scholarly journals Tumor Lymphangiogenesis as a Potential Therapeutic Target

2012 ◽  
Vol 2012 ◽  
pp. 1-23 ◽  
Author(s):  
Tam Duong ◽  
Peter Koopman ◽  
Mathias Francois
Keyword(s):  
Lymph Node ◽  
Cancer Cells ◽  
Primary Tumor ◽  
Molecular Mechanisms ◽  
Patient Survival ◽  
Regional Lymph Node ◽  
Lymphatic Vessels ◽  
Potential Therapeutic Target ◽  
Tumor Lymphangiogenesis

Metastasis the spread of cancer cells to distant organs, is the main cause of death for cancer patients. Metastasis is often mediated by lymphatic vessels that invade the primary tumor, and an early sign of metastasis is the presence of cancer cells in the regional lymph node (the first lymph node colonized by metastasizing cancer cells from a primary tumor). Understanding the interplay between tumorigenesis and lymphangiogenesis (the formation of lymphatic vessels associated with tumor growth) will provide us with new insights into mechanisms that modulate metastatic spread. In the long term, these insights will help to define new molecular targets that could be used to block lymphatic vessel-mediated metastasis and increase patient survival. Here, we review the molecular mechanisms of embryonic lymphangiogenesis and those that are recapitulated in tumor lymphangiogenesis, with a view to identifying potential targets for therapies designed to suppress tumor lymphangiogenesis and hence metastasis.

Comparative Analysis of Coagulation System Proteins Distribution in Breast Cancer Primary Lesions and Lymph Node Metastases.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3137-3137
Author(s):  
Marek Wojtukiewicz ◽  
Ewa Sierko ◽  
Zbigniew Sawicki ◽  
Lech Zimnoch ◽  
Walter Kisiel
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Cancer Cells ◽  
Tissue Factor ◽  
Lymph Node Metastases ◽  
Primary Tumor ◽  
Regional Lymph Node ◽  
Coagulation System ◽  
Metastatic Lesions ◽  
Node Metastases

Abstract Breast cancer is the most frequent cause of morbidity and mortality due to cancer in women. Thromboembolic episodes are relatively common complication during the course of the disease. It was widely documented, that components of blood coagulation play a role in tumor progression and metastasis formation. Presence of hemostatic proteins was observed in primary lesions of different malignant tumors. However, information on expression and role of coagulation system components in regional lymph node metastases is scanty. The purpose of the study was to assess and compare the distribution of selected coagulation proteins - in primary versus metastatic lesions of breast cancer. Specimens of primary tumor of different degree of malignancy and metastatic lesions localized in regional lymph nodes were obtained during surgical treatment of previously untreated twenty five breast cancer patients and fixed in formalin. Immunohistochemical procedure was employed using monoclonal and polyclonal antibodies against tissue factor (TF), tissue factor pathway inhibitor (TFPI), factor IX, factor X, fibrinogen and fibrin. A strong expression of TF was demonstrated in cancer cells of both primary tumors and lymph node metastases. Coagulation factors IX and X were also present in primary and metastatic breast cancer lesions. However, the expression of the proteins was weaker in regional lymph node metastases than in primary tumor. Strong staining for fibrinogen was detected in the stroma of primary breast cancer, particularly at the area adjacent to the cancer foci. Stroma of metastatic lesions was characterized by much weaker staining for fibrinogen. Strong expression of fibrin and TFPI was demonstrated in cancer cells of primary tumor while much weaker expression of the antigens was visualized in cancer cells localized in lymph node metastatic lesions. Furthermore, the presence of all examined proteins was observed in small blood vessel walls and in macrophages infiltrating both primary tumor tissue as well as metastatic lesions. The results of the study indicate extravascular activation of blood coagulation in loco in breast cancer, both in the primary tumor and in the regional lymph node metastatic lesions. The presence of coagulation system proteins in cancer tissue (primary tumor and metastatic foci) suggests that they may play a role in the biology of breast cancer growth as well as they may modulate breast cancer metastatic dissemination.

scholarly journals Clinical Candidates Targeting the ATR–CHK1–WEE1 Axis in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 795
Author(s):  
Lukas Gorecki ◽  
Martin Andrs ◽  
Jan Korabecny
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Patient Survival ◽  
Current Status ◽  
Future Perspectives ◽  
Phase Ii Trials ◽  
Anticancer Treatment ◽  
Positive Outlook ◽  
Insight Into

Selective killing of cancer cells while sparing healthy ones is the principle of the perfect cancer treatment and the primary aim of many oncologists, molecular biologists, and medicinal chemists. To achieve this goal, it is crucial to understand the molecular mechanisms that distinguish cancer cells from healthy ones. Accordingly, several clinical candidates that use particular mutations in cell-cycle progressions have been developed to kill cancer cells. As the majority of cancer cells have defects in G1 control, targeting the subsequent intra‑S or G2/M checkpoints has also been extensively pursued. This review focuses on clinical candidates that target the kinases involved in intra‑S and G2/M checkpoints, namely, ATR, CHK1, and WEE1 inhibitors. It provides insight into their current status and future perspectives for anticancer treatment. Overall, even though CHK1 inhibitors are still far from clinical establishment, promising accomplishments with ATR and WEE1 inhibitors in phase II trials present a positive outlook for patient survival.

scholarly journals Inactivation of EMILIN-1 by Proteolysis and Secretion in Small Extracellular Vesicles Favors Melanoma Progression and Metastasis

2021 ◽  
Vol 22 (14) ◽  
pp. 7406
Author(s):  
Ana Amor López ◽  
Marina S. Mazariegos ◽  
Alessandra Capuano ◽  
Pilar Ximénez-Embún ◽  
Marta Hergueta-Redondo ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cell Viability ◽  
Extracellular Vesicles ◽  
Primary Tumor ◽  
Molecular Mechanisms ◽  
Primary Tumor Growth ◽  
Node Metastasis ◽  
Metastatic Cells ◽  
Tumor Growth And Metastasis

Several studies have demonstrated that melanoma-derived extracellular vesicles (EVs) are involved in lymph node metastasis; however, the molecular mechanisms involved are not completely defined. Here, we found that EMILIN-1 is proteolyzed and secreted in small EVs (sEVs) as a novel mechanism to reduce its intracellular levels favoring metastasis in mouse melanoma lymph node metastatic cells. Interestingly, we observed that EMILIN-1 has intrinsic tumor and metastasis suppressive-like properties reducing effective migration, cell viability, primary tumor growth, and metastasis. Overall, our analysis suggests that the inactivation of EMILIN-1 by proteolysis and secretion in sEVs reduce its intrinsic tumor suppressive activities in melanoma favoring tumor progression and metastasis.

Additional Prone 18F-FDG PET/CT Acquisition to Improve the Visualization of the Primary Tumor and Regional Lymph Node Metastases in Stage II/III Breast Cancer

2016 ◽  
Vol 41 (4) ◽  
pp. e181-e186 ◽  
Author(s):  
Suzana Cipriano Teixeira ◽  
Bas B. Koolen ◽  
Wouter V. Vogel ◽  
Jelle Wesseling ◽  
Marcel P. M. Stokkel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Lymph Node Metastases ◽  
Primary Tumor ◽  
Fdg Pet ◽  
Regional Lymph Node ◽  
Pet Ct ◽  
Node Metastases ◽  
18F Fdg ◽  
Fdg Pet Ct

scholarly journals Clonal evolution of esophageal squamous cell carcinoma from normal mucosa to primary tumor and metastases

2019 ◽  
Author(s):  
Wenqing Yuan ◽  
Zhen Liu ◽  
Yu Wang ◽  
Mengfei Liu ◽  
Yaqi Pan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Phylogenetic Analysis ◽  
Lymph Node ◽  
Esophageal Squamous Cell Carcinoma ◽  
Lymph Node Metastases ◽  
Primary Tumor ◽  
Regional Lymph Node ◽  
Clonal Evolution ◽  
Normal Mucosa ◽  
Node Metastases

Abstract The clonal evolution which drives esophageal squamous cell carcinoma (ESCC) from initiation in normal cell to primary carcinoma and metastases is poorly understood. In this study, multi-region whole-exome sequencing (WES) (284X) and whole-genome single nucleotide polymorphism genotyping were performed on a total of 109 samples of ESCC from 10 patients. This included 42 apparently normal samples of esophageal mucosa at increasing distances from the upper or lower boundaries of the primary tumor to the surgical margins of resection, 43 spatially separated tissue samples within primary tumor and 24 regional lymph node metastases. Phylogenetic analysis was performed to reconstruct ancestor–descendant relationships of clones and the clonal composition of multi-region samples. Mutations of cancer-related genes were validated by deep targeted sequencing (1,168X). Both inter- and intra-tumoral genetic heterogeneity were obvious across multi-region samples among ESCC patients. Clones varying in number from one to seven were discovered within each regional tumor or metastatic sample. Phylogenetic analysis demonstrated complex clonal evolution patterns. Regional lymph node metastases had characteristics of early initiation and polyclonal spreading, and could be derived from carcinoma in situ (CIS) directly. TP53 was the only gene harboring non-silent mutations identified across all multi-region tumor samples of all ten patients. Mutations of TP53 were also found in histologically normal mucosa in sites away from primary tumor.

scholarly journals The Primary Tumor and Regional Lymph Node Clinical Status of Distant Metastasis in Nasopharyngeal Carcinoma

2018 ◽  
Vol 1 (2) ◽  
pp. 9
Author(s):  
Sagung Indrasari ◽  
Kartono Sudarman ◽  
Jessica Fedriani
Keyword(s):  
Squamous Cell Carcinoma ◽  
Lymph Node ◽  
Nasopharyngeal Carcinoma ◽  
Distant Metastasis ◽  
Primary Tumor ◽  
Retrospective Studies ◽  
Regional Lymph Node ◽  
Clinical Status ◽  
Cross Sectional ◽  
Significant Difference

Background: Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma derived from nasopharyngeal epithelium. NPC characteristic is highly invasive and can metastasize rapidly. The presence of distant metastasis is a major factor in determining the patient’s management and prognosis. The magnitude of radiologic and molecular costs encouraging the need to know the clinical variables associated with distant metastasis of NPC. Methods: Cross-sectional analytical retrospective studies of undifferentiated NPC (WHO type III) patients at initial diagnosis in the ORL-HNS Department of Dr. Sardjito Hospital Yogyakarta from January 2014 to December 2016. Results: At 276 NPC patients with the ratio of 197 men (71.4%) and 79 women (28.6%) was 2.5:1, mean age 48.5 years, distant metastasis was found in 37 patients (13.4%). There was no significant difference in the frequency of sex (p = 0.346), age (p = 0.784), and primary tumor clinical status (p = 0.297) between NPC with distant metastasis and without distant metastasis. There was significant difference in the frequency of regional lymph node clinical status between NPC with distant metastasis and without distant metastasis (p = 0.004; PR = 3.866). Conclusions: There is no statistically significant difference of primary tumor clinical status between NPC with and without distant metastasis. There is statistically significant difference of lymph node clinical status between NPC with and without distant metastasis.

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