http://www.cancerci.com The most accessed research articles published by Cancer Cell International 2012-04-11T00:00:00Z For over 30 years, stem cells have been used in the replenishment of blood and immune systems damaged by the cancer cells or during treatment of cancer by chemotherapy or radiotherapy. Apart from their use in the immuno-reconstitution, the stem cells have been reported to contribute in the tissue regeneration and as delivery vehicles in the cancer treatments. The recent concept of 'cancer stem cells' has directed scientific communities towards a different wide new area of research field and possible potential future treatment modalities for the cancer. Aim of this review is primarily focus on the recent developments in the use of the stem cells in the cancer treatments, then to discuss the cancer stem cells, now considered as backbone in the development of the cancer; and their role in carcinogenesis and their implications in the development of possible new cancer treatment options in future. http://www.cancerci.com/content/7/1/9 Jayesh Sagar Boussad Chaib Kevin Sales Marc Winslet Alexander Seifalian Cancer Cell International 2007, null:9 2007-06-04T00:00:00Z doi:10.1186/1475-2867-7-9 /content/figures/1475-2867-7-9-toc.gif Cancer Cell International 1475-2867 ${item.volume} 9 2007-06-04T00:00:00Z XML Background: Dysregulation of many apoptotic related genes and androgens are critical in the development, progression, and treatment of prostate cancer. The differential sensitivity of tumour cells to TRAIL-induced apoptosis can be mediated by the modulation of surface TRAIL receptor expression related to androgen concentration. Our previous results led to the hypothesis that downregulation of TRAIL-decoy receptor DcR2 expression following androgen deprivation would leave hormone sensitive normal prostate cells vulnerable to the cell death signal generated by TRAIL via its pro-apoptotic receptors. We tested this hypothesis under pathological conditions by exploring the regulation of TRAIL-induced apoptosis related to their death and decoy receptor expression, as also to hormonal concentrations in androgen-sensitive human prostate cancer, LNCaP, cells. Results: In contrast to androgen-insensitive PC3 cells, decoy (DcR2) and death (DR5) receptor protein expression was correlated with hormone concentrations and TRAIL-induced apoptosis in LNCaP cells. Silencing of androgen-sensitive DcR2 protein expression by siRNA led to a significant increase in TRAIL-mediated apoptosis related to androgen concentration in LNCaP cells. Conclusions: The data support the hypothesis that hormone modulation of DcR2 expression regulates TRAIL-induced apoptosis in LNCaP cells, giving insight into cell death induction in apoptosis-resistant hormone-sensitive tumour cells from prostate cancer. TRAIL action and DcR2 expression modulation are potentially of clinical value in advanced tumour treatment. http://www.cancerci.com/content/11/1/42 David Vindrieux Marie Reveiller Jacqueline Chantepie Sadok Yakoub Catherine Deschildre Alain Ruffion Marian Devonec Mohamed Benahmed Renee Grataroli Cancer Cell International 2011, null:42 2011-12-02T00:00:00Z doi:10.1186/1475-2867-11-42 /content/figures/1475-2867-11-42-toc.gif Cancer Cell International 1475-2867 ${item.volume} 42 2011-12-02T00:00:00Z XML Background: Glioblastoma is the most aggressive form of brain tumors showing resistance to treatment with various chemotherapeutic agents. The most effective way to eradicate glioblastoma requires the concurrent inhibition of multiple signaling pathways and target molecules involved in the progression of glioblastoma. Recently, we obtained a series of 1,2,3,4-tetrahydroisoquinoline alkaloids with potent anti-cancer activities, including ecteinascidin-770 (ET-770; the compound 1a) and renieramycin M (RM; the compound 2a) from Thai marine invertebrates, together with a 2'-N-4"-pyridinecarbonyl derivative of ET-770 (the compound 3). We attempted to characterize the molecular pathways responsible for cytotoxic effects of these compounds on a human glioblastoma cell line U373MG. Methods: We studied the genome-wide gene expression profile on microarrays and molecular networks by using pathway analysis tools of bioinformatics. Results: All of these compounds induced apoptosis of U373MG cells at nanomolar concentrations. The compound 3 reduced the expression of 417 genes and elevated the levels of 84 genes, while ET-770 downregulated 426 genes and upregulated 45 genes. RM decreased the expression of 274 genes and increased the expression of 9 genes. The set of 196 downregulated genes and 6 upregulated genes showed an overlap among all the compounds, suggesting an existence of the common pathways involved in induction of apoptosis. We identified the ErbB (EGFR) signaling pathway as one of the common pathways enriched in the set of downregulated genes, composed of PTK2, AKT3, and GSK3B serving as key molecules that regulate cell movement and the nervous system development. Furthermore, a GSK3B-specific inhibitor induced apoptosis of U373MG cells, supporting an anti-apoptotic role of GSK3B. Conclusion: Molecular network analysis is a useful approach not only to characterize the glioma-relevant pathways but also to identify the network-based effective drug targets. http://www.cancerci.com/content/12/1/14 Hiroko Tabunoki Naoki Saito Khanit Suwanborirux Kornvika Charupant Jun-ichi Satoh Cancer Cell International 2012, null:14 2012-04-11T00:00:00Z doi:10.1186/1475-2867-12-14 /content/figures/1475-2867-12-14-toc.gif Cancer Cell International 1475-2867 ${item.volume} 14 2012-04-11T00:00:00Z PDF Background: The Notch signaling pathway is crucial in T-cell development, Notch1 mutations are frequently present in T-cell acute lymphoblastic leukemia (T-ALL). To investigate the feature of Notch1 mutation and its corresponding expression level in Chinese patients with T-ALL, detection of mutation and the expression level of Notch1 gene was preformed using RT-PCR, sequencing and real-time PCR respectively. Results: Two Notch1 point mutations (V1578E and L1593P) located on HD-N domain were identified in three cases out of 13 T-ALL patients. The mutation on 4733 position (V1578E) found in two cases was a novel mutation. The overexpression of Notch1 was detected in all samples with T-ALL, moreover, significantly higher expression of Notch1 was detected in the T-ALL with Notch1 mutation group compared with T-ALL with WT Notch1 group (p = 0.0192). Conclusions: Higher expression of Notch1 was associated with Notch1 mutation, more novel mutation of this gene might be identified in different populations and its contribution to the molecular pathogenesis of T-ALL is needed further research. http://www.cancerci.com/content/12/1/13 Chunlan Lin Haitao Zheng Chunyan Wang Lijian Yang Shaohua Chen Bo Li Yubing Zhou Huo Tan Yangqiu Li Cancer Cell International 2012, null:13 2012-04-05T00:00:00Z doi:10.1186/1475-2867-12-13 /content/figures/1475-2867-12-13-toc.gif Cancer Cell International 1475-2867 ${item.volume} 13 2012-04-05T00:00:00Z XML Background: Despite significant achievements in the treatment of cervical cancer, it is still a deadly disease; hence newer therapeutical modalities are needed. Preliminary investigations suggest that platelet-derived growth factor (PDGF) might have a role in the development of cervical cancer, therefore it is important to determine whether this growth factor pathway is functional and its targeting with imatinib mesylate leads to growth inhibition of cervical cancer cells. Results: PDGF receptors (PDGFR) and their ligands are frequently expressed in cervical cancer and the majority exhibited a combination of family members co-expression. A number of intronic and exonic variations but no known mutations in the coding sequence of the PDGFRα gene were found in cancer cell lines and primary tumors. Growth assays demonstrated that PDGFBB induces growth stimulation that can be blocked by imatinib and that this tyrosine kinase inhibitor on its own inhibits cell growth. These effects were associated with the phosphorylation status of the receptor. Conclusion: The PDGFR system may have a role in the pathogenesis of cervical cancer as their members are frequently expressed in this tumor and cervical cancer lines are growth inhibited by the PDGFR antagonist imatinib. http://www.cancerci.com/content/6/1/22 Lucia Taja-Chayeb Alma Chavez-Blanco Jorge Martinez-Tlahuel Aurora Gonzalez-Fierro Myrna Candelaria Jose Chanona-Vilchis Elizabeth Robles Alfonso Duenas-Gonzalez Cancer Cell International 2006, null:22 2006-10-02T00:00:00Z doi:10.1186/1475-2867-6-22 /content/figures/1475-2867-6-22-toc.gif Cancer Cell International 1475-2867 ${item.volume} 22 2006-10-02T00:00:00Z XML We describe the basic tenets of the current concepts of cancer biology, and review the recent advances on the suppressor role of senescence in tumor growth and the breakdown of this barrier during the origin of tumor growth. Senescence phenotype can be induced by (1) telomere attrition-induced senescence at the end of the cellular mitotic life span (MLS*) and (2) also by replication history-independent, accelerated senescence due to inadvertent activation of oncogenes or by exposure of cells to genotoxins. Tumor suppressor genes p53/pRB/p16INK4A and related senescence checkpoints are involved in effecting the onset of senescence. However, senescence as a tumor suppressor mechanism is a leaky process and senescent cells with mutations or epimutations in these genes escape mitotic catastrophe-induced cell death by becoming polyploid cells. These polyploid giant cells, before they die, give rise to several cells with viable genomes via nuclear budding and asymmetric cytokinesis. This mode of cell division has been termed neosis and the immediate neotic offspring the Raju cells. The latter inherit genomic instability and transiently display stem cell properties in that they differentiate into tumor cells and display extended, but, limited MLS, at the end of which they enter senescent phase and can undergo secondary/tertiary neosis to produce the next generation of Raju cells. Neosis is repeated several times during tumor growth in a non-synchronized fashion, is the mode of origin of resistant tumor growth and contributes to tumor cell heterogeneity and continuity. The main event during neosis appears to be the production of mitotically viable daughter genome after epigenetic modulation from the non-viable polyploid genome of neosis mother cell (NMC). This leads to the growth of resistant tumor cells. Since during neosis, spindle checkpoint is not activated, this may give rise to aneuploidy. Thus, tumor cells also are destined to die due to senescence, but may escape senescence due to mutations or epimutations in the senescent checkpoint pathway. A historical review of neosis-like events is presented and implications of neosis in relation to the current dogmas of cancer biology are discussed. Genesis and repetitive re-genesis of Raju cells with transient "stemness" via neosis are of vital importance to the origin and continuous growth of tumors, a process that appears to be common to all types of tumors. We suggest that unlike current anti-mitotic therapy of cancers, anti-neotic therapy would not cause undesirable side effects. We propose a rational hypothesis for the origin and progression of tumors in which neosis plays a major role in the multistep carcinogenesis in different types of cancers. We define cancers as a single disease of uncontrolled neosis due to failure of senescent checkpoint controls. http://www.cancerci.com/content/6/1/25 Rengaswami Rajaraman Duane Guernsey Murali Rajaraman Selva Rajaraman Cancer Cell International 2006, null:25 2006-11-08T00:00:00Z doi:10.1186/1475-2867-6-25 /content/figures/1475-2867-6-25-toc.gif Cancer Cell International 1475-2867 ${item.volume} 25 2006-11-08T00:00:00Z XML Background: Although the primary risk factors for developing oral cancers are well understood, less is known about the relationship among the secondary factors that may modulate the progression of oral cancers, such as high-risk human papillomavirus (HPV) infection and folic acid (FA) supplementation. This study examined high-risk HPV and FA supplementation effects, both singly and in combination, to modulate the proliferative phenotypes of the oral cancer cell lines CAL27, SCC25 and SCC15. Results: Using a comprehensive series of integrated in vitro assays, distinct effects of HPV infection and FA supplementation were observed. Both high-risk HPV strains 16 and 18 induced robust growth-stimulating effects in CAL27 and normal HGF-1 cells, although strain-specific responses were observed in SCC25 and SCC15 cells. Differential effects were also observed with FA administration, which significantly altered the growth rate of the oral cancer cell lines CAL27, SCC15, and SCC25, but not HGF-1 cells. Unlike HPV, FA administration induced broad, general increases in cell viability among all cell lines that were associated with p53 mRNA transcriptional down-regulation. None of these cell lines were found to harbor the common C677T mutation in methylenetetrahydrofolate reductase (MTHFR), which can reduce FA availability and may increase oral cancer risk. Conclusion: Increased FA utilization and DNA hypermethylation are common features of oral cancers, and in these cell lines, specifically. The results of this study provide further evidence that FA antimetabolites, such as Fluorouracil (f5U or 5-FU) and Raltitrexed, may be alternative therapies for tumors resistant to other therapies. Moreover, since the incidence of oral HPV infection has been increasing, and can influence oral cancer growth, the relationship between FA bioavailability and concomitant HPV infection must be elucidated. This study is among the first pre-clinical studies to evaluate FA- and HPV-induced effects in oral cancers, both separately and in combination, which provides additional rationale for clinical screening of HPV infection prior to treatment. http://www.cancerci.com/content/12/1/10 Michael Moody Oanh Le Megan Rickert Jeremy Manuele Sarah Chang Gary Robinson Jeffrey Hajibandeh John Silvaroli Mark Keiserman Christine Bergman Karl Kingsley Cancer Cell International 2012, null:10 2012-03-23T00:00:00Z doi:10.1186/1475-2867-12-10 /content/figures/1475-2867-12-10-toc.gif Cancer Cell International 1475-2867 ${item.volume} 10 2012-03-23T00:00:00Z XML Background: The effect of cell injury and apoptosis induced by ultrasound with contrast agent has been verified. Contrast agent enhanced apoptosis and expression of genes that related to apoptosis and are responsive to ultrasound. This effect was associated with reactive oxygen species (ROS) production induced by the sonochemical reaction, as reported in previous studies. NF-kappa B may be one of the factors involved in oxidizing reactions or modulation during the process of ultrasound inducing apoptosis. Results: Ultrasound irradiated gastric cancer cells (SGC7901 cell line) and hepatocellular carcinoma cells (SMMC-771 cell line) cultured in medium containing contrast agent. Significant cellular damage and apoptosis were observed in the bath cells incubated for 24 hours following 120 seconds ultrasonic irradiation. I kappa B alfa expression synchronously increased in the treatment groups of both the cell lines, and the down-regulated expression of NF-kappa B influenced its-regulated expression of genes that related to apoptosis. Production of intracellular ROS and elevation of NF-kappa B level occurred after incubation of the cells for 1 hour following ultrasonic treatment. Conclusions: Our result suggested that contrast agent enhanced the biological effect of ultrasound. Their reaction might stimulate the transitory expression of NF-kappaB, and subsequent elevation in IκBalfa expression could lead to the apoptosis of SGC7901 cells and SMMC-771 cells. http://www.cancerci.com/content/12/1/8 Zao Jiang Wei Wu Meng-Lu Qian Cancer Cell International 2012, null:8 2012-03-15T00:00:00Z doi:10.1186/1475-2867-12-8 /content/figures/1475-2867-12-8-toc.gif Cancer Cell International 1475-2867 ${item.volume} 8 2012-03-15T00:00:00Z XML Background: Zerumbone is a cytotoxic component isolated from Zingiber zerumbet Smith, a herbal plant which is also known as lempoyang. This new anticancer bioactive compound from Z. zerumbet was investigated for its activity and mechanism in human liver cancer cell lines. Results: Zerumbone significantly showed an antiproliferative activity upon HepG2 cells with an IC50 of 3.45 ± 0.026 μg/ml. Zerumbone was also found to inhibit the proliferation of non-malignant Chang Liver and MDBK cell lines. However the IC50 obtained was higher compared to the IC50 for HepG2 cells (> 10 μg/ml). The extent of DNA fragmentation was evaluated by the Tdt-mediated dUTP nick end labelling assay which showed that, zerumbone significantly increased apoptosis in HepG2 cells in a time-course manner. In detail, the apoptotic process triggered by zerumbone involved the up-regulation of pro-apoptotic Bax protein and the suppression of anti-apoptotic Bcl-2 protein expression. The changes that occurred in the levels of this antagonistic proteins Bax/Bcl-2, was independent of p53 since zerumbone did not affect the levels of p53 although this protein exists in a functional form. Western blotting analysis for Bax protein was further confirmed qualitatively with an immunoassay that showed the distribution of Bax protein in zerumbone-treated cells. Conclusion: Therefore, zerumbone was found to induce the apoptotic process in HepG2 cells through the up and down regulation of Bax/Bcl-2 protein independently of functional p53 activity. http://www.cancerci.com/content/7/1/4 S.a. Sharifah Sakinah S. Tri Handayani L.p. Azimahtol Hawariah Cancer Cell International 2007, null:4 2007-04-03T00:00:00Z doi:10.1186/1475-2867-7-4 /content/figures/1475-2867-7-4-toc.gif Cancer Cell International 1475-2867 ${item.volume} 4 2007-04-03T00:00:00Z XML This study progresses in the direction of identifying component(s) from the Mediterranean sponge, Spongia officinalis with anticonvulsant and analgesic activities. We investigated the efficacy of crude extract and its semi-purified fractions (F1-F3) of the defensive secretion from Spongia officinalis for their in vivo anticonvulsant activity using the pentylenetetrazole (PTZ) seizure model and analgesic activity using the writhing test in mice. Among the series the crude extract exhibited interesting analgesic activity in a dose dependent manner. Similarly the fraction F2 showed a partial protection of mice from PTZ-induced seizure and interesting analgesic activity in a dose dependent manner. The purification and the determination of chemical structure(s) of compound(s) of this active fraction are under investigation. http://www.cancerci.com/content/12/1/15 Afef Dellai Cancer Cell International 2012, null:15 2012-04-11T00:00:00Z doi:10.1186/1475-2867-12-15 /content/figures/1475-2867-12-15-toc.gif Cancer Cell International 1475-2867 ${item.volume} 15 2012-04-11T00:00:00Z PDF