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.

Does Trastuzumab Offer Good Value for Money for Breast Cancer Patients with Metastasis in Indonesia?

OBJECTIVE: Breast cancer is the most common cancer in Indonesia, with Indonesia's breast cancer mortality rate being the highest among Southeast Asian countries. This study aims to evaluate the cost-effectiveness and budget impacts of adding trastuzumab to chemotherapy versus chemotherapy alone for HER2-positive breast cancer patients in Indonesia. METHODS: We performed a Markov model-based economic evaluation to assess cost-effectiveness, cost-utility, and budget impact. Utility data, direct medical costs, and indirect costs were obtained primarily from interviewing patients. Clinical effectiveness data, on the other hand, were obtained from systematic reviews and real-world data and represented through progression free survival, overall survival, and quality-adjusted life years (QALYs). RESULT: From a healthcare provider's perspective, the total costs for the combined group were USD 14,516, while chemotherapy alone cost USD 7,489. While the cost-effectiveness analysis showed that the combination group had a higher total cost by USD 7,027, PFS was longer in the chemotherapy alone group, with a difference of 2.2 months. The ICER was USD 17,307 for every QALY gained. The total cost of adding trastuzumab over a 5-year period was USD 589 million. CONCLUSION: In conclusion, this economic evaluation suggests that the addition of trastuzumab to standard chemotherapy is not cost-effective in terms of PFS and OS compared with chemotherapy alone.
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The effect of imatinib and nilotinib on blood calcium and blood potassium levels in chronic myeloid leukemia patients: a literature review.

Imatinib and nilotinib are first-line treatments for chronic myeloid leukemia (CML) patients, which act specifically against target cells. However, these drugs may cause side effects, such as electrolyte disturbances. This literature review aimed to provide a comparison of the effects of imatinib and nilotinib on blood potassium and calcium levels. It also summarized their hypothetical mechanism. A comprehensive electronic search of the different databases was conducted using 'chronic myeloid leukemia', 'tyrosine kinase inhibitors', 'imatinib', 'nilotinib', 'potassium', 'calcium', 'electrolytes' as keywords. This review used PubMed- MEDLINE, Cochrane Library, and Google Scholar as the source databases. Sixteen articles published from 2006 to 2020 were reviewed. Changes in blood potassium levels range from increased to decreased levels, while changes in blood calcium levels range from the lower normal values to below normal values (hypocalcemia). Tyrosine kinase inhibitors (TKIs), including imatinib and nilotinib, have a non-specific target, namely plateletderived growth factor receptor (PDGFR), which indirectly affects blood potassium and calcium levels in CML patients. The clinical manifestations of these changes vary from being visible only in laboratory tests to displaying a variety of clinical signs and symptoms.

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.