Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy

<p>Abstract</p> <p>Background</p> <p>Breast cancer stem cells (BCSCs) are the source of breast tumors. Compared with other cancer cells, cancer stem cells show high resistance to both chemotherapy and radiotherapy. Targeting of BCSCs is thus a potentially promising and effective strategy for breast cancer treatment. Differentiation therapy represents one type of cancer stem-cell-targeting therapy, aimed at attacking the stemness of cancer stem cells, thus reducing their chemo- and radioresistance. In a previous study, we showed that down-regulation of CD44 sensitized BCSCs to the anti-tumor agent doxorubicin. This study aimed to determine if CD44 knockdown caused BCSCs to differentiate into breast cancer non-stem cells (non-BCSCs).</p> <p>Methods</p> <p>We isolated a breast cancer cell population (CD44⁺CD24^-cells) from primary cultures of malignant breast tumors. These cells were sorted into four sub-populations based on their expression of CD44 and CD24 surface markers. CD44 knockdown in the BCSC population was achieved using small hairpin RNA lentivirus particles. The differentiated status of CD44 knock-down BCSCs was evaluated on the basis of changes in CD44⁺CD24^-phenotype, tumorigenesis in NOD/SCID mice, and gene expression in relation to renewal status, metastasis, and cell cycle in comparison with BCSCs and non-BCSCs.</p> <p>Results</p> <p>Knockdown of CD44 caused BCSCs to differentiate into non-BCSCs with lower tumorigenic potential, and altered the cell cycle and expression profiles of some stem cell-related genes, making them more similar to those seen in non-BCSCs.</p> <p>Conclusions</p> <p>Knockdown of CD44 is an effective strategy for attacking the stemness of BCSCs, resulting in a loss of stemness and an increase in susceptibility to chemotherapy or radiation. The results of this study highlight a potential new strategy for breast cancer treatment through the targeting of BCSCs.</p

Spatiotemporal evolution of SARS-CoV-2 Alpha and Delta variants during large nationwide outbreak of COVID-19, Vietnam, 2021

We analyzed 1,303 SARS-CoV-2 whole-genome sequences from Vietnam, and found the Alpha and Delta variants were responsible for a large nationwide outbreak of COVID-19 in 2021. The Delta variant was confined to the AY.57 lineage and caused >1.7 million infections and >32,000 deaths. Viral transmission was strongly affected by nonpharmaceutical interventions

Evaluating novel engagement mechanisms, yields and acceptability of tuberculosis screening at retail pharmacies in Ho Chi Minh City, Viet Nam.

Pharmacies represent a key health system entry point for people with TB in Viet Nam, but high fragmentation hinders their broader engagement. Professional networking apps may be able to facilitate pharmacy engagement for systematic TB screening and referral. Between September and December 2019, we piloted the use of a social networking app, SwipeRx, to recruit pharmacists for a TB referral scheme across four districts of Ho Chi Minh City, Viet Nam. We measured chest X-ray (CXR) referrals and TB detection yields at participating pharmacies and fielded 100 acceptability surveys, divided into pharmacists who did and did not make a CXR referral. We then fitted mixed-effect odds proportional models to explore acceptability factors that were associated with making a CXR referral. 1,816 push notifications were sent to pharmacists via the SwipeRx app and 78 indicated their interest in participating; however, only one was within the pilot's intervention area. Additional in-person outreach resulted in the recruitment of 146 pharmacists, with 54 (37.0%) making at least one CXR referral. A total of 182 pharmacy customers were referred, resulting in a total of 64 (35.2%) CXR screens and seven people being diagnosed with TB. Compared to pharmacists who did not make any CXR referrals, pharmacists making at least one CXR referral understood the pilot's objectives more clearly (aOR = 2.6, 95% CI: 1.2-5.8) and they believed that TB screening increased customer trust (aOR = 2.7, 95% CI: 1.2-5.8), benefited their business (aOR = 2.8, 95% CI: 1.3-6.2) and constituted a competitive advantage (aOR = 4.4, 95% CI: 1.9-9.9). They were also more confident in using mHealth apps (aOR = 3.1, 95 CI%: 1.4-6.8). Pharmacies can play an important role in early and increased TB case finding. It is critical to highlight the value proposition of TB referral schemes to their business during recruitment. Digital networking platforms, such as SwipeRx, can facilitate referrals for TB screening by pharmacists, but their ability to identify and recruit pharmacists requires optimization, particularly when targeting specific segments of a nation-wide digital network