We identified drugs or mechanisms targeting ABCB1 (or P-glycoprotein; P-gp)-overexpressing drug-resistant cancer populations, given that these cells play a key role in tumor recurrence. Specifically, we searched for Akt inhibitors that could increase cytotoxicity in P-gp-overexpressing drug-resistant cancer cells. We performed cytotoxicity assays using five cell lines: 1. MCF-7/ADR, 2. KBV20C cancer cells (P-gp overexpression, vincristine [VIC] resistance, and GSK690693-resistance), 3. MCF-7, 4. normal HaCaT cells (non-P-gp-overexpressing, VIC-sensitive, and GSK690693-sensitive), and 5. MDA-MB-231 cancer cells (non-Pgp overexpression, relatively VIC-resistance, and GSK690693-sensitive). Herein, we found that low-dose perifosine markedly and selectively sensitizes both MCF-7/ADR and KBV20C drug-resistant cancer cells exhibiting P-gp overexpression. Compared with other Akt inhibitors (AZD5363, BKM120, and GSK690693), low-dose perifosine specifically sensitized P-gp-overexpressing resistant MCF-7/ADR cancer cells. Conversely, Akt inhibitors (other than perifosine) could enhance sensitization effects in drugsensitive MCF-7 and HaCaT cells. Considering that perifosine has both an alkyl-phospholipid structure and is an allosteric inhibitor for membrane-localizing Akt-targeting, we examined structurally and functionally similar Akt inhibitors (miltefosine and MK-2206).However, we found that these inhibitors were non-specific, suggesting that the specificity of perifosine in P-gp-overexpressing resistant cancer cells is unrelated to phospholipid localizing membranes or allosteric inhibition. Furthermore, we examined the molecular mechanism of low-dose perifosine in drug-resistant MCF-7/ADR cancer cells. MCF-7/ADR cells exhibited increased apoptosis via G2 arrest and autophagy induction. However, no increase in P-gp-inhibitory activity was observed in drug-resistant MCF-7/ADR cancer cells. Single low-dose perifosine treatment exerted a sensitization effect similar to co-treatment with VIC in P-gp-overexpressing drug-resistant MCF-7/ADR cancer cells, suggesting that single treatment with low-dose perifosine is a more powerful tool against P-gp-overexpressing drug-resistant cancer cells. These findings could contribute to its clinical use as a first-line treatment, explicitly targeting P-gp-overexpressing resistant cancer populations in heterogeneous tumor populations.Therefore, perifosine may be valuable in delaying or reducing cancer recurrence by targeting P-gp-overexpressing drug-resistant cancer cells.

Background: The nipple is a potential source of pathogens because its lactiferous ducts act as direct conduits from the nipple–areolar complex to the breast parenchyma. Our previous studies identified breast microbiota as a factor in postoperative complications following immediate breast reconstruction using silicone implants and acellular dermal matrix. This study aimed to investigate the correlation between preoperative nipple swab microbiota and the incidence of surgical site infections (SSIs) after autologous breast reconstruction. Methods: We conducted a retrospective chart review of patients who underwent autologous breast reconstruction following total mastectomy. Preoperative nipple swab cultures were obtained. Patient demographics, surgical characteristics, and complication rates were compared between culture-positive and culture-negative groups. Microbiological data, including antibiotic‑resistance profiles, were collected. Results: Among 39 reconstructed breasts, 18 (46.9%) had positive preoperative nipple cultures. The mean duration of drain placement was significantly longer in the culture‑positive group (14.39±3.96 days) than in the culture‑negative group (12.14±2.76 days, P=0.045). Methicillin‑susceptible Staphylococcus epidermidis accounted for 55.0% of isolates. Of the four SSIs observed, three occurred in patients with positive preoperative cultures. Conclusions Although pathogen strains differed between preoperative and postoperative settings, obtaining preoperative nipple microflora cultures and determining antibiotic‑resistance profiles can guide immediate antibiotic selection for SSIs and enhance postoperative management.

Background: The nipple is a potential source of pathogens because its lactiferous ducts act as direct conduits from the nipple–areolar complex to the breast parenchyma. Our previous studies identified breast microbiota as a factor in postoperative complications following immediate breast reconstruction using silicone implants and acellular dermal matrix. This study aimed to investigate the correlation between preoperative nipple swab microbiota and the incidence of surgical site infections (SSIs) after autologous breast reconstruction. Methods: We conducted a retrospective chart review of patients who underwent autologous breast reconstruction following total mastectomy. Preoperative nipple swab cultures were obtained. Patient demographics, surgical characteristics, and complication rates were compared between culture-positive and culture-negative groups. Microbiological data, including antibiotic‑resistance profiles, were collected. Results: Among 39 reconstructed breasts, 18 (46.9%) had positive preoperative nipple cultures. The mean duration of drain placement was significantly longer in the culture‑positive group (14.39±3.96 days) than in the culture‑negative group (12.14±2.76 days, P=0.045). Methicillin‑susceptible Staphylococcus epidermidis accounted for 55.0% of isolates. Of the four SSIs observed, three occurred in patients with positive preoperative cultures. Conclusions Although pathogen strains differed between preoperative and postoperative settings, obtaining preoperative nipple microflora cultures and determining antibiotic‑resistance profiles can guide immediate antibiotic selection for SSIs and enhance postoperative management.

We identified drugs or mechanisms targeting ABCB1 (or P-glycoprotein; P-gp)-overexpressing drug-resistant cancer populations, given that these cells play a key role in tumor recurrence. Specifically, we searched for Akt inhibitors that could increase cytotoxicity in P-gp-overexpressing drug-resistant cancer cells. We performed cytotoxicity assays using five cell lines: 1. MCF-7/ADR, 2. KBV20C cancer cells (P-gp overexpression, vincristine [VIC] resistance, and GSK690693-resistance), 3. MCF-7, 4. normal HaCaT cells (non-P-gp-overexpressing, VIC-sensitive, and GSK690693-sensitive), and 5. MDA-MB-231 cancer cells (non-Pgp overexpression, relatively VIC-resistance, and GSK690693-sensitive). Herein, we found that low-dose perifosine markedly and selectively sensitizes both MCF-7/ADR and KBV20C drug-resistant cancer cells exhibiting P-gp overexpression. Compared with other Akt inhibitors (AZD5363, BKM120, and GSK690693), low-dose perifosine specifically sensitized P-gp-overexpressing resistant MCF-7/ADR cancer cells. Conversely, Akt inhibitors (other than perifosine) could enhance sensitization effects in drugsensitive MCF-7 and HaCaT cells. Considering that perifosine has both an alkyl-phospholipid structure and is an allosteric inhibitor for membrane-localizing Akt-targeting, we examined structurally and functionally similar Akt inhibitors (miltefosine and MK-2206).However, we found that these inhibitors were non-specific, suggesting that the specificity of perifosine in P-gp-overexpressing resistant cancer cells is unrelated to phospholipid localizing membranes or allosteric inhibition. Furthermore, we examined the molecular mechanism of low-dose perifosine in drug-resistant MCF-7/ADR cancer cells. MCF-7/ADR cells exhibited increased apoptosis via G2 arrest and autophagy induction. However, no increase in P-gp-inhibitory activity was observed in drug-resistant MCF-7/ADR cancer cells. Single low-dose perifosine treatment exerted a sensitization effect similar to co-treatment with VIC in P-gp-overexpressing drug-resistant MCF-7/ADR cancer cells, suggesting that single treatment with low-dose perifosine is a more powerful tool against P-gp-overexpressing drug-resistant cancer cells. These findings could contribute to its clinical use as a first-line treatment, explicitly targeting P-gp-overexpressing resistant cancer populations in heterogeneous tumor populations.Therefore, perifosine may be valuable in delaying or reducing cancer recurrence by targeting P-gp-overexpressing drug-resistant cancer cells.

Background: The nipple is a potential source of pathogens because its lactiferous ducts act as direct conduits from the nipple–areolar complex to the breast parenchyma. Our previous studies identified breast microbiota as a factor in postoperative complications following immediate breast reconstruction using silicone implants and acellular dermal matrix. This study aimed to investigate the correlation between preoperative nipple swab microbiota and the incidence of surgical site infections (SSIs) after autologous breast reconstruction. Methods: We conducted a retrospective chart review of patients who underwent autologous breast reconstruction following total mastectomy. Preoperative nipple swab cultures were obtained. Patient demographics, surgical characteristics, and complication rates were compared between culture-positive and culture-negative groups. Microbiological data, including antibiotic‑resistance profiles, were collected. Results: Among 39 reconstructed breasts, 18 (46.9%) had positive preoperative nipple cultures. The mean duration of drain placement was significantly longer in the culture‑positive group (14.39±3.96 days) than in the culture‑negative group (12.14±2.76 days, P=0.045). Methicillin‑susceptible Staphylococcus epidermidis accounted for 55.0% of isolates. Of the four SSIs observed, three occurred in patients with positive preoperative cultures. Conclusions Although pathogen strains differed between preoperative and postoperative settings, obtaining preoperative nipple microflora cultures and determining antibiotic‑resistance profiles can guide immediate antibiotic selection for SSIs and enhance postoperative management.

We identified drugs or mechanisms targeting ABCB1 (or P-glycoprotein; P-gp)-overexpressing drug-resistant cancer populations, given that these cells play a key role in tumor recurrence. Specifically, we searched for Akt inhibitors that could increase cytotoxicity in P-gp-overexpressing drug-resistant cancer cells. We performed cytotoxicity assays using five cell lines: 1. MCF-7/ADR, 2. KBV20C cancer cells (P-gp overexpression, vincristine [VIC] resistance, and GSK690693-resistance), 3. MCF-7, 4. normal HaCaT cells (non-P-gp-overexpressing, VIC-sensitive, and GSK690693-sensitive), and 5. MDA-MB-231 cancer cells (non-Pgp overexpression, relatively VIC-resistance, and GSK690693-sensitive). Herein, we found that low-dose perifosine markedly and selectively sensitizes both MCF-7/ADR and KBV20C drug-resistant cancer cells exhibiting P-gp overexpression. Compared with other Akt inhibitors (AZD5363, BKM120, and GSK690693), low-dose perifosine specifically sensitized P-gp-overexpressing resistant MCF-7/ADR cancer cells. Conversely, Akt inhibitors (other than perifosine) could enhance sensitization effects in drugsensitive MCF-7 and HaCaT cells. Considering that perifosine has both an alkyl-phospholipid structure and is an allosteric inhibitor for membrane-localizing Akt-targeting, we examined structurally and functionally similar Akt inhibitors (miltefosine and MK-2206).However, we found that these inhibitors were non-specific, suggesting that the specificity of perifosine in P-gp-overexpressing resistant cancer cells is unrelated to phospholipid localizing membranes or allosteric inhibition. Furthermore, we examined the molecular mechanism of low-dose perifosine in drug-resistant MCF-7/ADR cancer cells. MCF-7/ADR cells exhibited increased apoptosis via G2 arrest and autophagy induction. However, no increase in P-gp-inhibitory activity was observed in drug-resistant MCF-7/ADR cancer cells. Single low-dose perifosine treatment exerted a sensitization effect similar to co-treatment with VIC in P-gp-overexpressing drug-resistant MCF-7/ADR cancer cells, suggesting that single treatment with low-dose perifosine is a more powerful tool against P-gp-overexpressing drug-resistant cancer cells. These findings could contribute to its clinical use as a first-line treatment, explicitly targeting P-gp-overexpressing resistant cancer populations in heterogeneous tumor populations.Therefore, perifosine may be valuable in delaying or reducing cancer recurrence by targeting P-gp-overexpressing drug-resistant cancer cells.

Prime editing (PE) is a recently developed genome-editing technique that enables versatile editing. Despite its flexibility and potential, applying PE in human induced pluripotent stem cells (hiPSCs) has not been extensively addressed. Genetic disease models using patient-derived hiPSCs have been used to study mechanisms and drug efficacy. However, genetic differences between patient and control cells have been attributed to the inaccuracy of the disease model, highlighting the significance of isogenic hiPSC models. Hereditary hemorrhagic telangiectasia 1 (HHT1) is a genetic disorder caused by an autosomal dominant mutation in endoglin (ENG). Although previous HHT models using mice and HUVEC have been used, these models did not sufficiently elucidate the relationship between the genotype and disease phenotype in HHT, demanding more clinically relevant models that reflect human genetics. Therefore, in this study, we used PE to propose a method for establishing an isogenic hiPSC line. Clinically reported target mutation in ENG was selected, and a strategy for PE was designed. After cloning the engineered PE guide RNA, hiPSCs were nucleofected along with PEmax and hMLH1dn plasmids. As a result, hiPSC clones with the intended mutation were obtained, which showed no changes in pluripotency or genetic integrity. Furthermore, introducing the ENG mutation increased the expression of proangiogenic markers during endothelial organoid differentiation. Consequently, our results suggest the potential of PE as a toolkit for establishing isogenic lines, enabling disease modeling based on hiPSC-derived disease-related cells or organoids.This approach is expected to stimulate mechanistic and therapeutic studies on genetic diseases.

OBJECTIVES: Long-term care facilities (LTCFs) are communal environments for patients with chronic diseases or older adults, making them particularly susceptible to significant harm during infectious disease outbreaks. Nonetheless, LTCFs have historically been subject to less stringent infection prevention and control (IPC) mandates. This study aimed to assess the current state of LTCFs and to develop an IPC system tailored for these facilities following the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted an online survey of 11,366 LTCFs in Korea from December 30, 2022 to January 20, 2023, to evaluate the components of IPC in LTCFs. The infectious diseases targeted for IPC included COVID-19, influenza, and scabies. Additionally, we compared institution-based and home-based long-term care insurance facilities. RESULTS: Overall, 3,537 (31.1%) LTCFs responded to the survey, comprising 1,819 (51.4%) institution-based and 1,718 (48.6%) home-based facilities. A majority (87.4%, 2,376/2,720) of these facilities experienced COVID-19 outbreaks. However, only 42.2% of home-based facilities, in contrast to 90.6% of institution-based facilities, were equipped to manage concurrent COVID-19 cases. Similarly, while 92.1% of institution-based facilities were capable of managing influenza, only 50.5% of home-based facilities could do the same. The incidence of scabies was significantly higher in institution-based facilities than in home-based ones (26.1 vs. 4.3%). Additionally, 88.7% of institution-based facilities managed scabies cases effectively, compared to only 42.1% of home-based facilities. CONCLUSIONS Approximately half of the LTCFs had a basic capacity to respond to infectious diseases. However, there were differences in response capabilities between institution-based facilities and home-based facilities.

Purpose: This study investigated the efficacy of intravesical gemcitabine as an alternative to bacillus Calmette–Guérin (BCG) therapy. Materials and Methods: Data were retrospectively collected across seven institutions from February 1999 to May 2023. Inclusion criteria included patients with intermediate- or high-risk non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumors (TURBT) and received at least four sessions of intravesical gemcitabine or BCG induction therapy. Patient characteristics, complete remission (CR), occurrence, and progression rates were compared. Results: In total, 149 patients were included in this study (gemcitabine, 63; BCG, 86). No differences were apparent between the two groups in baseline characteristics, except for the follow-up period (gemcitabine, 9.2±5.9 months vs. BCG, 43.9±41.4 months, p<0.001). There were no consistent significant differences observed between the two groups in the 3-month (gemcitabine, 98.4% vs. BCG, 95.3%; p=0.848), 6-month (94.9% vs. 90.0%, respectively; p=0.793) and 1-year CR rates (84.2% vs. 83.3%, respectively;p=0.950). Also, there was no significant statistical difference in progression-free survival between the two groups (p=0.953). The occurrence rates of adverse events were similar between the groups (22.2% vs. 22.1%; p=0.989); however, the rate of Clavien– Dindo grade 2 or higher was significantly higher in the BCG group (1.6% vs. 16.3%, respectively; p<0.001). Conclusions Intravesical gemcitabine demonstrated efficacy comparable to BCG therapy for the first year in patients with intermediate- and high-risk NMIBC. However, long-term follow-up studies are warranted.

OBJECTIVES: Long-term care facilities (LTCFs) are communal environments for patients with chronic diseases or older adults, making them particularly susceptible to significant harm during infectious disease outbreaks. Nonetheless, LTCFs have historically been subject to less stringent infection prevention and control (IPC) mandates. This study aimed to assess the current state of LTCFs and to develop an IPC system tailored for these facilities following the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted an online survey of 11,366 LTCFs in Korea from December 30, 2022 to January 20, 2023, to evaluate the components of IPC in LTCFs. The infectious diseases targeted for IPC included COVID-19, influenza, and scabies. Additionally, we compared institution-based and home-based long-term care insurance facilities. RESULTS: Overall, 3,537 (31.1%) LTCFs responded to the survey, comprising 1,819 (51.4%) institution-based and 1,718 (48.6%) home-based facilities. A majority (87.4%, 2,376/2,720) of these facilities experienced COVID-19 outbreaks. However, only 42.2% of home-based facilities, in contrast to 90.6% of institution-based facilities, were equipped to manage concurrent COVID-19 cases. Similarly, while 92.1% of institution-based facilities were capable of managing influenza, only 50.5% of home-based facilities could do the same. The incidence of scabies was significantly higher in institution-based facilities than in home-based ones (26.1 vs. 4.3%). Additionally, 88.7% of institution-based facilities managed scabies cases effectively, compared to only 42.1% of home-based facilities. CONCLUSIONS Approximately half of the LTCFs had a basic capacity to respond to infectious diseases. However, there were differences in response capabilities between institution-based facilities and home-based facilities.