149,824 research outputs found

    MiRNA-145 increases therapeutic sensibility to gemcitabine treatment of pancreatic adenocarcinoma cells.

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    Pancreatic adenocarcinoma is one of the most leading causes of cancer-related deaths worldwide. Although recent advances provide various treatment options, pancreatic adenocarcinoma has poor prognosis due to its late diagnosis and ineffective therapeutic multimodality. Gemcitabine is the effective first-line drug in pancreatic adenocarcinoma treatment. However, gemcitabine chemoresistance of pancreatic adenocarcinoma cells has been a major obstacle for limiting its treatment effect. Our study found that p70S6K1 plays an important role in gemcitabine chemoresistence. MiR-145 is a tumor suppressor which directly targets p70S6K1 for inhibiting its expression in pancreatic adenocarcinoma, providing new therapeutic scheme. Our findings revealed a new mechanism underlying gemcitabine chemoresistance in pancreatic adenocarcinoma cells

    Deregulation of the CEACAM Expression Pattern Causes Undifferentiated Cell Growth in Human Lung Adenocarcinoma Cells

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    CEACAM1, CEA/CEACAM5, and CEACAM6 are cell adhesion molecules (CAMs) of the carcinoembryonic antigen (CEA) family that have been shown to be deregulated in lung cancer and in up to 50% of all human cancers. However, little is known about the functional impact of these molecules on undifferentiated cell growth and tumor progression. Here we demonstrate that cell surface expression of CEACAM1 on confluent A549 human lung adenocarcinoma cells plays a critical role in differentiated, contact-inhibited cell growth. Interestingly, CEACAM1-L, but not CEACAM1-S, negatively regulates proliferation via its ITIM domain, while in proliferating cells no CEACAM expression is detectable. Furthermore, we show for the first time that CEACAM6 acts as an inducer of cellular proliferation in A549 cells, likely by interfering with the contact-inhibiting signal triggered by CEACAM1-4L, leading to undifferentiated anchorage-independent cell growth. We also found that A549 cells expressed significant amounts of non-membrane anchored variants of CEACAM5 and CEACAM6, representing a putative source for the increased CEACAM5/6 serum levels frequently found in lung cancer patients. Taken together, our data suggest that post-confluent contact inhibition is established and maintained by CEACAM1-4L, but disturbances of CEACAM1 signalling by CEACAM1-4S and other CEACAMs lead to undifferentiated cell growth and malignant transformation

    Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway

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    BACKGROUND: Prostaglandin E(2) (PGE(2)) has been shown to modulate angiogenesis and tumour progression via the E-series prostanoid-2 (EP2) receptor. Endometrial adenocarcinomas may be exposed to endogenous PGE(2) and exogenous PGE(2), present at high concentration in seminal plasma. METHODS: This study investigated fibroblast growth factor 2 (FGF2) mRNA expression and cell signalling in response to seminal plasma or PGE(2), using an endometrial adenocarcinoma (Ishikawa) cell line stably expressing the EP2 receptor (EP2 sense cells) and endometrial adenocarcinoma explants. RESULTS: Seminal plasma and PGE(2) induced a significant up-regulation of FGF2 expression in EP2 sense but not parental untransfected Ishikawa (wild-type) cells (P < 0.05). These effects were inhibited by co-treatment with EP2 receptor antagonist or inhibitors of protein kinase A, c-Src, epidermal growth factor receptor (EGFR) kinase or extracellular signal-regulated kinase (ERK) signalling. The treatment of EP2 sense cells with seminal plasma induced cAMP accumulation and phosphorylation of c-Src, EGFR kinase and ERK via the EP2 receptor. Finally, seminal plasma and PGE(2) significantly increased FGF2 mRNA expression in endometrial adenocarcinoma tissue explants via the EP2 receptor (P < 0.05). CONCLUSIONS: Seminal plasma and PGE(2) can similarly activate FGF2 expression and EP2 receptor signalling in endometrial adenocarcinoma cells. These data highlight the potential for seminal plasma exposure to facilitate tumorigenesis–angiogenesis in endometrial adenocarcinomas in vivo

    Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway

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    We report a multiwavelength (X-ray, ultraviolet/optical/infrared, radio) analysis of the relativistic tidal disruption event candidate Sw J2058+05 from 3 months to 3 yr post-discovery in order to study its properties and compare its behavior with that of Sw J1644+57. Our main results are as follows. (1) The long-term X-ray light curve of Sw J2058+05 shows a remarkably similar trend to that of Sw J1644+57. After a prolonged power-law decay, the X-ray flux drops off rapidly by a factor of ≳160\gtrsim 160 within a span of Δ\Deltatt/tt ≤\le 0.95. Associating this sudden decline with the transition from super-Eddington to sub-Eddington accretion, we estimate the black hole mass to be in the range of 104−610^{4-6} M⊙_{\odot}. (2) We detect rapid (≲500\lesssim 500 s) X-ray variability before the dropoff, suggesting that, even at late times, the X-rays originate from close to the black hole (ruling out a forward-shock origin). (3) We confirm using HST and VLBA astrometry that the location of the source coincides with the galaxy's center to within ≲400\lesssim 400 pc (in projection). (4) We modeled Sw J2058+05's ultraviolet/optical/infrared spectral energy distribution with a single-temperature blackbody and find that while the radius remains more or less constant at a value of 63.4±4.563.4 \pm 4.5 AU (∼1015\sim 10^{15} cm) at all times during the outburst, the blackbody temperature drops significantly from ∼\sim 30,000 K at early times to a value of ∼\sim 15,000 K at late times (before the X-ray dropoff). Our results strengthen Sw J2058+05's interpretation as a tidal disruption event similar to Sw J1644+57.Comment: Replaced with the published version of the manuscrip

    Analysis Expression of ZIP1 and Caspase-3 Protein in Adenocarsinoma of the Prostate

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    Background: Carcinogenesis of adenocarcinoma of the prostate occurs due to dysregulation of zinc level within the cells. Intracellular zinc molecules influx is regulated by a transporter protein ZIP1, whose non-presence is predicted to inhibit apoptosis, thus leads to the development of prostate adenocarcinoma. Methods: This study was aimed to analyse the correlation of ZIP1 and Caspase-3 expression in prostate adenocarcinoma on its grading as represented by Gleason Score. This was a cross-sectional, retrospective analytical study on 31 Formalin-fixed, paraffin-embedded tissue that meets inclusion criteria. The specimen was stained using the immune-histochemistry technique for ZIP1 and Caspase-3. Protein expression of each case was counted using ImageJ analysis. Gleason score was acquired as secondary data from the cases' reports. The correlation of their expression with respect to Gleason score was analysed with Pearson's correlation using SPSS 11.5. Results: Mean expression level of ZIP1 and Caspase-3 in prostate adenocarcinoma were 35% and 33%, respectively. There was a significantly positive correlation between ZIP1 and Caspase-3 expression (r=0.379; p=0.018). However, their correlation was stronger in intermediate-grade group (r=0.73; p=0.01) and the correlation was much weaker in high-grade group (r=0.04; p=0.48). Conclusions: There was a positive correlation between ZIP1 and Caspase-3 expression in prostate adenocarcinoma.&nbsp

    Endocervical glandular neoplasia associated with lobular endocervical glandular hyperplasia is HPV-independent and correlates with carbonic anhydrase-IX expression: a Gynaecological Oncology Group Study.

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    BackgroundLobular endocervical glandular hyperplasia (LEGH) is a rare lesion of the uterine cervix. It has been proposed that LEGH may represent a precursor lesion to a group of mucinous adenocarcinoma with gastric phenotype (GA) that is independent of high-risk human papillomavirus (H-HPV) infection. Carbonic anhydrase-IX (CA-IX) is highly expressed in conventional glandular lesions (CGLs). However, expression of CA-IX in LEGH or GA has not been studied.MethodsIn all, 12 CGLs, 7 LEGHs, 6 LEGHs with coexisting adenocarcinoma in situ (AIS, 3) and GA (3) were identified from Japanese women with a cytological diagnosis of atypical glandular cells of undetermined significance. Immunostaining was used to detect CA-IX and p16(INK)4(a) (hereafter termed p16) protein expression in the tissues and CA-IX protein expression in the Papanicolaou smears (PSs). Polymerase chain reaction was used to detect H-HPV DNA in liquid-based cytology.ResultsOut of 12 (83%) CGLs, 10 were positive with H-HPV and high levels of CA-IX expression were seen in all (100%) cases. P16 protein expression was observed in 11 out of 12 (92%) cases. None of the LEGHs, LEGHs with AIS or GA were positive for H-HPV and only 8 out of 13 (62%) showed focal weak (1+) p16 expression. In contrast, all cases (100%) exhibited strong CA-IX protein expression.ConclusionOur study suggests that there are different molecular mechanisms of carcinogenesis resulting in CGLs vs LEGHs associated with AIS or GA. There is also a possible link between LEGHs and GAs. Furthermore, CA-IX expression may serve as a useful biomarker for the detection of GAs in the absence of H-HPV infection

    Common activation of canonical Wnt signaling in pancreatic adenocarcinoma.

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    Pancreatic ductal adenocarcinoma (PDA) is an extremely aggressive malignancy, which carries a dismal prognosis. Activating mutations of the Kras gene are common to the vast majority of human PDA. In addition, recent studies have demonstrated that embryonic signaling pathway such as Hedgehog and Notch are inappropriately upregulated in this disease. The role of another embryonic signaling pathway, namely the canonical Wnt cascade, is still controversial. Here, we use gene array analysis as a platform to demonstrate general activation of the canonical arm of the Wnt pathway in human PDA. Furthermore, we provide evidence for Wnt activation in mouse models of pancreatic cancer. Our results also indicate that Wnt signaling might be activated downstream of Hedgehog signaling, which is an early event in PDA evolution. Wnt inhibition blocked proliferation and induced apoptosis of cultured adenocarcinoma cells, thereby providing evidence to support the development of novel therapeutical strategies for Wnt inhibition in pancreatic adenocarcinoma

    Inhibition of yes-associated protein suppresses brain metastasis of human lung adenocarcinoma in a murine model.

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    Yes-associated protein (YAP) is a main mediator of the Hippo pathway and promotes cancer development and progression in human lung cancer. We sought to determine whether inhibition of YAP suppresses metastasis of human lung adenocarcinoma in a murine model. We found that metastatic NSCLC cell lines H2030-BrM3(K-rasG12C mutation) and PC9-BrM3 (EGFRΔexon19 mutation) had a significantly decreased p-YAP(S127)/YAP ratio compared to parental H2030 (K-rasG12C mutation) and PC9 (EGFRΔexon19 mutation) cells (P&nbsp;&lt;&nbsp;.05). H2030-BrM3 cells had significantly increased YAP mRNA and expression of Hippo downstream genes CTGF and CYR61 compared to parental H2030 cells (P&nbsp;&lt;&nbsp;.05). Inhibition of YAP by short hairpin RNA (shRNA) and small interfering RNA (siRNA) significantly decreased mRNA expression in downstream genes CTGF and CYR61 in H2030-BrM3 cells (P&nbsp;&lt;&nbsp;.05). In addition, inhibiting YAP by YAP shRNA significantly decreased migration and invasion abilities of H2030-BrM3 cells (P&nbsp;&lt;&nbsp;.05). We are first to show that mice inoculated with YAP shRNA-transfected H2030-BrM3 cells had significantly decreased metastatic tumour burden and survived longer than control mice (P&nbsp;&lt;&nbsp;.05). Collectively, our results suggest that YAP plays an important role in promoting lung adenocarcinoma brain metastasis and that direct inhibition of YAP by shRNA suppresses H2030-BrM3 cell brain metastasis in a murine model

    Periacinar clefting and p63 immunostaining in prostatic intraepithelial neoplasia and prostatic carcinoma

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    The aim of the present study was to correlate the presence and extent of retraction clefting and the expression of p63 in neoplastic glands and glands with prostatic intraepithelial neoplasia (PIN) in needle core biopsies. We analyzed needle core biopsies from 28 patients with PIN and 41 patients with adenocarcinoma. Neoplastic glands and those with PIN were analyzed on high power field (400x) and classified in three groups according to the extent of clefting. Immunohistochemical staining was performed following Microwave Streptavidin ImmunoPeroxidase (MSIP) protocol on DAKO TechMate Horizon automated immunostainer. Periacinar retraction clefting was significantly more prominent in prostatic carcinoma compared to PIN (p<0.0001) and nonneoplastic glands (p<0.0001). There was no difference between normal glands and PIN regarding clefting (p=0.8064). p63 was positive around the whole circumference in 12 out of 28 cases with PIN, and discontinuously positive in remaining 16 PIN cases suggesting initial disruption of the basal cell layer. p63 immunostaining was also positive in all nonneoplastic glands, and negative in all carcinomas. We conclude that retraction clefting was associated with cancer and lack of basal cells, but not with PIN. The relationship between clefting and p63 immunostaining in prostatic cancer should be further analyzed
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