The Indonesian Biomedical Journal (Prodia Education and Research Institute)
Not a member yet
431 research outputs found
Sort by
Total and Intratumoral CD8+ T Cell Expressions are Correlated with Miller Payne Grading and WHO Clinical Response of Neoadjuvant Chemotherapy
Get PDFBACKGROUND: Chemotherapy has reported to stimulate immune system through direct activation of cluster of differentiation (CD)8+ T cells. Neoadjuvant chemotherapy (NAC) is known to improve the clinical response of locally advanced breast cancer (LABC) patients. However, the immune response-related factor evaluation of NAC in LABC patients has not been routinely performed. Therefore, current study was conducted to evaluate the correlation of NAC-induced CD8+ T cell with chemotherapy response based on Miller Payne grading and World Health Organization (WHO) criteria.METHODS: LABC patients were recruited and data regarding age, gender, tumor, nodal stages, histopathological grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki67 were obtained. Biopsy and mastectomy tissues were collected and processed for hematoxylin-eosin and CD8 immunohistochemical staining. CD8+ T cell expression in peritumoral and intratumoral areas were documented and measured. Clinical responses based on Miller Payne grading and WHO were analyzed and correlated with CD8+ T cell expression.RESULTS: There were more subjects with high expression of total (80%), intratumoral (82.5%) and peritumoral (65%) CD8+ T cell expressions. The total (p=0.013) and intratumoral (p=0.015) CD8+ T cell expression, but not peritumoral CD8+ T cell expression, were significantly correlated with Miller Payne Grading. The total (p=0.009) and intratumoral (p=0.001) CD8+ T cell expressions were also significantly correlated with WHO clinical response.CONCLUSION: Total and intratumoral CD8+ T cell expressions are correlated with Miller Payne grading and WHO clinical response of NAC. Therefore, total and intratumoral CD8+ T cell expressions could be suggested as a predictive marker for clinical response of NAC.KEYWORDS: breast cancer, neoadjuvant chemotherapy, CD8, clinical response, Miller Payne, intratumoral, peritumoral
Rosmarinus officinalis Essential Oil Increases Hair Length and Follicle Diameter of Ultraviolet B-exposed Mice Through VEGF
Get PDFBACKGROUND: Ultraviolet (UVB) radiation induces hair photoaging by triggering oxidative stress, causing alterations in hair diameter and length, which contribute to the development of senile alopecia. Development of alternative anti-photoaging agents to prevent hair loss from various materials, including natural products, is currently being explored. Rosmarinus officinalis essential oil (ROEO) has been known to have antioxidant and vasodilation properties. However, the effect and mechanism of ROEO on UVB-exposed hair are still unclear. Therefore, this study was conducted to evaluate the effects of ROEO on the hair length and follicle diameter in UVB-exposed mice as well as the skin vascular endothelial growth factor (VEGF) level.METHODS: Thirty male Swiss mice were treated topically with/without paraffin oil, 2% minoxidil, or various concentrations of ROEO, every day for 21 days. Meanwhile, UVB exposure was performed 3×/week. On day 21, the hair length was measured, the skin tissue was collected for hair follicle diameter and VEGF measurements.RESULTS: ROEO contained phenolic, including flavonoids and tannins, as well as non-phenolic antioxidants, including 1.8-cineole, α-pinene, and camphor. The IC50 value of ROEO was 15.977 ppm. Significant higher hair length, follicle diameter, and VEGF level of 10% ROEO+UVB-treated mice were observed, compared with the ones of mice exposed with UVB merely (LSD test, p<0.05).CONCLUSION: Since 10% ROEO could significantly increase hair length, follicle diameter and VEGF level, and contained antioxidant compounds, it can be suggested that ROEO might increase hair length, follicle diameter, and VEGF level through its antioxidant component.KEYWORDS: Rosmarinus officinalis, hair follicle diameter, hair length, VEGF, ultraviolet B, antioxidan
The Synergistic Cytotoxic Effect of Pentagamavunon-1 (PGV-1) and Curcumin Correlates with the Cell Cycle Arrest to Induce Mitotic Catastrophe in 4T1 and T47D Breast Cancer Cells
Get PDFBACKGROUND: The anti-cancer properties of pentagamavunon-1 (PGV-1) and curcumin have been documented. This study aimed to evaluate the cytotoxic effect of this combination on breast cancer cell growth using 4T1 and T47D cells, representing triple-negative breast cancer (TNBC) and non-TNBC, respectively.METHODS: Cytotoxic assay was evaluated using MTT reagent for single and combination treatment of PGV-1 and curcumin in 4T1 and T47D cells. Cell cycle analysis was examined through flowcytometry with propidium iodide dye. May Grünwald-Giemsa staining was also performed to analyze the mitotic catastropheRESULTS: PGV-1 and curcumin alone had significant cytotoxic effects against two breast cancer cell lines, with IC50 values of 4 μM and 40 μM for 4T1 and 2 μM and 20 μM for T47D, respectively. Both compounds showed high selectivity for the 4T1 and T47D cells (selectivity index >3). In addition, when PGV-1 and curcumin were combined, a synergistic effect was observed in both cell types with a combination index of <0.7. This combination results in cell cycle arrest in the G2/M phase, increased cell accumulation in the sub-G1 phase, and a synergistic increase in mitotic catastrophe.CONCLUSION: Combined intervention of PGV-1 and curcumin on TNBC and non-TNBC breast cancer cells substantially augments cell cycle arrest in the G2/M and sub-G1 phases, coupled with the occurrence of mitotic catastrophe. In summary, the results suggest that PGV-1 coupled with curcumin holds promise as an effective approach to addressing breast cancer and warrants further investigation.KEYWORDS: 4T1 cells, T47D cells, breast cancer, curcumin, mitotic catastrophe, PGV-
CHEK1 and GFPT1 as Potential Blood-Based Biomarkers for Colorectal Cancer
Get PDFBACKGROUND: The checkpoint kinase 1 (CHEK1) and glutamine-fructose-6-phosphate aminotransferase 1 (GFPT1) genes have been reported to have a crucial role in carcinogenesis in colorectal cancer (CRC). However, their association with the pathogenesis of CRC remains unclear. This study was conducted to study the expression of CHEK1 and GFPT1 genes in adenoma and adenocarcinoma CRC patients’ whole blood samples compared to the healthy controls.METHODS: A comparative cross‑sectional study to examine the expression of CHEK1 and GFPT1 genes were conducted in 6 colorectal adenoma and 6 colorectal adenocarcinoma patients along with 6 healthy controls. Blood samples were taken from subjects, and CHEK1 and GFPT1 genes were analyzed by using reverse transcription quantitative polymerase chain reaction (RT-qPCR). RESULTS: CHEK1 gene expression in blood samples has the highest in adenoma patients meanwhile for the GFPT1 gene expression has the highest in adenocarcinoma patients. Higher CHEK1 gene expression were also found in adenoma patients compared to healthy controls (p=0.040) and adenocarcinoma patients (p=0.025). Besides, at the 5% level of significance, the median GFPT1 gene expression was higher in colorectal adenocarcinoma patients compared to colorectal adenoma patients and healthy controls.CONCLUSION: CHEK1 and GFPT1 may function as potential regulators in adenoma and adenocarcinoma and measuring their expression might be a potential tool to determine the CRC progression and could be further explored as blood diagnostic biomarkers for CRC patients.KEYWORDS: CHEK1, GFPT1, colorectal cancer, adenoma, adenocarcinom
Polyscias scutellaria Aqueous Leaves Extract Increases Insulin Levels and Improves Mammary Gland Histology in Lactating Rats
Get PDFBACKGROUND: Exclusive breastfeeding could be a protective step to avoid infant stunting. During lactation, several hormones are involved in milk secretion, including insulin. Polyscias scutellaria is a perennial plant which has traditionally been used to increase breast milk production. This study was conducted to examine the impact of P. scutellaria leaf extract on the mammary gland histology, expression of insulin in the mammary gland, as well as plasma insulin and the insulin receptor levels.METHODS: Five female unmated rats (UR) and twenty female lactating rats were divided into five groups, namely UR, lactating rats only (LRO), lactating rats treated with Asifit (LRA), lactating rats treated with PSAE at a dosage of 250 and 500 mg/kg body weight (BW) (LRPSAE 250 and 500). Treatments were given orally for 14 days. The dams were sacrificed after the weaning stage (third week after parturition), and the serum, mammary gland, liver, and muscle were collected for further analysis.RESULTS: The histoarchitecture of mammary gland between the LRA and LRPSAE groups were similar. The LRPSAE 250 group had higher plasma level and immunofluorescent expression of insulin than the LRA group. PSAE did not affect insulin receptor beta subunit (INSR-β) levels in both liver and muscle of lactating rats.CONCLUSION: PSAE could be used as an herbal treatment to increase breast milk production by improving mammary gland histology and maintaining the mother's insulin levels.KEYWORDS: Polyscias scutellaria, lactating rats, insulin, INSR-
Oxidative Stress Mediates the Association between Thyroid Dysfunction and Breast Cancer
Get PDFBACKGROUND: Breast Cancer (BC) and thyroid dysfunction are commonly observed ailments in females, and two may occur synchronously. The present study was conducted to find the role of oxidative stress and its association with thyroid dysfunction and BC.METHODS: In this cross-sectional study, 288 and 100 subjects were included in case and control groups, respectively. Serum samples were obtained from consented subjects. Thyroid profile, thyroid antibodies, antioxidant and oxidant profiles, as well as cathepsin S (CTSS), prolactin, and estradiol levels were estimated using specific enzyme-linked immunosorbent assay kits. The data was analyzed using independent Student's t-test and Pearson correlation test.RESULTS: BC cases had higher levels of thyroid antibodies and thyroid stimulating hormone than controls. Prolactin and estradiol levels were also deranged in the case group. Higher oxidative stress biomarkers were evident in the case group; 8-hydroxy-2'-deoxyguanosine (8-OHdG), a DNA damage marker, increased concomitantly. Correlation analysis showed a positive correlation between the antioxidant (catalase) and the oxidant (8-OHdG) levels. Furthermore, the higher level of CTSS in BC cases than in the controls is the hallmark of this study, demonstrating the pathogenesis and progression of the disease.CONCLUSION: Results suggest the mediating role of oxidative stress in the association between thyroid dysfunction and BC. It concludes that the parameters assessed in this study could be indicative of disease progression and metastasis in BC as well as thyroid dysfunction.KEYWORDS: breast cancer, thyroid, oxidant, antioxidant, RO
Dendritic Cell as Potential Immunotherapy for Nasopharyngeal Cancer: A Review
Get PDFBACKGROUND: Dendritic cell (DC)-based cancer therapy is a promising adjuvant therapy for nasopharyngeal cancer (NPC) after chemoradiation. Owing to low immunity after chemoradiation, DC therapy activates immune responses. Moreover, DC-based cancer therapy can decrease tumor progression, prolong lifespan, and increase the quality of life of patients. Various studies regarding the use of DC therapy for NPC have been reported, however there are limited reviews on the implementation and foundation of DC immunotherapy to expand this technology.METHODS: A literature search was performed on EMBASE, ScienceDirect, PubMed (MEDLINE), and Cochrane Library, with the term dendritic cells therapy for nasopharyngeal cancer, dendritic cell immunotherapy in nasopharyngeal cancer patients, and DC therapy in NPC, as the search keywords.RESULTS: A total of 199 literatures were reviewed, and four clinical trials were identified as relevant for this review. DC vaccines can be processed with various maturation and activation processes. Selected literatures reported antigens used when incubating the DC are latent membrane protein (LMP) 1, LMP2, and Epstein–Barr virus nuclear antigen 1 (EBNA1). Although DC therapy was produced from different pathways, it has been reported that there are increases of cluster of differentiation (CD)8+ T cells, CD4+ T cells, and the progression free survival (PFS) rate in DC immunotherapy patients than the radiochemotherapy patients.CONCLUSION: It can be concluded that DC could be used as an adjuvant therapy alongside the standard therapy of NPC, which prolongs NPC patient survival.KEYWORDS: adjuvant cell therapy, nasopharyngeal cancer therapy, dendritic cell
Andrographolide Reverses Doxorubicin Resistance in Human Breast Cancer Stem Cells by Regulating Apoptotic Gene Expressions
Get PDFBACKGROUND: Breast cancer stem cells (BCSCs) have been identified as playing a crucial role in therapeutic resistance. This resistance can be attributed to the anti-apoptotic protein survivin and the antioxidant MnSOD high expression. To overcome the resistance to doxorubicin (DOX), this study proposed the utilization of andrographolide (ANDRO), the primary bioactive compound in Andrographis paniculata leaves. The objective was to examine the role of andrographolide in regulating survivin, caspase-9, and caspase-3 gene expressions to reverse doxorubicin resistance in human BCSCs.METHODS: BCSCs were exposed to 0.1 µM DOX every two days or 50 µM rotenone (ROT) for 6 hours, subsequently supplemented with 0.3 mM ANDRO. Superoxide and peroxide levels were measured using DHE and DCFH-DA assay. The MnSOD, survivin, caspase-9, and caspase-3 mRNA expression levels were analyzed using qRT-PCR. Protein expressions were evaluated using Western blotting assay. MnSOD activity was determined using xanthine oxidase inhibition assay. The apoptotic cells were determined using Annexin-V/PI staining.RESULTS: This study indicated that the cytotoxic mechanisms of DOX, similar to ROT, in BCSCs were attributed to oxidative stress, as evidenced by an elevation in superoxide rather than peroxide levels, accompanied by a decrease in MnSOD activity. This study also highlighted that ANDRO reversed DOX resistance in BCSCs subjected to repeated DOX treatment by downregulating survivin and upregulating caspase-9 and caspase-3 mRNA expressions, thereby activating the intrinsic apoptotic pathway.CONCLUSION: This study provides insights into the role of ANDRO in modulating the expression of apoptotic genes, such as survivin, caspase-9, and caspase-3, to overcome DOX resistance in BCSCs.KEYWORDS: breast cancer, breast cancer stem cell, andrographolide, doxorubicin, oxidative stress, apoptosi
Hydrolyzed VCO Cream Reduces Neutrophil Number and Increases Angiogenesis in Mid Dermal Burn Wound Healing
Get PDFBACKGROUND: Researches on plant active substances are conducted to find effective topical drugs for mid dermal burns wound. The 70% hydrolyzed VCO (hVCO) cream has been known to accelerate macroscopic healing of mid dermal burns compared to 30% and 50% hVCO creams. This study was conducted to further investigate the effectiveness of 70% hVCO cream and find the most effective doses of hVCO to heal mid dermal burns based on the macroscopic diameter, neutrophil number and angiogenesis.METHODS: Thirty mid dermal burns-induced male Rattus norvegicus were randomly divided into 6 groups that were either treated with 70% hVCO cream, 100% hVCO cream, or basic cream for 6 or 12 days. Macroscopic appearance of mid dermal burn was documented, and the diameter was calculated. Hematoxylin Eosin (HE) examination was conducted to measure the neutrophil and angiogenesis in mid dermal burn wound.RESULTS: The decrease of wound macroscopic size was found to be significant after 6 and 12 days of treatment (p=0.004 and p<0.001, respectively), with the smallest diameter was found in 70% hVCO group. The lowest number of neutrophils was found in the 70% hVCO group at day-6 (p=0.039) and day-12 (p=0.013). There was a significant increase of angiogenesis at day-12 (p=0.025) with the highest value obtained in the 70% hVCO group.CONCLUSION: The 70% hVCO decreases the wound macroscopic size, decreases neutrophil number, and increases angiogenesis compared to the 100% hVCO. Hence, 70% hVCO isshown to be the most effective dose in accelerating mid dermal burns wound healing andcan be explored further as topical medication.KEYWORDS: hVCO, neutrophil, angiogenesis, wound healin
Combining Epigenetic and Immunotherapy in Cancer: Molecular Mechanisms
Get PDFBACKGROUND: Immunotherapy, particularly the idea of immune checkpoint blockage is currently draw much attention in cancer treatment. It has been approved as an adjuvant, however, it cannot be a single cancer treatment.CONTENT: The discovery of the basic ligand-receptor interactions between immune and cancer cells inside the tumor microenvironment has led to the current interest in immunotherapy, specifically immune checkpoint inhibition. Different ligands produced by cancer cells interact with immune cells' surface receptors, activating inhibitory pathways, such programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1), that cause immune cells to become immunologically tolerant. On the other side, epigenetic modulators also play a critical role in enhancing the tumor microenvironment and regaining immunological recognition and immunogenicity. Some findings showed that such immune suppression can be reversed through various mechanisms involving antigens pathways, immune genetic, and epigenetic pathways. These findings have created a very encouraging foundation for research on the combination of epigenetic and immunotherapeutic drugs as cancer treatments.SUMMARY: The effectiveness of this suggested paradigm can only be demonstrated by clinical studies. Epigenetic treatment might replace immune checkpoint therapy as a powerful new cancer care technique that is generally well tolerated and should be proven with adequate clinical trials.KEYWORDS: epigenetics, immunotherapy, PTM, DNMT, HDAC, immune check poin