Factor Of Poor Prognosis In Patients Research Articles

The Impact of High D-Dimer on The Clinical Outcome of Covid-19 patients at A Private Hospital in Jakarta

D-Dimer is a fibrin degradation product as the resultof thrombus degradation by fibrinolysis. Elevated D-dimer in the blood is a presumptive marker of thrombosis. D-dimer levels above 1g/mL are risk factors for poorprognosis in patients with COVID-19. To evaluate the impact of high D-Dimer on the clinical outcome of Covid-19 patients at Private Hospital in Jakarta. A retrospective cohort study with convenience sampling was applied in this study. There were 980 patients but only 320 patients were eligible for inclusion criteria. This study only included confirmed COVID-19 patients who were hospitalized from March to June 2021, and the study was conducted from March to June 2022. The gender of the majority patients as the sample was male, 165 (52%) and 155(48%) female patients with moderate severity. Correlation between D-dimer and clinical outcome of COVID-19 patients using Fisher's exact method showed a higher survival rate of 287(89.7%) patients compared to 33(10.3%) patients who died with a p-value <0.05. The survival analysis for COVID-19 patients using the Kaplan Meier method showed that patients receiving D-dimer <500ng/mL had a median survival rate of about 90% after approximately 21 days of treatments, whereas patients whowere receiving >500 ng/mL had a 50% survival rate after 30 days of treatment. Patients receiving D-dimer <500ng/mL had a survival rate of about 90% after undergoing treatment for approximately 21 days, while patients who had D-dimer>500 ng/mL had a survival rate of about 50% after 30 days of treatment. Anticoagulants were given to almost all patients, roughly 10 percent died during hospitalization with hypercoagulation complications.

The Vessels That Encapsulate Tumor Clusters (VETC) Pattern Is a Poor Prognosis Factor in Patients with Hepatocellular Carcinoma: An Analysis of Microvessel Density.

The outcomes of patients with hepatocellular carcinoma (HCC) are unsatisfactory because of its high recurrence rate. The Vessels that encapsulate tumor clusters (VETC) pattern is a unique vascular structure. In this study, we investigated the clinical-pathological features of HCC patients with the VETC pattern. We retrospectively reviewed patients with HCC who underwent curative hepatectomy at Chang Gung Memorial Hospital between 2007 and 2013. The form of the VETC pattern was established using an anti-CD31 stain. The results were classified into positive (VETC+) and negative (VETC-) patterns. We investigated and compared demographic data between these two groups. Overall, 174 patients were classified into either the VETC+ or VETC- groups. The median followed-up period was 80.5 months. There were significant differences in the number of hepatitis B carriers, the occurrence of vascular invasion, tumor size, TNM staging, microvessel density, and recurrence (all p < 0.05). Regarding the prediction of disease-free survival, after COX regression multivariate analysis, VETC+ remained independently associated with recurrent episodes (p = 0.003). The intra-tumoral microvessel density, demonstrated by CD-31, was the only clinical-pathological feature independently associated with VETC+. Our study demonstrated that the VETC pattern is an independent factor of poor prognosis for DFS. Higher intra-tumoral microvessel density was significantly associated with the VETC pattern. Further studies are needed to validate our findings.

Tumor multifocality and serum albumin levels can identify groups of patients with hepatocellular carcinoma and portal vein thrombosis having distinct survival outcomes

BackgroundMacroscopic portal vein thrombosis (PVT) is a major poor prognosis factor in patients with hepatocellular carcinoma (HCC), but constitute a heterogeneous group. AimsTo examine blood and tumor parameters of 1667 HCC patients who had PVT to identify factors that could differentiate different survival subsets. Methodsa large HCC database was examined for presence of patients with PVT and analyzed retrospectively for PVT-associated factors and prognosis. ResultsA logistic regression model was calculated for presence of PVT. Highest odds ratios were found for tumor multifocality and serum albumin levels, as well as serum alpha-fetoprotein (AFP) and bilirubin levels. A Kaplan-Meier and Cox model on survival also showed the highest hazard ratios for tumor multifocality and serum albumin. A model was constructed on all 4 possible combinations of tumor focality and serum albumin in PVT patients. The longest survival group had <2 tumor nodules plus serum albumin >3.5 g/dL. Conversely, the shortest survival group had >2 tumor nodules plus serum albumin <3.5 g/dL. These 2 patient groups differed in maximum tumor diameter and levels of serum AFP, AST and bilirubin. ConclusionsCombination low tumor focality and high serum albumin identifies prognostically better PVT patient subgroups that might benefit from aggressive therapies.

Cytolytic activity score as a biomarker for antitumor immunity and clinical outcome in patients with gastric cancer.

BackgroundA simple measure of immune cytolytic activity (CYT) base on mRNA expression levels of two genes, GZMA and PRF1, was recently reported. Here, we aimed to evaluate the CYT score's potential as a measure of antitumor immunity and predictor of clinical outcome in gastric cancer (GC) patients.Materials and MethodsWe evaluated the correlations between tumor‐infiltrating immune cells and the CYT score in 238 GC samples from The Cancer Genome Atlas (TCGA). Next, we investigated CYT score associations with molecular subtypes, somatic mutation load, and immune checkpoint molecules in GC samples from TCGA and Asian Cancer Research Group (ACRG). Moreover, we evaluated the clinical significance of the CYT score calculated by reverse transcription (RT)‐quantitative PCR (qPCR) data in 123 GC samples and the association of the CYT score with the response to anti‐PD‐1 therapy in 7 GC samples from Kyushu University Hospital.ResultsThe CYT score positively correlated with the proportions of tumor‐infiltrating CD8+ T cells and macrophages and negatively correlated with the proportion of regulatory T cells in GC tissues. A high CYT score was associated with common immune checkpoint molecules, a high mutation, the Epstein–Barr virus subtype, and the microsatellite instability subtype in GC. Moreover, a low CYT score was a poor prognosis factor in patients with GC. Finally, the CYT score was higher in a responder to anti‐PD‐1 therapy compared to nonresponders.ConclusionThe CYT score reflects antitumor immunity and predicts clinical outcome in GC patients.

Myoinositol to Total Choline Ratio in Glioblastomas as a Potential Prognostic Factor in Preoperative Magnetic Resonance Spectroscopy.

Isocitrate dehydrogenase (IDH) wild-type diffuse astrocytic tumors tend to be pathologically diagnosed as glioblastomas (GBMs). We previously reported that myoinositol to total choline (Ins/Cho) ratio in GBMs on magnetic resonance (MR) spectroscopy was significantly lower than that in IDH-mutant gliomas. We then hypothesized that a low Ins/Cho ratio is a poor prognosis factor in patients with GBMs, IDH-wild-type. In the present study, we calculated the Ins/Cho ratios of patients with GBMs and investigated their progression-free survival (PFS) and overall survival (OS) to determine their utility as prognostic marker. We classified patients with GBMs harboring wild-type IDH (n = 27) into two groups based on the Ins/Cho ratio, and compared patient backgrounds, pathological findings, PFS, OS, and copy number aberrations between the high and low Ins/Cho groups. Patients with GBMs in the low Ins/Cho ratio group indicated shorter PFS (P = 0.021) and OS (P = 0.048) than those in the high Ins/Cho group. Multivariate analysis demonstrated that the Ins/Cho ratio was significantly correlated with PFS (hazard ratio 0.24, P = 0.028). In conclusion, the preoperative Ins/Cho ratio can be used as a novel potential prognostic factor for GBM, IDH-wild-type.

High Expression of UBE2B as a Poor Prognosis Factor in Patients With Rectal Cancer Following Chemoradiotherapy.

Neoadjuvant concurrent chemoradiotherapy (CCRT) is the standard therapeutic strategy for rectal cancer. However, 15-20% of patients undergoing neoadjuvant CCRT progress to recurrence or distant metastases. Therefore, identifying a predictive biomarker is necessary for treating CCRT. We investigated the relationship between the levels of histone ubiquitination enzyme and clinicopathological outcomes in patients with rectal cancer who were administered CCRT and confirm the role of histone ubiquitination enzyme in regulating the cell response to ionizing radiation (IR). Clinical data indicated that UBE2B expression was significantly correlated with tumor regression grade. Inhibition of UBE2B elevated the genotoxicity of IR to radioresistant cell lines. In contrast, UBE2B over-expression reduced cell sensitivity to IR. Importantly, the recruitment of 53BP1 and Rad51 was remarkably prolonged in cells after pre-treatment with UBE2B inhibitor, TZ9, suggesting a defective DNA repair pathway in UBE2B-deficient cells. These results indicate that over-expression of UBE2B correlates with poor response and low survival rate in patients who are administered preoperative CCRT.

Portal Vein Thrombosis and Markers of Inflammation in Hepatocellular Carcinoma.

Macroscopic portal vein thrombosis (PVT) is a major poor prognosis factor in patients with hepatocellular carcinoma (HCC). Inflammation is increasingly recognized to be part of the hepatocarcinogenic process and its markers are also prognostically useful. To examine the relationship of inflammation biomarkers to the presence of PVT and to survival in PVT patients with HCC. A large HCC cohort was examined for the presence of PVT and analyzed retrospectively. Blood levels of NLR, PLR, ESR, CRP, AFP and GGTP were significantly related to the presence of PVT, but not the Glasgow Index. For patients with low alpha-fetoprotein levels, blood ESR and GGTP levels were also significantly increased in patients with PVT compared with those in patients without PVT. In a Cox regression model, serum GGTP levels had a significantly increased hazard ratio on death (1.52, p = 0.008). Kaplan-Meier analysis showed that PVT patients with low serum GGTP levels had significantly longer survival than PVT patients with high GGTP levels (p = 0.0041). Indices of inflammation, especially serum GGTP levels, related significantly to the presence of PVT and to survival in HCC patients with PVT.

High HLA-F Expression Is a Poor Prognosis Factor in Patients with Nasopharyngeal Carcinoma.

Background and Aims In patients with nasopharyngeal carcinoma (NPC), local treatment failure and distant metastasis contribute largely to poor outcomes. The nasopharynx is an important lymphoid tissue, and NPC tumourigenesis and development are partly attributed to immune system disorders. Human leukocyte antigen F (HLA-F) has shown a close correlation with NPC in many genome-wide association studies (GWASs). However, clinical studies rarely explore the relationship of HLA-F expression with the clinical parameters and outcomes in patients with NPC. Methods In this study, we used immunohistochemistry to evaluate HLA-F expression in 74 paraffin-embedded NPC tissue sections and then analysed the association between HLA-F expression and clinical parameters and outcomes. The plasma concentration of soluble HLA-F (sHLA-F) in NPC patients and normal controls was also detected, via enzyme-linked immunosorbent assay (ELISA). Results Low, moderate, and high HLA-F expression levels were observed in 47.3% (35/74), 35.1% (26/74), and 17.6% (13/74), respectively, of the tissue samples. HLA-F expression showed a significant correlation with local recurrence (p = 0.037) and distant metastasis (p = 0.024) and was also an independent factor for local recurrence-free survival (LRFS; p = 0.016) and distant metastasis-free survival (DMFS; p = 0.004). Although the mean concentration of plasma sHLA-F in the NPC patients was higher than that in the normal controls (13.63 pg/ml vs. 10.06 pg/ml), no statistical significance was observed (p = 0.118). Conclusions Our study provides the first evidence that high HLA-F expression is associated with NPC local recurrence and distant metastasis and may be regarded as a poor prognostic factor for NPC patients. Additional studies using larger sample sizes may be necessary to determine whether sHLA-F is a feasible NPC diagnostic indicator.

Tumor circulating microemboli as poor prognosis factor in patients with locally advanced head and neck squamous cell carcinoma under treatment

Tumor circulating microemboli as poor prognosis factor in patients with locally advanced head and neck squamous cell carcinoma under treatment

Decentralized Data Storage to Promote Epidemiological Analysis for Subtypes Non Hodgkin Lymphoma

Advanced disease means a poor prognosis factor in patients with non-Hodgkin Lymphoma (NHL). There are few Brazilian data about epidemiologic incidence of NHL, however it was observed that high grade B cell Lymphoma is more frequent than in North America, Argentina and Chile, besides that we have deficient information about Brazilian private service care. Such knowledge is essential to plan economic resources to promote the best treatment and diagnosis. Moreover, is fundamental to elaborate electronic data storage to promote a continuous supply flow of information during clinical practice. We have designed an accessible and automated data collection model built into the electronic medical records for patients with NHL. Here, we show some epidemiological parameters and classic risk factors about NHL in a private care institute stocked by continuous electronic data storage.We evaluated data from patients with NHL during November 2015 to May 2016. Information was obtained by decentralized automated model after each outpatient care. We studied 229 patients with NHL. It was observed 112(48.9%) patients with Diffuse Large B cell Lymphoma not otherwise specified (DLBCL), 65(28.3%) Follicular Lymphoma (FL), 21(9.1%) Mantle Cell Lymphoma (MCL), 12(5.2%) Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue gastric lymphoma (GMALT), 6(2.9%) Extranodal marginal zone lymphoma of nonGastric MALT lymphoma (non-GMALT), 4(1.7%) Splenic B-cell marginal zone lymphoma (SL), 1(0.4%) nodal marginal zone lymphoma (NMZL), 1(0.4%) Sporadic Burkitt Lymphoma (BL), 2(0.8%) peripheral T cell lymphoma not otherwise specified (PTCL), 2(0.8%) anaplastic large T Cell lymphoma, ALK negative (ALTCL), 2(0.8%) Extranodal NK/T-cell lymphoma, basal type and 1(0.4%) mycosis fungoides (MF).It was evidenced advanced disease stage III/IV in DLBCL, FL and MCL: 70(62.5%), 54 (87.1%), 18 (85.7%); Extranodal infiltration sites in DLBCL, FL, MCL: 35/94 (37.2%), 11/50 (22%) and 5/18( 27.7%); Elevated serum LDH in DLBCL, FL, MCL: 31/74( 43.6%), 10/38 (26.3%) and 4/14 (28.5%), Performance status ≥ 2 in DLBCL, FL, MCL: 18/75(24%), 2/28 (4.1) 12/20 (60%), respectively.In this study, we have demonstrated that decentralized electronic data storage was useful and could appear an attractive model for clinical practice; moreover, it was possible observed high incidence of DLCBL and FL with advanced disease. DisclosuresNo relevant conflicts of interest to declare.

Obstructive coronary artery disease in patients hospitalized for severe sepsis or septic shock with concomitant acute myocardial infarction

PurposeIt is difficult to differentiate type 1 acute myocardial infarction (AMI) with obstructive coronary artery disease (OCAD) from type 2 AMI in patients admitted for severe sepsis. The aims of this study were to assess the risk factors and prognosis of OCAD in patients admitted to the intensive care unit for severe sepsis with concomitant AMI. Materials and methodsThis is a single-center retrospective cohort study including all consecutive patients who were hospitalized for severe sepsis or septic shock between March 2006 and September 2014 and who underwent coronary angiography in the intensive care unit to identify AMI. ResultsOverall, 78 (5.5%) of 1418 patients hospitalized for severe sepsis underwent coronary angiography to identify concomitant AMI. Thirty-two patients (41%) had OCAD. Following multivariate analysis, the risk factors of OCAD were peripheral vascular disease (odds ratio [OR] =5.7; 95% confidence interval [CI], 1.1-30.4; P = .042) and at least 2 cardiovascular risk factors (OR = 6.7; 95% CI, 1.9-23.8; P = .003). Obstructive coronary artery disease was associated with a significant mortality increase at 60 days (OR = 8.1; 95% CI, 1.9-30.2; P = .004). ConclusionsObstructive coronary artery disease is a poor prognosis factor in patients hospitalized for severe sepsis with concomitant AMI. In this setting, medical treatment should be considered for patients with peripheral vascular disease or with at least 2 cardiovascular risk factors; the need to perform coronary angiography should be considered carefully.

Chronic kidney disease and cerebral small vessel disease: a casual or causal cerebrorenal relationship?

Abstract is not required for Editorialis not required for Editorial (This page in not part of the published article.) International Journal of Case Reports and Images, Vol. 6 No. 8, August 2015. ISSN – [0976-3198] Int J Case Rep Images 2015;6(8):526–529. www.ijcasereportsandimages.com Rivera-Zambrano et al. 526 CASE REPORT OPEN ACCESS Chronic kidney disease and cerebral small vessel disease: A casual or causal cerebrorenal relationship? Marx Rivera-Zambrano, Adria Arboix, Maria-Jose Sanchez Recent studies show that individuals with progressive chronic kidney disease have a greater risk of cardiovascular events, hospitalization and death [1]. Chronic kidney disease (CKD) is prevalent in acute stroke patients with rates varying from 20–35% in ischemic stroke and from 20–46% in intracerebral hemorrhage [2, 3]. Previously, a higher four to ten times, prevalence of stroke in dialysis patients have been reported [3]. It can therefore be concluded that CKD is an established and emergent risk factor for cardiovascular disease in general and for cerebrovascular disease in particular. Chronic kidney disease is defined either by a decrease in the estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2 or by the presence of albuminuria as a marker of an increased glomerular permeability [4]. It represents also a poor prognosis factor in patients with acute stroke and its presence has been associated with stroke severity and poor outcomes in ischemic and hemorrhagic stroke. A study reported that patients with CKD had a 49% greater risk of neurological deterioration during hospital stay and in-hospital mortality, and higher degree of disability at discharge according to the modified Rankin scale score of 2 or more than patients without CKD [5]. Greater risk of recurrence of non-cardioembolic stroke in CKD patients has also been reported [3]. This Marx Rivera-Zambrano1, Adria Arboix2, Maria-JoseSanchez3 Affiliations: 1Internal Medicine Department, Hospital Universitari Sagrat Cor. Hospital Universitari Sagrat Cor, University of Barcelona, Barcelona, Catalonia, Spain; 2Cerebrovascular Division, Neurology Department, Hospital Universitari Sagrat Cor, University of Barcelona, Barcelona, Catalonia, Spain; 3Library Department. Hospital UniversitariSagratCor, University of Barcelona, Barcelona, Catalonia, Spain. Corresponding Author: Adria Arboix, Barcelona, Catalonia, Spain, 08029; Tel.: 34 934948940; Fax: 34 934948906; Email: aarboix@hscor.com, Received: 03 June 2015 Published: 01 August 2015 EdiTO iAlS OPEN A CE S worse neurological prognosis may be caused by the presence in these patients of proteinuria and albuminuria, and both conditions are significantly associated with high levels of inflammatory cytokines and oxidative stress, inflammation and conditions promoting coagulation, potentially causing excessive vascular damage at stroke onset. These factors are also associated with accelerated atherosclerosis and endothelial dysfunction. Albuminuria is also predictive of hemorrhagic transformation of stroke [2]. We must also point out that CKD patients have both high thromboembolic and high bleeding risks and this has implications for deciding the optimal therapeutic strategy for primary or secondary prevention in these clinical conditions. Thus, non-vitamin K antagonist oral anticoagulants (novel oral anticoagulants) seem to be safer and more effective for patients with nonvalvular atrial fibrillation than warfarin, but cannot be given to patients with advanced CKD because the activity of these drugs is greatly affected by renal function [2, 6]. Intravenous thrombolysis is not contraindicated for patients with CKD but experts have limited experience with this treatment in these patients [6]. It is worth mentioning that kidney impairment is strongly associated with cerebral small vessel diseases (SVDs), which occur as asymptomatic lacunar infarcts (Figure 1) often resulting in classical lacunar syndromes (pure motor hemiparesis, pure sensory syndrome, sensorimotor stroke, ataxic hemiparesis or dysarthriaclumsy hand) or, less frequently, in atypical lacunar syndromes [7,8]. They also result in leukoaraiosis or white matter hyperintensities, silent lacunes, prominent or enlarged perivascular spaces and cerebral microbleeds [9]. One study reported that the volume of white matter lesions increased when eGFR decreased [10], and another showed that proteinuria had strong relation with both the presence and number of microbleeds [11]. This special relationship between CKD and cerebral SVDs is still unclear and warrant further investigation but is probably due to the fact that the vasoregulation of the microvasculature of the two organs (kidney and

Novel Survivin Inhibitor YM-155 Combined with Rapamycin as a Potential Therapy for Recurrent Hepatocellular Carcinoma after Liver Transplantation

Overexpression of survivin, a member of the inhibitor of apoptosis protein family, has been confirmed as a poor prognosis factor in patients with hepatocellular carcinoma (HCC). Any treatment which aims to inhibit the expression of survivin may provide a new hope for HCC therapy. Liver transplantation (LT) has been demonstrated to provide the best treatment for patients with HCC since it removes both the tumor and the underlying cirrhotic liver, but the best treatment for HCC recurrence after LT needs further investigation. Sorafenib, a small molecule inhibitor of several tyrosine kinases and Raf kinases, has been used as the standard agent for the treatment of advanced HCC. Furthermore, sorafenib in combination with various immunosuppressants has been used for patients with recurrent HCC after LT with marginal outcome. In this study, we evaluated the cytotoxic effects of a novel survivin inhibitor, YM155, which has been investigated in several phase II clinical studies for the treatment of variant malignancies, plus rapamycin, everolimus, or tacrolimus in survivin-rich human HCC cell line HepG2 in vitro. YM155 at 100, 250, and 500 nM inhibited the proliferation of HepG2 after 72 hrs treatment. After 48-hr treatment, YM155 also elicited concentration-dependent cytotoxicity, measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, with IC50 of around 200 nM. In addition, after treatment of HepG2 cells with 250 nM YM155 for 48 hrs, apoptosis detected by the presence of DNA fragments in the cytoplasm was observed; the expression of survivin, securin, and livin measured by Western blotting was down-regulated, unchanged, and up-regulated, respectively. Increased LC3-II expression is a marker for autophagy activation, which subsequently may lead to type II death. After one 48 hr-treatment with 250 nM YM155, the expression of LC3-II was increased. Autophagy inhibitor 3-methyladenine at 1 mM ameliorated YM155-induced cytotoxicity. In contrast, YM155 plus mTOR (mammalian target of rapamycin) inhibitor, rapamycin, enhanced the LC3-II expression. Cell viability after treatment with 1μM rapamycin and 250 nM YM155 for 48 hrs was 78.71% and 61.65%, respectively. But cell viability was dropped to 26.33% after 48 hrs treatment with 1 μM rapamycin plus 250 nM YM155. Cell viability after treatment with another mTOR inhibitor, everolimus, at 1μM alone was 80.4%, and the viability dropped to 40.07% after treatment with 1 μM everolimus plus 250 nM YM155 for 48 hrs. Calcineurin inhibitor tacrolimus alone elicited no cytotoxic effect on HepG2 cells 48 hrs after treatment. And no additive or synergistic cytotoxicitiy on HepG2 cells was observed after treatment with YM155 combined with tacrolimus for 48 hrs. In conclusion, YM155 plus rapamycin exerted the most potent and synergistic cytotoxicity through both type I death (apoptosis) and type II death (autophagy). YM155 when used with rapamycin may be an effective therapy for recurrent HCC after liver transplantation.

Establishment of a malignant pleural effusion mouse model with Lewis lung carcinoma cell lines expressing enhanced green fluorescent protein

背景与目的恶性胸腔积液是晚期肺癌预后差的因素之一。本研究拟用Lewis肺癌细胞构建裸鼠恶性胸腔积液模型，从而建立一个良好的动物实验研究平台。方法经胸膜腔接种表达增强型绿色荧光蛋白的Lewis肺癌细胞，建立裸鼠恶性胸腔积液模型。定期解剖小鼠，经小动物活体荧光成像系统观察肿瘤的生长。剩余小鼠定期行胸部CT检查，计算各时间点的成胸水率，并观察建模后裸鼠的生存期和肿瘤转移情况。所有小鼠在解剖时发现有胸水，抽取并计量，同一时间点内获得多份胸水标本，计算其平均体积。利用相关性检验分析胸水体积与肿瘤积分光密度之间的相关性。结果接种后第4天，荧光体视镜下可发现胸膜上有绿色荧光，成瘤率100%。随接种时间延长，肿瘤体积逐渐增加，肿瘤侵及纵隔和肺门淋巴结、对侧胸膜、心包，转移率分别为87%、73%和20%。第7天、第14天和第21天成胸水率分别为13%、46%和53%。小鼠平均生存时间为28.8天，所有胸水均为血性，胸水平均体积在第10天以后逐渐增加，第16天达到峰值（0.5 mL）。胸水体积与积分光密度之间具有相关性（r=0.91, P < 0.000, 1）。结论本研究将表达增强型绿色荧光蛋白的肺癌细胞在显微镜下经胸膜腔接种成功建立肺癌恶性胸腔积液模型，有助于动态观察肿瘤细胞在胸腔内的生物学行为，该模型可应用于肺癌的基础研究及抗肿瘤药物开发。

Biological and Clinical Implications of Functional Promoter Polymorphism of CASPASE 9 Gene in Non Small Cell Lung Cancer Patients

Purpose: The study was conducted to determine the impact of promoter polymorphism in CASP9 gene on susceptibility and prognosis of Non Small Cell Lung Cancer patients of Indian origin. Patients and methods: Present case control study includes newly diagnosed 160 NSCLC patients and 160 healthy controls. Promoter polymorphism (-712C>T, rs4645981) in CASP9 gene was investigated using PCR-RFLP technique. Results: Our findings reveal that a statistically significant increased risk of about 2.6 fold was associated with homozygous TT genotype of CASP9 (-712C>T) promoter polymorphism (OR 4.3, 95%CI 2.2-8.3, p=0.0000) in Indian population .In addition smokers were at high risk for NSCLC which was more predominant in heavy smokers with pack-year >40 and in cigarette or beedi smokers. Compared to males, females were at high risk; about 2.3 fold more in association with homozygous TT genotype [OR, 3.9(1.9-8.2) in males vs. 6.2(1.4-27.1) in females]. Significant association was observed between advanced TNM stage (p<0.0001) and distant metastasis status (p<0.0001) of NSCLC patients with the polymorphism. Patients homozygous for T allele exhibited a significant poor overall survival compared with patients displaying CT+TT or CT or CC genotype (Median survival 6.0 vs. 9.0, 11.0, and 30.0, months respectively, p<0.0001). Also advanced stage patients with TT genotype showed lower median survival time than early stage NSCLC patients (Median 5.0 vs. 9.0 months respectively). Conclusion: The functional polymorphism (-712C>T) in the promoter region of CASP9 gene is associated with risk and susceptibility to NSCLC in north Indian population, and also is an important factor for poor prognosis in patients with NSCLC.

The Correlation of Brain Natriuretic Peptide (BNP), Pulmonary Arterial Pressure, and St. George Respiratory Questionnaire (SGRQ) and Their Changes with a Trial of an Angiotensin Converting Enzyme Inhibitor

Background: Pulmonary hypertension is considered as a poor prognosis factor in patients with chronic obstructive pulmonary disease (COPD). There has been reported brain natriuretic peptide (pro-BNP) is related with increased right ventricular (RV) workloads. However, there are few studies that evaluate the relationship between BNP and pulmonary arterial pressure (PAP), RV function and St. George Respiratory Questionnaire (SGRQ) score in patients with COPD, and the effects of angiotensin converting enzyme inhibitor (ACEI) on these parameters. Methods: Pulmonary function test, echocardiography, blood BNP, and SGRQ score were evaluated in stabilized moderate degree COPD patients (FEV1/FVC＜70%, 50%≤FEV1＜80%) aged 45 years and over, without worsening of symptoms within recent 3 months. After treating with ramipril 10 mg for 3 months, the same evaluation was repeated. Results: Twenty-two patients were included in this study. BNP was significantly correlated with PAP (Pearson coefficient ρ=0.51, p=0.02), but not with RV ejection fraction (EF) and predicted FEV1%. The values for predicted FEV1% showed significant correlation with SGRQ total score and activity score, but not with BNP or PAP. After ramipril treatment, PAP showed significant decrease (42.8±8.1vs.34.5±4.5 mm Hg p=0.0003), tricuspid annular plane systolic excursion significant increase (21.5±3.3vs.22.7±3.1 mm p=0.009). BNP showed a tendency to decrease without statistical significance (40.8±59.6vs.18.0±9.1 pg/mL p=0.55). SGRQ scores showed no significant change. Conclusion: BNP showed significant correlation with resting PAP, which means BNP could be used as markers for pulmonary hypertension. Treatment with ACEI didn`t show significant change in the Level of BNP, while pulmonary hypertension and RV function were improved.

Genetic detection for hematogenous micrometastasis in patients with various types of malignant tumors using Uroplakin II derived primers in polymerase chain reaction

The presence of circulatory metastasis is one of the most significant factors for poor-prognosis in patients with several types of cancer. To establish a sensitive reverse transcription PCR assay to detect micrometastasis in blood containing several cancer types, we first investigated Uroplakin II (UP II), a novel molecular marker for human transitional cell carcinoma of the bladder, in 25 types of normal organs. In our study, UP II mRNA was detected in 10 types of organs, including bladder, kidney, lung and pancreas, but was not detected in normal lymph nodes or leukocytes. The data indicated evidence of UP II expression in various types of normal tissues by RT-nested PCR analysis. UP II mRNA was detected in 2 of 11 (18.2%) peripheral blood samples from lung cancer patients with no metastasis, and in 5 of 12 (41.7%) peripheral blood samples of lung cancer patients with metastasis. UP II was also detected in 6 of 16 (37.5%) peripheral blood samples of patients with pancreatic cancer. The data are particularly important in that the molecular detection of micrometastasis in the blood by means of UP II mRNA identification is feasible for UP II-positive neoplasms, including lung and pancreatic cancers.

Reduced integrin alpha3 expression as a factor of poor prognosis of patients with adenocarcinoma of the lung.

We investigated the possible association between integrin alpha3 and motility-related protein (MRP-1), cluster of differentiation antigen 9 (CD9) gene expression in non-small-cell lung cancer (NSCLC) and evaluated the prognostic significance of integrin alpha3 expression. We performed a retrospective study of integrin alpha3 and MRP-1/CD9 expression in resected tumor tissues from 151 NSCLC patients using quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. The ratio of integrin alpha3/beta-actin expression ranged from 0 to 5.87 (mean was 0.80; median, 0.70). Using the cutoff value of 0.7, there were 78 (52%) integrin alpha3-positive tumors and 73 (48%) tumors with reduced integrin alpha3 expression. The immunohistochemical results agreed well with those of the RT-PCR assays, and 88% had no discrepancy. In case of discrepancy, the results of RT-PCR were used in specimen classification. Integrin alpha3 gene expression was independent from MRP-1/CD9 gene expression. No significant association was found between integrin alpha3 expression and the patients' clinical characteristics. The overall survival rate of patients with integrin alpha3-positive NSCLCs was only slightly better than that of individuals whose tumors had reduced integrin alpha3 expression (55.9% v 47.1%; P = .085). By comparison, the overall survival rate of patients with integrin alpha3-positive adenocarcinomas was strikingly greater than in those whose tumors had reduced gene expression (54.4% v 35.2%; P = .004). Multivariate analysis with the Cox regression model of NSCLC and adenocarcinoma indicated that integrin alpha3 expression correlated better (P = .0188 and P = .0008, respectively) with the overall survival rate than other variables, except lymph node status. No significant association was found between integrin alpha3 and MRP-1/CD9 gene expression in lung cancer. However, reduced integrin alpha3 expression is a poor prognosis factor in patients with adenocarcinomas.