Design, synthesis, and evaluation of purine and pyrimidine-based KRAS G12D inhibitors: Towards potential anticancer therapy.

Oncogenic RAS mutations, commonly observed in human tumors, affect approximately 30% of cancer cases and pose a significant challenge for effective cancer treatment. Current strategies to inhibit the KRAS G12D mutation have shown limited success, emphasizing the urgent need for new therapeutic approaches. In this study, we designed and synthesized several purine and pyrimidine analogs as inhibitors for the KRAS G12D mutation. Our synthesized compounds demonstrated potent anticancer activity against cell lines with the KRAS G12D mutation, effectively impeding their growth. They also exhibited low toxicity in normal cells, indicating their selective action against cancer cells harboring the KRAS G12D mutation. Notably, the lead compound, PU1-1 induced the programmed cell death of KRAS G12D-mutated cells and reduced the levels of active KRAS and its downstream signaling proteins. Moreover, PU1-1 significantly shrunk the tumor size in a pancreatic xenograft model induced by the KRAS G12D mutation, further validating its potential as a therapeutic agent. These findings highlight the potential of purine-based KRAS G12D inhibitors as candidates for targeted cancer therapy. However, further exploration and optimization of these compounds are essential to meet the unmet clinical needs of patients with KRAS-mutant cancers.

Knowledge and Acceptability about Adult Pertussis Immunization in Korean Women of Childbearing Age.

PURPOSE: The adult tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine has been introduced in order to provide individual protection and reduce the risk of transmitting pertussis to infants. We assessed the knowledge and acceptability of the Tdap vaccine around pregnancy. MATERIALS AND METHODS: This study was a cross-sectional survey of women of childbearing age (20-45 years) who visited obstetrics and gynecologic units of primary, secondary, or tertiary hospitals. They were asked to fill in a questionnaire assessing their knowledge, attitudes, and acceptability of Tdap. RESULTS: The questionnaire was completed by 308 women; 293 (95.1%) had not received information from doctors about Tdap, and 250 (81.2%) did not know about the need for vaccination. A significantly important factor related to subjects' intention to be vaccinated, identified by stepwise multiple logistic regression, was the knowledge (OR 13.5, CI 3.92-46.33) that adult Tdap is effective in preventing pertussis for infants aged 0-6 months. Additionally, 276 (89.6%) considered the recommendation of obstetric doctors as the most influencing factor about Tdap vaccination. CONCLUSION: In Korea, most women of childbearing age seem to be neither recommended nor adequately informed about the vaccination, although our population was not a nationwide representative sample. Information given by healthcare workers may be critical for improving awareness and preventing pertussis.

Knowledge, attitudes, and acceptability about influenza vaccination in Korean women of childbearing age.

OBJECTIVE: The aims of the present study were to investigate the women's perspective on influenza infection and vaccination and to evaluate how they influence vaccine acceptability, in Korean women of childbearing age. METHODS: This was a prospective study by random survey of women of childbearing age (20 to 45 years). They were asked to complete a questionnaire assessing their knowledge, attitudes and acceptability of influenza vaccination before and during pregnancy. This study utilized data from the Korea National Health and Nutrition Examination Survey (KNHANES) between 2008 and 2012, to analyze the recent influenza vaccination trends. RESULTS: According to KNHANES (2008-2012), influenza vaccination rates in women of childbearing age have increased up to 26.4%, after 2009. The questionnaire was completed by 308 women. Vaccination rate during pregnancy or planning a pregnancy was 38.6%. The immunization rate increased significantly with the mean number of correct answers (P<0.001). Women who received influenza vaccination were more likely to be previously informed of the recommendations concerning the influenza vaccination before or during pregnancy, received the influenza vaccination in the past, and of the opinion that influenza vaccination is not dangerous during pregnancy, with odds ratios of 14.6 (95% confidence interval [CI], 6.44 to 33.33; P<0.0001), 3.6 (95% CI, 1.84 to 6.97; P=0.0002) and 2.7 (95% CI, 1.34 to 5.47; P=0.0057). CONCLUSION: Influenza vaccination rate in women of childbearing age has increased in this study and national data. More information and recommendation by healthcare workers, especially obstetricians, including safety of vaccination, might be critical for improving vaccination rate in women of childbearing age.

The clinical significance of digital examination-indicated cerclage in women with a dilated cervix at 14 0/7-29 6/7 weeks.

OBJECTIVE: This study was to compare pregnancy outcomes between cerclage and expectant management in wemen with a dilated cervix. DESIGN: Retrospective multicenter cohort study. SETTING: Five hospitals of Catholic University Medical Center Network in Korea. POPULATION: A total of 173 women between 14 0/7 and 29 6/7 weeks' gestation with cervical dilation of 1 cm or greater by digital examination. METHODS: Pregnancy outcomes were compared according to cerclage or expectant management, with the use of propensity-score matching. MAIN OUTCOME MEASURES: Primary outcome was time from presentation until delivery (weeks). Secondary outcomes were gestational age at delivery, neonatal survival, morbidity, preterm birth, and so on. RESULTS: Of 173 women, 116 received a cerclage (cerclage group), and 57 were managed expectantly without cerclage (expectant group). Cervical dilation at presentation, and the use of amniocentesis performed to exclude subclinical chorioamnionitis differed between two groups. In the overall matched cohort, there was significant difference in the time from presentation until delivery (cerclage vs. expectant group, 10.6±6.2 vs. 2.9±3.2 weeks, p <0.0001). While there was no significant difference in the neonatal survival between two groups, there were lower neonatal morbidity as well as higher pregnancy maintenance rate at 28, 32, 34 and 37 weeks' gestation in the cerclage group, compared with the expectant group. CONCLUSION: This study suggests that digital examination-indicated cerclage appears to prolong gestation and decrease neonatal morbidity, compared with expectant management in women with cervical dilation between 14 0/7 and 29 6/7 weeks.