journal article
LitStream Collection
Home
Liu, Yiyao; Miyoshi, Hirokazu; Nakamura, Michihiro
doi: 10.1002/ijc.22709pmid: 17390371
The diagnosis and treatment of cancer or tumor at the cellular level will be greatly improved with the development of techniques that enable the delivery of analyte probes and therapeutic agents into cells and cellular compartments. Organic and inorganic nanoparticles that interface with biological systems have recently attracted widespread interest in the fields of biology and medicine. The new term nanomedicine has been used recently. Nanoparticles are considered to have the potential as novel intravascular or cellular probes for both diagnostic (imaging) and therapeutic purposes (drug/gene delivery), which is expected to generate innovations and play a critical role in medicine. Target‐specific drug/gene delivery and early diagnosis in cancer treatment is one of the priority research areas in which nanomedicine will play a vital role. Some recent breakthroughs in this field recently also proved this trend. Nanoparticles for drug delivery and imaging have gradually been developed as new modalities for cancer therapy and diagnosis. In this article, we review the significance and recent advances of gene/drug delivery to cancer cells, and the molecular imaging and diagnosis of cancer by targeted functional nanoparticles. © 2007 Wiley‐Liss, Inc.
Comtesse, Nicole; Keller, Andreas; Diesinger, Isabel; Bauer, Christine; Kayser, Klaus; Huwer, Hanno; Lenhof, Hans‐Peter; Meese, Eckart
doi: 10.1002/ijc.22585pmid: 17290396
Previously, we reported gene amplification at chromosome 3q26‐27 in more than one third of squamous cell carcinomas of the lung. Frequent amplification of eukaryotic translation initiation factor 4G on 3q27.1 indicated a possible role of this amplification in translation initiation. The analysis of 61 squamous cell lung carcinomas shows that the percentage of carcinomas with a 3q27.1 amplification increases in higher malignant tumors. Non‐invasive (T1) and minimal‐invasive (T2) tumor stages showed similar percentages of amplified and non‐amplified tumors, whereas locally‐invasive (T3) tumors revealed a statistically significant (p < 0.05) increased percentage of amplified tumors. Microarrays were used to analyze the expression pattern of genes mapping in the amplified domain and its flanking regions (3q25‐28) as well as the expression of genes directly or indirectly associated with translation initiation in squamous cell carcinoma, large cell carcinoma, adenocarcinoma and small cell carcinoma. Three genes, namely FXR1, CLAPM1 and EIF4G, are most frequently overexpressed in the center of the amplified domain in squamous cell carcinomas. The eukaryotic translation initiation factors 4A1, 2B and 4B as well as the poly(A)‐binding protein PABPC1 where found to be overexpressed in all lung cancer entities. We found, however, no overexpression of eIF4E. Our results contribute to the understanding of the frequent amplification processes in squamous cell carcinomas of the lung and to the understanding of the translation initiation that appears not to require eIF4E in lung carcinogenesis. © 2007 Wiley‐Liss, Inc.
Sawhney, Meenakshi; Rohatgi, Nidhi; Kaur, Jatinder; Shishodia, Shishir; Sethi, Gautam; Gupta, Siddhartha D.; Deo, Suryanaryana V. S.; Shukla, Nootan K.; Aggarwal, Bharat B.; Ralhan, Ranju
doi: 10.1002/ijc.22657pmid:
Li, Yuejuan; Li, Lingli; Brown, Tracey J.; Heldin, Paraskevi
doi: 10.1002/ijc.22550pmid: 17315194
Accumulation of hyaluronan has been demonstrated in the peritumoral breast cancer stroma and nests of tumor cells. In this study, we have quantified the production of hyaluronan and the expression of mRNAs encoding hyaluronan synthesizing (HAS) and hyaluronan degrading (HYAL) enzymes in a panel of breast cancer cell lines. The analysis revealed that highly invasive breast cancer cells produce high amounts of hyaluronan and express preferentially HAS2 mRNA, whereas less invasive breast cancer cells produce low amount of hyaluronan and express HAS1 and HYAL1 mRNAs. We explored the importance of HAS2 expression for breast cancer tumorigenicity, by specifically silencing the HAS2 gene using RNA interference (RNAi)‐mediated suppression in the invasive breast cancer cell line Hs578T. This led to a less aggressive phenotype of the breast tumor cells, as assessed by cell growth, both in anchorage‐dependent and anchorage‐independent cultures. siRNA‐mediated knock down of HAS2 in Hs578T breast tumor cells led to an up‐regulation of HAS1, HAS3 and HYAL1 mRNAs, resulting in only a 50% decrease in the net hyaluronan production; however, the synthesized hyaluronan was of lower size and more polydisparse compared to control siRNA‐treated cells. Interestingly, Hs578T cells deprived of HAS2 migrated only half as efficiently as HAS2 expressing cells through cell‐free areas in a culture wounding assay and through Transwell polycarbonate membrane as well as invaded a Matrigel layer. These results imply that alterations in HAS2 expression and endogenously synthesized hyaluronan affect the malignant phenotype of Hs578T breast cancer cells. © 2007 Wiley‐Liss, Inc.
Reimer, Daniel; Steppan, Ilona; Wiedemair, Annemarie; Concin, Nicole; Marth, Gerda Hofstetter Christian; Müller‐Holzner, Elisabeth; Zeimet, Alain G.
doi: 10.1002/ijc.22580pmid: 17278108
The coxsackie‐adenovirus receptor (hCAR) has been extensively studied in context of adenoviral‐based gene therapy for cancer. However, there is strong evidence that besides its decisive role in coxsackie and adenovirus cell‐entry, hCAR is a component of epithelial tight junctions and involved in cell‐cell adhesions in normal and cancer cells. Furthermore, this adhesion molecule behaves like a cell surface receptor endowed with tumor suppressive properties via signal transduction. Moreover, 3 truncated soluble isoforms of hCAR were recently identified. We investigated the quantitative expression of all known CAR isoforms in a training set of 140 ovarian cancer samples and 21 controls by RT‐PCR. The expression levels of the various isoforms were compared with clinicopathologic parameters and their prognostic significance was assessed. Expression levels of all CAR isoforms were elevated in ovarian carcinomas as compared with those of non‐malignant controls. mRNA‐expression correlated with protein levels. Moreover, expression of the soluble isoforms CAR 3/7 and CAR 4/7 but not that of hCAR was significantly increased in advanced ovarian cancer as revealed by a highly significant correlation with FIGO stage and residual disease > 2 cm in diameter after debulking surgery. High expression of CAR 3/7 and 4/7 was shown to be of independent prognostic relevance for progression‐free (CAR 4/7) and overall survival (CAR 3/7 and CAR 4/7). In conclusion, soluble CAR isoforms 3/7 and 4/7 may play a pivotal role in ovarian cancer biology, possibly by counteracting migration‐ and growth‐inhibitory properties of the membranous hCAR and thus favoring cancer cell dissemination throughout the peritoneal cavity. © 2007 Wiley‐Liss, Inc.
Oka, Daizo; Nishimura, Kazuo; Shiba, Masahiro; Nakai, Yasutomo; Arai, Yasuyuki; Nakayama, Masashi; Takayama, Hitoshi; Inoue, Hitoshi; Okuyama, Akihiko; Nonomura, Norio
doi: 10.1002/ijc.22570pmid: 17290398
Silistino‐Souza, Rosana; Rodrigues‐Lisoni, Flávia C.; Cury, Patricia M.; Maniglia, José V.; Raposo, Luis S.; Tajara, Eloiza H.; Christian, Helen C.; Oliani, Sonia M.
doi: 10.1002/ijc.22639pmid: 17340616
Annexin 1 protein (ANXA1) expression was evaluated in tumor and mast cells in human larynx cancer and control epithelium. The effect of the exogenous ANXA1 (peptide Ac 2‐26) was also examined during the cellular growth of the Hep‐2 human larynx epidermoid carcinoma cell line. This peptide inhibited the proliferation of the Hep‐2 cells within 144 hr. In surgical tissue specimens from 20 patients with larynx cancer, ultrastructural immunocytochemistry analysis showed in vivo down‐regulation of ANXA1 expression in the tumor and increased in mast cells and Hep‐2 cells treated with peptide Ac2‐26. Combined in vivo and in vitro analysis demonstrated that ANXA1 plays a regulatory role in laryngeal cancer cell growth. We believe that a better understanding of the regulatory mechanisms of ANXA1 in tumor and mast cells may lead to future biological targets for the therapeutic intervention of human larynx cancer. © 2007 Wiley‐Liss, Inc.
Klemke, Martin; Rafael, Maria T.; Wabnitz, Guido H.; Weschenfelder, Tatjana; Konstandin, Mathias H.; Garbi, Natalio; Autschbach, Frank; Hartschuh, Wolfgang; Samstag, Yvonne
doi: 10.1002/ijc.22589pmid: 17290393
The leukocyte specific actin‐binding protein L‐plastin is aberrantly expressed in several nonhematopoetic malignant tumors. However, little is known about the functional consequences of L‐plastin expression. Here, we investigated the function of L‐plastin in human malignant melanoma cells. Knock‐down of endogenous L‐plastin by siRNA treatment reduced migration of the melanoma cell line IF6. However, in melanoma patients, no correlation existed between L‐plastin expression and tumor stages. This implied that additional factors such as phosphorylation of L‐plastin may influence its function in tumor cells. To investigate this further, EGFP‐tagged wild‐type L‐plastin (wt‐LPL‐EGFP) and a mutated, nonphosphorylatable L‐plastin protein (5A7A‐LPL‐EGFP), were expressed in the L‐plastin negative melanoma cell line MV3. Biochemical analysis revealed that wt‐LPL‐EGFP is phosphorylated in MV3 cells while 5A7A‐LPL‐EGFP is not. Although both wt‐LPL‐EGFP and 5A7A‐LPL‐EGFP were targeted to, and promote the formation of, vinculin‐containing adhesion sites, static adhesion to either Matrigel or isolated extracellular matrix molecules was neither influenced by expression of wt‐LPL‐EGFP nor by expression of 5A7A‐LPL‐EGFP when compared with EGFP expressing control cells. In contrast, haptotactic, but not chemotactic, migration of melanoma cells towards either Matrigel or isolated extracellular matrix molecules was similarly enhanced, if either 5A7A‐LPL‐EGFP or wt‐LPL‐EGFP were expressed in MV3 cells. Interestingly, only cells expressing the phosphorylatable wt‐LPL‐EGFP protein showed enhanced invasion into Matrigel. In line with these findings the in vivo metastatic capacity of mouse B16 melanoma cells correlates with expression and phosphorylation of L‐plastin. These data show that an increase in melanoma cell invasiveness requires not only expression but also phosphorylation of L‐plastin. © 2007 Wiley‐Liss, Inc.
Lin, Ming‐Tsan; Lin, Been‐Ren; Chang, Cheng‐Chi; Chu, Chia‐Yu; Su, Hsiang‐Ju; Chen, Szu‐Ta; Jeng, Yung‐Ming; Kuo, Min‐Liang
doi: 10.1002/ijc.22599pmid: 17304514
Interleukin‐6 (IL‐6) is a multifunctional cytokine that is associated with the disease status and outcomes of gastric cancer. Nonetheless, the underlying mechanism of how IL‐6 promotes the spread of gastric cancer is still unclear. In this study, we used a modified Boyden chamber assay to test the invasion ability of different gastric cancer cell lines. Liposome‐mediated transfection was used to introduce an IL‐6 expression vector into AGS cells, and the transfectants were further examined for the expression of active RhoA and phosphorylated Src using a pull‐down assay and coimmunoprecipitation/Western blot analysis. Furthermore, RhoA expression in gastric adenocarcinoma specimens was investigated immunohistochemically. We documented that IL‐6 could promote AGS cell motility and invasiveness, and inhibition of RhoA expression by dominant negative RhoA, C3 transferase, or dominant negative Src expressing plasmids could effectively decrease the invasiveness of IL‐6 transfectants. We also documented an interaction between active RhoA and phosphorylated‐Src following IL‐6 treatment. Gastric cancers displaying high expression of RhoA are highly correlated with aggressive lymph node metastasis, more advanced tumor stage, histologically diffuse type and poorer survival. In conclusion, IL‐6 induces AGS gastric cancer cell invasion via activation of the c‐Src/RhoA/ROCK signaling pathway and RhoA expression could be used as a prognostic factor in patients with gastric adenocarcinoma. © 2007 Wiley‐Liss, Inc.
Showing 1 to 10 of 34 Articles
Nuclear Factor‐κB (NF‐κB) activation and COX‐2 overexpression have been reported in head and neck cancer, but the relationship between these proteins remains to be investigated. To determine the relationship between NF‐κB and COX‐2 in Smokeless Tobacco (ST) associated oral tumorigenesis, we performed immunohistochemistry in serial sections from 107 OSCCs, 78 oral precancerous lesions (OPLs) (58 hyperplasias, 20 dysplasias) and 15 histologically normal oral tissues and correlated with clinicopathological data. Significant increase in NF‐κB and COX‐2 immunopositivity was observed from normal oral mucosa to OPLs to OSCCs (p = 0.009 and p = 0.002 respectively). Upregulation of NF‐κB and COX‐2 was observed as early as in hyperplasia [p = 0.006; OR = 6.1 and p = 0.003; OR = 7.6, respectively]. Expression of both proteins was found to be significantly associated in OPLs (p = 0.000; OR = 12.6) and OSCCs (p = 0.001; OR = 4.0). Intriguingly, khaini consumption correlated with NF‐κB immunopositivity in OPLs (p = 0.05, OR = 3.8) and OSCCs (p = 0.01, OR = 3.4) and with COX‐2 expression in OPLs (p = 0.03; OR = 4.3). In vitro experimental system of ST associated oral carcinogenesis was used to demonstrate ST (khaini) and NNK mediated activation of NF‐κB and COX‐2, supporting the clinical data. In conclusion, this study demonstrates correlation between over expression of NF‐κB and COX‐2 in early precancerous stages of development of oral cancer and sustained elevation down the tumorigenic pathway, underscoring their potential as targets for early intervention. In vitro studies demonstrated that NNK may be one of the carcinogenic components of ST (khaini) inducing activation of NF‐κB and COX‐2 in oral precancer and cancer cells, suggesting plausible role in ST‐induced oral carcinogenesis. © 2007 Wiley‐Liss, Inc.
The transcription factor nuclear factor‐κB (NF‐κB) has been shown to be constitutively activated in various human malignancies, including leukemia, lymphoma and a number of solid tumors. NF‐κB regulates the transcriptional of genes important for tumor invasion, metastasis and chemoresistance. The sesquiterpene lactone parthenolide, an inhibition of NF‐κB, has been used conventionally to treat migraines and inflammation. In this study, renal cancer cell lines OUR‐10 and ACHN were used for in vitro experiments to evaluate growth‐inhibitory effects of parthenolide. An OUR‐10 xenograft model in nude mice was also used to investigate the in vivo growth‐inhibitory effects of parthenolide. Apoptosis in response to treatment of OUR‐10 cells with parthenolide was confirmed. Localization of NF‐κB in response to parthenolide treatment was examined of by immunofluorostaining of OUR‐10 cells with antibody against NF‐κB p65 and by Western blot analysis of OUR‐10 cell and tumor nuclear and cytosol fraction. Parthenolide effectively inhibited proliferation of cultured OUR‐10 cells and triggered apoptosis in vitro. Subcutaneous injection or oral administration of parthenolide showed significant tumor growth inhibition in the xenograft model via decreased production of interleukin‐8 (IL‐8) or vascular endothelial growth factor (VEGF). Immunohistochemistry and Western blot analysis showed decreased nuclear localization of NF‐κB and phosphorylated NF‐κB protein and subsequently expression of MMP‐9, Bcl‐xL and Cox‐2 in response to parthenolide treatment. These results indicate that parthenolide is a useful in the treatment of renal cell carcinoma and acts via inhibition of NF‐κB. © 2007 Wiley‐Liss, Inc.