Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin alsoinhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.

Purpose: Despite the recent success of Bruton’s tyrosine kinase (BTK) inhibitors for the treatment of Waldenstrom macroglobulinemia (WM), their indefinite treatment duration ultimately tantamount to substantial financial and emotional burden. On the other hand, fixed duration of proteasome inhibitors (PI) have shown rapid and reasonable response in WM treatment. Despite the well-known synergism between PI and immunomodulatory drugs (IMiD), there is no trials evaluating such combination in WM. Materials and Methods: Based on above, we designed this phase II study to investigate the efficacy and safety of 6 cycles of 28-day bortezomib-thalidomide-dexamethasone (VTD) regimen for treatment-naïve WM. Results: A total of 15 patients were enrolled: major response rate was 64.3%, and overall response rate was 78.6%. During the median follow-up of 41 months, median progression-free survival (PFS) was 13 months and overall survival 40 months. For responders, median duration of response was 13 months and median PFS 19 months. The most common adverse event (AE) of any grade was constipation (57.1%). The most common grade ≥ 3 AE was anemia (21.4%). Conclusion All in all, we hereby provide proof-of-concept that PI + IMiD may be an attractive backbone for fixed duration treatment. It should be noted that granting the same level of access to newer drugs globally is virtually impossible. Thus efforts to develop regimens using readily available drugs to yield similar or adequate treatment outcomes should not be disregarded. In this sense, we believe our study holds its place for its novelty and eloquently addresses achieving the daunting societal quest of health equity.

Background: There is debate about ultrasonography screening for thyroid cancer and its cost-effectiveness. This study aimed to evaluate the cost-effectiveness of early screening (ES) versus symptomatic detection (SD) for differentiated thyroid cancer (DTC) in Korea. Methods: A Markov decision analysis model was constructed to compare the cost-effectiveness of ES and SD. The model considered direct medical costs, health outcomes, and different diagnostic and treatment pathways. Input data were derived from literature and Korean population studies. Incremental cost-effectiveness ratio (ICER) was calculated. Willingness-to-pay (WTP) threshold was set at USD 100,000 or 20,000 per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted to address uncertainties of the model’s variables. Results: In a base case scenario with 50 years of follow-up, ES was found to be cost-effective compared to SD, with an ICER of $2,852 per QALY. With WTP set at $100,000, in the case with follow-up less than 10 years, the SD was cost-effective. Sensitivity analysis showed that variables such as lobectomy probability, age, mortality, and utility scores significantly influenced the ICER. Despite variations in costs and other factors, all ICER values remained below the WTP threshold. Conclusion Findings of this study indicate that ES is a cost-effective strategy for DTC screening in the Korean medical system. Early detection and subsequent lobectomy contribute to the cost-effectiveness of ES, while SD at an advanced stage makes ES more cost-effective. Expected follow-up duration should be considered to determine an optimal strategy for DTC screening.

Background: s/Aims: Calcium is a preventive factor for colorectal cancer, which develops from colorectal adenoma. This study aimed to investigate the association between dietary calcium intake and prevalence of colorectal adenoma among Korean adults. Methods: Overall, 612 participants aged ≥ 20 years who underwent gastrointestinal endoscopy at 8 medical centers from 2021 to 2023 were included. Dietary calcium intake was assessed using a food frequency questionnaire and was energy-adjusted using the residual model. Multivariate logistic regression models were used to calculate for the odds ratios (ORs) and 95% confidence intervals (CIs). The associations between dietary calcium intake and colorectal adenoma prevalence were also assessed according to the anatomic subsites and adenoma status (advanced or nonadvanced). Results: Among the 612 participants, 269 were diagnosed with colorectal adenoma (170 men and 99 women). With respect to the gender-specific association, low dietary calcium intake was associated with higher prevalence of colorectal adenoma among men (ORs [95% CIs]: 2.13 [0.50– 9.00] for < 250 mg/day; 3.53 [1.06–11.76], 250 to < 350 mg/day; and 1.84 [0.63–5.35], 350 to < 650 mg/day, compared to ≥ 650 mg/day of dietary calcium [p for trend = 0.07]). Similar association was observed among women, but neither the association nor trend was statistically significant (p for trend = 0.59). These inverse associations remained similar for distal colon/rectal adenoma among women and advanced adenoma among men. Conclusions Low dietary calcium intake was associated with high colorectal adenoma prevalence, particularly among men. Given the limited number of studies among Asian populations, our findings should be replicated in other Asian groups.

Purpose: The use of gallium-68 prostate-specific membrane antigen-11 positron emission tomography/computed tomography (Ga-68 PSMA-11 PET/CT) is becoming increasingly common among men with prostate cancer (PCa). However, it remains uncertain which patients will derive the most benefit, and there is a scarcity of real-world data regarding its impact on altering treatment plans. This study investigated which patients would most benefit from Ga-68 PSMA-11 PET/CT, focusing on detection rates and changes in treatment strategies, drawing from a single-center experience. Materials and Methods: In total, 230 men with PCa who underwent Ga-68 PSMA-11 PET/CT between November 2021 and August 2022 were included in this retrospective study. The patients were classified into 5 groups based on their disease status: group 1, further work-up for high-risk localized PCa; group 2, de novo metastatic PCa; group 3, biochemical recurrence after definitive treatment; group 4, castration-resistant PCa; group 5, others. The positivity rate, positive lesions, predictive value of lymph node metastases, comparison with conventional images, and treatment changes after Ga-68 PSMA-11 PET/CT were analyzed in each group. Results: Of the 230 patients, 40 (17.4%), 20 (8.7%), 77 (33.5%), 76 (33.0%), and 17 (7.4%) were classified into groups 1–5, respectively. Ga-68 PSMA-11 PET/CT showed lesions in 74.8% of patients, and the optimal cutoff value for PSA was 1.99 ng/mL. Lesions not observed on conventional imaging were found in 62 patients (33.2%). In 38 patients (13.5%), treatment was changed due to Ga-68 PSMA-11 PET/CT. Conclusions These real-world data suggest that Ga-68 PSMA-11 PET/CT may be clinically useful for various disease conditions, as substantial stage migration and subsequent treatment changes occur in men with PCa. However, the prognostic impact of this modality remains unclear; thus, a well-designed prospective study is needed to address this issue.

Background: Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study. Methods: Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53. Results: CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history. Conclusions Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.