy compared to micronucleus frequency before receiving radiation therapy. The increase of micronucleus frequency occured along with increased of radiation dose.

ANALYSIS OF RADIATION DOSE DISTRIBUTION IN BREAST CANCER THERAPY WITH BORON NEUTRON CAPTURE THERAPY (BNCT) USING MCNP5

ABSTRACT: Boron Neutron Capture Therapy (BNCT) is therapy that utilizes the interaction of neutron with boron-10 to kill cancer cells. Boron Neutron Capture Therapy (BNCT) is currently being developed for the treatment of HER-2+ breast cancer. HER-2+ breast cancer is resistant and have a chance of recurrence. The purpose of this study is to research about dose distribution for treatment HER-2+ breast cancer. This study used MCNP 5 simulation program to calculate the thermal neutron flux on the cancer and the health tissue so absorbed dose can be calculated. Concentration of boron-10 was varied into 20, 30, 40, 50, 60 and 70 􀈝g/g, while variations on irradiation technique were en face technique and lateral technique. The result showed dose rate on the tumor volume increased and shorter irradiation times with increasing concentration of boron-10. So skin dose and lungs dose were reduced. En face technique gives the treatment time is shorter than lateral technique. Dose distribution in the concentration of boron-10 70 􀈝g/g by en face technique received by skin, CTV, cancer, health tissue and lungs, respectively, 0.86 Gy; 5.81 Gy; 50 Gy; 2.55 Gy and 0.63 Gy with treatment time is 67.17 minutes.