Objective
Thyroid cancer incidence has steadily increased in Indonesia. However, data on Kirsten rat sarcoma virus (KRAS) and EGFR mutations in thyroid cancer in Indonesia remain unavailable, except for BRAF-V600E, the most common BRAF gene mutation. This study aimed to analyze KRAS and EGFR mutation profiles in BRAF-V600E negative thyroid cancer samples.
Results
BRAF-V600E mutations were found in papillary thyroid carcinomas in 40.3% patients with mean age of 53 years old. In BRAF-V600E-negative samples, 41.3% had KRAS mutations with mean age of 55.5 years old. KRAS mutation was found in 52.6% of follicular carcinomas and 47.4% of papillary thyroid carcinomas. Additionally, 45.7% had EGFR mutations in patients with mean age of 50.5 years old. EGFR mutation was found in 71.4% of papillary thyroid carcinoma and 28.6% of follicular carcinoma. Nearly half of the BRAF-V600E negative thyroid carcinoma samples harbored either KRAS or EGFR mutations. This finding suggests that in BRAF-V600E negative thyroid carcinoma samples, testing for RAS and EGFR mutation may be warranted for further therapeutic consideration.
Background. Under the National Comprehensive Cancer Network (NCCN) guidelines for non-small-cell lung carcinoma (NSCLC), anaplastic lymphoma kinase (ALK) gene rearrangement is required to be assessed. However, data showing the prevalence of the ALK rearrangement is still deficient and is not yet available in Indonesia. This study used direct smear preparation from transthoracic needle specimens that are minimally invasive. The main objective of the study is to identify the prevalence of the ALK fusion rearrangement gene in cytological specimens. Materials and Methods. A total of 35 direct smear preparations diagnosed as lung adenocarcinoma and EGFR mutation negative were involved in this study. The samples were taken between 2017 and 2019. These samples were examined for EML4-ALK fusion rearrangement gene using qRT-PCR. The EML4-ALK rearrangement status was determined by qRT-PCR with high-resolution melting (HRM) analysis. Results. A total of 28 (80%) samples were from males, and 7 samples were from females. Seven (20% 95% CI: 8.4%-36.9%) samples were EML4-ALK rearrangement positive. The average age of the patients was 63.5 years old. The most common sites of metastasis in this study were pleural cavity, bone, liver, and CNS. Conclusions. qRT-PCR successfully identified EML4-ALK fusion rearrangement in direct smear preparations of lung adenocarcinoma. Direct smear samples can be used for EML4-ALK rearrangement detection using qRT-PCR. The EML4-ALK rearrangement gene has high prevalence in selected lung adenocarcinoma and EGFR mutation-negative populations. ALK inhibitors in lung cancer can be openly considered for use in Indonesian patients to improve the outcome of this subset of patients.
Hyperglycemia in Diabetes mellitus (DM) induces oxidative stress and mitochondrial disruptions in the liver, thereby triggering apoptosis through Bcl-2 family signaling. Excessive apoptosis leads to liver dysfunction. Chlorogenic acid (CGA) was elucidated in this study in preventing liver dysfunction as a progression of DM. The diabetic model was conducted in Wistar rats, divided into six groups. Blood examinations were done to measure the levels of blood glucose, SGOT, and SGPT. The liver was harvested for analysis of SOD2, Bax, and Bcl-2 mRNA. A paraffin section was used for p53 immunostaining. Liver dysfunction occurred in the DM 2 months group indicated by higher levels of SGPT and SGOT, higher expression of Bax, and lower expression of Bcl-2 compared to the control group. Giving CGA 12.5 mg/kgBW ameliorated blood glucose and liver enzyme levels, which were associated with lower expression of Bax, lower signaling of p53, and higher expression of Bcl-2 compared to DM 2 months group. Administration of CGA did not affect SOD2 expression in diabetic rats. CGA may attenuate liver dysfunction in diabetic rats through downregulation of Bax and p53, and upregulation of Bcl-2 signaling.
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