OCE-based quasistatic elasto-spectroscopy of living and freshly excised tumor tissue for histology-like morphological segmentation and express assessment of tumor subtypes

Author(s):  
Vladimir Y. Zaitsev ◽  
Aleksander L. Matveyev ◽  
Lev Matveev ◽  
Alexander Sovetsky ◽  
Anton Plekhanov ◽  
...  
2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15584-e15584
Author(s):  
Shailesh R. Satpute ◽  
Roelof Koster ◽  
Katherine L. Nathanson ◽  
David J. Vaughn ◽  
Costantine Albany ◽  
...  

e15584 Background: Presence of BRAF V600E mutation forms the basis of a successful targeted therapy against malignant melanoma. While this mutation is also demonstrated in various other tumor types, its presence in germ cell tumor (GCT) is inconsistent across various studies. In one study, 9 out of 35 (26%) platinum-refractory GCTs were positive for BRAF V600E mutation (Honecker et al, JCO 2009 May 1; 27(13):2129-36). In the current study we tested tumor tissue of patients for BRAF V600E mutation in order to correlate it with known tumor subtypes and treatment outcomes. Methods: We obtained tumor specimen of 59 patients with GCT that were treated at either Indiana University or University of Pennsylvania from 2000 to 2011 and tested them for presence of BRAF V600E mutation by Sanger sequencing with exon 15 specific primers. Out of 59 tumors, 12 (20%) were seminomas and 47 (80%) were non-seminomas. 26 (44%) patients had no recurrence after first line cisplatin-based chemotherapy whereas 33 (56%) patients had either platinum-refractory disease or had a disease recurrence within 2 years of completing chemotherapy. Tumors from 10 patients contained only mature teratoma after chemotherapy. 31 (52%) patients were classified at the time of diagnosis as good risk, 8 (14%) patients as intermediate risk and 20 (34%) patients as poor risk according to international germ cell consensus classification. Results: We found that all 59 tumor tissue were wild-type or lacked BRAF V600E mutation. Appropriate positive and negative controls were used for the assay. Conclusions: BRAF V600E mutation is not a feature of GCT. In our study, we failed to observe any correlation of the mutation with tumor subtypes or with treatment outcomes. Based on this study, BRAF inhibiting drugs may not be beneficial in germ cell tumors.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 506-506
Author(s):  
Robin Mjelle ◽  
Wenche Sjursen ◽  
Liv Thommesen ◽  
Eva Hofsli

506 Background: MicroRNAs (miRNAs) are promising biomarkers and therapeutic agents for colorectal cancer (CRC). However, much remains to be known about the biology of miRNAs and miRNA variants in tumor tissue and why the expression differs from normal tissue. Methods: RNA from 48 normal and 48 cancer tissue samples were sequenced using the Illumina small RNA sequencing protocol. Samples were taken from both male and female patients with tumor stage 1-4. Results: We show that almost 50% of microRNAs (miRNAs) are differentially expressed between normal and cancer tissue. When analyzing pre-miRNAs that map to genomic clusters, so-called clustered miRNAs, we show that miRNAs in the same cluster often have similar expression profiles. This shows that common changes in co-expressed miRNAs seem to explain some of the miRNA expression changes between normal and tumor samples and indicates that altered pri-miRNA transcription is the mechanism for at least some of the miRNA changes. Analyses of miRNA variants, so-called isomiRs, revealed large variations between tumor and normal samples, similar to those observed for the canonical miRNAs. Different isomiR types show different expression profiles in tumor vs normal samples, indicating that miRNA processing is altered in tumor cells. Finally, we show that several canonical miRNAs and isomiRs correlate with genetic signatures in the tumor samples, including KRAS and BRAF mutation, Microsatellite instability and MLH1 methylation, indicating that tumor subtypes have different miRNA expression. Conclusions: Our results show that miRNA expression predicts tumor subtypes with different genetic signatures. We show that some of the changes in miRNA expression are due to different transcription programs in cancer vs normal tissue.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xiangsheng Zhang ◽  
Liye Zhong ◽  
Zhilin Zou ◽  
Guosheng Liang ◽  
Zhenye Tang ◽  
...  

N6-methyladenosine (m6A) is one of the most active modification factors of mRNA, which is closely related to cell proliferation, differentiation, and tumor development. Here, we explored the relationship between the pathogenesis of hematological malignancies and the clinicopathologic parameters. The datasets of hematological malignancies and controls were obtained from the TCGA [AML (n = 200), DLBCL (n = 48)] and GTEx [whole blood (n = 337), blood vascular artery (n = 606)]. We analyzed the m6A factor expression differences in normal tissue and tumor tissue and their correlations, clustered the express obvious clinical tumor subtypes, determined the tumor risk score, established Cox regression model, performed univariate and multivariate analysis on all datasets. We found that the AML patients with high expression of IGF2BP3, ALKBH5, and IGF2BP2 had poor survival, while the DLBCL patients with high expression of METTL14 had poor survival. In addition, “Total” datasets analysis revealed that IGF2BP1, ALKBH5, IGF2BP2, RBM15, METTL3, and ZNF217 were potential oncogenes for hematologic system tumors. Collectively, the expressions of some m6A regulators are closely related to the occurrence and development of hematologic system tumors, and the intervention of specific regulatory factors may lead to a breakthrough in the treatment in the future.


Author(s):  
D. C. Swartzendruber ◽  
Norma L. Idoyaga-Vargas

The radionuclide gallium-67 (67Ga) localizes preferentially but not specifically in many human and experimental soft-tissue tumors. Because of this localization, 67Ga is used in clinical trials to detect humar. cancers by external scintiscanning methods. However, the fact that 67Ga does not localize specifically in tumors requires for its eventual clinical usefulness a fuller understanding of the mechanisms that control its deposition in both malignant and normal cells. We have previously reported that 67Ga localizes in lysosomal-like bodies, notably, although not exclusively, in macrophages of the spocytaneous AKR thymoma. Further studies on the uptake of 67Ga by macrophages are needed to determine whether there are factors related to malignancy that might alter the localization of 67Ga in these cells and thus provide clues to discovering the mechanism of 67Ga localization in tumor tissue.


1989 ◽  
Vol 28 (05) ◽  
pp. 193-200 ◽  
Author(s):  
E. Aulbert

Cellular uptake of 67Ga-labelled transferrin by the tumor tissue was studied in rats with tumors of different malignancy and different tumor mass using the slowly growing Morris hepatoma 5123C, the moderately growing Novikoff hepatoma and the very fast and aggressive Yoshida hepatoma AH130. The cellular accumulation of 67Ga-transferrin was found to correlate with the proliferation activity of the tumor. The 67Ga-transferrin concentration in the very fast growing Yoshida hepatoma was 4.8 times higher than the concentration in the slowly growing Morris hepatoma. The uptake of 67Ga-transferrin by the tumors resulted in a faster disappearance of circulating 67Ga-transferrin from the blood. The rate of disappearance correlated with the proliferation activity and the spread of the tumors. Using tumors of identical size the elimination of 67Ga-transferrin from the blood was much faster in the rats with Yoshida hepatoma than in those with the slowly growing Morris hepatoma. On the other hand, using tumors of different tumor size it could be demonstrated that the rate of disappearance of 67Ga-transferrin from the blood correlated directly with tumor mass. It is concluded that cellular incorporation of transferrin within the tumor cells results in a loss of circulating transferrin, which correlates with tumor mass and proliferation of tumor. This mechanism is supposed to be the cause for the hypotransferrinemia seen in patients with malignant tumors.


1969 ◽  
Vol 8 (02) ◽  
pp. 84-90 ◽  
Author(s):  
A. W. Pratt ◽  
M. Pacak

The system for the identification and subsequent transformation of terminal morphemes in medical English is a part of the information system for processing pathology data which was developed at the National Institutes of Health.The recognition and transformation of terminal morphemes is restricted to classes of adjectivals including the -ING and -ED forms, nominals and homographic adjective/noun forms.The adjective-to-noun and noun-to-noun transforms consist basically of a set of substitutions of adjectival and certain nominal suffixes by a set of suffixes which indicate the corresponding nominal form(s).The adjectival/nominal suffix has a polymorphosyntactic transformational function if it has the property of being transformed into more than one nominalizing suffix (e.g., the adjectival suffix -IC can be substituted by a set of nominalizing suffixes -Ø, -A, -E, -Y, -IS, -IA, -ICS): the adjectival suffix has a monomorphosyntactic transformational property if there is only one admissible transform (e.g., -CIC → -X).The morphological segmentation and the subsequent transformations are based on the following principles:a. The word form is segmented according to the principle of »double consonant cut,« i.e., terminal characters following the last set of double consonants are analyzed and treated as a potential suffix. For practical purposes only such terminal suffixes of a maximum length of four have been analyzed.b. The principle that the largest segment of a word form common to both adjective and noun or to both noun stems is retained as a word base for transformational operations, and the non-identical segment is considered to be a »suffix.«The backward right-to-left character search is initiated by the identification of the terminal grapheme of the given word form and is extended to certain admissible sequences of immediately preceding graphemes.The nodes which represent fixed sequences of graphemes are labeled according to their recognition and/or transformation properties.The tree nodes are divided into two groups:a. productive or activatedb. non-productive or non-activatedThe productive (activated) nodes are sequences of sets of graphemes which possess certain properties, such as the indication about part-of-speech class membership, the transformation properties, or both. The non-productive (non-activated) nodes have the function of connectors, i.e., they specify the admissible path to the productive nodes.The computer program for the identification and transformation of the terminal morphemes is open-ended and is already operational. It will be extended to other sub-fields of medicine in the near future.


2019 ◽  
Author(s):  
M Maktabi ◽  
H Köhler ◽  
R Thieme ◽  
JP Takoh ◽  
SM Rabe ◽  
...  

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