Clinical and Experimental Metastasis
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Inhibition of metastasis in a murine 4T1 breast cancer model by liposomes preventing tumor cell-platelet interactions
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In this study, we prepared liposomes containing the platelet aggregation inhibitor Cilostazol (Cil-L). The objective of this
study was to investigate the effect of this Cil-L on platelet aggregation and complex formation with murine 4T1 breast cancer
cells in vitro and to determine their anti-metastatic potency in a spontaneous metastasis model of 4T1 breast cancer. Cil-L
significantly inhibited the aggregation of platelets by up to 78% and completely abolished the complex formation of 4T1 tumor
cells in the presence of activated platelets in vitro. Intravenous (i.v.) injection of Cil-L into mice significantly reduced
...
Source: Clinical and Experimental Metastasis - November 14, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Leptomeningeal metastases from prostate cancer: an emerging clinical conundrum
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Abstract Leptomeningeal metastases from solid tumors are relatively uncommon events with dismal prognosis. They can be seen mainly
in patients with breast and lung cancer, and malignant melanoma, but have also been described in a variety of other tumor
types. Leptomeningeal carcinomatosis from prostate cancer is an extremely rare complication, but as patients’ survival is
prolonged due to more effective treatments, it is expected that more patients will present with leptomeningeal involvement
in advanced stages of the disease. In these cases high levels of prostate-specific antigen can be found in the cere...
Source: Clinical and Experimental Metastasis - November 11, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Similar expression profiles of a core of genes and proteins in cells that have acquired a metastatic phenotype, genetically or by in vivo evolution
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Abstract We compared gene expression patterns related to cancer progression, cell adhesion and cytokine expression in v-Src-transformed
isogenic cell lines with different levels of metastatic aggressiveness in syngenic animals: a high (HM) and a low metastatic
(LM) cell lines, both predetermined by in vitro oncogenic transformation, and a high metastatic (NM) cell line resulting from
in vivo selection of grafted LM cells. While LM and NM shared a common v-Src transforming variant different from that of HM,
gene expression patterns were similar in HM and NM but different from that of LM. In this model, the in...
Source: Clinical and Experimental Metastasis - November 11, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Gene expression profiling of primary and metastatic colon cancers identifies a reduced proliferative rate in metastatic tumors
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The objective of this study was to gain insights into the biological basis of the metastatic process by characterizing the
gene expression differences between primary and metastatic colon cancers. Recent studies have demonstrated that few new mutational
changes are acquired during the metastatic progression of colon tumors [Jones et al., Proc Natl Acad Sci USA 105 (11): 4283–4288,
2008]. However, the extent to which epigenetic and transcriptional changes occur between primary and metastatic colon cancer
remains unknown. We approached these issues using Affymetrix microarrays to assess the similarities and differences...
Source: Clinical and Experimental Metastasis - October 31, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Modeling liver metastasis using a tumor cell line derived from an enhanced green fluorescent protein transgenic mouse
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Abstract The liver is a common repository for metastases, second only to lymph nodes. The majority of gastrointestinal cancer deaths
are attributed to liver metastasis. Researchers have widely used stable transfection of green florescent protein (GFP) to
track tumor cells in the liver metastasis cascade. However, stable, sustained GFP expression in these tumor cells requires
proper drug selection to avoid its loss in animal models. To overcome this, we generated a pancreatic tumor cell line that
stably expressed enhanced GFP (EGFP). First, we induced a pancreatic tumor by administering 3-methylcholanthrene i...
Source: Clinical and Experimental Metastasis - October 31, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Strong expression of chemokine receptor CXCR4 by renal cell carcinoma cells correlates with metastasis
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Abstract The chemokine receptor CXCR4 is involved in the metastasis of many cancers. Recent evidence suggests that CXCR4 may be also
involved in the metastasis of renal cell carcinoma. We analyzed the expression of CXCR4 in primary carcinomas, metastatic
tissues and normal tissues using immunohistochemistry. We further investigated the migration of renal carcinoma cells in response
to stimulation by CXCL12 in vitro. We also studied the subcellular localization of CXCR4 in renal cell carcinoma cells in
response to CXCL12 by confocal microscopy. We observed the highest percentage of CXCR4 expression in renal c...
Source: Clinical and Experimental Metastasis - October 26, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Evaluation of metastatic and angiogenic potentials of human colon carcinoma cells in chick embryo model systems
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Abstract Increased metastatic and angiogenic potentials of aggressive human colon carcinoma cells were verified in independent chick
embryo models by comparing in vivo highly metastatic SW620 colon carcinoma cell line with its isogenic, non-metastatic SW480
cell variant. In the experimental metastasis model, both cell types rapidly arrested in the chorioallantoic membrane (CAM)
vasculature as demonstrated by quantitative PCR and immunohistochemistry. Live cell imaging also indicated that both SW620
and SW480 cells efficiently extravasated from the CAM capillary system. However, only few SW480 cells were pres...
Source: Clinical and Experimental Metastasis - October 20, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Twist, an independent prognostic marker for predicting distant metastasis and survival rates of esophageal squamous cell carcinoma patients
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In conclusion, upregulated
Twist expression in the primary ESCC significantly correlates with the high risk of subsequent development of distant metastasis
and low postoperative survival rates; the latter was not significantly correlated with patients’ age, gender, tumor location
and differentiation. Twist may serve as an independent prognostic marker for predicting development of distant metastasis
in ESCC patients and their survival.
Content Type Journal ArticleCategory Research PaperDOI 10.1007/s10585-009-9292-5Authors
Fangwei Xie, Fuzhou General Hospital Department of Oncology 156 Western Two-Circle North Ro...
Source: Clinical and Experimental Metastasis - October 9, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Metastasis-induction and apoptosis-protection by TWIST in gastric cancer cells
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Abstract TWIST, a basic helix-loop-helix transcription factor, has been recently reported to play an important role in tumorigenesis
of human cancer through converting the early stage tumors into invasive malignancies. Upregulation of TWIST is often found
in cancer patients, especially those with shorter survival period and poor response to chemotherapy. Here we studied the functions
of TWIST on regulating migration rate, apoptosis, and gene expression in gastric cancer cells. TWIST expression is elevated
in MGC-803 and HGC-27 cells that exhibit high invasive potential; whereas it is reduced in BGC-823 and S...
Source: Clinical and Experimental Metastasis - October 6, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Prognostic value of indoleamine 2,3-dioxygenase expression in high grade osteosarcoma
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This study aimed to investigate IDO expression
as related to prognosis in osteosarcoma. IDO expression was immunohistochemically scored as five grades. IDO was expressed
in most of the cases. Univariate analysis revealed no significant correlation between IDO staining intensity and various variables
including sex, age, anatomical site, chemotherapy regimen, necrosis after chemotherapy, and surgical stage. Patients with
high IDO expression had significantly lower metastasis-free survival (P = 0.016) and overall survival (P = 0.005). On univariate analysis, age over 20 years and high IDO expressi...
Source: Clinical and Experimental Metastasis - October 5, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Modulation of prostate cancer cell gene expression by cell-to-cell contact with bone marrow stromal cells or osteoblasts
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Abstract After prostate cancer cells (PCa) arrive in bone, interactions with cells that include long bone osteoblasts (LBOB) and bone
marrow stromal cells (BMSC) lead to metastasis formation. The effect of heterotypic cell–cell contact between PCa cells and
BMSC or LBOB on PCa cell gene expression is poorly understood. To establish the role of heterotypic contact in bone metastasis
formation, we mixed and co-cultured PC3 cells with rat BMSC, LBOB, or human prostate stromal cells (PS15). PC3 cells were
then re-isolated for gene array analysis, and imaged using in situ hybridization to confirm that heterotyp...
Source: Clinical and Experimental Metastasis - September 29, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Prognostic factors and recurrence of hepatitis B-related hepatocellular carcinoma after argon-helium cryoablation: a prospective study
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Abstract To determine the long-term prognosis of hepatocellular carcinoma (HCC) after argon-helium cryoablation and identify the risk
factors that predict metastasis and recurrence. A total of 156 patients with hepatitis B-related HCC less than 5 cm in diameter
who underwent curative cryoablation were followed up prospectively for tumor metastasis and recurrence. Immunohistochemistry
was used to analyze the expression of vascular endothelial growth factor (VEGF). HBV basal core promoter (BCP) and precore
mutations were detected by DNA sequence analysis. Post-treatment prognostic factors influencing surv...
Source: Clinical and Experimental Metastasis - September 29, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Anti-metastatic effects of liposomal gemcitabine in a human orthotopic LNCaP prostate cancer xenograft model
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Abstract Fatal outcomes of prostate carcinoma (PCa) mostly result from metastatic spread rather than from primary tumor burden. Here,
we monitored growth and metastatic spread of an orthotopic luciferase/GFP-expressing LNCaP PCa xenograft model in SCID mice
by in vivo imaging and in vitro luciferase assay of tissues homogenates. Although the metastatic spread generally shows a
significant correlation to primary tumor volumes, the susceptibility of various tissues to metastatic invasion was different
in the number of affected animals as well as in absolute metastatic burden in the individual tissues. Using th...
Source: Clinical and Experimental Metastasis - September 29, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
MicroRNA-17-3p is a prostate tumor suppressor in vitro and in vivo, and is decreased in high grade prostate tumors analyzed by laser capture microdissection
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Abstract MicroRNAs (miRs) are a novel class of RNAs with important roles in regulating gene expression. To identify miRs controlling
prostate tumor progression, we utilized unique human prostate sublines derived from the parental P69 cell line, which differ
in their tumorigenic properties in vivo. Grown embedded in laminin-rich extracellular matrix (lrECM) gels these genetically-related
sublines displayed drastically different morphologies correlating with their behaviour in vivo. The non-tumorigenic P69 subline
grew as multicellular acini with a defined lumen and basal/polar expression of relevant marker pr...
Source: Clinical and Experimental Metastasis - September 22, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Osteoblasts modulate Ca2+ signaling in bone-metastatic prostate and breast cancer cells
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Abstract Metastatic prostate and breast cancers display a predilection for the skeleton. The high incidence of skeletal metastasis
may be a reflection of favorable reciprocal interactions between the bone microenvironment and disseminated cancer cells.
Here we show that bone-metastatic PC3-ML prostate cancer cells and MDA-231 breast cancer cells—when co-cultured with human
osteoblasts—down-regulate the increase in cytosolic free calcium (Ca2+) induced by agonist stimulation. This osteoblast promoted alteration of Ca2+ signaling develops and reverts in a time-dependent manner. Most importantly, the Ca2+ re...
Source: Clinical and Experimental Metastasis - September 20, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Establishment and validation of an in vitro co-culture model to study the interactions between bone and prostate cancer cells
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Abstract Bone is the preferred site for prostate cancer (PCa) metastases. Once the tumor has established itself within the bone there
is virtually no cure. To better understand the interactions between the PCa cells and bone environment in the metastatic process
new model systems are needed. We have established a two-compartment in vitro co-culturing model that can be used to follow
the trans-activation of bone and/or tumor cells. The model was validated using two PCa tumor cell lines (PC-3; lytic and LNCaP;
mixed/osteoblastic) and one osteolytic inducing factor, 1,25-dihydroxyvitamin D3 (D3). Results were i...
Source: Clinical and Experimental Metastasis - September 3, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Mechanisms and pathways of bone metastasis: challenges and pitfalls of performing molecular research on patient samples
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This study explored the analysable yield of genetic material from human biopsy samples in
order to describe differences in gene expression between DTCs and bone MTCs. Thirteen breast cancer patients with bone metastases
underwent a CT-guided bone metastasis biopsy and a bone marrow biopsy. Tumour cells were enriched and gene expression profiling
was conducted to identify differentially expressed genes. The analysable yield of sufficient RNA for microarray analysis was
60% from bone metastasis biopsies and 80% from bone marrow biopsies. A signature of 133 candidate genes differentially expressed
between DTCs and MTCs w...
Source: Clinical and Experimental Metastasis - August 21, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Deficiencies in the CD40 and CD154 receptor-ligand system reduce experimental lung metastasis
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Abstract It is established that experimental metastasis requires platelet activity. CD154 expressed on and released from activated
platelets induces an inflammatory response in endothelial cells and monocytes, including tissue factor production. CD154 has
also been shown to activate platelets in vitro and promote thrombus stability in vivo. These CD154 effects may be mediated,
at least in part, by CD40 signaling on platelets and vascular endothelial cells. We have previously demonstrated prolonged
bleeding and PFA-100 closure times in mice deficient for Cd154 or its receptor Cd40. In the present study, we hy...
Source: Clinical and Experimental Metastasis - July 30, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
MET Y1253D-activating point mutation and development of distant metastasis in advanced head and neck cancers
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Abstract We investigated if the MET-activating point mutation Y1253D influences clinical outcomes in patients with advanced squamous cell carcinoma of the head
and neck (HNSCC). The study population consisted of 152 HNSCC patients treated by hyperfractionated radiotherapy alone or
concomitant with chemotherapy between September 1994 and July 2000. Tumors were screened for the presence of the MET-activating point mutation Y1253D. Seventy-eight patients (51%) received radiotherapy alone, 74 patients (49%) underwent radiotherapy
concomitant with chemotherapy. Median patient age was 54 years and median follo...
Source: Clinical and Experimental Metastasis - July 29, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Chemokine CCL2/MCP-1 negatively regulates metastasis in a highly bone marrow-metastatic mouse breast cancer model
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Abstract Bone is the most frequent site of breast cancer metastasis, and once such metastasis occurs, complete remission is extremely
difficult to achieve. In an effort to define the mechanisms underlying metastatic spread of breast cancer to bone, we previously
developed and characterized the highly bone metastatic 4T1E/M3 mouse breast cancer cells. We found that following injection
into mice, 4T1E/M3 cells exhibited greater bone metastasis and greater in vitro anchorage-independent growth and cell migration
than their parental cells (4T1E). We also found that expression of intracellular adhesion molecule-1...
Source: Clinical and Experimental Metastasis - July 25, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Enhanced expression and shedding of receptor activator of NF-κB ligand during tumor–bone interaction potentiates mammary tumor-induced osteolysis
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In this report, we examined the role of tumor–stromal interaction in the regulation of RANKL expression and
its functional significance in tumor-induced osteolysis. Using a novel mammary tumor model, we identified that RANKL expression
was upregulated at the TB-interface as compared to the tumor alone area. We demonstrate increased generation of sRANKL at
the TB-interface, which is associated with tumor-induced osteolysis. The ratio of RANKL to osteoprotegrin (OPG), a decoy receptor
for RANKL, at the TB-interface was also increased. Targeting RANKL expression with antisense oligonucleotides (RANKL-ASO),
significantl...
Source: Clinical and Experimental Metastasis - July 10, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Allelic loss at TP53 in metastatic human endometrial carcinomas
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In conclusion, LOH occurs not only in primary uterine tumors but also in corresponding metastases, with the higher
incidence being reported at intron 4 of the TP53. A significant link existed between LOH TP53 at intron 1 and p53 overexpression in primary ECs, but not in the corresponding metastatic lesions.
Content Type Journal ArticleCategory Research PaperDOI 10.1007/s10585-009-9278-3Authors
Wiktor Szewczuk, Medical University of Lublin IInd Department of Gynecology 8 Jaczewski street 20-954 Lublin PolandDanuta Skomra, Medical University of Lublin Department of Pathology Lublin PolandMarek Cybulski, Medical Univers...
Source: Clinical and Experimental Metastasis - June 30, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Functional blocking of specific integrins inhibit colonic cancer migration
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In conclusion, integrin subunits α2, α6 and β4 are expressed in unrelated colorectal cancer cell strains and appear to play a key role in cancer cell migration.
Content Type Journal ArticleCategory Research PaperDOI 10.1007/s10585-009-9276-5Authors
John H. Robertson, University College London GI & Hepatobiliary Research Group, UCL Division of Surgery and Interventional Science Rowland Hill Street London NW3 2PF UKShi Yu Yang, University College London GI & Hepatobiliary Research Group, UCL Division of Surgery and Interventional Science Rowland Hill Street London NW3 2PF UKMarc C. Winslet, University College London ...
Source: Clinical and Experimental Metastasis - June 26, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
High expression of Snail mRNA in blood from hepatocellular carcinoma patients with extra-hepatic metastasis
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This study suggests the possibility that circulating Snail mRNA levels may have been associated with extra-hepatic metastasis
in HCC patients.
Content Type Journal ArticleCategory Research PaperDOI 10.1007/s10585-009-9275-6Authors
Ae Lyoung Min, The Catholic University of Korea Department of Internal Medicine, College of Medicine Seoul KoreaJong Young Choi, The Catholic University of Korea Department of Internal Medicine, College of Medicine Seoul KoreaHyun Young Woo, The Catholic University of Korea Department of Internal Medicine, College of Medicine Seoul KoreaJin Dong Kim, The Catholic University of Korea Departm...
Source: Clinical and Experimental Metastasis - June 17, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Cancer cell lines release glutamate into the extracellular environment
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Abstract Bone is one of the most frequent sites for metastasis of breast and prostate cancers. Bone metastases are associated with
pathologic changes in bone turnover and severe pain. The mechanisms that trigger these effects are not well understood, but
it is postulated that tumour cells release factors which interfere with signalling processes critical to bone homeostasis.
We have identified that several cancer cell lines known to cause bone disruption in animal models of bone metastasis appear
to secrete glutamate into their extracellular environment in vitro. Although these cells also express specific gl...
Source: Clinical and Experimental Metastasis - June 13, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Hepatocyte growth factor induced up-regulations of VEGF through Egr-1 in hepatocellular carcinoma cells
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Abstract The potential role of hepatocyte growth factor (HGF) in the regulation of angiogenesis factors in hepatoma cells is not widely
appreciated. We investigated the role of HGF-induced activation of a transcription factor, Egr-1, in the expression of pro-angiogenic
factors. Genes associated with angiogenesis induced by HGF were screened by using cDNA microarray technology in hepatocellular
carcinoma cell lines, HepG2 and Hep3B. Expression levels of Egr-1, vascular endothelial growth factor (VEGF), and interleukin
(IL)-8 were further confirmed by real time RT-PCR and Western blot analysis. Roles of Egr-1 ...
Source: Clinical and Experimental Metastasis - June 13, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Detection of survivin-expressing circulating cancer cells in the peripheral blood of patients with esophageal squamous cell carcinoma and its clinical significance
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Abstract We previously demonstrated that the detection of circulating cancer cells (CCC) expressing survivin mRNA could provide valuable
information for predicting recurrence in patients with breast, lung, gastric and colorectal carcinoma. The purpose of this
study is to investigate whether the detection of survivin-expressing CCC in the peripheral blood is also useful for predicting
recurrence in patients with esophageal squamous cell carcinoma (ESCC). Blood samples obtained from 108 ESCC patients and 75
healthy volunteers were quantitatively investigated by a technique that detected reverse transcription-p...
Source: Clinical and Experimental Metastasis - June 12, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Impact of Octreotide and SOM-230 on liver metastasis and hepatic lipidperoxidation in ductal pancreatic adenocarcinoma in Syrian Hamster
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Abstract Octreotide is a somatostatin analogue binding on two receptor subtypes. In previous trials Octreotide showed inhibitory effects
on tumour growth and liver metastasis in experimental pancreatic cancer. Thus we evaluated whether the new somatostatin analogue
SOM-230 binding on 4 receptor subtypes has superior effects on carcinogenesis in pancreatic carcinoma. About 120 Syrian hamsters
were randomised into six groups (n = 20): Gr.1: Aqua/Aqua, Gr.2: BOP/Aqua, Gr.3: Aqua/Octreotide, Gr.4: BOP/Octreotide, Gr.5: Aqua/SOM-230, Gr.6: BOP/SOM-230.
Tumour groups 2,4,6 subcutaneously received 10 ...
Source: Clinical and Experimental Metastasis - June 12, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Evaluation of pulsed high intensity focused ultrasound exposures on metastasis in a murine model
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Abstract High intensity focused ultrasound (HIFU) may be employed in two ways: continuous exposures for thermal ablation of tissue
(>60°C), and pulsed-exposures for non-ablative effects, including low temperature hyperthermia (37–45°C), and non thermal
effects (e.g. acoustic cavitation and radiation forces). Pulsed-HIFU effects may enhance the tissue’s permeability for improved
delivery of drugs and genes, for example, by opening up gaps between cells in the vasculature and parenchyma. Inducing these
effects may improve local targeting of therapeutic agents, however; concerns exist that pulsed expos...
Source: Clinical and Experimental Metastasis - June 11, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Expression and functional analysis of the WAP four disulfide core domain 1 gene in human melanoma
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Abstract The exact cellular and molecular mechanisms involved in melanoma tumorigenesis remain obscure. Previous gene expression profiling
analyses performed upon NHEM and human melanoma samples identified WFDC1 as one of the most frequently down-regulated genes.
Here we further showed that NHEM readily express WFDC1 but expression is reduced or completely lost in 80% of the patients-derived
melanoma cell lines and tissue samples examined. Furthermore, we show that promoter hypermethylation accounts for the silencing
of the WFDC1 gene in 20% of the melanoma cell lines examined. The over-expression of WFDC1 i...
Source: Clinical and Experimental Metastasis - June 2, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Comparative analysis of tumorbiology and CD133 positivity in primary and recurrent pancreatic ductal adenocarcinoma
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This study analyzes tumorbiology, expression of the metastasis-promoting CXCR4 and actinin-4, and of the CSC marker
CD133 in primary and recurrent PDAC. Twenty-six patients underwent resection for primary and recurrent PDAC and most developed
tumor recurrence within 2 years. In 81% the histologic tumor grade was unchanged. Immunohistochemistry could be performed
with 15 pairs of primary and recurrent PDAC. The mean Ki-67 proliferation index increased (P = 0.06). About 30% of tumor cells were positive for CXCR4 and almost all tumor cells expressed actinin-4, but there were
neither significant changes in t...
Source: Clinical and Experimental Metastasis - June 2, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Significance of manipulating intratumor hypoxia in the effect on lung metastases in radiotherapy, with reference to its effect on the sensitivity of intratumor quiescent cells
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Conclusion Hypoxia manipulation in solid tumors has the potential to influence lung metastases. Notably, acute hypoxia-releasing nicotinamide
may be promising for reducing the number of lung metastases.
Content Type Journal ArticleCategory Research PaperDOI 10.1007/s10585-009-9268-5Authors
Shin-ichiro Masunaga, Kyoto University Particle Radiation Oncology Research Center, Research Reactor Institute 2-1010, Asashiro-nishi, Kumatori-cho, Sennan-gun Osaka 590-0494 JapanYoshitaka Matsumoto, National Institute of Radiological Sciences Heavy-Ion Radiobiology Research Group, Research Center for Charged Particle Therapy Chib...
Source: Clinical and Experimental Metastasis - May 24, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Management of small pulmonary nodules in patients with sarcoma
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This study reviewed 38 patients with metastatic nodules and
15 patients with benign nodules. A statistically significant relationship was observed between the size of the nodules and
final clinical decision. The patients with pulmonary nodules which did not exceed 5 mm in size showed significantly better
cumulative overall survival rate after the detection of pulmonary nodules than those with larger nodules (5-years: 58.4 vs.
20.4%). There was no significant difference in the overall survival rate between the patients with smaller pulmonary benign
lesions which did not exceed 5 mm in size and those with a no...
Source: Clinical and Experimental Metastasis - May 24, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
An improved model to study tumor cell autonomous metastasis programs using MTLn3 cells and the Rag2−/− γc−/− mouse
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Abstract The occurrence of metastases is a critical determinant of the prognosis for breast cancer patients. Effective treatment of
breast cancer metastases is hampered by a poor understanding of the mechanisms involved in the formation of these secondary
tumor deposits. To study the processes of metastasis, valid in vivo tumor metastasis models are required. Here, we show that
increased expression of the EGF receptor in the MTLn3 rat mammary tumor cell-line is essential for efficient lung metastasis
formation in the Rag mouse model. EGFR expression resulted in delayed orthotopic tumor growth but at the same...
Source: Clinical and Experimental Metastasis - May 24, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Activated platelets enhance ovarian cancer cell invasion in a cellular model of metastasis
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Abstract Increased platelet counts and systemic coagulation activation are associated with ovarian cancer progression. Platelet activation
occurs in the tumor microenvironment and may influence local invasion and metastasis. We used a cellular model of tumor invasion
to investigate the effect of activated platelets on the human ovarian cancer cell line, SKOV3. SKOV3 cells were exposed to
washed, thrombin receptor activating peptide (TRAP)-activated or TRAP-naïve platelets under various experimental conditions,
and tumor cell invasion was assayed in Matrigel® chambers. The effect of platelets on the content...
Source: Clinical and Experimental Metastasis - May 15, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Expression of GRP and its receptor is associated with improved survival in patients with colon cancer
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Abstract Epithelial cells lining the adult human colon do not normally express gastrin releasing peptide (GRP) or its receptor (GRPR),
but both can be up regulated post malignant transformation. However, controversy exists as to the contribution these proteins
make to tumor cell behavior once present. Since GRPR activation promotes proliferation, it has been assumed that their aberrant
expression promotes colon cancer (CC) growth and progression. Yet we have contended that when expressed, GRP/GRPR benefits
the host since in vitro studies demonstrate they enhance tumor cell attachment to the extracellular mat...
Source: Clinical and Experimental Metastasis - May 10, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Characterization and functional analysis of a slow cycling stem cell-like subpopulation in pancreas adenocarcinoma
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In this study, a particular focus was put on identifying a subpopulation
of stem cell-like, slow cycling tumor cells in a pancreas adenocarcinoma cell lines. Using a label retention technique a subpopulation
of slow cycling cells (DiI+/SCC) was identified and further evaluated in the BxPC-3 and Panc03.27 cell lines. These slowly
cycling cells managed to retain the lipophilic labeling dye DiI, while the bulk of the cells (>94%) did not. The DiI+/SCC
population, showed only a partial overlap with the CSC markers CD24+/CD44+, CD133+ and ALDH but they survived chemotherapeutic treatment, and were able to recreate the in...
Source: Clinical and Experimental Metastasis - May 7, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Osteosclerotic prostate cancer metastasis to murine bone are enhanced with increased bone formation
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Abstract Spontaneous development of osteoblastic lesions of prostate cancer (PCa) in mice is modeled by orthotopic (intraprostatic)
deposition of neoplastic cells followed by an extremely long latency associated with low incidence of spontaneous bone metastasis.
Intracardial injection results in overt bone metastases only with osteoclastic PCa cells (i.e., PC-3). Herein, we report that
androgen independent osteoblastic PCa cells readily colonize bone when in a high remodeling state. SCID/Beige mice were subjected
to periods of intermittent human parathyroid hormone 1–34 (hPTH) exposure, followed by an intr...
Source: Clinical and Experimental Metastasis - May 7, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs
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Abstract Tumor treating fields (TTFields) are low intensity, intermediate frequency, alternating electric fields used to treat cancerous
tumors. This novel treatment modality effectively inhibits the growth of solid tumors in vivo and has shown promise in pilot
clinical trials in patients with advanced stage solid tumors. TTFields were tested for their potential to inhibit metastatic
spread of solid tumors to the lungs in two animal models: (1) Mice injected with malignant melanoma cells (B16F10) into the
tail vein, (2) New Zealand White rabbits implanted with VX-2 tumors within the kidney capsule. Mice and ...
Source: Clinical and Experimental Metastasis - April 23, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Metastatic gene signatures and emerging novel prognostic tests in the management of early stage breast cancer
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Abstract Gene expression profiling using DNA microarrays allows simultaneous measurement of thousands of mRNA transcripts in a single
experiment. Results from gene expression profiling studies have fundamentally altered our view of breast cancer, which is
no longer regarded as a single disease but as several molecularly and biologically distinct neoplastic diseases. This technology
has also yielded novel diagnostic assays that have started to have an impact on clinical care. This is a rapidly evolving
field, and the constraints of space do not allow us to discuss many of the published studies. Therefore, in ...
Source: Clinical and Experimental Metastasis - April 21, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Establishment and characterization of a new highly metastatic human osteosarcoma cell line
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Abstract Osteosarcoma is the most common primary malignancy of bone in children and young adults. There is a paucity of tumorigenic
and highly metastatic human osteosarcoma cell lines that have not been further transformed by exogenous means. Here we establish
and characterize a highly metastatic human osteosarcoma cell line that is derived from a poorly metastatic MG63 line through
serial passage in nude mice via intratibial injections. The occasional pulmonary metastases developed from MG63 were harvested
and repassaged in mice until a highly metastatic subline (MG63.2) was established. The parental MG63 a...
Source: Clinical and Experimental Metastasis - April 11, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Gene expression profiles and breast cancer metastasis: a genetic perspective
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Abstract The majority of cancer mortality is attributed to metastasis, which is the spread of tumor cells to a secondary site. Several
studies have demonstrated that the genetic background on which a tumor arises has a major effect on both metastatic efficiency
and on predictive gene expression profiles. These observations suggest that there is variability in metastasis frequency between
individuals and that some individuals could be more prone to secondary tumor formation and development than others. Thus,
genetic background might have important clinical implications in metastasis detection, management and ...
Source: Clinical and Experimental Metastasis - April 5, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Multi-faceted role of HSP40 in cancer
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Abstract HSP40 (DNAJ) is an understudied family of co-chaperones. The human genome codes for over 41 members of HSP40 family that reside
at distinct intracellular locations. Despite their large numbers, little is known about their physiologic roles. Recent research
has revealed involvement of some of the DNAJ family members in various types of cancers. In this article we summarize the
information about the involvement of human DNAJ family members in various aspects of cancer biology. Furthermore we discuss
the potential role of the J domain of DNAJ proteins in cancer biology.
Content Type Journal ArticleC...
Source: Clinical and Experimental Metastasis - April 2, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
A molecular signature for Epithelial to Mesenchymal transition in a human colon cancer cell system is revealed by large-scale microarray analysis
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Abstract Sporadic colorectal cancer is a major cause of death worldwide. Development takes place in a sequential manner from benign
adenomas leading to carcinomas. In 90% of tumours bearing a Ras mutation it is Ki-Ras that is mutated. We have developed a
model cell system to study oncogenic Ras mutations in colorectal cancer cell lines. In this analysis two Caco-2 derived cell
lines expressing Ha-RasV12 (Caco-H) and Ki-RasV12 (Caco-K), respectively, have been used in large-scale microarray profiling
against a Caco-2 control. This was carried out using an Illumina microarray containing 24,000 genes. Genes hav...
Source: Clinical and Experimental Metastasis - April 2, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Early incorporated endothelial cells as origin of metastatic tumor vasculogenesis
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Abstract Vascularization of solid tumors is thought to occur by sprouting or intussusceptive angiogenesis, co-option of existing vessels,
and vasculogenic mimicry after the onset of tumor hypoxia, when the tumor radius exceeds the oxygen diffusion distance. In
contrast, here we show that individual endothelial cells that are incorporated into pre-hypoxic tumors give rise to tumor
blood vessels via vasculogenesis. Small metastatic lung tumor sections obtained after tail-vein injection of a syngeneic breast
cancer cell line in the nude mice were labeled with antibodies against endothelial cell markers. Immunof...
Source: Clinical and Experimental Metastasis - March 29, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Nuclear magnetic resonance and circular dichroism study of metastin (Kisspeptin-54) structure in solution
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Abstract KISS1 was first discovered as a metastasis suppressor, but also plays crucial roles in the onset of puberty. The KISS1 gene
encodes a secreted protein of 145 amino acids that exhibits no sequence similarity with any known proteins. KISS1 protein
is proteolytically processed to generate a number of so-called kisspeptins (KP), the most well characterized is known as KP-54
or metastin. KP-54 is carboxy-terminally amidated and binds to and activates the KISS1 receptor (KISS1R). The current studies
were undertaken in order to determine structure of KP-54 using nuclear magnetic resonance and circular dich...
Source: Clinical and Experimental Metastasis - March 24, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Prediction of breast cancer metastasis by genomic profiling: where do we stand?
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Abstract Current concepts conceive “breast cancer” as a complex disease that comprises several very different types of neoplasms. Nonetheless,
breast cancer treatment has considerably improved through early diagnosis, adjuvant chemotherapy, and endocrine treatments.
The limited prognostic power of classical classifiers determines considerable over-treatment of women who either do not benefit
from, or do not at all need, chemotherapy. Several gene expression based molecular classifiers (signatures) have been developed
for a more reliable prognostication. Gene expression profiling identifies profound diffe...
Source: Clinical and Experimental Metastasis - March 24, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Arylsulfatase B regulates colonic epithelial cell migration by effects on MMP9 expression and RhoA activation
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In this study, we report how variation in expression of ASB affected the migration of human colonic epithelial cells. In the
T84 cell line, derived from lung metastasis of malignant colonic epithelial cells, the activity of ASB, as well as steroid
sulfatase, arylsulfatase A, and galactose-6-sulfatase, were significantly less than in normal, primary colonic epithelial
cells and in the NCM460 cell line which was derived from normal colonocytes. In the T84 cells, matrix metalloproteinase 9
(MMP9), activated RhoA, and cell migration, as well as C4S content, were significantly more than in the NCM460 cells. Silencing
and o...
Source: Clinical and Experimental Metastasis - March 22, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Regulator of calcineurin 1 modulates cancer cell migration in vitro
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Abstract Metastasis suppressors and other regulators of cell motility play an important role in tumor invasion and metastases. We previously
identified that activation of the G protein coupled receptor 54 (GPR54) by the metastasis suppressor metastin inhibits cell
migration in association with overexpression of Regulator of calcineurin 1 (RCAN1), an endogenous regulator of calcineurin. Calcineurin inhibitors also blocked cell migration in vitro and RCAN1 protein levels
were reduced in nodal metastases in thyroid cancer. The purpose of the current study was to determine directly if RCAN1 functions as a motilit...
Source: Clinical and Experimental Metastasis - March 22, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
Osteoblast-induced EGFR/ERBB2 signaling in androgen-sensitive prostate carcinoma cells characterized by multiplex kinase activity profiling
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Abstract Bone metastases in prostate cancer are predominantly osteoblastic. To study regulatory mechanisms underlying the establishment
of prostate cancer within an osteoblastic microenvironment, human androgen-sensitive prostate carcinoma cells (LNCaP) were
treated with culture medium conditioned by human osteoblast-derived sarcoma cells (OHS), and activated signalling pathways
in the carcinoma cells were analyzed using microarrays with tyrosine kinase substrates. Network interaction analysis of substrates
with significantly increased phosphorylation levels revealed that signalling pathways mediated by EGFR...
Source: Clinical and Experimental Metastasis - March 18, 2009 Category: Cancer & Oncology Tags: Clinical and Experimental Metastasis Source Type: journals
