Enhancing the Anticancer Activity of Squamocin for Breast Cancer Treatment Using Nanodiamond Nanoparticles: An In Vivo Study

Squamocin is one of the annonaceous acetogenins produced by the Annonaceae family and displays potent anti-cancer activity against cancer cell lines. This study aimed to investigate the growth inhibition activity of squamocin coupled with nanodiamond on rats (Rattus norvegicus)-induced breast cancer. Twenty-five female R. norvegicus were divided into five groups (n = 5), including normal control (without any treatment), negative control, group treated with nanodiamond only (ND), group treated with squamocin only (SQ), and the group treated with squamocin coupled with nanodiamond (NDSQ). All of the animal models were induced for breast cancer, except for the normal control group. Breast cancer induction was performed using two doses of N-nitroso-N-methylurea (NMU) injection (50 and 30 mg/kg body weight) intraperitoneally and waited for 22 weeks until the tumor was detected to formed. Nanodiamond coupled with squamocin were administered by intraperitoneal injection (1.5 mg/kg body weight) for 5 weeks, one injection per 3 days. This study showed that the treatment with squamocin coupled with nanodiamond (NDSQ) significantly reduced the proliferation (Ki-67) and induced apoptosis (Caspase-3) of breast cancer cells, corresponding to the reduction of the thickness of the mammary ductal epithelium (p<0.001) and the lower level of CA-153 in serum. In addition, the treatment significantly reduced the malondioldehyde (MDA) and PI3KCA and increased the p53 level significantly. Altogether, in this study, we are the first to report the anti-cancer activity of squamocin in rat-induced breast cancer and the potency of nanodiamond as a carrier of squamocin to increase its anti-cancer activity

Increasing the effect of annonacin using nanodiamonds to inhibit breast cancer cells growth in rats (Rattus norvegicus)-Induced breast cancer

Background: Annonaceous acetogenins have been reported to have anti-cancer properties but low viability. In this study, we aimed to investigate the potency of nanodiamonds to be employed as a carrier of annonacin to help increase its viability and inhibit the growth of breast cancer cells. Methods: The annonacin was coupled with nanodiamond and characterized using UV-Vis spectrophotometer, FTIR, SEM, and PSA, and determined their stability and drug release. A cell growth inhibition assay and cell migration assay was performed using the breast cancer MCF7 and T747D cell lines, and in vivo analysis was performed in rats (Rattus norvegicus). MCF7 and T747D cells were treated with 12.5 μg/mL annonacin coupled with nanodiamonds for 24 and 48 h and further analyzed by MTT, cell migration, and reactive oxygen species (ROS) assays. Twenty-five female rats were divided into five groups. Breast cancer was induced using two intraperitoneal doses of N-nitroso-N-methylurea (NMU) (50 and 30 mg/kg body weight). Annonacin coupled with nanodiamonds was administered by intraperitoneal injection (17.5 mg/kg body weight) for 5 weeks, one injection per 3 days. Results: Administration of annonacin coupled with nanodiamonds significantly reduced MCF7 cell growth and reactive oxygen species (ROS) levels. The in vivo study showed that administration of annonacin coupled with nanodiamonds significantly reduced PI3KCA levels and increased p53 expression, reduced cancer antigen-15-3 (CA-15-3) levels in serum, increased caspase-3 expression, reduced Ki-67 levels, and reduced the thickness of the mammary ductal epithelium. Conclusions: Collectively, this study demonstrated the effectiveness of nanodiamonds as a carrier of annonacin to inhibit breast cancer cell growth through inhibition of the PI3K/Akt signaling pathway

IDENTIA Registry: Incidence of Deep Vein Thrombosis in Medically Ill Subjects at High Risk in Indonesia: A Prospective Study

Background: medically ill hospitalized patients are at risk of deep vein thrombosis (DVT) and consequentially have high chances of mortality. In Indonesia, there is disparity in healthcare facility and data on incidence of DVT in this multi-ethnic, geographically unique country with large population are limited. Hence, we determined the incidence of DVT and evaluated mean Wells score among medically ill hospitalized persons at increased risk. Methods: in this multicenter, prospective, observational registry in Indonesia, subjects (age >40 years) with acute medical illness (like cancer, acute infection, or severe respiratory disease) confined to bed for >3 days were enrolled between January 2016 and November 2017. Data for medical history, Wells score, and DVT diagnosis with compression ultrasonography (CUS) were recorded. DVT incidence was analyzed in eligible and evaluable groups. Data were analyzed by descriptive method. Results: out of 360 subjects enrolled, 334 were included in the eligible group for analyses. CUS could not be performed in 26 subjects. Thus, 308 subjects who completed the study were included in the evaluable group. Javanese were predominant in the eligible group and obesity was the most common medical history at presentation. Overall, incidence of DVT in eligible and evaluable patients was 37.1% and 40.3%, respectively. Mean (SD) Wells score and bedridden days were 3 (1.20) and 9 (6.89), respectively. Conclusion: this study indicated that the incidence of DVT is high in medically ill patients in Indonesia and will provide new insights and awareness about DVT in Indonesia