Artemisia argyi extracts overcome lapatinib resistance via enhancing TMPRSS2 activation in HER2-positive breast cancer.

Breast cancer stands as the predominant malignancy and primary cause of cancer-related mortality among females globally. Approximately 25% of breast cancers exhibit HER2 overexpression, imparting a more aggressive tumor phenotype and correlating with poor prognoses. Patients with metastatic breast cancer receiving HER2 tyrosine kinase inhibitors (HER2 TKIs), such as Lapatinib, develop acquired resistance within a year, posing a critical challenge in managing this disease. Here, we explore the potential of Artemisia argyi, a Chinese herbal medicine known for its anti-cancer properties, in mitigating HER2 TKI resistance in breast cancer. Analysis of the Cancer Genome Atlas (TCGA) revealed diminished expression of transmembrane serine protease 2 (TMPRSS2), a subfamily of membrane proteolytic enzymes, in breast cancer patients, correlating with unfavorable outcomes. Intriguingly, lapatinib-responsive patients exhibited higher TMPRSS2 expression. Our study unveiled that the compounds from Artemisia argyi, eriodictyol, and umbelliferone could inhibit the growth of lapatinib-resistant HER2-positive breast cancer cells. Mechanistically, they suppressed HER2 kinase activation by enhancing TMPRSS2 activity. Our findings propose TMPRSS2 as a critical determinant in lapatinib sensitivity, and Artemisia argyi emerges as a potential agent to overcome lapatinib via activating TMPRSS2 in HER2-positive breast cancer. This study not only unravels the molecular mechanisms driving cell death in HER2-positive breast cancer cells induced by Artemisia argyi but also lays the groundwork for developing novel inhibitors to enhance therapy outcomes.

Thrombomodulin mediates the progression of epithelial ovarian cancer cells.

Thrombomodulin (TM), a natural anticoagulation factor, maintains circulation homeostasis in endothelial cells. TM has additional roles in modulating inflammation, thrombosis, and carcinogenesis. However, there is little information on the role of TM in the progression and metastasis of ovarian cancer. RNA silencing and cDNA expression vectors were used to manipulate target gene expression in ovarian cancer cells. Cell growth and migration were evaluated by an MTT assay, a wound-healing migration assay, a transwell migration assay, and a biosensor system. In this study, we found that TM silencing may enhance the growth rate of cells. The migratory ability of ovarian cancer cells was enhanced dramatically after TM silencing. TM overexpression in ovarian cells suppressed the proliferation and migration capability. Furthermore, we found that skov-3 cells treated with TM shRNA expressed high levels of fibronectin and vimentin and that the expression of these markers correlated positively with their migratory ability. Our results demonstrate that TM expression may regulate cell growth and migration in ovarian cancer cells. This finding suggests that TM may be a novel prognostic and therapeutic target for ovarian cancer.

Panax notoginseng Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice.

Panax notoginseng (PN) is a traditional Chinese herb experimentally proven to have anti-inflammatory effects, and it is used clinically for the treatment of atherosclerosis, cerebral infarction, and cerebral ischemia. This study aimed to determine the anti-inflammatory effects of PN against bleomycin-induced pulmonary fibrosis in mice. First, in an in vitro study, culture media containing lipopolysaccharide (LPS) was used to stimulate macrophage cells (RAW 264.7 cell line). TNF-α and IL-6 levels were then determined before and after treatment with PN extract. In an animal model (C57BL/6 mice), a single dose of PN (0.5 mg/kg) was administered orally on Day 2 or Day 7 postbleomycin treatment. The results showed that TNF-α and IL-6 levels increased in the culture media of LPS-stimulated macrophage cells, and this effect was significantly inhibited in a concentration-dependent manner by PN extract. Histopathologic examination revealed that PN administered on Day 7 postbleomycin treatment significantly decreased inflammatory cell infiltrates, fibrosis scores, and TNF-α, TGF-ß, IL-1ß, and IL-6 levels in bronchoalveolar lavage fluid when compared with PN given on Day 2 postbleomycin treatment. These results suggest that PN administered in the early fibrotic stage can attenuate pulmonary fibrosis in an animal model of idiopathic pulmonary fibrosis.

Pigtail catheters vs large-bore chest tubes for management of secondary spontaneous pneumothoraces in adults.

It is still uncertain if large-bore chest tubes (20F-28F) is superior to pigtail catheter (10F-14F) in terms of the management of secondary spontaneous pneumothoraces (SSP). This study was designed to compare the efficacy and safety associated with placement of large-bore chest tubes vs pigtail catheters in adults experiencing the first episode of SSP. We conducted a retrospective chart review of 91 patients experiencing the first episode of SSP in a university hospital over a 3.5-year period who received treatment by either a large-bore chest tube or a pigtail catheter. Any patient who was younger than 18 years or experiencing mechanical ventilation-related barotraumas or pyopneumothorax was excluded from this study. Various parameters including demographical characteristics, size of pneumothorax, complications, time of pigtail or chest tube extubation, and length of hospital stay were collected and analyzed. Among the enrolled 91 patients, including 76 (83.5%) men with a mean age of 60 +/- 19 years, 69 were initially treated with a pigtail, and 22 patients received conventional chest tubes. Fifty patients (72.5%) undergoing the pigtail drainage and 16 (72.7%) undergoing large-bore chest tube treatment of SSP were successfully treated (P = .88). In addition, there was no significant difference in terms of length of hospital stay, extubation time, recurrence rate, and complication. Pigtail catheters offer a safe and effective alternative for large-bore chest tubes to adult patients experiencing the first episode of SSP, and we strongly suggested that pigtail tube drainage should be considered as the initial treatment of choice.

Polymorphisms of p53 and p21 genes in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a multifactorial disease influenced by genetic and environmental factors, particularly cigarette smoking. Although cigarette smoke may be directly mutagenic, polymorphisms in the genes controlling acquired somatic mutations may also contribute, at least to some extent, to the observed differing susceptibilities to COPD. To investigate the involvement of genetic polymorphisms of p53 and p21 in the pathogenesis of COPD, the authors performed a case-control study involving 206 subjects with COPD and 210 healthy smokers as control subjects. METHODS: Polymorphisms of p53 and p21 genes were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique on genomic DNA isolated from peripheral lymphocytes. The distribution of the p53 and p21 polymorphisms in healthy subjects and COPD patients was examined and compared using the Pearson X2 test. Significance was accepted at P < 0.05. Odds ratios (ORs) and 95% confidence intervals (CIs) of each specific genotype were calculated using logistic regression analysis to quantitatively assess the degree of association observed. RESULTS: The distribution frequencies of genotypes of p53 codon 72 and p21 codon 31 were significantly different between the COPD and the control groups. Higher ORs for COPD were seen for persons with p53 Pro/Pro or Pro/Arg genotypes against Arg/Arg genotype [OR = 2.35, 95% CI 1.27-4.39, P = 0.008], or p21 Arg/Arg and Arg/Ser genotypes against Ser/Ser genotype [OR = 2.07, 95% CI 1.06-4.05, P = 0.033]. CONCLUSIONS: The polymorphisms of p53 and p21 were significantly associated with the occurrence of smoking-related COPD in Taiwan Chinese patients.