scholarly journals Clinical significance of RBM3 expression in surgically treated colorectal lung metastases and paired primary tumors

2021 ◽  
Vol 123 (4) ◽  
pp. 1144-1156
Author(s):  
Halla Vidarsdottir ◽  
Christina Siesing ◽  
Björn Nodin ◽  
Per Jönsson ◽  
Jakob Eberhard ◽  
...  
2021 ◽  
Vol 10 (11) ◽  
pp. 2340
Author(s):  
Lucia Borriello ◽  
John Condeelis ◽  
David Entenberg ◽  
Maja H. Oktay

Although metastatic disease is the primary cause of mortality in cancer patients, the mechanisms leading to overwhelming metastatic burden are still incompletely understood. Metastases are the endpoint of a series of multi-step events involving cancer cell intravasation, dissemination to distant organs, and outgrowth to metastatic colonies. Here we show, for the first-time, that breast cancer cells do not solely disseminate to distant organs from primary tumors and metastatic nodules in the lymph nodes, but also do so from lung metastases. Thus, our findings indicate that metastatic dissemination could continue even after the removal of the primary tumor. Provided that the re-disseminated cancer cells initiate growth upon arrival to distant sites, cancer cell re-dissemination from metastatic foci could be one of the crucial mechanisms leading to overt metastases and patient demise. Therefore, the development of new therapeutic strategies to block cancer cell re-dissemination would be crucial to improving survival of patients with metastatic disease.


Author(s):  
Bobby Bhartia ◽  
Jim Zhong ◽  
Nilanjan Chaudhuri ◽  
Richard Milton ◽  
Jonathan Smith ◽  
...  

2021 ◽  
Vol 66 (12) ◽  
pp. 718-721
Author(s):  
Larisa Mikhailovna Obukhova ◽  
I. A. Medyanik ◽  
K. N. Kontorshchikova ◽  
S. A. Simagina ◽  
L. T. Musaelyan ◽  
...  

It has been established that the non-neuronal cholinergic system is related to the oncogenesis which increases the attractiveness of its components as the promising markers of oncologic diseases. The purpose of this work is to evaluate the clinical significance of the analysis of the activity of acetyl cholinesterase as a new marker of gliomas. The activity of acetyl cholinesterase was assessed by photo colorimetric analysis according to the Hestrin method recalculating the activity of the enzyme in the tumor tissue per 1 g of protein, and in the blood - by 0.1 g of hemoglobin. The data obtained in the primary tumors of the brain (28) in the tissue of the brain of persons who died as a result of injury (6) and in whole blood of patients with gliomas (28) and practically healthy people (10) were compared with the use of a number of statistical programs. A significant decrease in the activity of acetyl cholinesterase in tumor tissue and in whole blood is revealed as the degree of anaplasia of tumors increases, starting with Grade II. It is for the first time that a significant direct correlation was noted showing the consistency between the decrease in the activity of acetyl cholinesterase in the tumor tissue of the brain and blood. Bioinformatic analysis showed the connection of the enzyme of acetyl cholinesterase with proteins of the PI3K-AKT and Notch signaling pathways providing antiapoptotic and proliferative effects. The found dependences provide new insights into understanding of the mechanisms of gliomas genesis and can be used for selection of new diagnostic markers of brain tumors.


2019 ◽  
Vol 119 (5) ◽  
pp. 629-635 ◽  
Author(s):  
Joseph D. Phillips ◽  
Rian M. Hasson

2013 ◽  
Vol 20 (3) ◽  
pp. 391-401 ◽  
Author(s):  
Rosalyn D Ferguson ◽  
Emily J Gallagher ◽  
Dara Cohen ◽  
Aviva Tobin-Hess ◽  
Nyosha Alikhani ◽  
...  

The Her2 oncogene is expressed in ∼25% of human breast cancers and is associated with metastatic progression and poor outcome. Epidemiological studies report that breast cancer incidence and mortality rates are higher in women with type 2 diabetes. Here, we use a mouse model of Her2-mediated breast cancer on a background of hyperinsulinemia to determine how elevated circulating insulin levels affect Her2-mediated primary tumor growth and lung metastasis. Hyperinsulinemic (MKR+/+) mice were crossed with doxycycline-inducible Neu-NT (MTB/TAN) mice to produce the MTB/TAN/MKR+/+ mouse model. Both MTB/TAN and MTB/TAN/MKR+/+ mice were administered doxycycline in drinking water to induce Neu-NT mammary tumor formation. In tumor tissues removed at 2, 4, and 6 weeks of Neu-NT overexpression, we observed increased tumor mass and higher phosphorylation of the insulin receptor/IGF1 receptor, suggesting that activation of these receptors in conditions of hyperinsulinemia could contribute to the increased growth of mammary tumors. After 12 weeks on doxycycline, although no further increase in tumor weight was observed in MTB/TAN/MKR+/+ compared with MTB/TAN mice, the number of lung metastases was significantly higher in MTB/TAN/MKR+/+ mice compared with controls (MTB/TAN/MKR+/+ 16.41±4.18 vs MTB/TAN 5.36±2.72). In tumors at the 6-week time point, we observed an increase in vimentin, a cytoskeletal protein and marker of mesenchymal cells, associated with epithelial-to-mesenchymal transition and cancer-associated fibroblasts. We conclude that hyperinsulinemia in MTB/TAN/MKR+/+ mice resulted in larger primary tumors, with more mesenchymal cells and therefore more aggressive tumors with more numerous pulmonary metastases.


Author(s):  
Oleg V. Bilokon ◽  
Elen V. Shaida ◽  
Petro P. Sokur ◽  
Borys O. Kravchuk

Today, it is relevant to search for new, better methods of surgical treatment of tumors and organ-preserving and video-assisted surgery is gaining more and more popularity. The aim of the study was to improve the results of surgical treatment of children with primary and secondary (metastatic) lung tumors using high-frequency live tissue welding (HF LTW) in order to increase the treatment effectiveness. Novelty of the study lies in the expanding the knowledge of the new researched method, for enhancement of survivability relatively to chemotherapy and radiation methods, that are studied in the previous works. Advantages of the introduced method are bloodless, fast, low traumatic operations 103 case reports in children with primary and metastatic lung tumors were analyzed, including 34 patients with benign and malignant lung tumors and 69 children with metastatic bronchial and pulmonary lesions undergoing treatment from 2002 to 2018 were examined. Benign lung tumors were diagnosed in 17 patients. Malignant tumors were observed in 17 patients, including 11 lung carcinoid tumors. Metastatic bronchial and pulmonary lesions most often occurred with osteosarcoma (28) and nephroblastoma (17). In 34 children with primary tumors, 37 were undergone surgical interventions. Most often, atypical resection was used – 16 (43.3%), in particular, with carcinoid – in 7 (43.8%) patients and with hamartoma – in 4 (25%) patients. In metastatic lesions, in most cases, the same resection was performed. From 58 resections 25 (43%) were performed for osteosarcoma and 15 (26%) for nephroblastoma. The HF LTW method was used in 29 patients for benign and malignant primary tumors and in 62 (73%) surgical procedures for lung metastases to remove a tumor, vascular coagulation and sealing of the lung tissue. Using HF LTW surgical operations of different directions and volumes can be performed effectively in benign, malignant and metastatic bronchial and pulmonary lesions in children.


Author(s):  
Chinmayee Sethy ◽  
Kunal Goutam ◽  
Deepika Nayak ◽  
Rajalaxmi Pradhan ◽  
Sefinew Molla ◽  
...  

In the present study, we have systematically examined the clinical significance of Nectin-4 (encoded by the PVRL-4 gene), a marker for breast cancer stem cells (CSCs), in cancer metastasis and angiogenesis using a variety of human specimens, including invasive duct carcinoma (IDC) with multiple grades, several types of primary tumors to local and distant relapses, lymph node metastases and circulating tumor cells (CTCs). Nectin-4 was overexpressed in more than 92% of samples with 65.2% Nectin-4 positive cells. The level of expression was increased with increasing tumor grade (GI-III) and size (T1-4) of IDC specimens. More induction of Nectin-4 was noted in relapsed samples from a variety of tumors (colon, tongue, liver, kidney, ovary, buccal mucosa) in comparison to primary tumors, while paired adjacent normal tissues do not express any Nectin-4. A high expression of Nectin-4 along with other representative markers in CTCs and lymph node metastasis was also observed in cancer specimens. An increased level of Nectin-4 along with representative metastatic (CD-44, Sca1, ALDH1, Nanog) and angiogenic (Ang-I, Ang-II, VEGF) markers was noted in metastatic tumors (local and distant) in comparison to primary tumors that were correlated with different grades of tumor progression. In addition, greater expression of Nectin-4 was observed in secondary tumors (distant metastasis, e.g., breast to liver or stomach to gallbladder) in comparison to primary tumors. Nectin-4 was overexpressed at all stages of metastasis and angiogenesis, thus appearing to play a major role in tumor relapse through the PI3K-Akt-NFκβ pathway.


2020 ◽  
Author(s):  
Weijie Zhang ◽  
Igor L. Bado ◽  
Hai Wang ◽  
Swarnima Singh ◽  
Hin-Ching Lo ◽  
...  

SUMMARYMetastasis has been considered as the terminal step of tumor progression. However, recent clinical studies suggest that many metastases are seeded from other metastases, rather than primary tumors. Thus, some metastases can further spread, but the corresponding pre-clinical models are lacking. By using several approaches including parabiosis and an evolving barcode system, we demonstrated that the bone microenvironment facilitates breast and prostate cancer cells to further metastasize and establish multi-organ secondary metastases. Importantly, dissemination from the bone microenvironment appears to be more aggressive compared to that from mammary tumors and lung metastases. We further uncovered that this metastasis-promoting effect is independent from genetic selection, as single cell-derived cancer cell populations (SCPs) exhibited enhanced metastasis capacity after being extracted from the bone microenvironment. Taken together, our work revealed a previously unappreciated effect of the bone microenvironment on metastasis evolution, and suggested a stable reprogramming process that engenders cancer cells more metastatic.


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