http://www.cancerci.com The latest research articles published by Cancer Cell International 2010-07-28T00:00:00Z This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ We have shown that the microtopography (mT) underlying colon cancer changes as a tumor de-differentiates. We distinguish the well-differentiated mT based on the increasing number of "pits" and poorly differentiated mT on the basis of increasing number of "posts." We investigated Rho A as a mechanosensing protein using mT features derived from those observed in the ECM of colon cancer. We evaluated Rho A activity in less-tumorogenic (Caco 2 E) and more tumorigenic (SW620) colon cancer cell-lines on microfabricated pits and posts at 2.5 m diameter and 200 nm depth/ height. In Caco-2 E cells, we observed a decrease in Rho A activity as well as in the ratio of G/F actin on surfaces with either pits or posts but despite this low activity, knockdown of Rho A led to a significant decrease in confined motility suggesting that while Rho A activity is reduced on these surfaces it still plays an important role in controlling cellular response to barriers. In SW620 cells, we observed that Rho A activity was greatest in cells plated on a post microtopography which led to increased cell motility, and an increase in actin cytoskeletal turnover. http://www.cancerci.com/content/10/1/24 Rebecca Rapier Jameela Huq Ramana Vishnubhotla Marinka Bulic Cecile Perrault Vitali Metlushko Michael Cho Roger Tran Son Tay Sarah Glover Cancer Cell International 2010, 10:24 2010-07-28T00:00:00Z doi:10.1186/1475-2867-10-24 Cancer Cell International 1475-2867 10 24 2010-07-28T00:00:00Z PDF Recent advances in oncology have lead to identification of a plethora of alterations in signaling pathways that are critical to oncogenesis and propagation of malignancy. Among the biomarkers identified, dysregulated kinases and associated changes in signaling cascade received the lion's share of scientific attention and have been under extensive investigations with goal of targeting them for anti-cancer therapy. Discovery of new drugs is immensely facilitated by molecular imaging technology which enables non-invasive, real time, dynamic imaging and quantification of kinase activity. Here, we review recent development of novel kinase reporters based on conformation dependent complementation of firefly luciferase to monitor kinase activity. Such reporter system provides unique insights into the pharmacokinetics and pharmacodynamics of drugs that modulate kinase signaling and have a huge potential in drug discovery, validation, and drug-target interactions. http://www.cancerci.com/content/10/1/23 Shyam Nyati Brian Ross Alnawaz Rehemtulla Mahaveer Bhojani Cancer Cell International 2010, 10:23 2010-07-08T00:00:00Z doi:10.1186/1475-2867-10-23 Cancer Cell International 1475-2867 10 23 2010-07-08T00:00:00Z PDF The association between the wnt signaling pathway and apoptosis has become more firmly established in the recent scientific literature. Many reports indicate that the wnt signaling pathway regulates apoptosis through a variety of mechanisms.The activity of wnt signaling according to specific cellular environment stimuli can either foster or restrain the processes of apoptosis. Wnt signaling regulates the early and late stages of apoptosis in both development and cellular injury in populations of neurons, endothelial cells, vascular smooth muscle cells and cardiomyocytes.In this review I draw attention to genes and proteins of the wnt signaling pathway involved in apoptosis and describe some of their functional effects. http://www.cancerci.com/content/10/1/22 Nives Pecina-Slaus Cancer Cell International 2010, 10:22 2010-06-30T00:00:00Z doi:10.1186/1475-2867-10-22 Cancer Cell International 1475-2867 10 22 2010-06-30T00:00:00Z XML Background: Intravesical immunotherapy with Mycobacterium bovis bacillus Calmette-Guérin has been established as the most effective adjuvant treatment for high risk non-muscle-invasive bladder cancer (NMIBC). We investigated the differences between the S4-Jena BCG strain and commercially available BCG strains. We tested the genotypic varieties between S4-Jena and other BCG strains and analysed the effect of the BCG strains TICE and S4-Jena on two bladder cancer cell lines. Results: In contrast to commercially available BCG strains the S4-Jena strain shows genotypic differences. Spoligotyping verifies the S4-Jena strain as a BCG strain. Infection with viable S4-Jena or TICE decreased proliferation in the T24 cell line. Additionally, hallmarks of apoptosis were detectable. In contrast, Cal29 cells showed only a slightly decreased proliferation with TICE. Cal29 cells infected with S4-Jena, though, showed a significantly decreased proliferation in contrast to TICE. Concordantly with these results, infection with TICE had no effect on the morphology and hallmarks of apoptosis of Cal29 cells. However, S4-Jena strain led to clearly visible morphological changes and caspases 3/7 activation and PS flip. Conclusions: S4-Jena strain has a direct influence on bladder cancer cell lines as shown by inhibition of cell proliferation and induction of apoptosis. The data implicate that the T24 cells are responder for S4-Jena and TICE BCG. However, the Cal29 cells are only responder for S4-Jena and they are non-responder for TICE BCG. S4-Jena strain may represent an effective therapeutic agent for NMIBC. http://www.cancerci.com/content/10/1/21 Katja Schwarzer Martin Foerster Thomas Steiner Inge-Marie Hermann Eberhard Straube Cancer Cell International 2010, 10:21 2010-06-29T00:00:00Z doi:10.1186/1475-2867-10-21 Cancer Cell International 1475-2867 10 21 2010-06-29T00:00:00Z XML Background: Chondrosarcoma responds poorly to adjuvant therapy and new, clinically relevant animal models are required to test targeted therapy. Methods: Two human chondrosarcoma cell lines, JJ012 and FS090, were evaluated for proliferation, colony formation, invasion, angiogenesis and osteoclastogenesis. Cell lines were also investigated for VEGF, MMP-2, MMP-9, and RECK expression. JJ012 and FS090 were injected separately into the mouse tibia intramedullary canal or tibial periosteum. Animal limbs were measured, and x-rayed for evidence of tumour take and progression. Tibias and lungs were harvested to determine the presence of tumour and lung metastases. Results: JJ012 demonstrated significantly higher proliferative capacity, invasion, and colony formation in collagen I gel. JJ012 conditioned medium stimulated endothelial tube formation and osteoclastogenesis with a greater potency than FS090 conditioned medium, perhaps related to the effects of VEGF and MMP-9. In vivo, tumours formed in intratibial and periosteal groups injected with JJ012, however no mice injected with FS090 developed tumours. JJ012 periosteal tumours grew to 3 times the non-injected limb size by 7 weeks, whereas intratibial injected limbs required 10 weeks to achieve a similar tumour size. Sectioned tumour tissue demonstrated features of grade III chondrosarcoma. All JJ012 periosteal tumours (5/5) resulted in lung micro-metastases, while only 2/4 JJ012 intratibial tumours demonstrated metastases. Conclusions: The established JJ012 models replicate the site, morphology, and many behavioural characteristics of human chondrosarcoma. Local tumour invasion of bone and spontaneous lung metastasis offer valuable assessment tools to test the potential of novel agents for future chondrosarcoma therapy. http://www.cancerci.com/content/10/1/20 Jonathan Clark Toru Akiyama Crispin Dass Peter Choong Cancer Cell International 2010, 10:20 2010-06-28T00:00:00Z doi:10.1186/1475-2867-10-20 Cancer Cell International 1475-2867 10 20 2010-06-28T00:00:00Z XML Background: Blockade of the angiotensin (ANG) II type 1 receptor (AT1R) inhibits tumour growth in several cancers, including colorectal cancer (CRC) liver metastases. While AT1R blockade has been extensively studied, the potential of targeting the antagonistically acting AT2R in cancer has not been investigated. This study examined the effect of AT2R activation with the agonist CGP42112A in a mouse model of CRC liver metastases. Results: In vitro, mouse CRC cell (MoCR) proliferation was inhibited by treatment with CGP42112A in a dose dependent manner while apoptosis was increased. Immunofluorescent staining for key signalling and secondary messengers, PLA2 and iNOS, were also increased by CGP42112A treatment in vitro. Immunohistochemical staining for proliferation (PCNA) and the apoptosis (active caspase 3) markers confirmed a CGP42112A-associated inhibition of proliferation and induction of apoptosis of mouse CRC cells (MoCR) in vivo. However, angiogenesis and vascular endothelial growth factor (VEGF) appeared to be increased by CGP42112A treatment in vivo. This increase in VEGF secretion by MoCRs was confirmed in vitro. Despite this apparent pro-angiogenic effect, a syngenic orthotopic mouse model of CRC liver metastases showed a reduction in liver to body weight ratio, an indication of tumour burden, following CGP42112A treatment compared to untreated controls. Conclusions: These results suggest that AT2R activation might provide a novel target to inhibit tumour growth. Its potential to stimulate angiogenesis could be compensated by combination with anti-angiogenic agents. http://www.cancerci.com/content/10/1/19 Eleanor Ager Way Chong Shu-wen Wen Christopher Christophi Cancer Cell International 2010, 10:19 2010-06-28T00:00:00Z doi:10.1186/1475-2867-10-19 Cancer Cell International 1475-2867 10 19 2010-06-28T00:00:00Z XML Background: In this study the effect of myenteric denervation induced by benzalconium chloride (BAC) on distribution of fibrillar components of extracellular matrix (ECM) and inflammatory cells was investigated in gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Rats were divided in four experimental groups: non-denervated (I) and denervated stomach (II) without MNNG treatment; non-denervated (III) and denervated stomachs (IV) treated with MNNG. For histopathological, histochemical and stereological analysis, sections of gastric fragments were stained with Hematoxylin-Eosin, Picrosirius-Hematoxylin, Gomori reticulin, Weigert's Resorcin-Fuchsin, Toluidine Blue and Alcian-Blue/Safranin (AB-SAF). Results: BAC denervation causes an increase in the frequency of reticular and elastic fibers in the denervated (group II) compared to the non-denervated stomachs (group I). The treatment of the animals with MNNG induced the development of adenocarcinomas in non-denervated and denervated stomachs (groups III and IV, respectively) with a notable increase in the relative volume of the stroma, the frequency of reticular fibers and the inflammatory infiltrate that was more intense in group IV. An increase in the frequency of elastic fibers was observed in adenocarcinomas of denervated (group IV) compared to the non-denervated stomachs (group III) that showed degradation of these fibers. The development of lesions (groups III and IV) was also associated with an increase in the mast cell population, especially AB and AB-SAF positives, the latter mainly in the denervated group IV. Conclusions: The results show a strong association in the morphological alteration of the ECM fibrillar components, the increased density of mast cells and the development of tumors induced by MNNG in the non-denervated rat stomach or denervated by BAC. This suggests that the study of extracellular and intracellular components of tumor microenvironment contributes to understanding of tumor biology by action of myenteric denervation. http://www.cancerci.com/content/10/1/18 Cassia Estofolete Carla Botelho-Machado Sebastiao Taboga Sergio Zucoloto Ana Claudia Polli-Lopes Cristiane Gil Cancer Cell International 2010, 10:18 2010-06-22T00:00:00Z doi:10.1186/1475-2867-10-18 Cancer Cell International 1475-2867 10 18 2010-06-22T00:00:00Z XML Background: The present study mainly aimed to investigate the direct effects of Endostar (ES) on the proliferation and radiosensitivity of human lung squamous cancer cell line H-520. Results: ES significantly inhibited H-520 cell proliferation in a time- and dose-dependent manner. According to the colony-forming assays, ES could increase the H-520 cell radiosensitivity. ES induced cell apoptosis, the apoptosis rate increased with the raise of ES concentration. Irradiation induced significantly higher apoptosis rate in ES-treated H-520 cells than non-treated H-520 cells. ES induced cell cycle distribution and G0/G1 arrest in H-520 cells, whereas irradiation induced G2/M arrest. The phospho-p38-MAPK and p-Akt protein levels were decreased in H-520 cells after ES treatment. Furthermore, activated caspase protein level increased and Bcl-2 protein levels decreased after treatment with ES and irradiation. Conclusion: ES significantly enhanced the sensitivity of H-520 cells to irradiation by inhibition of cellular proliferation, promotion of cell apoptosis and redistribution of cell cycle, possibly via deactivation of Akt pathway. The present study supports the possibility to use the combination of ES and ionizing irradiation to treat patients with lung squamous cell cancer in clinics. http://www.cancerci.com/content/10/1/17 Zhen Y You Yong Zhao Feng Liu Ying D Zhang Jun J Wang Cancer Cell International 2010, 10:17 2010-05-24T00:00:00Z doi:10.1186/1475-2867-10-17 Cancer Cell International 1475-2867 10 17 2010-05-24T00:00:00Z XML Background: Ovarian cancer is one of the most significant malignancies in the western world. Studies showed that Ovarian cancers tend to grow resistance to cisplatin treatment. Therefore, new approaches are needed in ovarian cancer treatment. Kaempferol is a dietary flavonoid that is widely distributed in fruits and vegetables, and epidemiology studies have revealed a protective effect of kaempferol against ovarian cancer risk. Our early studies also found that kaempferol is effective in reducing vascular endothelial growth factor (VEGF) expression in ovarian cancer cells. In this study, we investigated kaempferol's effects on sensitizing ovarian cancer cell growth in response to cisplatin treatment. Results: Ten chemicals were screened for sensitizing OVCAR-3 ovarian cancer cell growth in response to cisplatin treatment. For kaempferol, which shows a significant synergistic interaction with cisplatin, expression of ABCC1, ABCC5, ABCC6, NFkB1, cMyc, and CDKN1A genes was further examined. For cisplatin/kaempferol treatments on OVCAR-3 cancer cells, the mRNA levels of ABCC1, ABCC5, and NFkB1 did not change. However, significant inhibition of ABCC6 and cMyc mRNA levels was observed for the cisplatin/kaempferol combined treatment. The CDKN1A mRNA levels were significantly up-regulated by cisplatin/kaempferol treatment. A plot of CDKN1A mRNA levels against that of cMyc gene further revealed a reverse, linear relationship, proving cMyc's regulation on CDKN1A gene expressions. Our work found that kaempferol works synergistically with cisplatin in inhibiting ovarian cancer cell viability, and their inhibition on cell viabilities was induced through inhibiting ABCC6 and cMyc gene transcription. Apoptosis assay showed the addition of 20 μM kaempferol to the cisplatin treatment induces the apoptosis of the cancer cells. Conclusions: Kaempferol enhances the effect of cisplatin through down regulation of cMyc in promoting apoptosis of ovarian cancer cells. As a dietary component, kaempferol sensitizes ovarian cancer cells to cisplatin treatment and deserves further studies for possible applications in chemotherapy of ovarian cancers. http://www.cancerci.com/content/10/1/16 Haitao Luo Matthew Daddysman Gary Rankin Bing-Hua Jiang Yi Chen Cancer Cell International 2010, 10:16 2010-05-11T00:00:00Z doi:10.1186/1475-2867-10-16 Cancer Cell International 1475-2867 10 16 2010-05-11T00:00:00Z XML Background: Micro(mi)RNAs are a class of small non-coding RNAs that play critical roles in the induction of various cancers, including lymphomas induced by oncogenic viruses. While some of the miRNAs are oncogenic, miRNAs such as miR-26a are consistently downregulated in a number of cancers, demonstrating their potential tumor suppressor functions. Global miRNA expression profiles of a number of virus-transformed avian lymphoma cell lines have shown downregulation of gga-miR-26a expression, irrespective of molecular mechanisms of transformation or the viral aetiology. The neoplastic transformation of lymphocytes by many viruses accompanies high levels of proliferative responses, mostly mediated through cytokines such as IL-2. Chicken IL-2 can modulate T-cell proliferation and cytotoxicity in vitro and in vivo and dysregulation of IL-2 expression is observed in diseases such as leukaemia. Results: The expression levels of gga-miR-26a in chicken lymphoma cells transformed by 3 distinct avian oncogenic viruses, viz Marek's disease virus (MDV), avian leukosis virus (ALV) and Reticuloendotheliosis virus (REV) were consistently downregulated compared to the levels in the normal lymphocytes. This downregulation of miR-26a regardless of the viral etiology and molecular mechanisms of transformation was consistent with the tumor suppressor role of this miRNA. Notwithstanding this well-established role in cancer, we demonstrate the additional role of this miRNA in directly targeting chicken IL-2 through reporter and biochemical assays. The downregulation of miR-26a can relieve the suppressive effect of this miRNA on IL-2 expression. Conclusions: We show that miR-26a is globally downregulated in a number of avian lymphoma cells irrespective of the mechanisms of transformation, reiterating the highly conserved tumor suppressor function of this miRNA. However, with the potential for directly targeting chicken IL-2, the downregulation of miR-26a in these tumor cells could relieve the inhibitory effect on IL-2 expression assisting in the proliferative features of the transformed lymphocyte lines. http://www.cancerci.com/content/10/1/15 Hongtao Xu Yongxiu Yao Lorraine Smith Venugopal Nair Cancer Cell International 2010, 10:15 2010-05-04T00:00:00Z doi:10.1186/1475-2867-10-15 Cancer Cell International 1475-2867 10 15 2010-05-04T00:00:00Z XML