Relationship Between High Density of Peritumoral Lymphatic Vessels and Biological Behavior of Cervical Cancer

2012 ◽  
Vol 22 (8) ◽  
pp. 1435-1441 ◽  
Author(s):  
Song En-lin ◽  
Yu Wei-wei ◽  
Xiong Xiao-liang ◽  
Xu Juan
Keyword(s):  
Cervical Cancer ◽  
Lymphatic Vessel ◽  
Lymphatic Vessels ◽  
High Density ◽  
Vessel Density ◽  
Proliferation Index ◽  
Lymphatic Vessel Density ◽  
Ki 67 ◽  
Squamous Cancer ◽  
Cervical Squamous Cancer

ObjectiveTo investigate the relationship between lymphangiogenesis and lymphatic metastasis in cervical squamous carcinoma.MethodsEighty cases of invasive cervical squamous cancer were selected as objects of our study. Double immunohistochemical staining with antibodies against lymphatic vessel endothelial hyaluronan receptor 1 and Ki-67 was used to label the lymphatic vessels and mark the proliferative lymphatic vessels in cervical squamous cancer. The peritumoral lymphatic vessel density and intratumoral lymphatic vessel density was assessed. The lymphatic vessels proliferation index was evaluated by calculating Ki-67 proliferation index (PI) to reflect the lymphangiogenesis of cervical squamous cancer. Then the correlation between lymphangiogenesis and clinicopathologic features of cervical squamous cancer was analyzed.ResultsThe LVD of cervical cancer (15.23 ± 3.6) was clearly higher than that of the adjacent normal cervical subepithelial tissues (9.9 ± 2.5, P < 0.001). The peritumoral lymphatic vessel density of cervical cancer (18.75 ± 4.3) was significantly higher than the intratumoral lymphatic vessel density of cervical cancer (11.71 ± 4.9, P < 0.001). Lymphatic PI (LPI) of cervical cancer (0.258 ± 0.07) was higher than that of the adjacent normal cervical subepithelial tissues (0.068 ± 0.08, P < 0.001). The peritumoral lymphatic vessel PI of cervical cancer (0.324 ± 0.06) was notably higher than the intratumoral lymphatic vessel PI of cervical cancer (0.232 ± 0.06, P < 0.001). Peritumoral lymphatic vessel density and peritumoral lymphatic vessel were clearly associated with the lymph node metastasis (P = 0.001 and P = 0.002, respectively) and lymphovascular space invasion (P = 0.024 and P = 0.01, respectively).ConclusionsThe high density of peritumoral lymphatic vessels is a potential predictor of more aggressive phenotype of cervical squamous cancer.

Intratumoral Lymphatic Vessel Density and Clinicopathologic Features of Patients With Early-Stage Cervical Cancer After Radical Hysterectomy

2010 ◽  
Vol 20 (7) ◽  
pp. 1225-1231 ◽  
Author(s):  
Fabricia L. Zaganelli ◽  
Filomena M. Carvalho ◽  
Bernardo G.L. Almeida ◽  
Carlos E. Bacchi ◽  
Joao Carlos Sampaio Goes ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Radical Hysterectomy ◽  
Lymphatic Vessel ◽  
Early Stage ◽  
Vessel Density ◽  
Lymphatic Vessel Density ◽  
Clinicopathologic Features ◽  
Early Stage Cervical Cancer

scholarly journals Whole Slide Quantification of Stromal Lymphatic Vessel Distribution and Peritumoral Lymphatic Vessel Density in Early Invasive Cervical Cancer: A Method Description

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
C. Balsat ◽  
S. Blacher ◽  
N. Signolle ◽  
A. Beliard ◽  
C. Munaut ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Lymphatic Vessel ◽  
Hot Spot ◽  
Invasive Cervical Cancer ◽  
Predictive Marker ◽  
Original Method ◽  
Vessel Density ◽  
Lymphatic Vessel Density ◽  
Therapeutic Decisions ◽  
Node Metastases

Peritumoral Lymphatic Vessel Density (LVD) is considered to be a predictive marker for the presence of lymph node metastases in cervical cancer. However, when LVD quantification relies on conventional optical microscopy and the hot spot technique, interobserver variability is significant and yields inconsistent conclusions. In this work, we describe an original method that applies computed image analysis to whole slide scanned tissue sections following immunohistochemical lymphatic vessel staining. This procedure allows to determine an objective LVD quantification as well as the lymphatic vessel distribution and its heterogeneity within the stroma surrounding the invasive tumor bundles. The proposed technique can be useful to better characterize lymphatic vessel interactions with tumor cells and could potentially impact on prognosis and therapeutic decisions.

Effects of acute exercise, exercise training, and diabetes on the expression of lymphangiogenic growth factors and lymphatic vessels in skeletal muscle

2007 ◽  
Vol 293 (4) ◽  
pp. H2573-H2579 ◽  
Author(s):  
Riikka Kivelä ◽  
Mika Silvennoinen ◽  
Maarit Lehti ◽  
Heikki Kainulainen ◽  
Veikko Vihko
Keyword(s):  
Skeletal Muscle ◽  
Growth Factors ◽  
Exercise Training ◽  
Mrna Expression ◽  
Lymphatic Vessel ◽  
Acute Exercise ◽  
Lymphatic Vessels ◽  
Vessel Density ◽  
Lymphatic Vessel Density ◽  
Diabetic Mice

Blood and lymphatic vessels together form the circulatory system, allowing the passage of fluids and molecules within the body. Recently we showed that lymphatic capillaries are also found in the capillary bed of skeletal muscle. Exercise is known to induce angiogenesis in skeletal muscle, but it is not known whether exercise has effects on lymphangiogenesis or lymphangiogenic growth factors. We studied lymphatic vessel density and expression of the main lymphangiogenic growth factors VEGF-C and VEGF-D and their receptor VEGFR-3 in response to acute running exercise and endurance exercise training in the skeletal muscle of healthy and diabetic mice. VEGF-C mRNA expression increased after the acute exercise bout ( P < 0.05) in healthy muscles, but there was no change in diabetic muscles. VEGF-C levels were not changed either in healthy or in diabetic muscle after the exercise training. Neither acute exercise nor exercise training had an effect on the mRNA expression of VEGF-D or VEGFR-3 in healthy or diabetic muscles. Lymphatic vessel density was similar in sedentary and trained mice and was >10-fold smaller than blood capillary density. Diabetes increased the mRNA expression of VEGF-D ( P < 0.01). Increased immunohistochemical staining of VEGF-D was found in degenerative muscle fibers in the diabetic mice. In conclusion, the results suggest that acute exercise or exercise training does not significantly affect lymphangiogenesis in skeletal muscle. Diabetes increased the expression of VEGF-D in skeletal muscle, and this increase may be related to muscle fiber damage.

scholarly journals Renal inflammation and injury are associated with lymphangiogenesis in hypertension

2017 ◽  
Vol 312 (5) ◽  
pp. F861-F869 ◽  
Author(s):  
Sterling C. Kneedler ◽  
Lauren E. Phillips ◽  
Kayla R. Hudson ◽  
Katharine M. Beckman ◽  
Catalina A. Lopez Gelston ◽  
...  
Keyword(s):  
Immune Cells ◽  
Renal Injury ◽  
Proinflammatory Cytokine ◽  
Lymphatic Vessel ◽  
Lymphatic Vessels ◽  
Vessel Density ◽  
Macrophage Infiltration ◽  
Cytokine Gene Expression ◽  
Lymphatic Vessel Density ◽  
Hypertensive Rats

Lymphatic vessels are vital for the trafficking of immune cells from the interstitium to draining lymph nodes during inflammation. Hypertension is associated with renal infiltration of activated immune cells and inflammation; however, it is unknown how renal lymphatic vessels change in hypertension. We hypothesized that renal macrophage infiltration and inflammation would cause increased lymphatic vessel density in hypertensive rats. Spontaneously hypertensive rats (SHR) that exhibit hypertension and renal injury (SHR-A3 strain) had significantly increased renal lymphatic vessel density and macrophages at 40 wk of age compared with Wistar-Kyoto (WKY) controls. SHR rats that exhibit hypertension but minimal renal injury (SHR-B2 strain) had significantly less renal lymphatic vessel density compared with WKY rats. The signals for lymphangiogenesis, VEGF-C and its receptor VEGF-R3, and proinflammatory cytokine genes increased significantly in the kidneys of SHR-A3 rats but not in SHR-B2 rats. Fischer 344 rats exhibit normal blood pressure but develop renal injury as they age. Kidneys from 24-mo- and/or 20-mo-old Fischer rats had significantly increased lymphatic vessel density, macrophage infiltration, VEGF-C and VEGF-R3 expression, and proinflammatory cytokine gene expression compared with 4-mo-old controls. These data together demonstrate that renal immune cell infiltration and inflammation cause lymphangiogenesis in hypertension- and aging-associated renal injury.

Abstract P339: Genetically Induced Renal Lymphangiogenesis Prevents the Development of L-NAME Hypertension in Mice

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Catalina A Lopez Gelston ◽  
Dakshnapriya Balasubbramanian ◽  
Gabriella R Abouelkheir ◽  
Alexandra H Lopez ◽  
Kayla R Hudson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Pressure ◽  
Drinking Water ◽  
Immune Cells ◽  
Lymphatic Vessel ◽  
Lymphatic Vessels ◽  
Vessel Density ◽  
Lymphatic Vessel Density ◽  
Cell Marker ◽  
Immune System Activation

In humans and experimental animals, persistent immune system activation, accumulation of immune cells in the kidney, and subsequent inflammation plays an essential role in the development of hypertension (HTN). To reduce inflammation, lymphatic vessels drain extracellular fluid from the interstitium and traffic immune cells to draining lymph nodes. However, little is known about the connection between hypertension and renal lymphatic vessels. We hypothesized that renal lymphatic vessel density would increase in mice with L-NAME HTN and that genetically induced renal lymphangiogenesis would prevent this increase in blood pressure. L-NAME (0.5 mg/mL) was administered in the drinking water for two weeks and caused HTN (SBP: 153±3 vs. 103±3 mmHg; p<0.05) and renal lymphatic vessel dilation compared to control mice. Kidneys from mice with L-NAME HTN had significantly increased gene expression of the lymphangiogenic marker Vegfc , macrophage marker Adgre1 (F4/80), dendritic cell marker Cd11c , Th1 cell marker Tbx21 , and the pro-inflammatory cytokine Il6 . Blood pressure decreased after a two-week washout period following L-NAME (SBP: 113±2 mmHg) which was associated with a decrease in renal gene expression of Adgre1 (F4/80) and Cd11c , however renal lymphatic vessels remained dilated. To determine if augmenting renal lymphatic vessel density prior to L-NAME treatment would prevent HTN, we used transgenic mice that in response to doxycycline undergo kidney-specific VEGF-D overexpression (KidVD+ mice) and renal lymphangiogenesis. Doxycycline (200 mg/L) was administered in the drinking water of KidVD+ and KidVD- mice for four weeks with L-NAME being added during the final three weeks. Starting doxycycline one week prior to L-NAME prevented HTN in KidVD+ mice while slightly decreasing SBP in KidVD- mice (SBP: 112±4 vs. 134±2 mmHg; p<0.05). Renal gene expression of the Th17 cell marker Rorc was decreased and the lymphatic chemokine markers Ccl21 and Ccl19 were increased significantly in KidVD+ mice. These data together demonstrate that L-NAME HTN can alter the size of renal lymphatic vessels and genetically augmenting renal lymphatic vessel density prior to L-NAME can prevent the development of HTN.

Tumour expression of lymphangiogenic growth factors but not lymphatic vessel density is implicated in human cervical cancer progression

Pathology ◽  
2010 ◽  
Vol 42 (7) ◽  
pp. 629-636 ◽  
Author(s):  
Nikolia Sotiropoulou ◽  
Vasiliki Bravou ◽  
Sofia Kounelis ◽  
Vasileia Damaskou ◽  
Eirini Papaspirou ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Growth Factors ◽  
Cancer Progression ◽  
Lymphatic Vessel ◽  
Vessel Density ◽  
Lymphatic Vessel Density ◽  
Human Cervical Cancer

Abstract 098: Augmenting Renal Lymphatic Vessel Density Prevents Salt-sensitive Hypertension in Mice

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Dakshnapriya Balasubbramanian ◽  
Catalina A Lopez Gelston ◽  
Gabriella R Abouelkheir ◽  
Alexandra H Lopez ◽  
Kayla R Hudson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lymphatic Vessel ◽  
Immune Cell ◽  
Lymphatic Vessels ◽  
High Salt ◽  
Vessel Density ◽  
Lymphatic Vessel Density ◽  
High Salt Diet ◽  
Salt Diet ◽  
Salt Sensitive Hypertension

Salt-sensitive hypertension (SSHTN) is associated with renal immune cell infiltration and interstitial inflammation. Lymphatic vessels drain the interstitial compartment and traffic immune cells to draining lymph nodes; however little is known about the role of lymphatics and immune cell trafficking in the kidney during SSHTN. Our hypotheses were that renal lymphatic vessel density is increased in mice with SSHTN and that further augmenting renal lymphatic vessels will prevent SSHTN. SSHTN mice were made by administering L-NAME for two weeks, followed by a two week washout, and then were fed a 4% high salt diet for three weeks. Compared to control mice, mice with SSHTN (SBP: 103±3 vs. 136±2 mmHg; p<0.05) had markedly increased renal lymphatic vessel density. Kidneys of SSHTN mice had significantly increased gene expression of the lymphatic vessel marker Lyve1 , the macrophage marker Adgre1 (F4/80), the Th1 cell marker Tbx21 , and the pro-inflammatory cytokine Il6 while expression of the immune cell-lymphatic chemokine receptor Ccr7 was decreased significantly. Mice solely fed a 4% salt diet for three weeks did not exhibit hypertension or increased renal lymphatic vessel density. To determine whether augmenting renal lymphatic vessels prior to the high salt diet could prevent SSHTN, we used transgenic mice that overexpress the lymphangiogenic signal VEGF-D only in the kidney under the control of doxycycline (KidVD+ mice) and thus exhibit renal lymphangiogenesis. Doxycycline initiated one week prior to the high salt diet prevented SSHTN in KidVD+ mice while having no effect on blood pressure in KidVD- mice (SBP: 117±4 vs. 139±5 mmHg; p<0.05). Renal gene expression of Tbx21 was decreased in KidVD+ mice while Ccr7 gene expression was increased significantly. These data demonstrate that renal lymphatic vessel density is increased in SSHTN and that augmenting renal lymphatic vessel density prior to a high salt diet can prevent SSHTN by improving renal immune cell exfiltration.

scholarly journals Immune negative regulator TIPE2 inhibits cervical squamous cancer progression through Erk1/2 signaling

2019 ◽  
Vol 14 (1) ◽  
pp. 528-536
Author(s):  
Li-Qiong Huang ◽  
Bo Zheng ◽  
Yi He
Keyword(s):  
Cervical Cancer ◽  
Western Blot ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Erk Signaling ◽  
Over Expression ◽  
Squamous Cancer ◽  
Cancer Tissues ◽  
Proliferation And Invasion ◽  
Cervical Squamous Cancer

AbstractTumor necrosis factor (TNF)-α-induced protein-8-like 2, or TIPE2, is a newly found immune negative regulatory molecule. This study further investigated the role of TIPE2 on proliferation and invasion of cervical squamous cancer cells. Expression of TIPE2 was compared in cervical squamous cancer tissues and adjacent normal tissues by Western blot and immunohistochemistry (IHC). Cervical squamous cancer cell lines, SiHa and C33A, were transfected with recombinant plasmid encoding TIPE2 and tested for cytologic characteristics. The impact of TIPE2 on phosphorylation of extracellular signal-regulated kinase (Erk) signaling pathway was also tested by Western blot analysis of key factors. TIPE2 expression was higher in cervical cancer tissues than that in normal tissue. IHC score of tumor tissue was negatively associated with lymphatic metastasis. Over expression of TIPE2 effectively inhibited the proliferation of cervical cancer cells. Wound healing and transwell assay showed that over expression of TIPE2 suppressed cell migration and invasion in vitro. Meanwhile, phosphorylation of Erk1/2 and upstream mitogen-activated protein kinase kinase (MEK) 1/2 was reduced by TIPE2. TIPE2 is negatively related with development of cervical squamous cancer. TIPE2 is an inhibitory factor of proliferation and invasion of cervical squamous cancer cells, probably through inhibiting Erk signaling pathway.

Lymphatic Vessel Density as a Prognostic Marker in Clinical Stage I Endocervical Adenocarcinoma

2010 ◽  
Vol 29 (4) ◽  
pp. 386-393 ◽  
Author(s):  
Reda S. Saad ◽  
Nadia Ismiil ◽  
Zeina Ghorab ◽  
Sharon Nofech-Mozes ◽  
Valérie Dubé ◽  
...  
Keyword(s):  
Prognostic Marker ◽  
Lymphatic Vessel ◽  
Clinical Stage ◽  
Vessel Density ◽  
Stage I ◽  
Lymphatic Vessel Density ◽  
Endocervical Adenocarcinoma
Sign in / Sign up

Export Citation Format

Share Document