• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7281-7285
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• 2014

Background: Gastric cancer is the second most common gastrointestinal cancer and is more common in the East, compared to the West. This study assesses the trend of gastric cancers in Brunei Darussalam, a developing nation with a predominantly Malay population. Materials and Methods: The cancer registry from 1986 to 2012 maintained by the Department of Pathology, the only State Laboratory at the RIPAS Hospital, Ministry of Health, was reviewed and data extracted for analyses. The age standardised rate (ASR) and age specific incidence rate were calculated based on the projected population. Cancers diagnosed below 45 years were categorised as young gastric cancer. Results: Over the study period, there were a total of 551 cases of gastric cancer diagnosed. The most common type was adenocarcinoma (87.9%), followed by lymphoma (6.1%) and gastrointestinal stromal tumour (2.8%). The overall mean age at diagnosis was 61.9 years old (range 15 to 98) with an increasing trend observed, but this was not significant (ANOVA). There were differences in the mean age at diagnosis for the different races (p=0.003 for trend), but not the gender (p=0.105). Young gastric cancer accounted for 14.9%, being more common in women, and in Expatriate and Malay populations compared to the Chinese. There was a decrease in the ASR, from 17.3/100,000 in 1986-1990 to 12.5/100,000 in 2006-2010. Chinese had a higher overall ASR (20.2/100,000) compared to the Malays (11.8/100,000). The age specific rates were comparable between men and women until the age group 55-59 years when the rates started to diverge, becoming higher in men. Chinese men had higher rates then Malay men whereas, the rates were higher or comparable between the women until the age group >70 when the rate for Chinese women overtook their Malay counterpart. Conclusions: Our study showed that there is a declining trend in the incidence of gastric cancer and higher rates were observed in men and Chinese.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3173-3177
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• 2016

Background: The Ministry of Public Health (MOPH) in Lebanon provides cancer drugs free of charge for uninsured patients who account for more than half the total case-load. Other categories of cancer care are subsidized under more stringent eligibility criteria. MOPH's large database offers an excellent opportunity to analyze the cost of cancer treatment in Lebanon. Materials and Methods: Using utilization and spending data accumulated at MOPH during 2008-2013, the cost to the public budget of cancer drugs was assessed per case and per drug type. Results: The average annual cost of cancer drugs was 6,475$ per patient. Total cancer drug costs were highest for breast cancer, followed by chronic myeloid leukemia (CML), colorectal cancer, lung cancer, and Non-Hodgkin's lymphoma (NHL), which together represented 74% of total MOPH cancer drug expenditure. The annual average cancer drug cost per case was highest for CML ($31,037), followed by NHL ($11,566). Trastuzumab represented 26% and Imatinib 15% of total MOPH cancer drug expenditure over six years. Conclusions: Sustained increase in cancer drug cost threatens the sustainability of MOPH coverage, so crucial for socially vulnerable citizens. To enhance the bargaining position with pharmaceutical firms for drug cost containment in a small market like Lebanon, drug price comparisons with neighboring countries which have already obtained lower prices may succeed in lowering drug costs.

• Journal of Korean Neurosurgical Society
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• 제44권3호
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• pp.146-150
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• 2008

Objective : The authors reviewed the experience of 19 patients with orbital tumors and summarize the clinical features, surgical treatment and outcomes. Methods : The authors searched the database for all patients who underwent surgery for the treatment of orbital tumors at a single institution between 1999 and 2007. Data from clinical notes, surgical reports, and radiological findings were obtained for the analysis. Results : Orbital tumors constituted a heterogenous array of histopathology. The presenting symptoms were exophthalmos (52.6%), visual disturbance (26.3%) and pain (21.1%). The surgical approaches used were transcranial in 17 patients. Tumors located in the intraconal or perioptic space were surgically excised using a frontoorbital approach (8 cases). while pterional (3 cases). orbital (2 cases) and combined approaches (6 cases) were used for tumors in other sites. Total resection of tumors was achieved in 12 of 19 patients. In 4 patients with glioma and lymphoma only diagnostic biopsy was done. Three patients experienced visual deterioration postoperatively. Two patients had temporary diplopia, and one patient had temporary ptosis. Conclusion : Surgical treatment could be the mainstay of therapy for the majority of symptomatic orbital tumors. Many orbital tumors can be treated safely via a transcranial approach. Frontoorbital approach allows the surgeon to reach both the intraorbital and intracranial structures. Knowledge of the microanatomy of the orbit and meticulous surgical skills are necessary to overcome the pitfalls of intraorbital surgery.

• 한국정보과학회논문지:소프트웨어및응용
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• 제31권4호
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• pp.525-536
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• 2004

유전발현 데이타는 생명체의 특정 조직에서 채취한 샘플을 microarray상에서 측정한 것으로, 유전자들의 발현 정도가 수치로 나타난 데이타이다. 일반적으로 정상조직과 이상조직에서 관련 유전자들의 발현정도는 차이를 보이기 때문에, 유전발현 데이타를 통하여 질병을 분류할 수 있다. 이러한 분류에 모든 유전자들이 관여하지는 않으므로 관련 유전자를 선별하는 작업인 특징선택이 필요하며, 선택된 유전자들을 적절히 분류하는 방법이 필요하다. 본 논문에서는 상관계수, 유사도, 정보이론 등에 기반을 둔 7가지 특징선택 방법과 대표적인 6가지 분류기에 대하여 특징-분류기 쌍의 최적 앙상블을 탐색하기 위한 유전자 알고리즘 기반 방법을 제안한다. 두 가지 암 관련 유전자 발현 데이타에 대하여 leave-one-out cross validation을 포함한 실험을 해본 결과, 림프종 데이타와 대장암 데이타 모두 단일 특징-분류기 쌍보다 훨씬 우수한 성능을 보이는 앙상블들을 발견할 수 있었다.

• 대한약침학회지
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• 제18권1호
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• pp.19-26
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• 2015

Objectives: Quercetin, a flavonoid compound, has been reported to induce apoptosis in cancer cells, but its anti-inflammatory effects, which are also closely linked with apoptosis, if any, on non-small-cell lung cancer (NSCLC) have not so far been critically examined. In this study, we tried to determine if quercetin had any demonstrable anti-inflammatory potential, which also could significantly contribute to inducing apoptosis in a NSCLC cell line, A549. Methods: In this context, several assays, including cytotoxicity, flow cytometry and fluorimetry, were done. Gene expression was analyzed by using a western blot analysis. Results: Results revealed that quercetin could induce apoptosis in A549 cells through mitochondrial depolarization by causing an imbalance in B-cell lymphoma 2/Bcl2 Antagonist X (Bcl2/Bax) ratio and by down-regulating the interleukine-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling pathway. An analysis of the data revealed that quercetin could block nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$) activity at early hours, which might cause a down-regulation of the IL-6 titer, and the IL-6 expression, in turn, could inhibit p-STAT3 expression. Down-regulation of both the STAT3 and the NF-${\kappa}B$ expressions might, therefore, cause down-regulation of Bcl2 activity because both are major upstream effectors of Bcl2. Alteration in Bcl2 responses might result in an imbalance in the Bcl2/Bax ratio, which could ultimately bring about mitochondria mediated apoptosis in A549 cells. Conclusion: Overall, the finding of this study indicates that a quercetin induced anti-inflammatory pathway in A549 cells appeared to make a significant contribution towards induction of apoptosis in NSCLC and, thus, may have a therapeutic use such as a strong apoptosis inducer in cancer cells.

• Current Research on Agriculture and Life Sciences
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• 제31권3호
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• pp.157-164
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• 2013

Chromatin remodelers that include histone methyl transferases (HMTases) are becoming a focal point in cancer drug development. The NSD family of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L are bona fide oncogenes found aberrantly expressed in several cancers, suggesting their potential role for novel therapeutic strategies. Several histone modifiers including HMTase have clear roles in human carcinogenesis but the extent of their functions and regulations are not well understood, especially in pathological conditions. The extents of the NSDs biological roles in normal and pathological conditions remain unclear. In particular, the substrate specificity of the NSDs remains unsettled and discrepant data has been reported. NSD2/MMSET is a focal point for therapeutic interventions against multiple myeloma and especially for t(4;14) myeloma, which is associated with a significantly worse prognosis than other biological subgroups. Multiple myeloma is the second most common hematological malignancy in the United States, after non-Hodgkin lymphoma. Herein, as a first step before entering a pipeline for protein x-ray crystallography, we cloned, recombinantly expressed and purified the catalytic SET domain of NSD2. Next, we demonstrated the catalytic activities, in vitro, of the recombinantly expressed NSD2-SET on H3K36 and H4K20, its biological targets at the chromatin.

• Biomolecules & Therapeutics
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• 제27권2호
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• pp.178-184
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• 2019

Parkinson's disease is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons within the substantia nigra pars compacta. In the present study, we investigated whether ${\beta}-Lapachone$ (${\beta}-LAP$), a natural naphthoquinone compound isolated from the lapacho tree (Tabebuia avellanedae), elicits neuroprotective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. ${\beta}-LAP$ reduced the tyrosine hydroxylase (TH)-immunoreactive fiber loss induced by MPTP in the dorsolateral striatum, and alleviated motor dysfunction as determined by the rotarod test. In addition, ${\beta}-LAP$ protected against MPTP-induced loss of TH positive neurons, and upregulated B-cell lymphoma 2 protein (Bcl-2) expression in the substantia nigra. Based on previous reports on the neuroprotective role of nuclear factor-E2-related factor-2 (Nrf2) in neurodegenerative diseases, we investigated whether ${\beta}-LAP$ induces upregulation of the Nrf2-hemeoxygenae-1 (HO-1) signaling pathway molecules in MPTP-injected mouse brains. Western blot and immunohistochemical analyses indicated that ${\beta}-LAP$ increased HO-1 expression in glial fibrillary acidic protein-positive astrocytes. Moreover, ${\beta}-LAP$ increased the nuclear translocation and DNA binding activity of Nrf2, and the phosphorylation of upstream adenosine monophosphate-activated protein kinase (AMPK). ${\beta}-LAP$ also increased the localization of p-AMPK and Nrf2 in astrocytes. Collectively, our data suggest that ${\beta}-LAP$ exerts neuroprotective effect in MPTP-injected mice by upregulating the p-AMPK/Nrf2/HO-1 signaling pathways in astrocytes.

• Journal of Microbiology and Biotechnology
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• 제31권7호
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• pp.921-932
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• 2021

LINC01272 is a long non-coding RNA (lncRNA) that has been considered as a biomarker for many diseases including lung squamous cell carcinoma. Here, we investigated the function and mechanism of LINC01272 on lung cancer (LC). The differential expression of LINC01272 in LC and normal samples was analyzed by GEPIA based on the data from TCGA-LUAD database, as survival prognosis was analyzed through Kaplan-Meier Plotter. LINC01272 overexpression plasmid and miR-7-5p mimic were transfected into A549 and PC-9 cells. LINC01272, miR-7-5p and cardiolipin synthase 1 (CRLS1) mRNA expression was measured by quantitative reverse transcription-polymerase chain reaction. Cell viability was detected through MTT assay. Cell multiplication was evaluated by cell formation assay. Cell apoptosis was assessed through flow cytometry assay. Through bioinformatics, the target miRNA of LINC01272 and downstream genes of miR-7-5p were predicted. The targeting relationship was tested by dual luciferase reporter analysis. CRLS1, B-cell lymphoma-2 (Bcl-2), BCL2-associated X (Bax) and cleaved caspase-3 protein levels were detected through western blot. LINC01272 was downregulated in LC and low LINC01272 expression had poor prognosis. In A549 and PC-9 cells, LINC01272 inhibited cell viability and multiplication and induced apoptosis. LINC01272 negatively regulated miR-7-5p and CRLS1 was a target of miR-7-5p. MiR-7-5p reversed the effect of LINC01272 on viability, multiplication, apoptosis and expression of miR-7-5p and CRLS1 as well as apoptosis-related factors (Bcl-2, Bax and cleaved caspase-3). LINC01272 suppressed cell multiplication and induced apoptosis via regulating the miR-7-5p/CRLS1 axis in LC.

• Applied Microscopy
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• 제51권
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• pp.4.1-4.12
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• 2021

Fluorescence in situ hybridization (FISH) is a technique to visualize specific DNA/RNA sequences within the cell nuclei and provide the presence, location and structural integrity of genes on chromosomes. A confocal Whole Slide Imaging (WSI) scanner technology has superior depth resolution compared to wide-field fluorescence imaging. Confocal WSI has the ability to perform serial optical sections with specimen imaging, which is critical for 3D tissue reconstruction for volumetric spatial analysis. The standard clinical manual scoring for FISH is labor-intensive, time-consuming and subjective. Application of multi-gene FISH analysis alongside 3D imaging, significantly increase the level of complexity required for an accurate 3D analysis. Therefore, the purpose of this study is to establish automated 3D FISH scoring for z-stack images from confocal WSI scanner. The algorithm and the application we developed, SHIMARIS PAFQ, successfully employs 3D calculations for clear individual cell nuclei segmentation, gene signals detection and distribution of break-apart probes signal patterns, including standard break-apart, and variant patterns due to truncation, and deletion, etc. The analysis was accurate and precise when compared with ground truth clinical manual counting and scoring reported in ten lymphoma and solid tumors cases. The algorithm and the application we developed, SHIMARIS PAFQ, is objective and more efficient than the conventional procedure. It enables the automated counting of more nuclei, precisely detecting additional abnormal signal variations in nuclei patterns and analyzes gigabyte multi-layer stacking imaging data of tissue samples from patients. Currently, we are developing a deep learning algorithm for automated tumor area detection to be integrated with SHIMARIS PAFQ.

• Korean Journal of Radiology
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• 제25권5호
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• pp.473-480
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• 2024

We systematically reviewed radiological abnormalities in patients with prolonged SARS-CoV-2 infection, defined as persistently positive polymerase chain reaction (PCR) results for SARS-CoV-2 for > 21 days, with either persistent or relapsed symptoms. We extracted data from 24 patients (median age, 54.5 [interquartile range, 44-64 years]) reported in the literature and analyzed their representative CT images based on the timing of the CT scan relative to the initial PCR positivity. Our analysis focused on the patterns and distribution of CT findings, severity scores of lung involvement on a scale of 0-4, and the presence of migration. All patients were immunocompromised, including 62.5% (15/24) with underlying lymphoma and 83.3% (20/24) who had received anti-CD20 therapy within one year. Median duration of infection was 90 days. Most patients exhibited typical CT appearance of coronavirus disease 19 (COVID-19), including ground-glass opacities with or without consolidation, throughout the follow-up period. Notably, CT severity scores were significantly lower during ≤ 21 days than during > 21 days (P < 0.001). Migration was observed on CT in 22.7% (5/22) of patients at ≤ 21 days and in 68.2% (15/22) to 87.5% (14/16) of patients at > 21 days, with rare instances of parenchymal bands in previously affected areas. Prolonged SARS-CoV-2 infection usually presents as migrating typical COVID-19 pneumonia in immunocompromised patients, especially those with impaired B-cell immunity.