scholarly journals Construction of a CXCL12-KDEL Fusion Gene to Inhibit Head and Neck Squamous Cell Carcinoma Metastasis by Intracellular Sequestration of CXCR4

2015 ◽  
Vol 2015 ◽  
pp. 1-9
Author(s):  
Wenchao Zhang ◽  
Xudong Wang ◽  
Kai Yue ◽  
Su Liu ◽  
Xiaonan Liu
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cell Surface ◽  
Cancer Metastasis ◽  
Fusion Gene ◽  
Specific Receptor ◽  
Tumor Cell Membrane ◽  
Node Metastasis ◽  
Squamous Cancer ◽  
Intracellular Sequestration

The CXCL12-CXCR4 biological axis consisting of the chemotactic factor CXCL12 and its specific receptor CXCR4 plays an important role in oral cancer metastasis. High expression of CXCR4 may help oral squamous cancer cells invade local tissues and metastasize to lymph nodes. No obvious association was observed between CXCL12 expression and lymph node metastasis, suggesting that CXCL12 chemotaxis may only be related to CXCR4 expression on the tumor cell membrane. KDEL can be retained by receptors on the surface of the intracellular endoplasmic reticulum (ER) and also be called an ER retention signal sequence. So we adopted the KDEL sequence in this study to generate a CXCL12-KDEL fusion protein in combination with a traceable E-tag label. As such, CXCL12 was retained in the ER. Specific receptor CXCR4 binds to the CXCL12-KDEL, was also retained in the ER, and was thus prevented from reaching the oral squamous cancer cell surface. We reduced the cell surface level of CXCR4 and called the technique “intracellular sequestration.” By this way, we have finished blocking of CXCL12-CXCR4 biological axis and inhibiting lymph node metastasis of oral carcinoma.

scholarly journals Landscape of Genome-Wide DNA Methylation of Colorectal Cancer Metastasis

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2710
Author(s):  
Carmen Ili ◽  
Kurt Buchegger ◽  
Hannah Demond ◽  
Juan Castillo-Fernandez ◽  
Gavin Kelsey ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Cpg Island ◽  
The Cancer Genome Atlas ◽  
Node Metastasis ◽  
Genome Wide

Colorectal cancer is a heterogeneous disease caused by both genetic and epigenetics factors. Analysing DNA methylation changes occurring during colorectal cancer progression and metastasis formation is crucial for the identification of novel epigenetic markers of patient prognosis. Genome-wide methylation sequencing of paired samples of colon (normal adjacent, primary tumour and lymph node metastasis) showed global hypomethylation and CpG island (CGI) hypermethylation of primary tumours compared to normal. In metastasis we observed high global and non-CGI regions methylation, but lower CGI methylation, compared to primary tumours. Gene ontology analysis showed shared biological processes between hypermethylated CGIs in metastasis and primary tumours. After complementary analysis with The Cancer Genome Atlas (TCGA) cohort, FIGN, HTRA3, BDNF, HCN4 and STAC2 genes were found associated with poor survival. We mapped the methylation landscape of colon normal tissues, primary tumours and lymph node metastasis, being capable of identified methylation changes throughout the genome. Furthermore, we found five genes with potential for methylation biomarkers of poor prognosis in colorectal cancer patients.

scholarly journals Lipoma HMGIC fusion partner expression differs in primary tumors and lymph node metastases in malignancy.

2021 ◽  
Author(s):  
Vijay S
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lymph Node Metastases ◽  
Cancer Metastasis ◽  
Breast Tumors ◽  
Breast Cancer Metastasis ◽  
Axillary Lymph ◽  
Node Metastasis ◽  
Node Metastases

Abstract Breast cancer is the most common cancer found in women. 1. Metastasis is the leading cause of mortality among cancer patients. 2. As the number of axillary lymph nodes with metastases grows the prognosis for patients with breast cancer worsens3. We used a published microarray dataset4 to find genes linked to lymph node metastasis, which is an early stage of breast cancer metastasis. When comparing original breast tumors to lymph node metastases from patients diagnosed with breast cancer, we discovered substantial differences in LHFP gene expression. When comparing primary breast tumors to neighboring normal breast tissue, LHFP was shown to be one of the most differentially expressed genes in a separate microarray dataset5. In individuals with breast cancer, LHFP expression was shown to be substantially linked with median overall survival. LHFP may be involved in the mechanisms that lead to the transformation or progression of the original tumor in human breast cancer, as well as lymph node metastasis. Breast cancer, breast cancer metastasis, lymph node metastasis, LHFP, breast cancer systems biology, and breast cancer targeted treatments.

scholarly journals Peptidomics-driven strategy reveals peptides and predicted proteases associated with oral cancer prognosis

2020 ◽  
pp. mcp.RA120.002227
Author(s):  
Leandro Xavier Neves ◽  
Daniela C. Granato ◽  
Ariane Fidelis Busso-Lopes ◽  
Carolina Moretto Carnielli ◽  
Fábio M. de Sá Patroni ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Oral Cancer ◽  
Cancer Metastasis ◽  
Survival Rates ◽  
Cancer Prognosis ◽  
Cancer Tissue ◽  
Proteomic Profiling ◽  
Node Metastasis ◽  
Molecular Features

Protease activity has been associated with pathological processes that can lead to cancer development and progression. However, understanding the pathological unbalance in proteolysis is challenging since changes can occur simultaneously at protease, their inhibitor and substrate levels. Here, we present a pipeline that combines peptidomics, proteomics and peptidase predictions for studying proteolytic events in the saliva of seventy-nine patients and their association with oral squamous cell carcinoma (OSCC) prognosis. Our findings revealed differences in the saliva peptidome of patients with (pN+) or without (pN0) lymph node metastasis and delivered a panel of ten endogenous peptides correlated with poor prognostic factors plus five molecules able to classify pN0 and pN+ patients (ROC-AUC>0.85). In addition, endo- and exopeptidases putatively implicated in the processing of differential peptides were investigated using cancer tissue gene expression data from publicly repositories reinforcing their association with poorer survival rates and prognosis in oral cancer. The dynamics of the OSCC-related proteolysis was further explored via the proteomic profiling of saliva. This revealed that peptidase/endopeptidase inhibitors exhibited reduced levels in the saliva of pN+ patients, as confirmed by SRM-MS, whilst minor changes were detected in the level of saliva proteases. Taken together, our results indicated that proteolytic activity is accentuated in the saliva of OSCC patients with lymph node metastasis and, at least in part, this is modulated by reduced levels of salivary peptidase inhibitors. Therefore, this integrated pipeline provided better comprehension and discovery of molecular features with implications in the oral cancer metastasis prognosis.

Tyrosine kinase receptor AXL in human breast cancer is expressed differentially in metastasis of the lymph node

2021 ◽  
Author(s):  
Mairead Paul ◽  
Brandon Weston ◽  
Oliwier Morin
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lymph Nodes ◽  
Cancer Metastasis ◽  
Disease Free Survival ◽  
Tyrosine Kinase Receptor ◽  
Axillary Lymph ◽  
Primary Tumors ◽  
Node Metastasis

The most diagnosed malignancy in women is breast cancer1. Metastases in people diagnosed with cancer are the main cause of mortality. 2. Patients with breast cancer are predicted to do worse as the number of metastasized axillary lymph nodes increases3. In order to uncover the genes related with metastases in lymph nodes, the early events of the breast cancer metastasis, we mined the published and multiplexed mRNA quantitation datasets4, 5. When lymph node metastasis was compared to original breast tumors by patients diagnosed with breast cancer, we identified substantial differential expression of AXL encoding. The lower expression of AXL in primary tumors is associated with reduced disease-free survival in patients with breast cancer. AXL may be important in mechanisms that underlie lymph node metastasis.

scholarly journals Management of Para-Aortic Lymph Node Metastasis in Rectal Squamous Carcinoma

2020 ◽  
pp. 1-3
Author(s):  
Mário Rino Martins ◽  
Cecília Araújo Carneiro Lima ◽  
Juliana Karine Ferreira Santos Lessa ◽  
Luciana Mata da Silva ◽  
Mário Rino Martins ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cancer Metastasis ◽  
Squamous Carcinoma ◽  
En Bloc Resection ◽  
Bloc Resection ◽  
Nodal Metastasis ◽  
En Bloc ◽  
Retroperitoneal Lymphadenectomy ◽  
Node Metastasis

Background: Squamous cell carcinoma (SCC) of the rectum is a rare malignancy, and retroperitoneal nodal metastasis (RNM) represent 1-2% of colorectal cancer metastasis (CRC), and radical retroperitoneal lymphadenectomy (RRL) in this setting remains controversial. However, there are no reports in the literature on how to treat SCC retroperitoneal lymph node metastasis. Case Presentation: The patient was a 47-years-old woman with SCC of the rectum. Concomitant chemoradiotherapy (CRT) followed by surgery was planned. After 8 weeks, CT of the abdomen for restaging showed a 6 cm para-aortic mass involving and obstructing the medium third of the left ureter. The patient was submitted to abdominoperineal rectal resection with left nephrectomy and en-bloc resection of para-aortic tumor (nodal bulking). Conclusion: After a thorough review of the literature regarding RNM for rectal SCC, we found no mention of how to treat RNM for rectal SCC. The purpose of this paper is to report a very rare case of RNM for rectal SCC and to discuss the surgical approach. Surgery seems to be the best option for local control and improvement in overall survival (OS).

scholarly journals The Cell Surface Estrogen Receptor, G Protein- Coupled Receptor 30 (GPR30), is Markedly down Regulated during Breast Tumorigenesis

2008 ◽  
Vol 1 ◽  
pp. BCBCR.S557 ◽  
Author(s):  
Indira Poola ◽  
Jessy Abraham ◽  
Aiyi Liu ◽  
Josephine J. Marshalleck ◽  
Robert L. Dewitty
Keyword(s):  
Estrogen Receptor ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cell Surface ◽  
Mrna Levels ◽  
Breast Tumorigenesis ◽  
Normal Tissues ◽  
Node Metastasis ◽  
Tumor Tissues ◽  
Cancer Tissues

Background GPR30 is a cell surface estrogen receptor that has been shown to mediate a number of non-genomic rapid effects of estrogen and appear to balance the signaling of estrogen and growth factors. In addition, progestins appear to use GPR30 for their actions. Therefore, GPR30 could play a critical role in hormonal regulation of breast epithelial cell integrity. Deregulation of the events mediated by GPR30 could contribute to tumorigenesis. Methods To understand the role of GPR30 in the deregulation of estrogen signaling processes during breast carcinogenesis, we have undertaken this study to investigate its expression at mRNA levels in tumor tissues and their matched normal tissues. We compared its expression at mRNA levels by RT quantitative real-time PCR relative to GAPDH in ERα”—positive (n = 54) and ERα”—negative (n = 45) breast cancer tissues to their matched normal tissues. Results We report here, for the first time, that GPR30 mRNA levels were significantly down-regulated in cancer tissues in comparison with their matched normal tissues (p < 0.0001 by two sided paired t-test). The GPR30 expression levels were significantly lower in tumor tissues from patients (n = 29) who had lymph node metastasis in comparison with tumors from patients (n = 53) who were negative for lymph node metastasis (two sample t-test, p < 0.02), but no association was found with ERα, PR and other tumor characteristics. Conclusions Down-regulation of GPR30 could contribute to breast tumorigenesis and lymph node metastasis.

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