The role of germline BRCA1 & BRCA2 mutations in familial pancreatic cancer: A systematic review and meta-analysis.

BACKGROUND: Familial Pancreatic Cancer (FPC) presents a notable risk, with 3-10% of pancreatic adenocarcinoma cases having a family history. Studies link FPC to syndromes like HBOC, suggesting BRCA1/BRCA2 mutations play a role. BRCA gene functions in DNA repair impact FPC management, influencing sensitivity to therapies like PARP inhibitors. Identifying mutations not only aids FPC treatment but also reveals broader cancer risks. However, challenges persist in selectively applying genetic testing due to cost constraints. This Systematic Review focuses on BRCA1/BRCA2 significance in FPC, diagnostic criteria, prognostic value, and limitations. METHOD: Original articles published from 2013 to January 2023 were sourced from databases such as Scopus, PubMed, ProQuest, and ScienceDirect. Inclusion criteria comprised observational cohort or diagnostic studies related to the role of BRCA1/2 mutation in correlation to familial pancreatic cancer (FPC), while article reviews, narrative reviews, and non-relevant content were excluded. The assessment of bias used ROBINS-I, and the results were organized using PICOS criteria in a Google spreadsheet table. The systematic review adhered to the PRISMA 2020 checklist. RESULT: We analyzed 9 diagnostic studies encompassing 1325 families and 4267 patients from Italy, USA, and Poland. Despite the limitation of limited homogenous PICO studies, our findings effectively present evidence. BRCA1/2 demonstrates benefits in detecting first-degree relatives FPC involvement with 2.26-10 times higher risk. These mutation findings also play an important role since with the BRCA1/2 targeted therapy, Poly-ADP Ribose Polymerase inhibitors (PARP) may give better outcomes of FPC treatment. Analysis of BRCA1 and BRCA2 administration's impact on odds ratio (OR) based on six and five studies respectively. BRCA1 exhibited non-significant effects (OR = 1.26, P = 0.51), while BRCA2 showed significance (OR = 1.68, P = 0.04). No heterogeneity observed, indicating consistent results. Further research on BRCA1 is warranted. CONCLUSION: Detecting the BRCA1/2 mutation gene offers numerous advantages, particularly in its correlation with FPC. For diagnostic and prognostic purposes, testing is strongly recommended for first-degree relatives, who face a significantly higher risk (2.26-10 times) of being affected. Additionally, FPC patients with identified BRCA1/2 mutations exhibit a more favorable prognosis compared to the non-mutated population. This is attributed to the availability of targeted BRCA1/2 therapy, which maximizes treatment outcomes.

Revealing Novel Source of Breast Cancer Inhibitors from Seagrass Enhalus acoroides: In Silico and In Vitro Studies.

Enhalus arcoides is a highly beneficial type of seagrass. Prior studies have presented proof of the bioactivity of E. acoroides, suggesting its potential to combat cancer. Therefore, this study aims to delve deeper into E. acoroides bioactive molecule profiles and their direct biological anticancer activities potentials through the combination of in-silico and in-vitro studies. This study conducted metabolite profile analysis on E. acoroides utilizing HPLC-ESI-HRMS/MS analysis. Two extraction techniques, ethanol and hexane, were employed for the extraction process. Furthermore, the in-silico study was conducted using molecular docking simulations on the HER2, EGFR tyrosine kinase and HIF-1α protein receptor. Afterward, the antioxidant activity of E. acoroides metabolites was examined to ABTS, and the antiproliferative activity was tested using an MTT assay. An in-silico study revealed its ability to combat breast cancer by inhibiting the HER2/EGFR/HIF-1α pathway through molecular docking. In addition, the MTT assay demonstrated that higher dosages of metabolites from E. acoroides increased the effectiveness of toxicity against cancer cell lines. Additionally, the study demonstrated that the metabolites possess the ability to function as potent antioxidants, effectively inhibiting a series of carcinogenic mechanisms. Ultimately, this study showed a new approach to unveiling the E. acoroides metabolites' anticancer activity through inhibiting HER2/EGFR/HIF-1α receptors, with great cytotoxicity and a potent antioxidant property to prevent a carcinogenic cascade.

Radiotherapy service amidst COVID-19: Experience from Tertiary Referral Hospital in Semarang, Indonesia.

Background: Several changes in hospital policies took place to mitigate the spread of Coronavirus disease 2019 (COVID-19). However, the patient's perception to these abrupt changes in medical services is not known. This study analyzed the quality of radiotherapy service during the COVID-19 pandemic and the patient's perception of them. Methods: This descriptive study will qualitatively assess cancer patient perception of the quality of radiotherapy service during COVID-19 pandemic. Willing participants were given a questionnaire that explore two major aspects: the patient's general knowledge of COVID-19 and their perception of radiotherapy service during the pandemic. Results: The 145 participants of this study were generally well-informed about the significance of COVID-19 pandemic. Most respondents claimed to adequately practice preventive measures and put high regards in personal protective equipment (PPE) worn by them and healthcare workers for their safety. Their level of trust to all healthcare workers remained high and identified hospital announcements (television, brochures) educated them the most in regards to the relationship of COVID-19 and cancer. Conclusion: The changes in hospital policies and radiation oncology service in our institution were well-received by the study population. Despite the majority of respondents were afraid and anxious of being infected of COVID-19 while undergoing treatment, only a minority of them contemplated to delay or completely stop going for treatment. By adhering to major guidelines and adjustments of local resources, the delivery of radiotherapy service can remain consistent during the pandemic.

A Quasi-experimental of a Virtual Reality Content Intervention for Level of Comfort of Indonesian Cancer Patients.

This study aims to determine the effect of virtual reality content on the comfort level of cancer patients. This study used a quasi-experimental non-equivalent control group design and was conducted on 60 cancer patients. The intervention uses the virtual reality content "My Comfortable Environment," which was developed based on Kolcaba's comfort theory. Comfort level was measured using the Shortened General Comfort Questionnaire. The Wilcoxon and Mann-Whitney U tests were used to determine the differences before and after the intervention within the group and between the study groups. There was a significant mean difference between pre-test and post-test in the intervention group with P < .000, Z = -4.785, and in the control group with P < .041, Z = -2.032. These results indicate that interventions with virtual reality content and guided imagery both affect the comfort level of cancer patients. However, if the test was conducted between groups, there was a significant difference between the intervention group and the control group with a P value of <.000. These results indicate that the virtual reality content intervention can significantly increase the level of patient comfort through modifying various aspects of patient comfort, especially environmental aspects.

The Role of Beetroot Extract in Overcoming Chemoresistance of Neoadjuvant Adriamycin Cyclophosphamide Regimen by Targeting Immune Response in Tumor Microenvironment: A Preclinical Study in Mammary Adenocarcinoma Rats.

OBJECTIVE: This study aims to determine the role of beetroot extract in overcoming the chemoresistance of Neoadjuvant Adriamycin Cyclophosphamide (NAC) regimens with a target immune response in the tumour microenvironment at the pre-clinical stage. METHODS: This study was conducted on rats with 7,12-Dimethyl Benz (α) Anthracene (DMBA) induced mammary adenocarcinoma. Adriamycin Cyclophosphamide was given in 4 cycles, whereas beetroot extract was administered three times each cycle. Observations of CD8 T cells and Myeloid Derivative Suppressive Cells (MDSC) expression levels and pathological responses were carried out on tumour tissue taken at the end of the observation. RESULTS: Supplementation of beetroot extract to NAC could significantly increase CD8 T cells and decrease MDSC in the tumour microenvironment. The addition of beetroot extract gave a better pathological response. CONCLUSION: Beetroot extract enhances the immune response in the tumor microenvironment so that it has the potential to overcome chemoresistance in NAC.
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The Association Between Triglyceride-Glucose Index as a Marker of Insulin Resistance and the Risk of Breast Cancer.

Background: This study aims to evaluate the association and dose-response between triglyceride-glucose (TyG) index and breast cancer. Method: This is a multicenter case-control study conducted in six public referral hospitals in Indonesia. Cases are individuals aged 19 years or above who were diagnosed with breast cancer within 1 year of diagnosis, based on histopathology and immunohistochemistry. Controls were recruited from corresponding hospitals. TyG index was determined by the formula: ln (fasting TG [mg/dl] × fasting glucose [mg/dl]). Results: There were 212 participants in the breast cancer group and 212 participants in the control group. TyG index was higher in patients with breast cancer (median 8.65 [7.38, 10.9] vs. 8.30 [7.09, 10.84], p < 0.001). When compared with TyG quartile of Q1, Q4 was associated with an OR of 2.42 (1.77, 3.31), p < 0.001, Q3 was associated with an OR of 1.53 (1.21, 1.93), p < 0.001, Q2 was associated with an OR of 1.39 (1.12, 1.73), p = 0.002 for the risk of breast cancer. The dose-response relationship was nonlinear (p < 0.001). On univariate analysis, smoking (OR 2.15 [1.44, 3.22], p < 0.001), use of contraception (1.73 [1.15, 2.60], p = 0.008), alcohol consumption (OR 2.04 [0.96, 4.35], p = 0.064), and TyG Index >8.87 (OR 3.08 [1.93, 4.93], p < 0.001) were associated with risk of breast cancer. Independently associated with increased risk of breast cancer included smoking (OR 1.93 [1.23, 3.01], p = 0.004), use of contraception (OR 1.59 [1.02, 2.48], p = 0.039), and TyG Index >8.87 (OR 2.93 [1.72, 4.98], p < 0.001). Conclusion: TyG index was associated with breast cancer in a nonlinear dose-response fashion.

The Effect of P-Glycoprotein (P-gp), Nuclear Factor-Kappa B (Nf-κb), and Aldehyde Dehydrogenase-1 (ALDH-1) Expression on Metastases, Recurrence and Survival in Advanced Breast Cancer Patients

Objective: To investigate the level of three drug resistance proteins; P-glycoprotein 1 (P-gp), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and aldehyde dehydrogenase isoform 1 (ALDH1) expression and their relationship to metastasis, recurrence and survival in advanced breast cancer patients that received neoadjuvant chemotherapy. Methods: This study is a combination of prospective and retrospective cohort study involving one hundred and thirty one cases of advanced stage invasive breast cancer that have received neoadjuvant chemotherapy. Initial biopsy specimens (incisional biopsy or core biopsy) were taken from paraffin blocks. Immunohistochemistry (IHC) was used to detect P-gp, NF-κB, and ALDH1 expression. Prospectively analysed patients were followed for five years and evaluated for recurrence and death. Results: The expression of P-gp has no significant statistical correlation to metastases (p = 0.659), recurrence (p = 0.862) and survival (p = 0.835) in advanced stage breast cancer patients who received neoadjuvant chemotherapy. Similarly, ALDH1 was not correlated to metastases (p=0.120), recurrence (p = 0.186) and survival (p = 0.254) statistically. We found that NF-κB expression showed a significant correlation to metastases (p=0.004), recurrence (p = 0.016) and overall survival (p = 0.041) in advanced stage breast cancer patients after neoadjuvant chemotherapy. Conclusion: NF-κB expression is a potential marker that can be used to assess or to predict increasing risk of metastases, recurrence and survival in advanced stage breast cancer patients who receive neoadjuvant chemotherapy.

BRCA1 Gene Mutation Screening for the Hereditary Breast and/or Ovarian Cancer Syndrome in Breast Cancer Cases: a First High Resolution DNA Melting Analysis in Indonesia.

Specific patterns of the hereditary breast and ovarian cancer (HBOC) syndrome are related to mutations in the BRCA1 gene. One hundred unrelated breast cancer patients were interviewed to obtain clinical symptoms and signs, pedigree and familial history of HBOC syndrome related cancer. Subsequently, data were calculated using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk prediction model. Patients with high score of BOADICEA were offered genetic testing. Eleven patients with high score of BOADICEA, 2 patients with low score of BOADICEA, 2 patient's family members and 15 controls underwent BRCA1 genetic testing. Mutation screening using PCR-HRM was carried out in 22 exons (41 amplicons) of BRCA1 gene. Sanger sequencing was subjected in all samples with aberrant graph. This study identified 10 variants in the BRCA1 gene, consisting of 6 missense mutations (c.1480C>A, c.2612C>T, c.2566T>C, c.3113A>G, c.3548 A>G, c.4837 A>G), 3 synonymous mutations (c.2082 C> T, c.2311 T> C and c.4308T>C) and one intronic mutation (c.134+35 G>T). All variants tend to be polymorphisms and unclassified variants. However, no known pathogenic mutations were found.

Expression of nuclear factor kappa B (NF-κB) as a predictor of poor pathologic response to chemotherapy in patients with locally advanced breast cancer.

BACKGROUND: NF-κB inhibits apoptosis through induction of antiapoptotic proteins and suppression of proapoptotic genes. Various chemotherapy agents induce NF-κB translocation and target gene activation. We conducted the present study to assess the predictive value of NF-κB regarding pathologic responses after receiving neoadjuvant chemotherapy. MATERIALS AND METHODS: We enrolled 131 patients with locally advanced invasive ductal breast carcinoma. Immunohistochemistry (IHC) was used to detect NF-κB expression. Evaluation of pathologic response was elaborated with the Ribero classification. RESULTS: Expression of NF-κB was significantly associated with poor pathological response (p=0.02). From the multivariate analysis, it was found that the positive expression of NF-κB yielded RR=1.74 (95%CI 0.77 to 3.94). CONCLUSIONS: NF-κB can be used as a predictor of poor pathological response after neoadjuvant chemotherapy.