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Sariyeh Mohammadi Hadloo, Homa Mohseni Kouchesfahani, Ali Khanlarkhani, Maryam Saeidifar,
Volume 12, Issue 3 (11-2023)
Abstract

Background: To overcome cisplatin resistance, the cytotoxicity of a novel antitumor agent on two ovarian cancer cell lines sensitive and resistant to cisplatin was investigated.

Methods: MTT assay and flow cytometry were performed to assess the cytotoxicity of a novel water-soluble Pd (II) complex, [Pd(bpy)(pyr-dtc)]NO3 (PBPD), on cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines. Furthermore, variations in the expression of drug resistance gene cluster of differentiation 99 (CD99), signal transducer and activator of transcription 3 (STAT3), octamer-binding transcription factor 4 (OCT4), and multidrug resistance mutation 1 (MDR1) were evaluated using Real-Time PCR.

Results: The IC50 values of PBPD in resistant cells were higher than those in sensitive cells. Furthermore, PBPD has a deadlier effect on sensitive cells compared to resistant cells, and the cell survival rate is reduced over time. Flow cytometry revealed that PBPD enhanced the population of living-resistant cells while driving them to apoptosis. PBPD, on the other hand, has a greater effect on the living cell population and has dramatically shifted the population toward apoptosis and necrosis in the sensitive cells. Furthermore, gene expression analysis showed that when sensitive and resistant cells were treated with cisplatin, all resistance genes increased significantly relative to the control. In contrast to OCT4, MDR1, STAT3, and CD99 resistance genes were not significantly elevated in sensitive cells treated with PBPD compared to the control. Thus, the expression of resistance genes in resistant cells treated with PBPD was lower than cisplatin.

Conclusions: As a result, PBPD is a promising anticancer agent for CDDP-resistant ovarian cancer.

Desak Made Wihandani, Putu Anda Tusta Adiputra, Gede Wikania Wira Wiguna Wiguna, Putu Gede Septiawan Saputra, Made Violin Weda Yani, Ida Ayu Widya Anjani, Wayan Ardyan Sudartha Putra, Gede Putu Supadmanaba,
Volume 13, Issue 4 (1-2025)
Abstract

Background: SF3B1 is a splicing factor that plays a crucial role in cancer progression and is commonly found in various types of solid cancers. However, the reports regarding the clinical implications of SF3B1 in terms of therapy response, survival, and its relationship with patients' clinicopathological features are still limited. This study aimed to assess SF3B1 expression for neoadjuvant chemotherapy response in stage III triple-negative breast cancer.

Methods: This case-control study was conducted at Prof. Dr. I.G.N.G. Ngoerah General Hospital from March to October 2021. Stage III TNBC breast cancer patients who received neoadjuvant chemotherapy were included. Variables assessed included SF3B1 expression, NAC response, and various histological and clinical parameters. Immunohistochemistry (IHC) for SF3B1 expression was performed using the avidin-biotin method. Data analysis involved univariate, bivariate (chi-square), and multivariate (logistic regression) methods using SPSS, with significance set at p ≤ 0.05.

Results: Analysis showed that high Ki-67, tumor-infiltrating lymphocytes (TILs), and SF3B1 status significantly increased the risk of chemoresistance in TNBC breast cancer (OR=6.4, 95%CI=1.20-34.19, p-value=0.017; OR=4.8, 95%CI=1.05-21.75, p-value=0.031; OR=13.5, 95%CI=1.56-116.24, p-value=0.008, respectively) No significant relationships were found with age, grading, or menopausal status. Multivariate analysis confirmed these variables independently influenced chemoresistance, with aOR=14.4, 95%CI=1.80-115.73 for Ki-67 (p-value=0.012), aOR=6.7, 95%CI=1.12-40.46 for TIL (p-value=0.037), and aOR=13.714, 95%CI=1.56-116.24 for SF3B1 (p-value=0.018).

Conclusion: High SF3B1 expression, alongside high Ki-67 and TIL levels, is potentially a prognostic marker for chemoresistance in stage III TNBC. These findings suggest that targeting SF3B1 could offer a novel therapeutic approach in TNBC patients.


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