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

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

PURPOSE: Loss of cholinergic neurons in the hippocampus is a hallmark of many dementias. Administration of stem cells as a therapeutic intervention for patients is under active investigation, but the optimal stem cell type and transplantation modality has not yet been established. In this study, we studied the therapeutic effects of human placenta-derived mesenchymal stem cells (pMSCs) in dementia rat model using either intracerebroventricular (ICV) or intravenous (IV) injections and analyzed their mechanisms of therapeutic action. MATERIALS AND METHODS: Dementia modeling was established by intraventricular injection of 192 IgG-saporin, which causes lesion of cholinergic neurons. Sixty-five male Sprague-Dawley rats were divided into five groups: control, lesion, lesion+ICV injection of pMSCs, lesion+IV injection of pMSCs, and lesion+donepezil. Rats were subjected to the Morris water maze and subsequent immunostaining analyses. RESULTS: Both ICV and IV pMSC administrations allowed significant cognitive recovery compared to the lesioned rats. Acetylcholinesterase activity was significantly rescued in the hippocampus of rats injected with pMSCs post-lesion. Choline acetyltransferase did not co-localize with pMSCs, showing that pMSCs did not directly differentiate into cholinergic cells. Number of microglial cells increased in lesioned rats and significantly decreased back to normal levels with pMSC injection. CONCLUSION: Our results suggest that ICV and IV injections of pMSCs facilitate the recovery of cholinergic neuronal populations and cognitive behavior. This recovery likely occurs through paracrine effects that resemble microglia function rather than direct differentiation of injected pMSCs into cholinergic neurons.
Acetylcholinesterase ; Animals ; Choline O-Acetyltransferase ; Cholinergic Neurons ; Dementia* ; Hippocampus ; Humans ; Injections, Intraventricular ; Male ; Mesenchymal Stromal Cells* ; Methods* ; Microglia ; Models, Animal* ; Negotiating* ; Placenta ; Rats* ; Rats, Sprague-Dawley ; Stem Cells* ; Therapeutic Uses ; Water

Radish (Raphanus sativus L.) is a cruciferous vegetable, and its leaves have antioxidant and anticancer properties. This study was conducted to evaluate the effects of ethyl acetate extracts from radish leaves on hypertension in 11-week-old spontaneously hypertensive rats (SHRs). The SHRs were randomly divided into 3 groups of 6 rats each on the basis of initial systolic blood pressure (SBP) and were treated with oral administration of radish leaf extract (0, 30, or 90 mg/kg body weight [bw], respectively) for 5 weeks. Six Wistar rats were used as normotensive controls. The amount of the radish leaf extract had no effect on body weight. The SBP of the SHRs showed a decreasing trend with the consumption of the radish leaf extract. In the third week, the SBP of the group fed 90 mg extract/kg bw reduced from 214 mmHg to 166 mmHg and was significantly lower than that of the normotensive and hypertensive controls. The extract did not show a significant effect on the angiotensin-converting enzyme (ACE) activity in the serum, kidney, and lung. The extract increased the concentration of NO in serum and the activities of antioxidant enzymes such as glutathione peroxidase and catalase in red blood cells (RBCs). The serum concentrations of Na+ and K+ were not significantly different between all groups. However, the fecal concentrations of Na+ and K+ increased; the fecal concentrations of Na+ and K+ for the normotensive and hypertensive controls were not different. Urinary excretion of Na+ was higher in the normotensive Wistar rats than in the SHRs, while that of K+ was not significantly different. These findings indicate that consumption of radish leaves might have had antihypertensive effects in SHRs by increasing the serum concentration of NO and fecal concentration of Na+ and enhancing antioxidant activities.
Acetates ; Administration, Oral ; Animals ; Blood Pressure ; Body Weight ; Catalase ; Erythrocytes ; Glutathione Peroxidase ; Hypertension ; Kidney ; Lung ; Raphanus ; Rats ; Rats, Inbred SHR ; Rats, Wistar ; Vegetables

BACKGROUND: Composite grafts have advantages for small nasal defect coverage. However, if the the outer skin defect and the inner skin defect have a different location, conventional composite grafts encounter considerable limitations. Therefore, we devised a 4-limbed graft to overcome this limitation by use of soft tissue transposition. METHODS: Over the course of 5 years, this auricular composite graft was used in 10 cases of reconstruction. We harvested skin and cartilage from the helix. The composite graft had 2 limbs of soft tissue to cover the nasal defect and another 2 limbs of cartilage to support nasal framework. The cartilage limbs extended 3 to 5 mm beyond the margin of the skin. The direction of each limb was modified according to defect position. RESULTS: All 10 composite grafts survived completely. All composite grafts shrank by a small percentage of their bulk. Nonetheless, the nasal framework was maintained to an acceptable extent because of the cartilage limbs. CONCLUSIONS: This technique was capable not only of covering defects in the alar and columellar area, but also of maintaining a satisfactory external appearance, because the 2 limbs of cartilage included in the graft strengthened the nasal framework and provided modest support to the nostril margin. The 2 limbs of soft tissue covered the defect area. Our 4-limbed auricular chondrocutaneous composite graft is reliable option for the reconstruction of alar and columellar defects in a single-stage procedure.
Cartilage ; Extremities* ; Reconstructive Surgical Procedures ; Skin ; Transplants*