Background: ${\beta}$-catenin plays a crucial role in the progression of breast cancer (BC) and a prognostic role of in BC patients has been widely reported. However, controversy still remains. Materials and Methods: Identical search strategies were used to search relevant literature in electronic databases updated to July 1, 2014. Individual hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled HRs with 95%CIs were used to evaluate the strength of association between positive ${\beta}$-catenin expression in different subcellular locations and survival results of BC patients. Subgroup and meta-regression analyses were performed to explore heterogeneity. Funnel plots of Begg's and Egger's linear regression test were used to investigate publication bias. Heterogeneity and sensitivity were also assessed. All the work was completed using STATA. Results: A total of 2,204 patients from 12 evaluative studies were finally included. Pooled HRs and 95%CIs suggested that ${\beta}$-catenin expression in cytoplasm/nucleus had an unfavorable impact on both overall survival (OS) (HR: 1.93, 95%CI: 1.40-2.65) and disease free survival (DFS)/ recurrent free survival (RFS) (HR: 1.60, 95%CI: 1.20-2.13) in BC patients. However, here was no significant association between ${\beta}$-catenin expression in the membranes with OS (HR: 0.65, 95%CI: 0.42-1.02) or DFS/RFS (HR: 0.66, 95%CI: 0.38-1.13). Publication bias was absent in all of the four outcomes. Sensitivity analysis revealed that the results of this meta-analysis were robust. Conclusions: Positive ${\beta}$-catenin expression in cytoplasm/nucleus rather than in membrane is a significant prognostic factor in patients with BC who have been surgically treated.
MicroRNAs (miRNAs) are emerging as critical regulators in carcinogenesis and tumor progression. Recently, miR-99a has been reported as a tumor suppressor gene in various human cancers, but its functions in the context of anaplastic thyroid cancer (ATC) remain unknown. In this study, we reported that miR-99a was commonly downregulated in ATC tissue specimens and cell lines with important functional consequences. Overexpression of miR-99a not only dramatically reduced ATC cell viability by inducing cell apoptosis and accumulation of cells at G1 phase, but also inhibited tumorigenicity in vivo. We then screened and identified a novel miR-99a target, mammalian target of rapamycin (mTOR), and it was further confirmed by luciferase assay. Up-regulation of miR-99a would markedly reduce the expression of mTOR and its downstream phosphorylated proteins (p-4E-BP1 and p-S6K1). Similar to restoring miR-99a expression, mTOR down-regulation suppressed cell viability and increased cell apoptosis, whereas restoration of mTOR expression significantly reversed the miR-99a antitumor activity and the inhibition of mTOR/p-4E-BP1/p-S6K1 signal pathway profile. In clinical specimens and cell lines, mTOR was commonly overexpressed and its protein levels were statistically inversely correlated with miR-99a expression. Taken together, our results demonstrated for the first time that miR-99a functions as a tumor suppressor and plays an important role in inhibiting the tumorigenesis through targeting the mTOR/p-4E-BP1/p-S6K1 pathway in ATC cells. Given these, miR-99a may serve as a novel prognostic/diagnostic and therapeutic target for treating ATC.
Purpose: To research the association between pre-treatment elevated platelet count and clinicopathologic characteristics in breast cancer (BC), as well as explore the relationship between pre-treatment elevated platelet count and HER2 status and prognosis of BC patients. Materials and Methods: A retrospective cohort of BC patients who were newly diagnosed or treated by surgery only and had pathological detection results and platelet values in the Department of Oncology, the First Affiliated Hospital of Liaoning Medical College were enrolled from 1/1/2008 until 31/12/2009, and followed up until 31/12/2014. Age, thrombocyte parameters before chemotherapy and/or radiotherapy, immunohistochemical (IHM) indexes, and regional lymph node (LN) involvement and progression-free survival (PFS) were recorded. Results: A total of 447 eligible subjects were included in this research. As we analyzed, for HER2, positive and negative, the incidence rates of elevated platelet count were 25.8% and 14.7% (P<0.05). In the Cox proportional hazards model both variables were independent risk factors for BC (for HER2, OR, 0.592, 95% confidence interval, CI, 0.355 to 0.985, P=0.044;f or PLT, OR, 0.998, 95% CI, 0.996 to 1.000, P=0.042). For ER, PR, Ki67 and LN involvement, the differences were not statistically significant (P>0.05). Conclusions: In this research, pre-treatment elevated level of platelet count demostrated a significantrelationship with HER2 amplification/overexpression, and both variables significantly influenced the prognosis of BC. However, elevated platelet count did not exhibit any association with ER, PR, Ki67 and LN involvement.
Background: The aim of this study was to explore the prognostic role of metabolic response to chemotherapy, determined by FDG-PET, in patients with metastatic non-small-cell lung cancer (NSCLC). Materials and Methods: Thirty patients with metastatic NSCLC were analyzed for prognostic factors related to overall survival (OS) and progression free survival (PFS). Disease evaluation was conducted with FDG-PET/CT and contrast-enhanced CT prior to and at the end of first-line chemotherapy. Response evaluation of 19 of 30 patients was also performed after 2-3 cycles of chemotherapy. Morphological and metabolic responses were assessed according to RECIST and PERCIST, respectively. Results: The median OS and PFS were 11 months and 6.2 months, respectively. At the end of first-line chemotherapy, 10 patients achieved metabolic and anatomic responses. Of the 19 patients who had an interim response analysis after 2-3 cycles of chemotherapy, 3 achieved an anatomic response, while 9 achieved a metabolic response. In univariate analyses, favorable prognostic factors for OS were number of cycles of first-line chemotherapy, and achieving a response to chemotherapy at completion of therapy according to the PERCIST and RECIST. The OS of patients with a metabolic response after 2-3 cycles of chemotherapy was also significantly extended. Anatomic response at interim analysis did not predict OS, probably due to few patients with anatomic response. In multivariate analyses, metabolic response after completion of therapy was an independent prognostic factor for OS. Conclusions: Metabolic response is at least as effective as anatomic response in predicting survival. Metabolic response may be an earlier predictive factor for treatment response and OS in NSCLC patients.
Background: Increasing evidence suggests that stromal monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CA IX) may play key roles in tumor development. However, their clinical value remains largely unexplored in gastric cancer (GC). The present study aimed to determine clinicopathological significance and prognostic values of stromal MCT4 and CA IX in GC. Materials and Methods: Specimens from 143 GC patients were immunohistochemically stained using polyclonal anti-MCT4 and anti-CA IX antibodies. Expression was correlated with patient clinicopathologic characteristics and survival data. Results: High stromal MCT4 expression was detected in 72 of 143 (50.3%) GCs and high CA IX in 74 (51.7%). Both high stromal MCT4 and CA IX were correlated with advanced TNM stage (p=0.000; p=0.000). High CA IX expression was positively related to depth of invasion (p=0.022) and positive lymph nodes (p=0.002) as well. Survival analysis indicated high expression of stromal MCT4 to be an independent factor in predicting poor overall survival (OS) (HR and 95%CI=1.962, 1.032-3.729, p=0.040) and disease free survival (DFS) (HR and 95%CI=2.081, 1.158-3.741, p=0.014) of GC patients. However, high CA IX expression exhibited no significant predictive value. Conclusions: These findings suggest that high expression of stromal MCT4 and CA IX proteins is significantly correlated with GC progression. High stromal MCT4 heralds worse outcome of GC patient, suggesting a novel candidate prognostic marker and therapeutic target.
Background: miR-200a expression is frequently altered in numerous cancers. The aim of the present study was to determine the role of microRNA-200a in advanced ovarian carcinomas. Materials and Methods: We measured miR-200a expression in 72 matched normal ovarian tissues and advanced ovarian carcinomas, and also two ovarian carcinoma cell lines (SKOV3 and SKOV3.ip1 - the latter being more invasive and metastatic than the parental SKOV3) by stem-loop real-time RT-PCR based on TaqMan microRNA assay using U6 as a reference. Levels of miR-200a expression were compared by disease stage, tumor grade, histology, and lymph node involvement. To evaluate the role of microRNA-200a, cell proliferation and invasion of SKOV-3 and SKOV-3.ip1 were analyzed with miR-200a inhibitor/mimic transfected cells. Results: Of 72 paired samples, 65 cancer tissues overexpressed microRNA-200a greater than two fold in comparison with matched normal epithelium. Specifically, patients with lymph node metastasis showed significant elevation. The level correlated with clinicopathological features, including high tumor grade, late disease stage, most notably with lymph node metastasis, but not with tumor histology. In addition, SKOV-3.ip1 cells also overexpressed miR-200a compared with SKOV-3, and miR-200a inhibitor transfected SKOV-3.ip1 cells showed significant reduction in cellular proliferation and invasion, while a miR-200a mimic stimulated the opposite behavior. Conclusions: We provide definitive evidence that miR-200a is up-regulated in a significant proportion of advanced ovarian carcinomas, and that elevated miR-200a expression facilitates tumor progression. Our findings support the notion that miR-200a is an onco-microRNA for ovarian cancer, and elevation is a useful potential diagnostic indicator. This study also provides a solid basis for further functional analysis of miR-200a in advanced ovarian cancer.
Overexpression of aquaporins (AQPs) has been reported in several human cancers. Epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinases 1/2 (Erk1/2) are associated with tumorigenesis and cancer progression and may upregulate AQP expression. In this study, we demonstrated that EGF (epidermal growth factor) induces SiHa cells migration and AQP8 expression. Wound healing results showed that cell migration was increased by 2.79-1.50-fold at 24h and 48h after EGF treatment. AQP8 expression was significantly increased (3.33-fold) at 48h after EGF treatment in SiHa cells. An EGFR kinase inhibitor, PD153035, blocked EGF-induced AQP8 expression and cell migration and AQP8 expression was decreased from 1.59-fold (EGF-treated) to 0.43-fold (PD153035-treated) in SiHa. Furthermore, the MEK (MAPK (mitogen-activated protein kinase)/Erk (extracellular signal regulated kinase)/Erk inhibitor U0126 also inhibited EGF-induced AQP8 expression and cell migration. AQP8 expression was decreased from 1.21-fold (EGF-treated) to 0.43-fold (U0126-treated). Immunofluorescence microscopy further confirmed the results. Collectively, our findings show that EGF induces AQP8 expression and cell migration in human cervical cancer SiHa cells via the EGFR/Erk1/2 signal transduction pathway.
Background: Renal cancer is a serious public health problem which may be under reported and registered in our setup, since the Karachi cancer registry documented only 43 cases out of 4,268 incident cancer cases over 3 year duration. Therefore we aimed to determine the clinicopathologic characteristics of adult renal tumors in our setup. Materials and Methods: The study was conducted in histopathology department, Liaquat National Hospital and included total of 68 cases of adult renal tumors over 4 years. Detailed histopathologic characteristics of tumors were analyzed. Results: Mean age of patients was 56.4 (18-84) years. Renal cell carcinoma (RCC) was the most common cell type (78%) cases; followed by transitional/urothelial carcinoma (12.5%), leiomyosarcoma (4.7%), oncocytoma (1.6%), squamous cell carcinoma (1.6%) and high grade pleomorphic undifferentiated sarcoma (1.6%). Among 50 RCC cases; 62% were conventional/clear cell RCC (CCRCC) type followed by papillary RCC(PRCC), 24%; chromophobe RCC(CRCC), 6% and sarcomatoid RCC(SRCC), 8%. Mean tumor size for RCC was 7.2 cm. Most RCCs were intermediate to high grade (60% and 40% respectively). Capsular invasion, renal sinus invasion, adrenal gland involvement and renal vein invasion was seen in 40%, 18%, 2% and 10% of cases respectively. Conclusions: We found that RCC presents at an earlier age in our setup compared to Western populations. Tumor size was significantly larger and most of the tumors were of intermediate to high grade. This reflects late presentation of patients after disease progression which necessitates effective measures to be taken in primary care setup to diagnose this disease at an early stage.
Objective: To investigate the clinical effects of whole brain radiotherapy concomitant with targeted therapy for brain metastasis in non-small cell lung cancer (NSCLC) patients with chemotherapy failure. Materials and Methods: Of the 157 NSCLC patients with chemotherapy failure followed by brain metastasis admitted in our hospital from January 2009 to August 2012, the combination group (65 cases) were treated with EGFR-TKI combined with whole brain radiotherapy while the radiotherapy group (92 cases) were given whole brain radiotherapy only. Short-term effects were evaluated based on the increased MRI in brain 1 month after whole brain radiotherapy. Intracranial hypertension responses, hematological toxicity reactions and clinical effects of both groups were observed. Results: There were more adverse reactions in the combination group than in radiotherapy group, but no significant differences were observed between the two groups in response rate (RR) and disease control rate (DCR) (P>0.05). Medium progression free survival (PFS), medium overall survival (OS) and 1-year survival rate in combination group were 6.0 months, 10.6 months and 42.3%, while in the radiotherapy group they were 3.4 months, 7.7 months and 28.0%, respectively, which indicated that there were significant differences in PFS and OS between the two groups (P<0.05). Additionally, RPA grading of each factor in the combination group was a risk factor closely related with survival, with medium PFS in EGFR and KRAS mutation patients being 8.2 months and 11.2 months, and OS being 3.6 months and 6.3 months, respectively. Conclusions: Whole brain radiotherapy concomitant with target therapy is favorable for adverse reaction tolerance and clinical effects, being superior in treating brain metastasis in NSCLC patients with chemotherapy failure and thus deserves to be widely applied in the clinic.
Background: To investigate the preventive and therapeutic potential of garlic oil on human pancreatic carcinoma cells. Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was performed to study the effects of garlic oil on three human pancreatic cancer cell lines, AsPC-1, Mia PaCa-2 and PANC-1. Cell cycle progression and apoptosis were detected by flow cytometry (FCM), staining with PI and annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI), respectively. Morphologic changes of pancreatic cancer cells were observed under transmission electron microscopy (TEM) after treatment with garlic oil at low inhibitory concentrations ($2.5{\mu}M$ and $10{\mu}M$) for 24 hours. Results: Proliferation of the AsPC-1, PANC-1, and Mia PaCa-2 cells was obviously inhibited in the first 24 hours with the MTT assay. The inhibition effect was more significant after 48 hours. When cells were exposed to garlic oil at higher concentrations, an early change of the apoptotic tendency was detected by FCM and TEM. Conclusion: Garlic oil could inhibit the proliferation of AsPC-1, PANC-1, and Mia PaCa-2 cells in this study. Moreover, due to programmed cell death, cell cycle arrest, or both, pro-apoptosis effects on AsPC-1 cells were induced by garlic oil in a dose and time dependent manner in vitro.
본 웹사이트에 게시된 이메일 주소가 전자우편 수집 프로그램이나
그 밖의 기술적 장치를 이용하여 무단으로 수집되는 것을 거부하며,
이를 위반시 정보통신망법에 의해 형사 처벌됨을 유념하시기 바랍니다.
[게시일 2004년 10월 1일]
이용약관
제 1 장 총칙
제 1 조 (목적)
이 이용약관은 KoreaScience 홈페이지(이하 “당 사이트”)에서 제공하는 인터넷 서비스(이하 '서비스')의 가입조건 및 이용에 관한 제반 사항과 기타 필요한 사항을 구체적으로 규정함을 목적으로 합니다.
제 2 조 (용어의 정의)
① "이용자"라 함은 당 사이트에 접속하여 이 약관에 따라 당 사이트가 제공하는 서비스를 받는 회원 및 비회원을
말합니다.
② "회원"이라 함은 서비스를 이용하기 위하여 당 사이트에 개인정보를 제공하여 아이디(ID)와 비밀번호를 부여
받은 자를 말합니다.
③ "회원 아이디(ID)"라 함은 회원의 식별 및 서비스 이용을 위하여 자신이 선정한 문자 및 숫자의 조합을
말합니다.
④ "비밀번호(패스워드)"라 함은 회원이 자신의 비밀보호를 위하여 선정한 문자 및 숫자의 조합을 말합니다.
제 3 조 (이용약관의 효력 및 변경)
① 이 약관은 당 사이트에 게시하거나 기타의 방법으로 회원에게 공지함으로써 효력이 발생합니다.
② 당 사이트는 이 약관을 개정할 경우에 적용일자 및 개정사유를 명시하여 현행 약관과 함께 당 사이트의
초기화면에 그 적용일자 7일 이전부터 적용일자 전일까지 공지합니다. 다만, 회원에게 불리하게 약관내용을
변경하는 경우에는 최소한 30일 이상의 사전 유예기간을 두고 공지합니다. 이 경우 당 사이트는 개정 전
내용과 개정 후 내용을 명확하게 비교하여 이용자가 알기 쉽도록 표시합니다.
제 4 조(약관 외 준칙)
① 이 약관은 당 사이트가 제공하는 서비스에 관한 이용안내와 함께 적용됩니다.
② 이 약관에 명시되지 아니한 사항은 관계법령의 규정이 적용됩니다.
제 2 장 이용계약의 체결
제 5 조 (이용계약의 성립 등)
① 이용계약은 이용고객이 당 사이트가 정한 약관에 「동의합니다」를 선택하고, 당 사이트가 정한
온라인신청양식을 작성하여 서비스 이용을 신청한 후, 당 사이트가 이를 승낙함으로써 성립합니다.
② 제1항의 승낙은 당 사이트가 제공하는 과학기술정보검색, 맞춤정보, 서지정보 등 다른 서비스의 이용승낙을
포함합니다.
제 6 조 (회원가입)
서비스를 이용하고자 하는 고객은 당 사이트에서 정한 회원가입양식에 개인정보를 기재하여 가입을 하여야 합니다.
제 7 조 (개인정보의 보호 및 사용)
당 사이트는 관계법령이 정하는 바에 따라 회원 등록정보를 포함한 회원의 개인정보를 보호하기 위해 노력합니다. 회원 개인정보의 보호 및 사용에 대해서는 관련법령 및 당 사이트의 개인정보 보호정책이 적용됩니다.
제 8 조 (이용 신청의 승낙과 제한)
① 당 사이트는 제6조의 규정에 의한 이용신청고객에 대하여 서비스 이용을 승낙합니다.
② 당 사이트는 아래사항에 해당하는 경우에 대해서 승낙하지 아니 합니다.
- 이용계약 신청서의 내용을 허위로 기재한 경우
- 기타 규정한 제반사항을 위반하며 신청하는 경우
제 9 조 (회원 ID 부여 및 변경 등)
① 당 사이트는 이용고객에 대하여 약관에 정하는 바에 따라 자신이 선정한 회원 ID를 부여합니다.
② 회원 ID는 원칙적으로 변경이 불가하며 부득이한 사유로 인하여 변경 하고자 하는 경우에는 해당 ID를
해지하고 재가입해야 합니다.
③ 기타 회원 개인정보 관리 및 변경 등에 관한 사항은 서비스별 안내에 정하는 바에 의합니다.
제 3 장 계약 당사자의 의무
제 10 조 (KISTI의 의무)
① 당 사이트는 이용고객이 희망한 서비스 제공 개시일에 특별한 사정이 없는 한 서비스를 이용할 수 있도록
하여야 합니다.
② 당 사이트는 개인정보 보호를 위해 보안시스템을 구축하며 개인정보 보호정책을 공시하고 준수합니다.
③ 당 사이트는 회원으로부터 제기되는 의견이나 불만이 정당하다고 객관적으로 인정될 경우에는 적절한 절차를
거쳐 즉시 처리하여야 합니다. 다만, 즉시 처리가 곤란한 경우는 회원에게 그 사유와 처리일정을 통보하여야
합니다.
제 11 조 (회원의 의무)
① 이용자는 회원가입 신청 또는 회원정보 변경 시 실명으로 모든 사항을 사실에 근거하여 작성하여야 하며,
허위 또는 타인의 정보를 등록할 경우 일체의 권리를 주장할 수 없습니다.
② 당 사이트가 관계법령 및 개인정보 보호정책에 의거하여 그 책임을 지는 경우를 제외하고 회원에게 부여된
ID의 비밀번호 관리소홀, 부정사용에 의하여 발생하는 모든 결과에 대한 책임은 회원에게 있습니다.
③ 회원은 당 사이트 및 제 3자의 지적 재산권을 침해해서는 안 됩니다.
제 4 장 서비스의 이용
제 12 조 (서비스 이용 시간)
① 서비스 이용은 당 사이트의 업무상 또는 기술상 특별한 지장이 없는 한 연중무휴, 1일 24시간 운영을
원칙으로 합니다. 단, 당 사이트는 시스템 정기점검, 증설 및 교체를 위해 당 사이트가 정한 날이나 시간에
서비스를 일시 중단할 수 있으며, 예정되어 있는 작업으로 인한 서비스 일시중단은 당 사이트 홈페이지를
통해 사전에 공지합니다.
② 당 사이트는 서비스를 특정범위로 분할하여 각 범위별로 이용가능시간을 별도로 지정할 수 있습니다. 다만
이 경우 그 내용을 공지합니다.
제 13 조 (홈페이지 저작권)
① NDSL에서 제공하는 모든 저작물의 저작권은 원저작자에게 있으며, KISTI는 복제/배포/전송권을 확보하고
있습니다.
② NDSL에서 제공하는 콘텐츠를 상업적 및 기타 영리목적으로 복제/배포/전송할 경우 사전에 KISTI의 허락을
받아야 합니다.
③ NDSL에서 제공하는 콘텐츠를 보도, 비평, 교육, 연구 등을 위하여 정당한 범위 안에서 공정한 관행에
합치되게 인용할 수 있습니다.
④ NDSL에서 제공하는 콘텐츠를 무단 복제, 전송, 배포 기타 저작권법에 위반되는 방법으로 이용할 경우
저작권법 제136조에 따라 5년 이하의 징역 또는 5천만 원 이하의 벌금에 처해질 수 있습니다.
제 14 조 (유료서비스)
① 당 사이트 및 협력기관이 정한 유료서비스(원문복사 등)는 별도로 정해진 바에 따르며, 변경사항은 시행 전에
당 사이트 홈페이지를 통하여 회원에게 공지합니다.
② 유료서비스를 이용하려는 회원은 정해진 요금체계에 따라 요금을 납부해야 합니다.
제 5 장 계약 해지 및 이용 제한
제 15 조 (계약 해지)
회원이 이용계약을 해지하고자 하는 때에는 [가입해지] 메뉴를 이용해 직접 해지해야 합니다.
제 16 조 (서비스 이용제한)
① 당 사이트는 회원이 서비스 이용내용에 있어서 본 약관 제 11조 내용을 위반하거나, 다음 각 호에 해당하는
경우 서비스 이용을 제한할 수 있습니다.
- 2년 이상 서비스를 이용한 적이 없는 경우
- 기타 정상적인 서비스 운영에 방해가 될 경우
② 상기 이용제한 규정에 따라 서비스를 이용하는 회원에게 서비스 이용에 대하여 별도 공지 없이 서비스 이용의
일시정지, 이용계약 해지 할 수 있습니다.
제 17 조 (전자우편주소 수집 금지)
회원은 전자우편주소 추출기 등을 이용하여 전자우편주소를 수집 또는 제3자에게 제공할 수 없습니다.
제 6 장 손해배상 및 기타사항
제 18 조 (손해배상)
당 사이트는 무료로 제공되는 서비스와 관련하여 회원에게 어떠한 손해가 발생하더라도 당 사이트가 고의 또는 과실로 인한 손해발생을 제외하고는 이에 대하여 책임을 부담하지 아니합니다.
제 19 조 (관할 법원)
서비스 이용으로 발생한 분쟁에 대해 소송이 제기되는 경우 민사 소송법상의 관할 법원에 제기합니다.
[부 칙]
1. (시행일) 이 약관은 2016년 9월 5일부터 적용되며, 종전 약관은 본 약관으로 대체되며, 개정된 약관의 적용일 이전 가입자도 개정된 약관의 적용을 받습니다.