Application of green mussel (Perna viridis) shells hydroxyapatite on osteocalcin levels and osteoblast cells in rabbit femur bone defect.

Background: Bovine hydroxyapatite (HA) used for bone grafts is relatively expensive, necessitating the development of alternative sources. Alternative HA materials derived from green mussel shells with smaller molecular sizes are inexpensive and abundantly available throughout Indonesian waters. The purpose of this study is to investigate the effect of green mussel shells HA on bone healing. Methods: This post-test-only experimental research used male rabbits with femoral defects divided into three groups randomly: K (no treatment), P1 (bovine HA treatment), and P2 (green mussel shell HA treatment). The osteocalcin level was assessed biochemically while osteoblast cells were histopathologically at the second, fourth, and sixth weeks. Statistic tests were used to assess differences between groups and periods with statistical significance P<0.05. Results: Nine rabbits in each group showed significant differences between groups K, P1, and P2 in term osteocalcin levels at week 2 (2.60, 4.53±0.12, 4.47±0.23; P=0.046), week 4 (5.13±0.12, 8.53±0.12, 7.47±0.12; P=0.025), and week 6 (8.20, 11.93±0.23, 10.93±0.31, P=0.023), while in term osteoblast cells only at week 6 (16.33±3.46, 26.10±3.52, 30.40±3.29; P=0.006). The osteocalcin level and osteoblast increased significantly between groups K and P1/P2 from the initial trial until the last week. Osteoblast cells in the groups P1/P2 increased significantly, especially at week 6. Conclusion: Green mussel shell HA has the biochemical effectiveness of osteocalcin and can increase osteoblast cells comparable to bovine HA, which can enhance bone healing.

Sociodemographic disparities associated with advanced stages and distant metastatic breast cancers at diagnosis in Indonesia: a cross-sectional study.

Background: The global health burden of breast cancer is increasing with 5-year survival rates being much shorter in low-income and middle-income countries. Sociodemographic and clinical disparities in early cancer detection affect long-term outcome. Methods: The authors compared social, demographic, and pathological characteristics associated with metastatic and late stages of breast cancer diagnosis using data collected from a special registry developed by Perhimpunan Bedah Onkologi Indonesia (PERABOI) in 2015. Results: Of 4959 patients recruited in this study, 995 women (20.1%) were diagnosed with metastatic breast cancer. Lower education status and living in rural areas were significantly associated with Stage IV at diagnosis [odds ratio (OR)=1.256, 95% CI=1.093-1.445, P=0.001; and OR=1.197, 95% CI=1.042-1.377, P=0.012; respectively). Main complaints other than lump (ulceration, breast pain, and discharge) and occupation as a housewife were also associated with the presentation of metastatic diseases (OR=2.598, 95% CI=2.538-3.448, P<0.001 and OR=1.264, 95% CI=1.056-1.567, P=0.030, respectively). Having lower education and living outside Java and Bali islands were associated with the diagnosis of late-stage breast cancers (OR=1.908, 95% CI=1.629-2.232, P<0.001 and OR=3.039, 95% CI=2.238-4.126, P<0.001; respectively). A higher proportion of breast cancer patients were relatively younger with bigger tumour size, positive axillary nodal involvement, and more frequent Human epidermal growth factor receptor 2 overexpression. Conclusion: The authors identified sociodemographic disparities in the metastatic and late-stage diagnosis of breast cancers among Indonesian women. The subsequent action is required to reduce disparities faced by women with lower social and educational levels for early diagnosis and better healthcare access.

Effects of Omega-3 Supplementation on Ki-67 and VEGF Expression Levels and Clinical Outcomes of Locally Advanced Breast Cancer Patients Treated with Neoadjuvant CAF Chemotherapy: A Randomized Controlled Trial Report

Background: Omega-3 is a polyunsaturated fatty acid with an ability to regulate cell proliferation and apoptosis through interaction with inflammatory mediators. The potential additional beneficial effects of Omega-3 on chemotherapy patients with breast cancer is not yet completely revealed. Methods: A double-blind randomized control trial (RCT) involving a total of 48 locally advanced breast cancer patients was conducted. Ki-67 and VEGF expressions, as well as overall survival of patients receiving neoadjuvant cyclophosphamide-doxorubicin-5'fluorouracyl (CAF) chemotherapy plus Omega-3 (intervention group) or placebo (control group), were compared. Kaplan-Meier curve and Cox-regression tests were used to assess conditional disease-free survival (DFS) and overall survival (OS) between the two groups. Results: Decreased Ki-67 expression was observed in the intervention group compared to control (42.4±4.8 versus 39.2±5.3; T-test p=0.032). Decreased Ki-67 expression was observed in intervention compared to control group (42.4±4.8 versus 39.2±5.3; T-test p=0.032). Decreased VEGF expression was also seen in the intervention group compared to control (32.7±5.2 versus 29.5±5.4; T-test p=0.041). VEGF expression positively correlated with Ki-67 expression (Spearman's test p<0.001, R2=0.541). Overall survival in the intervention group was significantly longer in comparison to the control group (mean survival: 30.9 ± 3.71 versus 25.9 ± 3.6 weeks, Mantel-Cox test p=0.048; HR=0.411, 95%CI: 0.201-0.840). Disease-free survival was significantly longer in the intervention group compared to the control group (mean survival: 28.5 ± 3.3 versus 23.7 ± 3.6, respectively; Mantel-Cox test p=0.044, HR= 0.439, 95%CI: 0.222-0.869). Conclusion: Omega-3 fatty acid supplementation improved overall survival and progression-free survival of locally advanced breast cancer treated with CAF neoadjuvant chemotherapy and mastectomy.

Effect of phaleria macrocarpa supplementation on apoptosis and tumor growth of C3H mice with breast cancer under treatment with adriamycin-cyclophosphamide.

The objective of this study was to know the response of supplementation of Phaleria macrocarpa (PM) to adriamycin-cyclophosphamide (AC) in the treatment of C3H mice with breast cancer. Twenty-four C3H mice, who were successfully inoculated with breast cancer cells, were randomly allocated into 4 groups: without treatment, treated with AC, treated with AC + PM 0.07 mg/d, and treated with AC + PM 0.14 mg/d. The tumor size was measured using millimeter calipers before and 12 weeks after treatment. The tumor, liver, and kidneys were removed and prepared for pathologic examination using imunohistochemistry staining, and the apoptotic index was counted using the terminal deoxynucleotidyl transferase dUTP nick end labeling method. AC reduce the tumor growth significantly (P < 0.001), whereas supplementation of PM, which significantly reduced the tumor growth compared with AC only, was at the 0.14 mg/d dose (P = 0.007). AC increase the apoptotic index significantly (P < 0.001), and supplementation with PM showed that the higher dose increased the apoptotic index. The correlation between the apoptotic index and the diameter of tumor was significantly negative (r = -0.884; P = 0.020). The apoptotic index of the liver and kidney increased significantly in the AC group (P < 0.001 and P = 0.002, respectively); supplementation with PM decreased significantly the high apoptotic index caused by AC. We conclude that PM supplementation has a synergic effect to AC treatment in reducing the tumor growth, by increasing apoptosis, and protects the liver and kidney from damage caused by AC.