Figure 2 - uploaded by Dietmar W. Siemann
Content may be subject to copyright.
Example of two H&E sections taken 80 μm apart. Colonies 1-4 are readily apparent on both sections and volumes could be calculated according to Equation 1.
Source publication
Dissemination of cancer cells is strongly associated with reduction in quality of life, worsening of prognosis, and remains the primary cause of therapeutic failure and high mortality in cancer. A crucial factor in the progression of metastases is the ability to establish a functioning blood vessel network. Consequently therapeutic strategies which...
Contexts in source publication
Context 1
... aid quantification each of the output images was fitted with a calibration scale. Once a lung nodule had been marked for evaluation (Figure 2), additional tile field map images were taken (40X magnification) of their matched CD31 labeled [15] paraffin sections ( Figure 5). ...
Context 2
... volume of the tumor nodule was then calculated using Equa- tion 1. An example of two H&E stained sections that are 80 µm apart is shown in Figure 2. Only nodules 1-4 are apparent on both sections al- lowing volume determinations of these four Eq. 1 nodules to be made. ...
Context 3
... injecting a constant number of tumor cells, a predictable number of metastases are formed per animal. Even so when utilizing H&E stained sections to calculate lung tumor nodule volumes, from radii of sec- tions separated by a known distance (Figure 1), it became readily apparent (Figures 2 and 3) that there exists considerable variability in the time of establishment and subsequent growth of these metastases. ...
Citations
... Acctording to the images of H&E staining, the lung nodule numbers were quantified microscopically by three observers. According to Salmon et al (16), the adapted 'Prolate Spheroid' model was used to calculate the tumor volume. The volume of any given lung tumor nodule was determined, on the basis of measurements of the radii of two sections and known separation between the two sections. ...
... The diameter (2 x R 1 ) of the largest tumor nodule was 6.83 mm and the average diameter (2 x R 1 ) was 2.59 mm, which complies with the requirements of animal welfare. Then by Salmon's equation (16), the volume of each lung tumor nodule was determined. ...
The high metastatic rate of breast cancer is the significant cause of its poor prognosis. The long noncoding RNA (lncRNA) proliferating cell nuclear antigen pseudogene 1 (PCNAP1) plays important roles in the initiation and progression of cancers; however, its regulatory function and molecular mechanism in breast cancer metastasis remains unknown. Therefore, we investigated the roles of lncRNA PCNAP1 in breast cancer metastasis by modulating the microRNA (miR)‑340‑5p/SOX4 axis using quantitative real‑time PCR, in vivo mouse models, nucleo‑cytoplasmic separation, western blot analysis, scratch assays, Transwell assays, luciferase reporter assays and MS2‑RIP, in vitro and in vivo. lncRNA PCNAP1 was found to be upregulated in human breast cancer tissues, and high lncRNA PCNAP1 levels predicted poor overall survival. Function assays showed that knockdown of lncRNA PCNAP1 suppressed the migration and invasion of breast cancer cells in vitro and in vivo. Mechanistically, lncRNA PCNAP1 functioned as a competing endogenous (ce)RNA for miR‑340‑5p to facilitate the expression of its target gene SRY‑box transcription factor 4 (SOX4), promoting migration and invasion of breast cancer cells. Overall, we found that lncRNA PCNAP1 predicted a poor prognosis in breast cancer and promoted cancer metastasis via miR‑340‑5p‑dependent upregulation of SOX4 expression. These results suggest that lncRNA PCNAP1 has potential as an alternative therapeutic target to suppress breast cancer metastasis.
... Replication of animal models of human tumors is able to study the in vivo tumor occurrence and development, which provides experimental basis for demonstrating the mechanism of tumor metastasis. The development of molecular imaging makes the realtime non-invasive in-vivo imaging of small animal tumor models possible [7,8]. Optical imaging, due to non-ionizing low-energy radiation, high sensitivity, no need of radioactive reagent and low cost of the imaging system, is particularly suitable for the research of small animal tumors. ...
Distant metastasis is one of the most common causes for failure in treatment of advanced NSCLC, and it is a key factor to determine the patients' prognosis. This study aims to screen the microRNAs associated with non-small cell lung cancer metastasis, so as to provide theoretical basis for investigating their roles in non-small cell lung cancer metastasis. In this study, the fluorescent transfected human non-small cell lung cancer cell lines H460 developed tumors subcutaneously, which were then in situ transplanted into the left lung of nude mice to obtain the tissue specimens of primary tumor and metastatic tumor. The differentially expressed microRNAs associated with non-small cell lung cancer metastasis were identified using the microRNA microarray and real-time quantitative polymerase chain reaction (RT-PCR) analysis, and bioinformatics analysis of the microRNAs was performed. The microarray analysis results revealed that 17 microRNAs with up-regulated expression and 7 with down-regulated expression between the non-small cell lung cancer metastatic primary loci and the non-metastatic primary loci (Group A), while 20 microRNAs with up-regulated expression (ratio > 1.5 times, P < 0.05) and 16 with down-regulated expression (ratio < 0.65 times, P < 0.05) between the non-small cell lung cancer metastatic loci and the metastatic primary loci (Group B). RT-PCR validation and bioinformatics analysis of some microRNAs identified 2 microRNAs with up-regulated expression, miR-10b and miR-144, and 3 microRNAs with down-regulated expression, miR-9, miR-31 and miR-34b in Group A; and 4 microRNAs with down-regulated expression, miR-25, miR-92a, miR-202 and miR-326 in Group B, which may be mediated by transcription factors activator protein 1 (AP-1), p53, STATs and NF-κB, regulate cell development, proliferation and cycle, DNA and RNA metabolism and signal transduction pathway, and promote tumor growth and metastasis through the effects on target genes like RARβ, RASSF1 and E2F-1. In conclusion, there are differences in microRNA expression between the non-small cell lung cancer metastatic and non-metastatic tissues, which provides experimental basis for exploring the mechanism of non-small cell lung cancer metastasis and provides a potential idea for molecular diagnosis and treatment, as well as prognosis.
It is well known that aberrant microenvironmental conditions in solid tumors negatively impact their response to conventional anticancer therapies. Indeed the presence of hypoxia in the primary tumor has been identified as a prognostic indicator of treatment outcome in a number of clinical settings. Hypoxic conditions can arise at the limits of oxygen diffusion from blood vessels (diffusion or chronic hypoxia) or as a consequence of vascular collapse (perfusion or acute hypoxia). Both types of hypoxia upregulate key signaling pathways associated with metastasis and related tumor cell behavior and function; and although the impact of acute and chronic oxygen deprivation on these pathways may differ markedly, the effect of such exposures is to significantly enhance the metastatic phenotype. In lieu of the critical role of metastasis in treatment failures, there has been significant interest in developing molecular targeting strategies that impair signaling pathways associated with tumor cell dissemination. Many of these targeted tumor cell associated functions are enhanced by hypoxia, including invasion and angiogenesis. Agents targeting angiogenesis are of interest because they could interfere with the progression of established microtumor deposits to macroscopic size by interfering with blood vessel development but they also raise the caveat that the use of such agents might induce hypoxia in the primary tumor which could conceivably enhance the dissemination of tumor cells. This chapter discusses the impact of oxygen deficiencies on the maintenance of stem-like characteristics of tumor initiating cells, the potential interplay between genomic markers and hypoxia/HIFs, and the effect of hypoxia on signaling pathway critical to the metastatic process, including VEGF, c-Src, and the HGF/c-Met axis. It further explores how the interference with signaling molecules may have significant therapeutic potential in the development of novel therapeutic intervention approaches for the treatment of cancer metastasis.
