Combining lapatinib and palbociclib inhibits cell proliferation and invasion via AKT signaling pathway in endocrine-resistant breast cancer cells.

Endocrine therapy plays a critical role in patients with hormone receptor-positive breast cancer. Endocrine-resistant breast cancer cells exhibit more HER2 signaling proteins (pAKT and pERK) and mesenchymal biomarkers than wild-type cell lines. In head and neck squamous cell carcinoma, the combination of lapatinib and palbociclib demonstrated synergistic inhibitory effects on cell proliferation and suppressed ERK1/2 phosphorylation. The combination of lapatinib and palbociclib at half-maximal inhibitory concentrations resulted in an increasing cytotoxic effect on cell proliferation. Furthermore, invasion activity was significantly decreased when combining two drugs at nontoxic concentrations more than either single drug alone did. The combination also remarkably suppressed epithelial-mesenchymal transition transcription factors, such as Snail and pAKT, more than monotherapy. Combining drugs, particularly lapatinib and palbociclib for targeting endocrine-resistant breast cancer cells whose tumors overexpressed HER2 after resistance to hormonal therapy, demonstrated better antiproliferative, anti-invasive effects, and suppression of EMT protein and pAKT than a single drug. These results could be from the interruption of the EMT process via the AKT pathway. Thus, this study provides preliminary data for applying this combination to patients with endocrine-resistant breast cancer in further clinical trials.

Reproductive care in Thai women with diabetes mellitus: a descriptive cross-sectional study.

BACKGROUND: Pre-existing diabetes mellitus (DM) is a challenging pregnancy complication as poor glycemic control is associated with adverse maternal and fetal outcomes. In this study, we aimed to investigate DM-related knowledge, attitudes, preconception care practices, and contraceptive prevalence in women with DM. METHODS: This descriptive cross-sectional survey was conducted among reproductive-aged Thai women receiving DM treatment at King Chulalongkorn Memorial Hospital between August 1, 2021, and June 30, 2022. Patients with DM who were not pregnant or trying to conceive and could be contacted via the phone were included and a validated self-administered questionnaire was distributed electronically. RESULTS: A total of 238 participants were included in the final analysis, yielding 69.4% response rates. The mean (standard deviation) score for knowledge of pregnancy planning and pregnancy-related risks was 6.8 (3.5) out of 15. Only about half of the participants had discussed pregnancy planning with their physicians. Multivariable analysis showed that younger age at DM diagnosis, non-Buddhism, married, higher education, and medical personnel were significantly associated with higher knowledge scores. Women aged > 45 years and those with higher practice scores had significantly higher adjusted odds of using highly effective contraception; the most common methods included male condoms and combined oral contraceptive pills. There was an unmet need for contraception in 9.5% of women with DM. CONCLUSIONS: Although highly effective contraception is safe for patients with DM, only about half of our participants used tier one or two contraceptives or had received consultation regarding preconception planning. There was a notable gap in care coordination among specialists; integrating reproductive healthcare into DM therapy would improve access to preconception care.

We aimed to study the knowledge, attitudes, preconception care practices, and contraceptive usage among women with diabetes mellitus (DM) who were of reproductive age. A survey was conducted among Thai women receiving DM treatment at a university hospital. The results showed that participants had limited knowledge about pregnancy planning and diabetic-related risks. Only half of them had discussed pregnancy planning with their doctors. Factors such as younger age at DM diagnosis, being non-Buddhism, being married, having higher education, and being medical personnel were associated with higher knowledge scores. Older women and those with better practice scores were more likely to use highly effective contraception. However, there was still a need for contraception in some women with DM. We concluded that there was a lack of integration between specialists in reproductive healthcare and DM therapy, and improving this coordination would enhance access to preconception care for women with DM.