3D-Morphometry of the Microvascular Architecture in Normal Human Tissues, Precanceroses, and Primary Tumors: Quantitative Corrosion Casting Studies

2000 ◽  
Vol 6 (S2) ◽  
pp. 566-567
Author(s):  
M. A. Konerding ◽  
W. Malkusch ◽  
E. Fait ◽  
A. Gaumann

The important question as to whether the vascular architecture of an individual tumor is tumor type specific has been controversial. We have recently shown using a simple and accurate technique for 3D-measurements in microcorrosion casts that at least experimental tumors develop a characteristic vascular network. There is strong evidence that the basic vascular architecture is determined by the tumor cells themselves. However, for human primary tumors and their metastases as well as their possible precanceroses no data are available until today.Therefore we studied the microvascular architecture of different colorectal carcinomas and adenomas as well as the vascularity of different segments of the colon and rectum. For this, parameters defining the microvascular unit were analysed on 3D reconstructed images as recently described.Comparisons of the quantified parameters within a given segment of the colon as well as group comparisons of all segments did not reveal any significant inter-individual difference.

1999 ◽  
Vol 5 (S2) ◽  
pp. 1198-1199
Author(s):  
M. A. Konerding ◽  
W. Malkusch ◽  
M. Presta ◽  
A. Gaumann

The significance of angiogenesis and the vascular architecture have been stressed in numerous studies of the structure and biological properties of the tumor vasculature and blood flow (Folkman and D'Amore, 1996; Jain, 1988). The important question as to whether the vascular architecture of an individual tumor is tumor type specific has been controversial. This is due, at least in part, to the methodologies used. Most reports confine themselves to qualitative observations and comparisons of gross vascular patterns in host and tumor, or to blood vessel density, length and diameter measurements, which in turn vary with the staining and counting techniques.We studied the microvascular architecture of four different tumor cell lines (CaX, CaNT, SaS, HEC- 1B) in order to determine whether there is a characteristic vascular pattern for different tumor types and whether it differs significantly from two normal tissues, muscle and gut.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Michael Skaro ◽  
Marcus Hill ◽  
Yi Zhou ◽  
Shannon Quinn ◽  
Melissa B. Davis ◽  
...  

Abstract Background & Aims Cancer metastasis into distant organs is an evolutionarily selective process. A better understanding of the driving forces endowing proliferative plasticity of tumor seeds in distant soils is required to develop and adapt better treatment systems for this lethal stage of the disease. To this end, we aimed to utilize transcript expression profiling features to predict the site-specific metastases of primary tumors and second, to identify the determinants of tissue specific progression. Methods We used statistical machine learning for transcript feature selection to optimize classification and built tree-based classifiers to predict tissue specific sites of metastatic progression. Results We developed a novel machine learning architecture that analyzes 33 types of RNA transcriptome profiles from The Cancer Genome Atlas (TCGA) database. Our classifier identifies the tumor type, derives synthetic instances of primary tumors metastasizing to distant organs and classifies the site-specific metastases in 16 types of cancers metastasizing to 12 locations. Conclusions We have demonstrated that site specific metastatic progression is predictable using transcriptomic profiling data from primary tumors and that the overrepresented biological processes in tumors metastasizing to congruent distant loci are highly overlapping. These results indicate site-specific progression was organotropic and core features of biological signaling pathways are identifiable that may describe proliferative plasticity in distant soils.


Author(s):  
Keith L. Ligon ◽  
Karima Mokhtari ◽  
Thomas W. Smith

This chapter presents the most up-to-date classification of tumors of the nervous system, based on the histological appearance of the neoplasm and also on information derived from cytogenetics and molecular biology, now recognized worldwide as increasingly important for more precise diagnosis, prognosis, and therapeutic guidance. The chapter provides a detailed morphologic description of each major tumor type, with numerous illustrations of macroscopic and microscopic lesions. First we consider primary tumors of the nervous system, including those derived from neuroepithelial tissue (astrocytic, oligodendroglial, ependymal, neuronal, and glioneuronal), pineal tissue, peripheral nerve sheath, and meninges. Next lymphomas, hematopoietic neoplasms, and secondary (metastatic) neoplasms are described.


2009 ◽  
Vol 15 (S2) ◽  
pp. 984-985 ◽  
Author(s):  
F Hossler ◽  
A Lametschwandtner ◽  
R Kao ◽  
C Bills ◽  
F Finsterbusch

Extended abstract of a paper presented at Microscopy and Microanalysis 2009 in Richmond, Virginia, USA, July 26 – July 30, 2009


Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1546 ◽  
Author(s):  
Alena Kopkova ◽  
Jiri Sana ◽  
Tana Machackova ◽  
Marek Vecera ◽  
Lenka Radova ◽  
...  

Central nervous system (CNS) malignancies include primary tumors that originate within the CNS as well as secondary tumors that develop as a result of metastatic spread. Circulating microRNAs (miRNAs) were found in almost all human body fluids including cerebrospinal fluid (CSF), and they seem to be highly stable and resistant to even extreme conditions. The overall aim of our study was to identify specific CSF miRNA patterns that could differentiate among brain tumors. These new biomarkers could potentially aid borderline or uncertain imaging results onto diagnosis of CNS malignancies, avoiding most invasive procedures such as stereotactic biopsy or biopsy. In total, 175 brain tumor patients (glioblastomas, low-grade gliomas, meningiomas and brain metastases), and 40 non-tumor patients with hydrocephalus as controls were included in this prospective monocentric study. Firstly, we performed high-throughput miRNA profiling (Illumina small RNA sequencing) on a discovery cohort of 70 patients and 19 controls and identified specific miRNA signatures of all brain tumor types tested. Secondly, validation of 9 candidate miRNAs was carried out on an independent cohort of 105 brain tumor patients and 21 controls using qRT-PCR. Based on the successful results of validation and various combination patterns of only 5 miRNA levels (miR-30e, miR-140, let-7b, mR-10a and miR-21-3p) we proposed CSF-diagnostic scores for each tumor type which enabled to distinguish them from healthy donors and other tumor types tested. In addition to this primary diagnostic tool, we described the prognostic potential of the combination of miR-10b and miR-196b levels in CSF of glioblastoma patients. In conclusion, we performed the largest study so far focused on CSF miRNA profiling in patients with brain tumors, and we believe that this new class of biomarkers have a strong potential as a diagnostic and prognostic tool in these patients.


2019 ◽  
Vol 55 (3) ◽  
pp. 1900933 ◽  
Author(s):  
Maximilian Ackermann ◽  
Helge Stark ◽  
Lavinia Neubert ◽  
Stephanie Schubert ◽  
Paul Borchert ◽  
...  

The pathogenetic role of angiogenesis in interstitial lung diseases (ILDs) is controversial. This study represents the first investigation of the spatial complexity and molecular motifs of microvascular architecture in important subsets of human ILD. The aim of our study was to identify specific variants of neoangiogenesis in three common pulmonary injury patterns in human ILD.We performed comprehensive and compartment-specific analysis of 24 human lung explants with usual intersitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) and alveolar fibroelastosis (AFE) using histopathology, microvascular corrosion casting, micro-comupted tomography based volumetry and gene expression analysis using Nanostring as well as immunohistochemistry to assess remodelling-associated angiogenesis.Morphometrical assessment of vessel diameters and intervascular distances showed significant differences in neoangiogenesis in characteristically remodelled areas of UIP, NSIP and AFE lungs. Likewise, gene expression analysis revealed distinct and specific angiogenic profiles in UIP, NSIP and AFE lungs.Whereas UIP lungs showed a higher density of upstream vascularity and lower density in perifocal blood vessels, NSIP and AFE lungs revealed densely packed alveolar septal blood vessels. Vascular remodelling in NSIP and AFE is characterised by a prominent intussusceptive neoangiogenesis, in contrast to UIP, in which sprouting of new vessels into the fibrotic areas is characteristic. The molecular analyses of the gene expression provide a foundation for understanding these fundamental differences between AFE and UIP and give insight into the cellular functions involved.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15609-e15609
Author(s):  
S. Thieltges ◽  
T. Kalinina ◽  
A. Krohn ◽  
R. Simon ◽  
M. Moeller-Krull ◽  
...  

e15609 Background: Pancreatic adenocarcinoma is a genetically highly complex and heterogenous tumor type with strong genetic instability which makes it resistant to therapy. Known amplifications of oncogenes such as KRAS or MYC and deletions of tumor suppresor genes such as CDKN2A and SMAD4 have demonstrated the importance of genetic alteration in this tumor type. Methods: We report the use of an Affymetrix Genome-Wide Human single nucleotide polymorphism (SNP) Array 6.0 (906,600 SNPs) to screen for gene copy number changes and allelic imbalances in 8 microdissected primary pancreatic tumors and 7 established pancreatic cancer cell lines. Gene Chip Human Genome U133 2.0 Array was used to make an RNA expression profile. Mutation analysis of KRAS and M-FISH analysis of cell lines was performed. Results: SNP arrays confirmed the presence of previously reported cytogenetic abnormalities in the cell lines and primary tumor probes, including MYC amplifikation at 8q24, gain of 17q12 (ERBB2/HER2), 7p12 (EGFR) and 12p12.1 (KRAS). KRAS mutation was seen in 71% of cell lines (5/7). We identified several alterations in signaling pathways such as Wnt/Notch Signaling and KRAS signaling. A sizeable subset ( 7 of 15 cases; 47%) showed an amplikon at 19q13.1–13.2 in which the serine/threonine kinase Mirk/Dyrk1B is localized, a downstream effector of oncogenic k-ras. There was also strong concordance between primary tumors and cell lines with respect to gains on 8q, 12p and 18q. Analysis of gene expression was used to localize potential target genes. M-FISH analysis showed complex karyotypes with chromosomal deletions in 9p and 18q, regions that are known to harbor tumor suppressor genes (CDKN2A, SMAD4 and TP53). Conclusions: Several signaling pathways mediate tumor cell survival. Analysis of gene amplification and RNA expression profile provide molecular biological characteristics and an individual gene signature of the tumor which allow us to choose more efficient drugs to an individualized treatment. Pathways activated by KRAS such as DYRK1B may offer new therapeutic targets. Further functional characterization is needed to provide evidence for the actual role of any putative target gene. No significant financial relationships to disclose.


2020 ◽  
Author(s):  
Santasree Banerjee ◽  
Xianxiang Zhang ◽  
Shan Kuang ◽  
Jigang Wang ◽  
Lei Li ◽  
...  

AbstractIntratumor heterogeneity (ITH) enable us to understand the evolution of cancer. ITH and evolution of colorectal cancer (CRC) has not been well studied. In this prospective study, we recruited different stages of 68 CRC patients with primary tumor at right-sided colon, left-sided colon and rectum. We performed high-depth whole exome sequencing of 206 multi-region tumor samples including primary tumors, lymph node metastasis (LN) and extranodal tumor deposits (ENTD). Our result showed extreme ITH with Darwinian pattern of CRC evolution, evolution pattern of left-sided CRC was more complex and divergent than right-sided CRC and both LN and ENTD were of polyclonal in origin. Extensive ITH was found in driver mutations in KRAS and PIK3CA genes, suggesting major limitations of single biopsies in clinical diagnosis for the CRC patients. In conclusion, our study showed the Darwinian pattern of CRC evolution with differences in evolution pattern between right-sided and left-sided CRC patients.


2005 ◽  
pp. 061-065
Author(s):  
Dmitry Aleksandrovich Ptashnikov ◽  
Vladimir Dmitryevich Usikov

Objective. To validate the approach to treatment of patients with primary tumors of the spine. Material and Methods. The experience of surgical treatment of 47 patients with benign tumors of the spine was analyzed. The treatment approach was defined with the account of tumor type and localization, and of patient’s somatic status. The diseased area was examined with the help of X-ray, CT scanning, and MRI, and a punch biopsy in some patients. Results. The tumor recurrence was registered in 6 (14.6 %) patients. This shows that in some cases the exact margins of the tumor were not defined despite the comprehensive diagnostic possibilities. Functional results of the treatment implied the restoration of the spine support ability and the pain regress in all observations. Bone plasty was the method of choice for interbody defect replacement. Conclusion. The radical surgery (corpectomy and spondylectomy) considerably reduces the risk of tumor recurrence. Lumbosacral location of the tumor with paravertebral extension presents serious technical problems in its total removal. Autogenic cortical cancellous bone proved to be a good plastic material for defect replacement after vertebra resection and fusion.


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