Urothelial cancer is the seventh most common cancer among men worldwide. Bacille de Calmette-Guérin is a type of anticancer immunotherapy that has been used to treat targeted bladder cancer, but the number of patients with treatment-refractory advanced urothelial cancer, patients has been increasing recently. To overcome this, enfortumab vedotin (novel nectin-4 targeting antibody-drug conjugate) known as antibody-drug conjugate (ADC), was approved. We describe the clinical development process of ADC and the potential for future development as a bladder cancer treatment.

Air Pollutants ; Allergens ; Aspirin ; Asthma ; Base Sequence ; DNA Methylation ; DNA ; Epigenomics ; Genome ; Histone Code ; Hypersensitivity ; Methylation ; MicroRNAs ; Phenotype ; Polymorphism, Single Nucleotide ; Smoke ; Tobacco Products

For the past three decades, more than a thousand of genetic studies have been performed to find out the genetic variants responsible for the risk of asthma. Until now, all of the discovered single nucleotide polymorphisms have explained genetic effects less than initially expected. Thus, clarification of environmental factors has been brought up to overcome the ‘missing’ heritability. The most exciting solution is epigenesis because it intervenes at the junction between the genome and the environment. Epigenesis is an alteration of genetic expression without changes of DNA sequence caused by environmental factors such as nutrients, allergens, cigarette smoke, air pollutants, use of drugs and infectious agents during pre- and post-natal periods and even in adulthood. Three major forms of epigenesis are composed of DNA methylation, histone modifications, and specific microRNA. Recently, several studies have been published on epigenesis in asthma and allergy as a powerful tool for research of genetic heritability in asthma albeit epigenetic changes are at the starting point to obtain the data on specific phenotypes of asthma. In this presentation, we mainly review the potential role of DNA CpG methylation in the risk of asthma and its sub-phenotypes including nonsteroidal anti-inflammatory exacerbated respiratory diseases.

For the past three decades, more than a thousand of genetic studies have been performed to find out the genetic variants responsible for the risk of asthma. Until now, all of the discovered single nucleotide polymorphisms have explained genetic effects less than initially expected. Thus, clarification of environmental factors has been brought up to overcome the ‘missing’ heritability. The most exciting solution is epigenesis because it intervenes at the junction between the genome and the environment. Epigenesis is an alteration of genetic expression without changes of DNA sequence caused by environmental factors such as nutrients, allergens, cigarette smoke, air pollutants, use of drugs and infectious agents during pre- and post-natal periods and even in adulthood. Three major forms of epigenesis are composed of DNA methylation, histone modifications, and specific microRNA. Recently, several studies have been published on epigenesis in asthma and allergy as a powerful tool for research of genetic heritability in asthma albeit epigenetic changes are at the starting point to obtain the data on specific phenotypes of asthma. In this presentation, we mainly review the potential role of DNA CpG methylation in the risk of asthma and its sub-phenotypes including nonsteroidal anti-inflammatory exacerbated respiratory diseases.

In this study, we investigated the effects of the ethanol extract of aerial parts of Raphanus sativus L. (ERL) on breast cancer cell proliferation and gene expression associated with cell proliferation and apoptosis in MDA-MB-231 human breast cancer cells. The MDA-MB-231 cells were cultured in the presence or absence of various concentrations (100, 200, or 300 microg/mL) of ERL. ERL significantly decreased cell proliferation after 48 h of incubation (P < 0.05). The protein and mRNA expression of ErbB2 were decreased significantly in a dose-dependent manner (P < 0.05). The protein expression of ErbB3 was decreased significantly at an ERL concentration of 300 microg/mL (P < 0.05), and mRNA expression of ErbB3 was decreased significantly in a dose-dependent manner (P < 0.05). The protein expression of Akt was decreased significantly at the ERL concentration of 200 microg/mL (P < 0.05), and the protein expression of pAkt was decreased significantly in a dose-dependent manner (P < 0.05). The mRNA expression of Akt was decreased significantly at the ERL concentration of 200 microg/mL ERL (P < 0.05). The protein and mRNA expression of Bax were increased significantly at ERL concentrations of 200 microg/mL or higher (P < 0.05). The protein expression of Bcl2 was increased significantly at ERL concentrations of 100 microg/mL or higher (P < 0.05), and mRNA expression of Bcl2 was increased significantly at an ERL concentration of 300 microg/mL (P < 0.05). In conclusion, we suggest that Raphanus sativus, L. inhibits cell proliferation via the ErbB-Akt pathway in MDA-MB-231 cells.
Apoptosis ; Breast ; Breast Neoplasms ; Cell Proliferation ; Ethanol ; Gene Expression ; Humans ; Raphanus ; Receptor, Epidermal Growth Factor ; RNA, Messenger

Purpose: This study examined longitudinal changes in interstitial lung abnormalities (ILAs) and predictors of clinically significant interstitial lung diseases (ILDs) in a screening population with ILAs. Materials and Methods: We retrieved 36891 low-dose chest CT records from screenings between January 2003 and May 2021. After identifying 101 patients with ILAs, the clinical findings, spirometry results, and initial and follow-up CT findings, including visual and artificial intelligence-based quantitative analyses, were compared between patients diagnosed with ILD (n = 23, 23%) and those who were not (n = 78, 77%). Logistic regression analysis was used to identify significant parameters for the clinical diagnosis of ILD. Results: Twenty-three patients (n = 23, 23%) were subsequently diagnosed with clinically significant ILDs at follow-up (mean, 8.7 years). Subpleural fibrotic ILAs on initial CT and signs of progression on follow-up CT were common in the ILD group (both p < 0.05). Logistic regression analysis revealed that emerging respiratory symptoms (odds ratio [OR], 5.56; 95% confidence interval [CI], 1.28–24.21; p = 0.022) and progression of ILAs at follow-up chest CT (OR, 4.07; 95% CI, 1.00–16.54; p = 0.050) were significant parameters for clinical diagnosis of ILD. Conclusion Clinically significant ILD was subsequently diagnosed in approximately one-quarter of the screened population with ILAs. Emerging respiratory symptoms and progression of ILAs at followup chest CT can be predictors of clinically significant ILDs.

Purpose: This study examined longitudinal changes in interstitial lung abnormalities (ILAs) and predictors of clinically significant interstitial lung diseases (ILDs) in a screening population with ILAs. Materials and Methods: We retrieved 36891 low-dose chest CT records from screenings between January 2003 and May 2021. After identifying 101 patients with ILAs, the clinical findings, spirometry results, and initial and follow-up CT findings, including visual and artificial intelligence-based quantitative analyses, were compared between patients diagnosed with ILD (n = 23, 23%) and those who were not (n = 78, 77%). Logistic regression analysis was used to identify significant parameters for the clinical diagnosis of ILD. Results: Twenty-three patients (n = 23, 23%) were subsequently diagnosed with clinically significant ILDs at follow-up (mean, 8.7 years). Subpleural fibrotic ILAs on initial CT and signs of progression on follow-up CT were common in the ILD group (both p < 0.05). Logistic regression analysis revealed that emerging respiratory symptoms (odds ratio [OR], 5.56; 95% confidence interval [CI], 1.28–24.21; p = 0.022) and progression of ILAs at follow-up chest CT (OR, 4.07; 95% CI, 1.00–16.54; p = 0.050) were significant parameters for clinical diagnosis of ILD. Conclusion Clinically significant ILD was subsequently diagnosed in approximately one-quarter of the screened population with ILAs. Emerging respiratory symptoms and progression of ILAs at followup chest CT can be predictors of clinically significant ILDs.

Purpose: This study examined longitudinal changes in interstitial lung abnormalities (ILAs) and predictors of clinically significant interstitial lung diseases (ILDs) in a screening population with ILAs. Materials and Methods: We retrieved 36891 low-dose chest CT records from screenings between January 2003 and May 2021. After identifying 101 patients with ILAs, the clinical findings, spirometry results, and initial and follow-up CT findings, including visual and artificial intelligence-based quantitative analyses, were compared between patients diagnosed with ILD (n = 23, 23%) and those who were not (n = 78, 77%). Logistic regression analysis was used to identify significant parameters for the clinical diagnosis of ILD. Results: Twenty-three patients (n = 23, 23%) were subsequently diagnosed with clinically significant ILDs at follow-up (mean, 8.7 years). Subpleural fibrotic ILAs on initial CT and signs of progression on follow-up CT were common in the ILD group (both p < 0.05). Logistic regression analysis revealed that emerging respiratory symptoms (odds ratio [OR], 5.56; 95% confidence interval [CI], 1.28–24.21; p = 0.022) and progression of ILAs at follow-up chest CT (OR, 4.07; 95% CI, 1.00–16.54; p = 0.050) were significant parameters for clinical diagnosis of ILD. Conclusion Clinically significant ILD was subsequently diagnosed in approximately one-quarter of the screened population with ILAs. Emerging respiratory symptoms and progression of ILAs at followup chest CT can be predictors of clinically significant ILDs.

Helicobacter pylori (H. pylori) is the principle cause of type B gastritis and peptic ulcer disease and has been classified as group I carcinogen for gastric cancer. H. pylori may affect the normal balance between gastric cell proliferation and epithelial cell death, thus interfering with the maintenance of gastric mucosal integrity. The aim of this study was to investigate the effect of H. pylori on cell proliferation and apoptosis according to the effect of eradication of H. pylori. METHODS: The subjects were 45 patients who had undergone diagnostic gastroduodenoscopy; 11 with gastritis, seven with gastric ulcer and 27 duodenal ulcer. H. pylori infection was assessed by H&E and immunohistochemical stain with anti-H. pylori polyclonal antibody and rapid urease test. Acute and chronic inflammation, apoptosis and intestinal metaplasia were scored according to the updated Sydney system. Gastric epithelial cell proliferation was assessed by immunohostochemical method using Ki-67 monoclonal antibody. In situ apoptosis was detected with in situ terminal deoxyribonucleotide transferase (TdT)-mediated dUTP nick end labeling. RESULTS: Acute and chronic inflammation, intestinal metaplasia, Ki-67 labeling index, and apoptosis were significantly higher in H. pylori infected persons (n=45) than in uninfected persons (n=5)(p<0.05). Acute and chronic inflammation, intestinal metaplasia, Ki-67 labeling index and apoptosis in H. pylori eradicated group (n=25) significantly decreased after eradication therapy (p<0.05), but no significant differences of them was observed in H. pylori non-eradicated goup (n=20) after eradication therapy. Ki-67 labeling index was significantly correlated with acute inflammation, chronic inflammation and apoptosis (p<0.05). Apoptosis was significantly correlated with acute and chronic inflammation (p<0.05). CONCLUSION: In eradicated group, epithelial apoptosis and proliferation closely associated with gastric carcinogenesis are stabilized after treatment, which suggests H. pylori eradication therapymay preven the early step of gastric carcinogenesis.
Apoptosis* ; Carcinogenesis ; Cell Proliferation ; Duodenal Ulcer ; Epithelial Cells* ; Gastritis ; Helicobacter pylori* ; Helicobacter* ; Humans ; Inflammation ; Metaplasia ; Peptic Ulcer ; Stomach Neoplasms ; Stomach Ulcer ; Transferases ; Urease

PURPOSE: Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. MATERIALS AND METHODS: We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by 18F-2-fluoro-2-deoxyglucose positron emission tomography. RESULTS: During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. CONCLUSION: Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.
Acetylcholine/metabolism ; Alzheimer Disease ; Animals ; Antibodies, Monoclonal/*pharmacology ; Basal Forebrain/*drug effects/metabolism ; Cholinergic Agents/administration & dosage/*pharmacology ; Cholinergic Neurons/*drug effects/metabolism ; Fluorodeoxyglucose F18 ; GABAergic Neurons/*drug effects/metabolism ; Glucose/*metabolism ; Gyrus Cinguli/*drug effects/metabolism ; Humans ; Injections ; Maze Learning ; Motor Activity/physiology ; Positron-Emission Tomography ; Rats ; Ribosome Inactivating Proteins, Type 1/*pharmacology