Association of physical activity and socio-economic status on mortality in older adults: a retrospective cohort study of KNHANES-mortality linked data.

We examined the joint association of physical activity (PA) and socio-economic status (SES) on all-causes and cardiovascular disease (CVD) mortality in 6945 elderly Koreans (mean age: 71.6 years, 41.8% male) using data from the Korean National Health and Nutrition Examination Survey (2007-2013) and death data from Statistics Korea (2019). The SES included household income and education level. PA was assessed using the IPAQ and categorized according to the 2018 PA Guidelines. In stratified analyses using Cox proportional hazards by SES adherence to PA guidelines those who low household income group was associated with a reduced risk of all-cause mortality and CVD mortality, while in the lowest educational level group, it was associated with a reduced risk of all-cause mortality and CVD mortality. In the joint analysis, PA was associated with a significant reduction in all-cause mortality in all groups when compared with those who did not meet PA those who had the lowest SES. However, PA with CVD mortality risk was not significantly associated in the 'upper-middle' income and 'high school' education groups. The study revealed that PA significantly association mortality, particularly among older adults with low SES. This finding suggests the potential for targeted government interventions to promote healthy aging.

Background Breast Parenchymal Signal During Menstrual Cycle on Diffusion-Weighted MRI: A Prospective Study in Healthy Premenopausal Women.

OBJECTIVE: To prospectively investigate the influence of the menstrual cycle on the background parenchymal signal (BPS) and apparent diffusion coefficient (ADC) of the breast on diffusion-weighted MRI (DW-MRI) in healthy premenopausal women. MATERIALS AND METHODS: Seven healthy premenopausal women (median age, 37 years; range, 33-49 years) with regular menstrual cycles participated in this study. DW-MRI was performed during each of the four phases of the menstrual cycle (four examinations in total). Three radiologists independently assessed the BPS visual grade on images with b-values of 800 sec/mm² (b800), 1200 sec/mm² (b1200), and a synthetic 1500 sec/mm² (sb1500). Additionally, one radiologist conducted a quantitative analysis to measure the BPS volume (%) and ADC values of the BPS (ADCBPS) and fibroglandular tissue (ADCFGT). Changes in the visual grade, BPS volume (%), ADCBPS, and ADCFGT during the menstrual cycle were descriptively analyzed. RESULTS: The visual grade of BPS in seven women varied from mild to marked on b800 and from minimal to moderate on b1200 and sb1500. As the b-value increased, the visual grade of BPS decreased. On b800 and sb1500, two of the seven volunteers showed the highest visual grade in the early follicular phase (EFP). On b1200, three of the seven volunteers showed the highest visual grades in EFP. The BPS volume (%) on b800 and b1200 showed the highest value in three of the six volunteers with dense breasts in EFP. Three of the seven volunteers showed the lowest ADCBPS in the EFP. Four of the seven volunteers showed the highest ADCBPS in the early luteal phase (ELP) and the lowest ADCFGT in the late follicular phase (LFP). CONCLUSION: Most volunteers did not exhibit specific BPS patterns during their menstrual cycles. However, the highest BPS and lowest ADCBPS were more frequently observed in EFP than in the other menstrual cycle phases, whereas the highest ADCBPS was more common in ELP. The lowest ADCFGT was more frequent in LFP.

Effects of a Web-based Weight Management Education Program on Various Factors for Overweight and Obese Women: Randomized Controlled Trial.

BACKGROUND: Mediated diet and exercise methods yield effective short-term weight loss but are costly and hard to manage. However, web-based programs can serve many participants, offering ease of access and cost-efficiency. OBJECTIVE: This study aimed to compare the effectiveness of a web-based weight management program through web-based education alone (MINE) or combined with tailored video feedback (MINE Plus) with a control (CO) group. METHODS: This intervention included 60 Korean women with overweight and obesity (BMI≥23 kg/m2) aged 19 years to 39 years old. We randomly allocated 60 participants to each of 3 groups: (1) MINE group (web-based education video and self-monitoring app), (2) MINE Plus group (web-based education video, self-monitoring app, and 1:1 tailored video feedback), and (3) CO group (only self-monitoring app). Web-based education included nutrition, physical activity, psychological factors, medical knowledge for weight loss, goal setting, and cognitive and behavioral strategies. Tailored feedback aimed to motivate and provide solutions via weekly 10-minute real-time video sessions. The intervention lasted 6 weeks, followed by a 6-week observation period to assess the education's lasting effects, with evaluations at baseline, 6 weeks, and 12 weeks. A generalized linear mixed model was used to evaluate time and group interactions. RESULTS: In the intention-to-treat analysis including all 60 participants, there were significant differences in weight change at 6 weeks in the MINE and MINE Plus groups, with mean weight changes of -0.74 (SD 1.96) kg (P=.03) and -1.87 (SD 1.8) kg (P<.001), respectively, while no significant change was observed in the CO group, who had a mean weight increase of 0.03 (SD 1.68) kg (P=.91). After 12 weeks, changes in body weight were -1.65 (SD 2.64) kg in the MINE group, -1.59 (SD 2.79) kg in the MINE Plus group, and 0.43 (SD 1.42) kg in the CO group. There was a significant difference between the MINE and MINE Plus groups (P<.001). Significant group × time effects were found for body weight in the MINE and CO groups (P<.001) and in the MINE Plus and CO groups (P<.001), comparing baseline and 12 weeks. Regarding physical activity and psychological factors, only body shape satisfaction and health self-efficacy were associated with improvements in the MINE and MINE Plus groups (P<.001). CONCLUSIONS: This study found that the group receiving education and tailored feedback showed significant weight loss and improvements in several psychological factors, though there were differences in the sustainability of the effects. TRIAL REGISTRATION: Korea Disease Control and Prevention Agency (KDCA) KCT0007780: https://cris.nih.go.kr/cris/search/detailSearch.do/22861.

Uniportal video-assisted thoracoscopic surgery in the prone position for esophageal bronchogenic cyst.

Esophageal bronchogenic cysts are very rare. A bronchogenic cyst is a congenital malformation resulting from abnormal sprouting of primitive bronchi because of a foregut bronchopulmonary malformation. An 18-year-old patient with a cystic tumor in the left posterior mediastinum was identified. The mediastinal tumor was removed by uniportal video-assisted thoracoscopic surgery. The operation was performed in the prone position through a single 4-cm incision on the lateral scapular line in the left ninth intercostal space. After tumor resection, the dissected esophageal muscle and mediastinal pleura were sutured with two continuous barbed sutures. The operation took 80 min. A biopsy confirmed the diagnosis of esophageal bronchial cyst. Diet was started on the evening of the operation. The chest tube was removed on the 1st postoperative day, and the patient was discharged without any problems on the 2nd postoperative day.

Video-assisted thoracic surgery for an endobronchial ancient schwannoma obstructing the left main bronchus.

A schwannoma is a tumor that arises from the Schwann cells of the peripheral nerves. Primary pulmonary schwannomas are extremely rare, although they can occur anywhere in the body. Symptoms of endobronchial schwannoma vary depending upon the extent of bronchi blockage by the tumor. Schwannoma is a benign tumor. However, there is a risk of recurrence if a lesion that has developed extraluminal growth is incompletely resected. Here, a 76-year-old female patient presented with dyspnea and cough. An endobronchial tumor was identified originating from the left lower lobe bronchus and had collapsed the left lower lobe and grown to block most of the left main bronchus. Video-assisted thoracic surgery was performed to resect the left lower lobe. The tumor was diagnosed as an ancient schwannoma.

Life-threatening hemothorax due to rupture of pulmonary arteriovenous malformation during pregnancy.

Pulmonary arteriovenous malformation (PAVM) can worsen in pregnant women due to pregnancy-related physiological changes. If a PAVM ruptures, it can become life-threatening. A 24-year-old female patient at 22 weeks of gestation presented to the hospital with chest pain and dyspnea. A simple chest radiograph revealed that the right lung was almost completely collapsed due to massive pleural effusion, and the heart was displaced to the opposite side. Closed thoracostomy was performed and 2 l of blood was drained. Chest CT revealed the presence of a PAVM in the right upper lung. Emergency surgery was performed to resect the PAVM through thoracoscopic pulmonary wedge resection. The patient experienced disseminated intravascular coagulation and acute renal insufficiency after the surgery, but eventually recovered and was discharged without any complications on the sixth postoperative day.

Unenhanced Breast MRI With Diffusion-Weighted Imaging for Breast Cancer Detection: Effects of Training on Performance and Agreement of Subspecialty Radiologists.

OBJECTIVE: To investigate whether reader training improves the performance and agreement of radiologists in interpreting unenhanced breast magnetic resonance imaging (MRI) scans using diffusion-weighted imaging (DWI). MATERIALS AND METHODS: A study of 96 breasts (35 cancers, 24 benign, and 37 negative) in 48 asymptomatic women was performed between June 2019 and October 2020. High-resolution DWI with b-values of 0, 800, and 1200 sec/mm² was performed using a 3.0-T system. Sixteen breast radiologists independently reviewed the DWI, apparent diffusion coefficient maps, and T1-weighted MRI scans and recorded the Breast Imaging Reporting and Data System (BI-RADS) category for each breast. After a 2-h training session and a 5-month washout period, they re-evaluated the BI-RADS categories. A BI-RADS category of 4 (lesions with at least two suspicious criteria) or 5 (more than two suspicious criteria) was considered positive. The per-breast diagnostic performance of each reader was compared between the first and second reviews. Inter-reader agreement was evaluated using a multi-rater κ analysis and intraclass correlation coefficient (ICC). RESULTS: Before training, the mean sensitivity, specificity, and accuracy of the 16 readers were 70.7% (95% confidence interval [CI]: 59.4-79.9), 90.8% (95% CI: 85.6-94.2), and 83.5% (95% CI: 78.6-87.4), respectively. After training, significant improvements in specificity (95.2%; 95% CI: 90.8-97.5; P = 0.001) and accuracy (85.9%; 95% CI: 80.9-89.8; P = 0.01) were observed, but no difference in sensitivity (69.8%; 95% CI: 58.1-79.4; P = 0.58) was observed. Regarding inter-reader agreement, the κ values were 0.57 (95% CI: 0.52-0.63) before training and 0.68 (95% CI: 0.62-0.74) after training, with a difference of 0.11 (95% CI: 0.02-0.18; P = 0.01). The ICC was 0.73 (95% CI: 0.69-0.74) before training and 0.79 (95% CI: 0.76-0.80) after training (P = 0.002). CONCLUSION: Brief reader training improved the performance and agreement of interpretations by breast radiologists using unenhanced MRI with DWI.

Alternative splice variants of the mitochondrial fission protein DNM1L/Drp1 regulate mitochondrial dynamics and tumor progression in ovarian cancer.

Aberrant mitochondrial fission/fusion dynamics have been reported in cancer cells. While post translational modifications are known regulators of the mitochondrial fission/fusion machinery, we show that alternative splice variants of the fission protein Drp1 (DNM1L) have specific and unique roles in cancer, adding to the complexity of mitochondrial fission/fusion regulation in tumor cells. Ovarian cancer specimens express an alternative splice transcript variant of Drp1 lacking exon 16 of the variable domain, and high expression of this splice variant relative to other transcripts is associated with poor patient outcome. Unlike the full-length variant, expression of Drp1 lacking exon 16 leads to decreased association of Drp1 to mitochondrial fission sites, more fused mitochondrial networks, enhanced respiration, and TCA cycle metabolites, and is associated with a more metastatic phenotype in vitro and in vivo. These pro-tumorigenic effects can also be inhibited by specific siRNA-mediated inhibition of the endogenously expressed transcript lacking exon 16. Moreover, lack of exon 16 abrogates mitochondrial fission in response to pro-apoptotic stimuli and leads to decreased sensitivity to chemotherapeutics. These data emphasize the significance of the pathophysiological consequences of Drp1 alternative splicing and divergent functions of Drp1 splice variants, and strongly warrant consideration of Drp1 splicing in future studies.

Elevated level of PLRG1 is critical for the proliferation and maintenance of genome stability of tumor cells.

Pleiotropic regulator 1 (PLRG1), a highly conserved element in the spliceosome, can form a NineTeen Complex (NTC) with Prp19, SPF27, and CDC5L. This complex plays crucial roles in both pre-mRNA splicing and DNA repair processes. Here, we provide evidence that PLRG1 has a multifaceted impact on cancer cell proliferation. Comparing its expression levels in cancer and normal cells, we observed that PLRG1 was upregulated in various tumor tissues and cell lines. Knockdown of PLRG1 resulted in tumor-specific cell death. Depletion of PLRG1 had notable effects, including mitotic arrest, microtubule instability, endoplasmic reticulum (ER) stress, and accumulation of autophagy, ultimately culminating in apoptosis. Our results also demonstrated that PLRG1 downregulation contributed to DNA damage in cancer cells, which we confirmed through experimental validation as DNA repair impairment. Interestingly, when PLRG1 was decreased in normal cells, it induced G1 arrest as a self-protective mechanism, distinguishing it from effects observed in cancer cells. These results highlight multifaceted impacts of PLRG1 in cancer and underscore its potential as a novel anti-cancer strategy by selectively targeting cancer cells. [BMB Reports 2023; 56(11): 612-617].

Physical activity among adolescent-parent dyads: 2017-2019 Korea National Health and Nutrition Examination Surveys of Korean adolescents and that of their parents.

This study investigated physical activity (PA) levels among adolescents and their parents in South Korea. Repeated cross-sectional data from 2017-2019 Korea National Health and Nutrition Examination Survey (KNHANES) were used. The KNHANES uses a complex, multi-stage probability sample design. Data included 875 Korean adolescents aged 12 to 18years and their parents. Adolescents were asked how many days during the week they were physically active for at least 60 minutes. Compliance was defined as 4+ days per week. Logistic regressions were used and odds ratios and 95% confidence intervals were provided. The adherence to PA compliance and guideline among adolescents (≥60 min/d for at least 4 d/week) and their parents (≥600MET/min per week) were 11.54% and 23.09%, respectively. Parents who adhered to the PA guideline were more likely to have a child who also adhere to the PA than the parents who did not adhere to the PA guideline (OR=2.48, 95% CI=1.39-4.49). Only mothers (OR=1.31, 95% CI=0.65-2.57) and fathers (OR=1.37, 95% CI=0.74-2.55) were not significant in association to their adolescents' PA when complying with the PA guidelines, respectively. Parental PA appears to be important for PA among adolescents. Therefore, strategies to promote PA among adolescents should target families in South Korea.

Use of imaging prediction model for omission of axillary surgery in early-stage breast cancer patients.

PURPOSE: To develop a prediction model incorporating clinicopathological information, US, and MRI to diagnose axillary lymph node (LN) metastasis with acceptable false negative rate (FNR) in patients with early stage, clinically node-negative breast cancers. METHODS: In this single center retrospective study, the inclusion criteria comprised women with clinical T1 or T2 and N0 breast cancers who underwent preoperative US and MRI between January 2017 and July 2018. Patients were temporally divided into the development and validation cohorts. Clinicopathological information, US, and MRI findings were collected. Two prediction models (US model and combined US and MRI model) were created using logistic regression analysis from the development cohort. FNRs of the two models were compared using the McNemar test. RESULTS: A total of 964 women comprised the development (603 women, 54 ± 11 years) and validation (361 women, 53 ± 10 years) cohorts with 107 (18%) and 77 (21%) axillary LN metastases in each cohort, respectively. The US model consisted of tumor size and morphology of LN on US. The combined US and MRI model consisted of asymmetry of LN number, long diameter of LN, tumor type, and multiplicity of breast cancers on MRI, in addition to tumor size and morphology of LN on US. The combined model showed significantly lower FNR than the US model in both development (5% vs. 32%, P < .001) and validation (9% vs. 35%, P < .001) cohorts. CONCLUSION: Our prediction model combining US and MRI characteristics of index cancer and LN lowered FNR compared to using US alone, and could potentially lead to avoid unnecessary SLNB in early stage, clinically node-negative breast cancers.

Guideline for the Surgical Management of Locally Invasive Differentiated Thyroid Cancer From the Korean Society of Head and Neck Surgery.

The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC.

A rare case of endobronchial melanoma of unknown primary.

A 62-year-old man who presented with complaints of cough and hemoptysis was found to have an endobronchial tumor which obstructed the lingular bronchus. Histopathologic examination of a bronchoscopic biopsy of the tumor was consistent with malignant melanoma. Skin, mucosal, and eye examinations failed to detect the primary site of melanoma and the patient was diagnosed with endobronchial melanoma of unknown primary (MUP). Although the patient underwent a curative surgical resection, recurrence was detected in 4 months. Endobronchial MUP is a rare presentation of melanoma and better therapeutic strategies need to be established.

c-Src inhibitor PP2 inhibits head and neck cancer progression through regulation of the epithelial-mesenchymal transition.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancer, causing considerable mortality and morbidity worldwide. Although HNSCC management has been extensively studied, the treatment outcomes have not improved - the 5-year survival rate of patients with HNSCC is 40%. Recent studies on the development of a novel HNSCC treatment have highlighted proto-oncogene tyrosine-protein kinase Src (c-Src) as one of the major therapeutic targets. However, the clinical efficacy of c-Src inhibitors against HNSCC was not comparable to that obtained in vitro. Furthermore, the molecular mechanisms underlying the efficacy of c-Src inhibitors remain elusive. In this study, we assessed the efficacy of 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4-d] pyrimidine (PP2), a selective c-Src inhibitor on HSNCC. Nine HNSCC cell lines (SNU1041, Fraud, SNU46, SNU1076, SNU899, SCC1483, YD15, YD9, and YD10-) were screened, and the effects of PP2 were evaluated using wound healing, apoptosis, and invasion assays. Western blot analysis of downstream markers was conducted to assess the specific mechanism of action of PP2 in HNSCC. The therapeutic efficacy of PP2 was further evaluated in xenograft mice. PP2 reduced tumor cell growth both in vitro and in vivo. Furthermore, it enhanced tumor cell apoptosis in cell lines and prevented metastasis in mice. PP2 also regulated the epithelial-mesenchymal transition pathway downstream of c-Src. More specifically, in SCC1483 and YD15PP2 HNSCC cell lines, PP2 exposure downregulated Erk, Akt/Slug, and Snail but upregulated E-cadherin. These results suggest that PP2 inhibits cell growth and progression in HNSCC by regulating the epithelial-mesenchymal transition pathway.

Background Parenchymal Enhancement at Postoperative Surveillance Breast MRI: Association with Future Second Breast Cancer Risk.

Background Background parenchymal enhancement (BPE) is a known risk factor for breast cancer. However, studies on the association between BPE and second breast cancer risk are still lacking. Purpose To investigate whether BPE at surveillance breast MRI is associated with subsequent second breast cancer risk in women with a personal history of breast cancer. Materials and Methods A retrospective search of the imaging database of an academic medical center identified consecutive surveillance breast MRI examinations performed between January 2008 and December 2017 in women who underwent surgery for primary breast cancer and had no prior diagnosis of second breast cancer. BPE at surveillance breast MRI was qualitatively assessed using a four-category classification of minimal, mild, moderate, or marked. Future second breast cancer was defined as ipsilateral breast tumor recurrence or contralateral breast cancer diagnosed at least 1 year after each surveillance breast MRI examination. Factors associated with future second breast cancer risk were evaluated using the multivariable Fine-Gray subdistribution hazard model. Results Among the 2668 women (mean age at baseline surveillance breast MRI, 49 years ± 8 [SD]), 109 developed a second breast cancer (49 ipsilateral, 58 contralateral, and two ipsilateral and contralateral) at a median follow-up of 5.8 years. Mild, moderate, or marked BPE at surveillance breast MRI (hazard ratio [HR], 2.1 [95% CI: 1.4, 3.1]; P < .001), young age (<45 years) at initial breast cancer diagnosis (HR, 3.4 [95% CI: 1.7, 6.4]; P < .001), positive results from a BRCA1/2 genetic test (HR, 6.5 [95% CI: 3.5, 12.0]; P < .001), and negative hormone receptor expression in the initial breast cancer (HR, 1.6 [95% CI: 1.1, 2.6]; P = .02) were independently associated with an increased risk of future second breast cancer. Conclusion Background parenchymal enhancement at surveillance breast MRI was associated with future second breast cancer risk in women with a personal history of breast cancer. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Niell in this issue.

Use of Artificial Intelligence for Reducing Unnecessary Recalls at Screening Mammography: A Simulation Study.

OBJECTIVE: To conduct a simulation study to determine whether artificial intelligence (AI)-aided mammography reading can reduce unnecessary recalls while maintaining cancer detection ability in women recalled after mammography screening. MATERIALS AND METHODS: A retrospective reader study was performed by screening mammographies of 793 women (mean age ± standard deviation, 50 ± 9 years) recalled to obtain supplemental mammographic views regarding screening mammography-detected abnormalities between January 2016 and December 2019 at two screening centers. Initial screening mammography examinations were interpreted by three dedicated breast radiologists sequentially, case by case, with and without AI aid, in a single session. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and recall rate for breast cancer diagnosis were obtained and compared between the two reading modes. RESULTS: Fifty-four mammograms with cancer (35 invasive cancers and 19 ductal carcinomas in situ) and 739 mammograms with benign or negative findings were included. The reader-averaged AUC improved after AI aid, from 0.79 (95% confidence interval [CI], 0.74-0.85) to 0.89 (95% CI, 0.85-0.94) (p < 0.001). The reader-averaged specificities before and after AI aid were 41.9% (95% CI, 39.3%-44.5%) and 53.9% (95% CI, 50.9%-56.9%), respectively (p < 0.001). The reader-averaged sensitivity was not statistically different between AI-unaided and AI-aided readings: 89.5% (95% CI, 83.1%-95.9%) vs. 92.6% (95% CI, 86.2%-99.0%) (p = 0.053), although the sensitivities of the least experienced radiologists before and after AI aid were 79.6% (43 of 54 [95% CI, 66.5%-89.4%]) and 90.7% (49 of 54 [95% CI, 79.7%-96.9%]), respectively (p = 0.031). With AI aid, the reader-averaged recall rate decreased by from 60.4% (95% CI, 57.8%-62.9%) to 49.5% (95% CI, 46.5%-52.4%) (p < 0.001). CONCLUSION: AI-aided reading reduced the number of recalls and improved the diagnostic performance in our simulation using women initially recalled for supplemental mammographic views after mammography screening.

Split genome-based retroviral replicating vectors achieve efficient gene delivery and therapeutic effect in a human glioblastoma xenograft model.

The murine leukemia virus-based semi-retroviral replicating vectors (MuLV-based sRRV) had been developed to improve safety and transgene capacity for cancer gene therapy. However, despite the apparent advantages of the sRRV, improvements in the in vivo transduction efficiency are still required to deliver therapeutic genes efficiently for clinical use. In this study, we established a gibbon ape leukemia virus (GaLV) envelopepseudotyped semi-replication-competent retrovirus vector system (spRRV) which is composed of two transcomplementing replication-defective retroviral vectors termed MuLV-Gag-Pol and GaLV-Env. We found that the spRRV shows considerable improvement in efficiencies of gene transfer and spreading in both human glioblastoma cells and pre-established human glioblastoma mouse model compared with an sRRV system. When treated with ganciclovir after intratumoral injection of each vector system into pre-established U-87 MG glioblastomas, the group of mice injected with spRRV expressing the herpes simplex virus type 1-thymidine kinase (HSV1-tk) gene showed a survival rate of 100% for more than 150 days, but all control groups of mice (HSV1-tk/PBS-treated and GFP/GCV-treated groups) died within 45 days after tumor injection. In conclusion, these findings sug-gest that intratumoral delivery of the HSV1-tk gene by the spRRV system is worthy of development in clinical trials for the treatment of malignant solid tumors. [BMB Reports 2022; 55(12): 615-620].

Aß-induced mitochondrial dysfunction in neural progenitors controls KDM5A to influence neuronal differentiation.

Mitochondria in neural progenitors play a crucial role in adult hippocampal neurogenesis by being involved in fate decisions for differentiation. However, the molecular mechanisms by which mitochondria are related to the genetic regulation of neuronal differentiation in neural progenitors are poorly understood. Here, we show that mitochondrial dysfunction induced by amyloid-beta (Aß) in neural progenitors inhibits neuronal differentiation but has no effect on the neural progenitor stage. In line with the phenotypes shown in Alzheimer's disease (AD) model mice, Aß-induced mitochondrial damage in neural progenitors results in deficits in adult hippocampal neurogenesis and cognitive function. Based on hippocampal proteome changes after mitochondrial damage in neural progenitors identified through proteomic analysis, we found that lysine demethylase 5A (KDM5A) in neural progenitors epigenetically suppresses differentiation in response to mitochondrial damage. Mitochondrial damage characteristically causes KDM5A degradation in neural progenitors. Since KDM5A also binds to and activates neuronal genes involved in the early stage of differentiation, functional inhibition of KDM5A consequently inhibits adult hippocampal neurogenesis. We suggest that mitochondria in neural progenitors serve as the checkpoint for neuronal differentiation via KDM5A. Our findings not only reveal a cell-type-specific role of mitochondria but also suggest a new role of KDM5A in neural progenitors as a mediator of retrograde signaling from mitochondria to the nucleus, reflecting the mitochondrial status.

Relationship between Chronic Rhinosinusitis and the Incidence of Head and Neck Cancer: A National Population-Based Study.

We analyzed the relationship between chronic rhinosinusitis (CRS) and the incidence of head and neck cancers (HNCs) in a Korean adult population. This retrospective cohort study included data from the Korean National Health Insurance Service database. Adjustments were made to minimize risk variables for sex, age, diabetes, hypertension, dyslipidemia, and rhinitis between the two groups. The primary endpoint was newly diagnosed HNC between January 2009 and December 2018. Among 1,337,120 subjects in the Korean National Health Insurance Service database, data from 324,774 diagnosed with CRS (CRS group) and 649,548 control subjects (control group) were selected. Patients with CRS exhibited a statistically significant greater risk for nasal cavity/paranasal sinus cancer, hypopharynx/larynx cancer, and thyroid cancer compared with the control group. In the CRS group, the adjusted hazard ratios for nasal cavity/paranasal sinus cancer were 1.809 (95% confidence interval (CI) 1.085-3.016), 1.343 (95% CI 1.031-1.748) for hypopharynx and larynx cancer, and 1.116 (95% CI 1.063-1.173) for thyroid cancer. CRS was associated with a higher incidence of HNCs. Therefore, physicians should carefully consider the possibility of HNC progression and implement therapeutic strategies to minimize the impact of these diseases.

Bladder Cancer Patient-derived Organoids and Avatars for Personalized Cancer Discovery.

Prediction of treatment response has attracted growing attention in cancer research to improve clinical outcomes via individualized treatment regimens. Patient-derived organoids and xenografts are novel preclinical model systems that recapitulate the genetic and phenotypic features of parental tumors for this purpose. Organoid culture has been successfully established in multiple cancers and used for assessment of drug and immunotherapy responses. Patient-derived xenograft (PDX) models provide insights into in vivo tumor growth and metastatic potential. Continued improvements in these model systems to better maintain tumor architecture and microenvironment will advance patient-specific targeted therapies. PATIENT SUMMARY: This mini review describes up-to-date organoid and xenograft models of bladder cancer created using patient-derived tissue. These models are important for research and may provide information on mutations and expression patterns for cancer-related genes that are unique to each patient, and could facilitate personalized therapy for individual patients.