Impacts of Matrix Metalloproteinase-2 Promoter Genotypes on Breast Cancer Risk.

BACKGROUND/AIM: Matrix metalloproteinase-2 (MMP-2) has been implicated in the pathogenesis of breast cancer (BC). However, there is limited research on the role of MMP-2 genotypes in BC risk. This study aimed to investigate the associations between two MMP-2 promoter polymorphisms, rs243865 and rs2285053, and BC risk. MATERIALS AND METHODS: MMP-2 genotypes were analyzed using PCR-based RFLP methodology in a cohort comprising 1,232 BC cases and 1,232 controls. RESULTS: Genotypic frequencies of MMP-2 rs243865 and rs2285053 in controls were consistent with Hardy-Weinberg equilibrium (p=0.3702 and 0.2036, respectively). There were no significant differences in the distribution of rs243865 and rs2285053 genotypes between BC cases and controls (p for trend=0.1602 and 0.2170, respectively). Variant genotypes at rs243865 and rs2285053 appeared to confer a protective effect, although not statistically significant (all p>0.05). Similarly, the variant T allele at rs243865 and rs2285053 showed a non-significant trend towards decreased BC risk (OR=0.84 and 0.89, 95%CI=0.69-1.02 and 0.78-1.02, p=0.0811 and 0.1043, respectively). There was no interaction observed between MMP-2 rs243865 or rs2285053 genotypes and age. Stratified analysis did not reveal significant associations between MMP-2 rs243865 or rs2285053 genotypes and triple-negative breast cancer (TNBC) (p=0.6458 and 0.8745, respectively). Among both TNBC and non-TNBC cases, none of the variant genotypes at rs243865 or rs2285053 showed significant associations with TNBC (all p>0.05). CONCLUSION: MMP-2 rs243865 and rs2285053 genotypes appear to have a minimal impact on individual susceptibility to BC or TNBC.

Combination treatment of arsenic trioxide and osimertinib in recurrent and metastatic head and neck squamous cell carcinoma.

Recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) represents an advanced stage of the disease and frequently shows resistance to these current treatments, including platinum chemotherapy, cetuximab plus chemotherapy, and checkpoint inhibitors. EGFR overexpression and TP53 mutation are the most frequent genetic changes in patients with HNSCC. On the basis of this genetic feature, we proposed a combinatorial treatment using the EGFR tyrosine kinase inhibitor osimertinib (AZD) and arsenic trioxide (ATO) for compassionate use. The patient obtained treatment response and progression-free survival for about six months. In vitro mechanical verifications showed that ATO and AZD combination (ATO/AZD) significantly increased intracellular ROS levels and DNA damage. Additionally, ATO/AZD decreases the expression and activity of breast cancer type 1 susceptibility protein (BRCA1) and polo-like kinase 1 (PLK1), thereby impairing Rad51 recruitment to DNA double-strand lesion for repair and may ultimately cause tumor cell death. In conclusion, this study provides a concrete experience and an alternate strategy of ATO/AZD therapy for patients with R/M HNSCC.

Comparison of overall survival after neoadjuvant and adjuvant chemotherapy in patients with early breast cancer with immediate breast reconstruction after mastectomy: A retrospective, matched case-control study.

Immediate breast reconstruction after mastectomy combined with chemotherapy is the preferred option for patients with early-stage breast cancer who require both superior clinical and aesthetic outcomes. The present study aimed to determine the survival benefits of neoadjuvant and adjuvant chemotherapy for patients with early-stage breast cancer who have undergone immediate breast reconstruction after mastectomy in Taiwan. The present study compared overall survival (OS) following neoadjuvant or adjuvant chemotherapy in 139 patients with early-stage breast cancer who underwent immediate breast reconstruction after mastectomy. Patient data were used retrospectively as an unmatched cohort. Next, 37 neoadjuvant cases were matched with 37 adjuvant controls through 1:1 age-, clinical stage-, and molecular subtype-matching. OS differences between the cases and controls were determined using Kaplan-Meier survival curve analyses. Here, 77.7 and 81.1% of the unmatched and matched cohort patients were aged <50 years, respectively. Of the matched neoadjuvant cases, 10 (15.6%) reached pathologic complete response after neoadjuvant chemotherapy, whereas 5 (13.5%) neoadjuvant cases succumbed during the study period. The neoadjuvant matched cases demonstrated a significantly poor OS with their adjuvant matched controls (P=0.044); nevertheless, the stratification analysis results demonstrated that the survival differences between the neoadjuvant and the adjuvant controls decreased after matching. Targeted therapy demonstrated the same OS benefits for both the neoadjuvant matched cases and adjuvant matched controls (P=1.000). This study provided matched case-control evidence for the feasibility of neoadjuvant chemotherapy combined with targeted therapy for patients with early-stage breast cancer with immediate breast reconstruction after mastectomy in a Taiwanese female population.

The Efficacy of Pegylated Liposomal Doxorubicin-Based Neoadjuvant Chemotherapy in Breast Cancer: A Retrospective Case-Control Study in Taiwan.

Breast cancer is a global issue regarding women's health, and high incident rates remain in the Taiwanese female population. Chemotherapy, using anthracycline-based chemotherapeutic agents in neoadjuvant settings, has been introduced as a promising new therapeutic option for treatment of invasive breast cancer. Set apart from conventional anthracycline regimens such as epirubicin, pegylated liposomal doxorubicin (Lipo-Dox®, PLD) was introduced for providing a justifiable treatment effect, while offering a favorable toxicity profile for breast cancer patients in a metastatic setting. However, the efficacy of PLD in neoadjuvant settings for breast cancer patients has not yet been sufficiently reported. This study aims to investigate the efficacy of PLD-based neoadjuvant chemotherapy in breast cancer patients using a retrospective matched case-control study. A total of 183 PLD cases and 183 epirubicin-based controls were included after a 1 : 1 ratio case-control matching procedure was held, according to the matching criteria. These criteria included the patient's preoperative clinical stage, molecular subtype, chemotherapy regimen with taxanes prior to surgery, and histological grade. All data were collected according to an institutional review board approved protocol. The study results reported that the PLD and epirubicin groups both obtained similar outcomes in pathologic complete response (pCR), recurrence, and overall survival rate with no statistically significant differences. Overall, the study results demonstrate that PLD-based neoadjuvant chemotherapy offers a similar effect of treatment with a favorable toxicity profile within the study follow-up duration, when compared with conventional epirubicin-based neoadjuvant chemotherapy.

Exposure to sexually explicit media in early adolescence is related to risky sexual behavior in emerging adulthood.

BACKGROUND: Sexually explicit media exposure during early adolescence has been found to be associated with risky sexual behavior. However, previous study suffered from methodological issue, such as selection bias. Furthermore, little is known about the effect of multi-modality sexually explicit media exposure on risky sexual behavior, and how this relationship can be applied to non-western societies. OBJECTIVES: This study aimed to improve upon previous studies by using instrumental variable estimation. In addition, this study also included multi-modality of sexually explicit media and three risky sexual behavior measure from a sample of Taiwanese adolescents. METHODS: Participants were recruited from a prospective longitudinal study (Taiwan Youth Project). All were in 7th grade (mean age = 13.3) when the study was initiated in 2000. Sexually explicit media exposure, including ever-exposure and number of modalities exposed to, was measured in wave 2 (8th grade). Risky sexual behavior was measured in waves 8 (mean age = 20.3) and 10 (mean age = 24.3). A two-stage least squares regression was employed, with pubertal timing as the instrumental variable. RESULTS: About 50% of participants had been exposed to sexual media content by 8th grade, from an average of one modality. Sexually explicit media exposure predicted early sexual debut, unsafe sex, and multiple sexual partners (all: p < .05). Furthermore, exposure to more media modalities increased the likelihood of risky sexual behaviors. However, only the effect on early sexual debut was gender invariant. CONCLUSIONS: Exposure to sexually explicit media in early adolescence had a substantive relationship with risky sexual behavior in the emerging adulthood. Knowledge of this causal like effect provides a basis for building better preventive programs in early adolescence. One prominent way is early education on media literacy, and physicians themselves may need to be familiar with such content to initiate it.

Suppression of alpha-tocopherol ether-linked acetic acid in VEGF-induced angiogenesis and the possible mechanisms in human umbilical vein endothelial cells.

Alpha-tocopherol ether-linked acetic acid (α-TEA) has been reported to exhibit both anti-tumor and anti-metastatic activities in cell culture and animal studies. However, it is unclear whether α-TEA possesses anti-angiogenic effects. In this study, we investigated the effect of α-TEA on vascular endothelial growth factor (VEGF)-induced angiogenesis and matrix metalloproteinase (MMP) expression both in vitro and ex vivo. We found that the α-TEA inhibited tube formation, invasion, and migration in human umbilical vein endothelial cells (HUVECs) and that such actions were accompanied by reduced expression of MMP-2. α-TEA also inhibited ex vivo angiogenesis, as indicated by chicken egg chorioallantoic membrane assay. We further showed that α-TEA attenuated protein expression of VEGF receptor-2 (VEGFR-2)-mediated p38 mitogen-activated protein kinase (p38), phosphorylated p38, and focal adhesion kinase (FAK). Moreover, α-TEA (30 µM) significantly up-regulated protein expression of tissue inhibitors of MMP (TIMP)-2 (by 138%) and the metastasis suppressor gene nm23-H1 (by 54%). These results demonstrate that the anti-angiogenic effect of α-TEA both in vitro and ex vivo and its possible mechanistic action appears to involve the inhibition of MMP-2 level through VEGFR-2-mediated FAK and p38 signaling pathways and through up-regulation of TIMP-2 and nm23-H1 expression.

Isolation and characterization of lactic acid bacteria from jiang-sun (fermented bamboo shoots), a traditional fermented food in Taiwan.

BACKGROUND: In this study, lactic acid bacteria (LAB) were isolated, characterized and identified from jiang-sun (fermented bamboo shoots; a traditional fermented food in Taiwan). Samples were collected at seven time intervals from a fixed fermenting bucket during the fermentation process of jiang-sun and its initial ingredients, dochi (fermented soybeans) and bamboo shoots. RESULTS: A total of 57 LAB cultures were isolated; 42 cultures were isolated from jiang-sun samples and 15 cultures were isolated from dochi and bamboo shoots. These isolates were characterized phenotypically and then divided into three groups (A-C) by restriction fragment length polymorphism analysis and sequencing of 16S ribosomal DNA. Alteration of microbial populations during the fermentation process was observed. While various LAB were found in the dochi and bamboo shoots, it was mostly replaced by Lactobacillus plantarum after 1 day of fermentation. Furthermore, the antibacterial activities of the isolates were determined, and one Enterococcus faecium strain showed inhibitory activity against all the indicator strains. CONCLUSION: Results suggest that L. plantarum is the main LAB present during the fermentation of jiang-sun. To our knowledge, this is the first report describing the distribution and varieties of LAB that exist in the jiang-sun fermentation process.