Propolis is a resinous beehive product that has a wide range of biological activities, namely antimicrobial, antioxidant, and anti-inflammatory properties. Propolis is collected by the bees from plant resin and exudates to protect hives and maintain hive homeostasis. The aim of the present systematic scoping review is to explore the potential and suitability of propolis as an adjunctive treatment in breast cancers, based on the latest available experimental evidence (2012-2021). After applying the exclusion criteria, a total of 83 research publications were identified and retrieved from Scopus, Web of Science, and Pubmed. Several relevant key themes identified from the included studies were cytotoxicity, synergistic/combination treatment, improvement in bioavailability, human clinical trials, and others. A majority of the studies identified were still in the in vitro and in vivo stages. Nonetheless, we managed to identify 4 human clinical trials that demonstrated the successful use of propolis in alleviating side effects of chemotherapy and radiotherapy while increasing the quality of life of breast cancer patients, with minimal adverse effects. In conclusion, propolis, as an adjunctive treatment, may have therapeutic benefits in alleviating symptoms related to breast cancers. However, further clinical trials, preferably with higher number of participants/subjects/patients, are urgently needed.

Introduction: Liver fibrosis (LF) is the excessive deposition of extracellular matrix (ECM), produced by overactivated hepatic stellate cells, following prolonged transforming growth factor-β (TGF-β) stimulation. The ability of mesenchymal stem cells (MSCs) to improve LF has been reported. However, the mechanisms of MSCs to ameliorate LF through suppressing TGF-β and α-smooth muscle actin (α-SMA) remains unclear. Aim: To investigate the effects of MSCs treatment on suppressing TGF-β levels and decreasing α-SMA expression in an LF model. Methods: In this study, wenty-four male Wistar rats were injected intraperitoneal (IP) with carbon tetrachloride (CCL4), twice weekly, for eight weeks, to induce LF. Rats were randomly assigned to six groups: Sham, Control, Sham-lo, Sham-hi, and MSC-treated groups, at doses of 1 x 10 6 (T1) and 2x10 6 (T2) cells. TGF-β levels were analyzed by enzyme-linked immunosorbent assay (ELISA), whereas α-SMA expression was determined by immunohistochemistry staining. Results: MSCs decreased the expression of TGF-β in T1 and T2 groups on day 3 and 14. The T2 group showed lower TGF-β levels than that in the T1 group. This finding was in line with the observed decrease in α-SMA expression and the number of collagen. Conclusion: MSCs treatment ameliorated LF by suppressing TGF-β production, leading to decreased α-SMA expression in a CCL4-induced LF animal model.

AIM: This study aimed to investigate the synergistic effects of the combination between Curcuma longa extract (CL) and Phyllanthus niruri extract (PN) in inhibiting optimally the MDA-MB-231 breast cancer stem cells (BCSCs) growth and metastatic by exploring the target and molecular mechanism using integrative bioinformatics approaches and in vitro. METHODS: CL and PN extracts were prepared by maceration method using ethanol 70%. The antiproliferative effect of CL and PN single and combination treatment was examined by 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide assay. The bioinformatic approach was performed to identify molecular targets, key proteins, and molecular mechanism of curcumin and phyllanthin as CL and PN secondary metabolite, respectively, targeted at stemness and migration pathway of BCSCs. RESULTS: The in vitro study showed that CL and PN possess cytotoxic activity in time- and dose-dependent manner. The combination of CL and PN has a synergistic effect by modulating the sensitivity of cells. Using a bioinformatics approach, the annexin A2 (ANXA2), epidermal growth factor receptor (EGFR), matrix metalloproteinases (MMPs), and pyruvate kinase M1/2 (PKM) as potential targets of curcumin and phyllanthin correlated with metastatic inhibition of BC. In addition, molecular docking showed that curcumin and phyllanthin performed similar or better interaction to stemness differentiation regulator pathway particularly histone deacetylase 1, EGFR, Heat Shock Protein 90 Alpha Family Class B Member 1, Hypoxia Inducible Factor 1 Subunit Alpha, and MMP9. CONCLUSION: Combination of CL and PN has potential for the treatment of metastatic BCSCs by targeting ANXA2, EGFR, MMPs, and PKM to resolve stemness and inhibit of BCSCs.

No abstract

BACKGROUND: The histopathological grades identification is unquestionably essential to determine the most effective approach in oncologic management, specifically in breast cancer (BC) as the most common malignancy diagnosed worldwide. Complex and micro-level alterations of coagulation function of the host may occur at some point since the reactivity of the tumor cells byproduct will dysregulate its physiologic function; as represented by the higher rate of fibrinolysis which in turn increase the D-dimer level. AIM: The study aims to provide the correlation between the level of d-dimer and histopathological grades in BC patients. METHODS: A total of 111 females with confirmed BC were included in this study, which was conducted from March to September 2021 at the teaching hospital of Universitas Sumatera Utara. After thorough clinical information analysis, the histopathological examination (HPE) was conducted to confirm the malignancy and graded based on the Bloom-Richardson grading system; therefore, the HPEs were classified into slow/moderate or poorly differentiated. The D-dimer value of >0.5 mg/L was indicated as an elevated level. RESULTS: From the 102 eligible patients to be included in the final evaluation, it was observed that 46.1% and 52.9% of the participants were presumed with elevated D-dimer level and high-grade carcinoma, respectively. The elevated D-dimer level results percentage was substantially more common in high-grade BC (72.3%, the positive predictive value analysis. Other parameters, for example, sensitivity (63.0%), specificity (72.9%), and negative predictive value (63.6%) were found to be statistically accurate (p < 0.001). CONCLUSION: The influence of tumor cells differentiation toward coagulation system or fibrin metabolism dysfunction is observable in this study. Hence, the role D-dimer level measurement should be investigated further to assist the BCs’ grading determination workup.

No abstract

Background: Axillary lymph node (ALN) involvement in breast cancer (BC) is considered to be a significant factor in determining the diseases’ extent at the moment. The spreading capacity of cancerous cells may linearly correlate with its activity level, which in turn alter the coagulation function as commonly represented by fibrin degradation biomarker i.e., D-dimer. Although ALN metastatic status is eventually should be perceptible in physical examinations or other diagnostic modalities, an additional marker to estimate the lymph node extent should be considered in the pre-operative sessions. Objective: To provide the correlation between elevated D-dimer level and ALN metastatic status positivity among BC patients. Methods: This cross-sectional study was conducted at the Teaching Hospital of Universitas Sumatera Utara by retrieving outpatients’ medical records from June 2018 to January 2019, encompassing 111 female patients. The ALN involvement status was recorded along with plasma D-dimer level in which the value of 500 ng/mL was considered to be elevated. Results: From the 102 eligible participants, 47.1% and 70.6% were confirmed with elevated D-dimer level and ALN involved respectively. Further analysis of those variables demonstrated a considerable diagnostic performance for sensitivity (64.4%), specificity (79.1%), PPV (80.9%), NPV (61.8%), accuracy (70.6%) and statistically significant results (P = .001). Conclusion: Elevated D-dimer level may be influenced by cancerous spread capacity in the lymphatic system, as it also eventually correlated with coagulation system dysregulation. Therefore, it is suggested that the role of D-dimer measurement is recommended to be explored further in BC diagnostic workup.

Context: According to the World Health Organization, colorectal cancer (CRC) is the third most prevalent cancer globally, with the highest mortality rate after lung cancer. Some studies predicted risk factors provoking CRC recurrence. However, no single study discussed CRC recurrence. Objectives: This study aimed to quantitatively estimate the influence of several risk factors toward early recurrence of CRC. Methods: We utilized four medical databases, including Pubmed, Cochrane, Wiley library, and ScienceDirect, and a range of literature searches between July to October 2020 with output study, odds ratio (OR), and some risk factors. We used PRISMA protocol along with several relevant keywords with NOS method was utilized to assess the quality of the study. Fixed- and randomized effect model were utilized to control each numerical analysis’ bias. Results: We found six studies that compared the risk factor of CRC recurrence after curative resection with curative-intention encompassing a total of 15.457 patients. We found seven risk factors of colorectal cancer recurrence, including vascular invasion (OR 2.3; IK95%: 01.56 - 3.4; P < 0.0001), depth of invasion (T stage) (OR 2.27; IK95%: 1.14 - 4.51; P = 0.02), pre-operative CEA serum (OR 2.24 95 %IK: 1.57 - 3.2; P < 0.0001), post-operative CEA serum (OR 5.97 IK95% : 3.04 - 11.74; P < 0,0001), pre-operative CA19-9 serum (OR 3.03; IK95%: 1.74 - 5.25; P < 0.0001), and regional nodal metastasis (N stage) (OR 2.56; IK95% 1.41 - 4.62; P = 0.002). Conclusions: Risk factors of earlier CRC recurrence were diversely reviewed. The elevation of post-operative CEA serum was assumed as the main factor in this study; however, most of the studied parameters were statistically significant.