Cyclooxygenase-2 (COX-2) is an enzyme induced by various proinflammatory and mitogenic stimuli. Celecoxib is a selective inhibitor of COX-2 that have been shown to affect cell growth and apoptosis. Lung cancer cells expressing COX-2 is able to be a target of celecoxib, this study focuses on investigating that celecoxib induces apoptosis via endoplasmic reticulum (ER) stress on lung cancer cells. We investigated whether celecoxib induced apoptosis on non-small cell lung cancer cell line, A549 and H460. The 50 µM of celecoxib increased apoptotic cells and 100 µM of celecoxib significantly induced apoptosis. To check involvement of caspase cascade, pretreatment of z-VAD-fmk blocked celecoxib-induced apoptosis. However, caspase-3, -8, and -9 were not activated, but cleavage of non-classical caspase-4 was detected using western blot. As checking ER stress associated molecules, celecoxib did not increase expressions of growth arrest and DNA damage inducible protein 34, activating transcription factor 4, and spliced X-box binding protiens-1, but increase of both glucose-regulated protein 78 (GRP78) and C/EBP homologous transcription factor were detected. Salubrinal, inhibitor of eIF2 and siRNA for IRE1 did not alter celecoxib-induced apoptosis. Instead, celecoxib-induced apoptosis might be deeply associated with ER stress depending on GRP78 because siRNA for GRP78 enhanced apoptosis. Taken together, celecoxib triggered ER stress on lung cancer cells and celecoxib-induced apoptosis might be involved in both non-classical caspase-4 and GRP78.
Activating Transcription Factor 4 ; Apoptosis ; Blotting, Western ; Carcinoma, Non-Small-Cell Lung* ; Caspase 3 ; Celecoxib* ; Cell Death* ; Cell Line ; Cyclooxygenase 2 ; DNA Damage ; Endoplasmic Reticulum Stress* ; Endoplasmic Reticulum* ; Eukaryotic Initiation Factor-2 ; Lung Neoplasms ; RNA, Small Interfering ; Transcription Factors

This article is a mini-review that provides a general overview for next-generation sequencing (NGS) and introduces one of the most popular NGS applications, whole genome sequencing (WGS), developed from the expansion of human genomics. NGS technology has brought massively high throughput sequencing data to bear on research questions, enabling a new era of genomic research. Development of bioinformatic software for NGS has provided more opportunities for researchers to use various applications in genomic fields. De novo genome assembly and large scale DNA resequencing to understand genomic variations are popular genomic research tools for processing a tremendous amount of data at low cost. Studies on transcriptomes are now available, from previous-hybridization based microarray methods. Epigenetic studies are also available with NGS applications such as whole genome methylation sequencing and chromatin immunoprecipitation followed by sequencing. Human genetics has faced a new paradigm of research and medical genomics by sequencing technologies since the Human Genome Project. The trend of NGS technologies in human genomics has brought a new era of WGS by enabling the building of human genomes databases and providing appropriate human reference genomes, which is a necessary component of personalized medicine and precision medicine.
Chromatin Immunoprecipitation ; Computational Biology ; DNA ; Epigenomics ; Genetics, Medical ; Genome* ; Genome, Human ; Genomics ; High-Throughput Nucleotide Sequencing ; Human Genome Project ; Humans ; Methylation ; Precision Medicine ; Sequence Analysis, RNA ; Transcriptome

No abstract available.
Precision Medicine*

Interstitial cystitis (IC), also known as painful bladder syndrome or bladder pain syndrome, is a chronic lower urinary tract syndrome characterized by pelvic pain, urinary urgency, and increased urinary frequency in the absence of bacterial infection or identifiable clinicopathology. IC can lead to long-term adverse effects on the patient's quality of life. Therefore, early diagnosis and better understanding of the mechanisms underlying IC are needed. Metabolomic studies of biofluids have become a powerful method for assessing disease mechanisms and biomarker discovery, which potentially address these important clinical needs. However, limited intensive metabolic profiles have been elucidated in IC. The article is a short review on metabolomic analyses that provide a unique fingerprint of IC with a focus on its use in determining a potential diagnostic biomarker associated with symptoms, a response predictor of therapy, and a prognostic marker.
Bacterial Infections ; Biomarkers ; Cystitis, Interstitial* ; Dermatoglyphics ; Early Diagnosis ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Metabolome ; Metabolomics* ; Pelvic Pain ; Quality of Life ; Urinary Bladder ; Urinary Tract

Traditionally, schizophrenia is considered to be a result of dopaminergic hyperactivity while dopaminergic deficiency underlies Parkinson’s disease (PD). This opposing pathophysiology makes comorbid schizophrenia and PD seemingly impossible; however, they do coexist rarely in clinical practice. We present four patients with paranoid schizophrenia diagnosed in their youth who developed parkinsonian symptoms on a stable regimen of quetiapine or clozapine after several years. The diagnosis of comorbid schizophrenia and PD was made mainly according to clinical observation. In addition, dopamine transporter (DAT) imaging with 18F-FP-CIT PET was done in two patients, which showed normal DAT density. It is believed that dopaminergic dysfunction in distinct dopaminergic pathways may explain the coexistence of these two disorders

No abstract available.
Urinary Bladder*

Underactive bladder and impaired bladder compliance are irreversible problems associated with bladder fibrosis. Remodeling of the extracellular matrix is regarded as an important mechanism associated with bladder fibrosis. However, various risk factors and conditions contribute to the functional impairment of the bladder associated with fibrosis, and there is limited knowledge about bladder fibrosis-associated problems in the field of neurourology. Further studies are thus necessary to elucidate the underlying mechanism of bladder fibrosis and to identify effective treatment.

Underactive bladder and impaired bladder compliance are irreversible problems associated with bladder fibrosis. Remodeling of the extracellular matrix is regarded as an important mechanism associated with bladder fibrosis. However, various risk factors and conditions contribute to the functional impairment of the bladder associated with fibrosis, and there is limited knowledge about bladder fibrosis-associated problems in the field of neurourology. Further studies are thus necessary to elucidate the underlying mechanism of bladder fibrosis and to identify effective treatment.

PURPOSE: To evaluate outcome and morbidity in patients with vulvar cancer treated with radiotherapy, concurrent chemoradiotherapy or postoperative radiotherapy. MATERIALS AND METHODS: The records of 24 patients treated with radiotherapy for vulvar cancer between July 1993 and September 2009 were retrospectively reviewed. All patients received once daily 1.8-4 Gy fractions external beam radiotherapy to median 51.2 Gy (range, 19.8 to 81.6 Gy) on pelvis and inguinal nodes. Seven patients were treated with primary concurrent chemoradiotherapy, one patient was treated with primary radiotherapy alone, four patients received palliative radiotherapy, and twelve patients were treated with postoperative radiotherapy. RESULTS: Twenty patients were eligible for response evaluation. Response rate was 55% (11/20). The 5-year disease free survival was 42.2% and 5-year overall survival was 46.2%, respectively. Fifty percent (12/24) experienced with acute skin complications of grade III or more during radiotherapy. Late complications were found in 8 patients. 50% (6/12) of patients treated with lymph node dissection experienced severe late complications. One patient died of sepsis from lymphedema. However, only 16.6% (2/12) of patients treated with primary radiotherapy developed late complications. CONCLUSION: Outcome of patients with vulvar cancer treated with radiotherapy showed relatively good local control and low recurrence. Severe late toxicities remained higher in patients treated with both node dissection and radiotherapy.
Carcinoma, Squamous Cell ; Chemoradiotherapy ; Disease-Free Survival ; Humans ; Lymph Node Excision ; Lymphedema ; Pelvis ; Recurrence ; Retrospective Studies ; Sepsis ; Skin ; Treatment Outcome ; Vulvar Neoplasms