scholarly journals Role of Microenvironment in Ovarian Tumourisation

2021 ◽  
Vol 11 (4) ◽  
pp. 278-283
Author(s):  
L. V. Khalikova ◽  
N. N. Shevlyuk ◽  
Sh. Kh. Gantsev ◽  
A. A. Khalikov ◽  
I. R. Khasanova
Keyword(s):  
Disease Progression ◽  
Primary Tumour ◽  
Tumour Microenvironment ◽  
Greater Omentum ◽  
Malignant Neoplasms ◽  
Tissue Samples ◽  
Advanced Malignancy ◽  
Cell Counts ◽  
Multistep Process ◽  
The Impact

Background. Metastasis is a formidable complication of malignant neoplasms, with therapy not always effective in advanced malignancy. Metastasis is a multistep process involving the cancer cell detachment from primary tumour, intravasation, extravasation and invasion into the target organ. Early metastasis stages are well understood, whilst the impact of tumour microenvironment on the disease progression and advancement remains a matter of debate.Aim. An immunohistochemical study of the adaptive and reactive properties of greater omentum with metastatic involvement in ovarian cancer.Materials and methods. We examined greater omentum tissue samples from 40 patients with verifi ed stage 3a and b ovarian cancers. For light microscopy, samples were fi xed in 10 % formalin, dehydrated, paraffi n-embedded and stained with Mayer’s haematoxylin and eosin. Immunohistochemical assays used monoclonal antibodies against CD7, CD4, CD8, CD 68, VEGF, D2-40 and CD44 proteins. Statistical data analysis was performed with Statistica v. 7.0 soft ware.Results and discussion. Analyses of the greater omentum tissues revealed cases of leucocyte-bank encapsulation of metastatic foci. Higher CD7+ and CD8+ cell counts were observed in encapsulation, possibly influencing the greater omentum reactive and adaptive properties. Higher CD44-expressing cell counts were also detected in greater omentum samples lacking encapsulation. Angiogenesis marker-expressing cells (e.g., VEGF and CD34) predominated in greater omentum tissues lacking leucocyte-bank encapsulation of metastatic foci.Conclusion. Events in tumour microenvironment may be indicative of a preserved or reduced organ adaptivity, the latter facilitating disease progression.

scholarly journals A Tale of Two Viruses: Immunological Insights Into HCV/HIV Coinfection

2021 ◽  
Vol 12 ◽  
Author(s):  
Samaa T. Gobran ◽  
Petronela Ancuta ◽  
Naglaa H. Shoukry
Keyword(s):  
Disease Progression ◽  
Immune Reconstitution ◽  
Acute Infection ◽  
People Living With Hiv ◽  
Hiv Disease ◽  
Hiv Reservoir ◽  
Cell Counts ◽  
Hiv Coinfection ◽  
Hcv Coinfection ◽  
The Impact

Nearly 2.3 million individuals worldwide are coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Odds of HCV infection are six times higher in people living with HIV (PLWH) compared to their HIV-negative counterparts, with the highest prevalence among people who inject drugs (PWID) and men who have sex with men (MSM). HIV coinfection has a detrimental impact on the natural history of HCV, including higher rates of HCV persistence following acute infection, higher viral loads, and accelerated progression of liver fibrosis and development of end-stage liver disease compared to HCV monoinfection. Similarly, it has been reported that HCV coinfection impacts HIV disease progression in PLWH receiving anti-retroviral therapies (ART) where HCV coinfection negatively affects the homeostasis of CD4+ T cell counts and facilitates HIV replication and viral reservoir persistence. While ART does not cure HIV, direct acting antivirals (DAA) can now achieve HCV cure in nearly 95% of coinfected individuals. However, little is known about how HCV cure and the subsequent resolution of liver inflammation influence systemic immune activation, immune reconstitution and the latent HIV reservoir. In this review, we will summarize the current knowledge regarding the pathogenesis of HIV/HCV coinfection, the effects of HCV coinfection on HIV disease progression in the context of ART, the impact of HIV on HCV-associated liver morbidity, and the consequences of DAA-mediated HCV cure on immune reconstitution and HIV reservoir persistence in coinfected patients.

scholarly journals TIMP-2 secreted by monocyte-like cells is a potent suppressor of invadopodia formation in pancreatic cancer cells

2019 ◽  
Author(s):  
Christian Benzing ◽  
Hoyin Lam ◽  
Chi Man Tsang ◽  
Alexander Rimmer ◽  
Yoana Arroyo-Berdugo ◽  
...  
Keyword(s):  
Tumor Invasion ◽  
Primary Tumour ◽  
Tumour Microenvironment ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Ductal Adenocarcinoma ◽  
Complex Interactions ◽  
Pancreatic Cancer Cells ◽  
Therapeutic Opportunity ◽  
The Impact ◽  
Invadopodia Formation

Abstract Background Monocytes are a major component of the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC). However, the complex interactions between tumor cells and monocytes and their role in tumor invasion have not been fully established. Methods To specifically test the impact of interaction on invasive potential two PDAC cell lines PaTu8902 and CFPAC-1 were selected on their ability to form invasive adhesions, otherwise known as invadopodia and invade in a spheroid invasion assay. Results Interestingly when the PDAC cells were co-cultured with undifferentiated THP1 monocyte-like cells invadopodia formation was significantly suppressed. Moreover, conditioned media of THP1 cells (CM) was also able to suppress invadopodia formation. Further investigation revealed that both tissue inhibitor of metalloproteinase (TIMP) 1 and 2 were present in the CM. However, suppression of invadopodia formation was found that was specific to TIMP2 activity. Conclusions Our findings indicate that TIMP2 levels in the tumour microenvironment may have prognostic value in patients with PDAC. Furthermore, activation of TIMP2 expressing monocytes in the primary tumour could present a potential therapeutic opportunity to suppress cell invasion in PDAC

scholarly journals TIMP-2 secreted by monocytes is a potent suppressor of invadopodia formation in pancreatic cancer cells

2019 ◽  
Author(s):  
Christian Benzing ◽  
Hoyin Lam ◽  
Chi Man Tsang ◽  
Yoana Arroyo-Berdugo ◽  
Yolanda Calle-Patino ◽  
...  
Keyword(s):  
Primary Tumour ◽  
In Vitro Study ◽  
Tumour Microenvironment ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Cancer Cells ◽  
Therapeutic Opportunity ◽  
The Impact ◽  
Invadopodia Formation

Abstract Background Monocytes are a major component of the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC). However, the complex interactions between tumor cells and monocytes and their role in tumor invasion have not been fully established. Methods In this in vitro study, to specifically test the impact of interaction on invasive potential, two PDAC cell lines PaTu8902 and CFPAC-1 were selected on their ability to form invasive adhesions, otherwise known as invadopodia. Co-culture experiments were performed using undifferentiated THP1 monocytes. Results When the PDAC cells were co-cultured with undifferentiated THP1 monocytes invadopodia formation was significantly suppressed. Moreover, conditioned media of THP1 cells (CM) was also able to suppress invadopodia formation. Further investigation revealed that both tissue inhibitor of metalloproteinase (TIMP) 1 and 2 were present in the CM. However, suppression of invadopodia formation was found that was specific to TIMP2 activity. Conclusions Our findings indicate that TIMP2 levels in the tumour microenvironment may have prognostic value in patients with PDAC. Furthermore, activation of TIMP2 expressing monocytes in the primary tumour could present a potential therapeutic opportunity to suppress cell invasion in PDAC.

Loss of Id4 Accelerates CLL Progression in TCL1 Mice

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3153-3153
Author(s):  
Shih-Shih Chen ◽  
Amy J. Johnson ◽  
Rainer Claus ◽  
Fred Sablitzky ◽  
Christoph Plass ◽  
...  
Keyword(s):  
B Cells ◽  
Dna Binding ◽  
Disease Progression ◽  
Dominant Negative ◽  
P Value ◽  
Bhlh Transcription Factor ◽  
Lymphoid Tissues ◽  
Cell Counts ◽  
The Impact

Abstract The inhibitor of DNA binding protein 4 (ID4) is a member of dominant negative basic helix loop helix (bHLH) transcription factor family that has a HLH domain but lacking DNA-binding domain. Methylation of ID4 in B-cell lineage malignancies including CLL and germinal center non-Hodgkin lymphomas (GC-NHLs) has been described. To date, the impact of Id4 loss in CLL has not been demonstrated. We utilized the TCL1 transgenic mouse model of human CLL to study the importance of loss of ID4 in disease progression. We demonstrated that ID4 was silenced by methylation only at the time mice had symptomatic leukemia. We therefore sought to investigate if earlier loss of Id4 would accelerate CLL progression. We generated mice with haploid loss of Id4 in TCL1 transgenic background by breeding homozygous TCL1 transgenic mice and mice with heterozygous Id4 mutant gene. By comparing to the control littermates with heterozygous TCL1 oncogene, mice with the loss of Id4 occur to have significantly accelerated CLL disease progression with shorter overall survival (12 versus 16 months, p-value<0.0001). The pathological analysis on Id4 mutant mice demonstrated that the CLL symptoms such as the elevated white blood cell counts, enlarged spleen and lymphoid tissues. We then performed the microarray studies on 1 month old TCL1 mice with control or mutant Id4 to identify ID4-dependent transcriptional changes in primary B-cells. Among the identified targets, genes involved in cell proliferation and anti-apoptosis were then verified. Supportively, B-cells from Id4 mutant TCL1 mice have significantly (p-value<0.001) diminished apoptosis in response to dexamethasone treatment. Additionally, both significant in vitro (p-value<0.001) and in vivo (p-value=0.025) increased proliferation of Id4 mutant TCL1 B-cells after the stimulation by CpG685NO168 was demonstrated. These data provide support that Id4 acts as tumor suppressor in transformed B-lymphocytes and is silenced through the process of methylation. The Effort to identify binding partners of Id4 in CLL cells and targeting its re-expression is warranted.

scholarly journals Clinical and Virologic Outcomes Following Initiation of Antiretroviral Therapy Among Seroconverters in the Microbicide Trials Network-020 Phase III Trial of the Dapivirine Vaginal Ring

2018 ◽  
Vol 69 (3) ◽  
pp. 523-529 ◽  
Author(s):  
Sharon A Riddler ◽  
Jennifer E Balkus ◽  
Urvi M Parikh ◽  
John W Mellors ◽  
Carolyne Akello ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Disease Progression ◽  
Virologic Failure ◽  
Vaginal Ring ◽  
Phase Iii ◽  
Virologic Suppression ◽  
Cell Counts ◽  
The Impact ◽  
Hiv 1

Abstract Background A vaginal ring containing dapivirine, a non-nucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitor (NNRTI), was safe and effective in preventing HIV-1 infection in African women. We examined the impact of dapivirine ring use at the time of HIV-1 acquisition on subsequent HIV-1 disease progression and responses to NNRTI-containing antiretroviral therapy (ART). Methods HIV-1 disease progression and virologic failure following initiation of ART were assessed among women who acquired HIV-1 while participating in Microbicide Trials Network–020, a randomized, placebo-controlled trial of a monthly, dapivirine vaginal ring. Results Among the 158 participants who acquired HIV-1 (65 dapivirine, 93 placebo), no differences between dapivirine and placebo participants were observed in CD4+ cell counts or plasma HIV-1 RNA over the first year after infection (prior to ART). During follow-up, 100/158 (63%) participants initiated NNRTI-containing ART (dapivirine: 39/65; placebo: 61/93); the median time to HIV-1 RNA <200 copies/ml was approximately 90 days for both dapivirine and placebo ring recipients (log-rank P = .40). Among the 81 participants with at least 6 months of post-ART follow-up, 19 (24%) experienced virologic failure (dapivirine: 6/32, 19%; placebo: 13/39, 27%; P = .42). Conclusions The acquisition of HIV-1 infection during dapivirine or placebo treatment in ASPIRE did not lead to differences in HIV-1 disease progression. After the initiation of NNRTI-containing ART, dapivirine and placebo participants had similar times to virologic suppression and risks of virologic failure. These results provide reassurance that NNRTI-based ART regimens are effective among women who acquired HIV-1 while receiving the dapivirine vaginal ring. Clinical Trials Registration NCT016170096 and NCT00514098.

scholarly journals TIMP-2 secreted by monocytes is a potent suppressor of invadopodia formation in pancreatic cancer cells

2019 ◽  
Author(s):  
Christian Benzing ◽  
Hoyin Lam ◽  
Chi Man Tsang ◽  
Alexander Rimmer ◽  
Yoana Arroyo-Berdugo ◽  
...  
Keyword(s):  
Primary Tumour ◽  
In Vitro Study ◽  
Tumour Microenvironment ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Cancer Cells ◽  
Therapeutic Opportunity ◽  
The Impact ◽  
Invadopodia Formation

Abstract Background Monocytes are a major component of the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC). However, the complex interactions between tumor cells and monocytes and their role in tumor invasion have not been fully established. Methods In this in vitro study, to specifically test the impact of interaction on invasive potential, two PDAC cell lines PaTu8902 and CFPAC-1 were selected on their ability to form invasive adhesions, otherwise known as invadopodia. Co-culture experiments were performed using undifferentiated THP1 monocytes. Results When the PDAC cells were co-cultured with undifferentiated THP1 monocytes invadopodia formation was significantly suppressed. Moreover, conditioned media of THP1 cells (CM) was also able to suppress invadopodia formation. Further investigation revealed that both tissue inhibitor of metalloproteinase (TIMP) 1 and 2 were present in the CM. However, suppression of invadopodia formation was found that was specific to TIMP2 activity. Conclusions Our findings indicate that TIMP2 levels in the tumour microenvironment may have prognostic value in patients with PDAC. Furthermore, activation of TIMP2 expressing monocytes in the primary tumour could present a potential therapeutic opportunity to suppress cell invasion in PDAC.

scholarly journals TIMP-2 secreted by monocyte-like cells is a potent suppressor of invadopodia formation in pancreatic cancer cells

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Christian Benzing ◽  
Hoyin Lam ◽  
Chi Man Tsang ◽  
Alexander Rimmer ◽  
Yoana Arroyo-Berdugo ◽  
...  
Keyword(s):  
Tumor Invasion ◽  
Primary Tumour ◽  
Tumour Microenvironment ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Ductal Adenocarcinoma ◽  
Complex Interactions ◽  
Pancreatic Cancer Cells ◽  
Therapeutic Opportunity ◽  
The Impact ◽  
Invadopodia Formation

Abstract Background Monocytes are a major component of the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC). However, the complex interactions between tumor cells and monocytes and their role in tumor invasion have not been fully established. Methods To specifically test the impact of interaction on invasive potential two PDAC cell lines PaTu8902 and CFPAC-1 were selected on their ability to form invasive adhesions, otherwise known as invadopodia and invade in a spheroid invasion assay. Results Interestingly when the PDAC cells were co-cultured with undifferentiated THP1 monocyte-like cells invadopodia formation was significantly suppressed. Moreover, conditioned media of THP1 cells (CM) was also able to suppress invadopodia formation. Further investigation revealed that both tissue inhibitor of metalloproteinase (TIMP) 1 and 2 were present in the CM. However, suppression of invadopodia formation was found that was specific to TIMP2 activity. Conclusions Our findings indicate that TIMP2 levels in the tumour microenvironment may have prognostic value in patients with PDAC. Furthermore, activation of TIMP2 expressing monocytes in the primary tumour could present a potential therapeutic opportunity to suppress cell invasion in PDAC.

scholarly journals TIMP-2 secreted by monocytes-like cells is a potent suppressor of invadopodia formation in pancreatic cancer cells

2019 ◽  
Author(s):  
Christian Benzing ◽  
Hoyin Lam ◽  
Chi Man Tsang ◽  
Alexander Rimmer ◽  
Yoana Arroyo-Berdugo ◽  
...  
Keyword(s):  
Tumor Invasion ◽  
Primary Tumour ◽  
Tumour Microenvironment ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Ductal Adenocarcinoma ◽  
Complex Interactions ◽  
Pancreatic Cancer Cells ◽  
Therapeutic Opportunity ◽  
The Impact ◽  
Invadopodia Formation

Abstract Background Monocytes are a major component of the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC). However, the complex interactions between tumor cells and monocytes and their role in tumor invasion have not been fully established. Methods To specifically test the impact of interaction on invasive potential two PDAC cell lines PaTu8902 and CFPAC-1 were selected on their ability to form invasive adhesions, otherwise known as invadopodia and invade in a spheroid invasion assay. Results Interestingly when the PDAC cells were co-cultured with undifferentiated THP1 monocyte-like cells invadopodia formation was significantly suppressed. Moreover, conditioned media of THP1 cells (CM) was also able to suppress invadopodia formation. Further investigation revealed that both tissue inhibitor of metalloproteinase (TIMP) 1 and 2 were present in the CM. However, suppression of invadopodia formation was found that was specific to TIMP2 activity. Conclusions Our findings indicate that TIMP2 levels in the tumour microenvironment may have prognostic value in patients with PDAC. Furthermore, activation of TIMP2 expressing monocytes in the primary tumour could present a potential therapeutic opportunity to suppress cell invasion in PDAC

Bone tissue engineering in the greater omentum with computer-aided design/computer-aided manufacturing scaffolds is enhanced by a periosteum transplant

2020 ◽  
Author(s):  
Hendrik Naujokat ◽  
Klaas Loger ◽  
Juliane Schulz ◽  
Yahya Açil ◽  
Jörg Wiltfang
Keyword(s):  
Bone Formation ◽  
Bone Tissue ◽  
Computer Aided Design ◽  
Bone Tissue Regeneration ◽  
Histological Evaluation ◽  
Greater Omentum ◽  
Collagen Membrane ◽  
Computer Aided ◽  
3D Printed ◽  
The Impact

Aim: This study aimed to evaluate two different vascularized bone flap scaffolds and the impact of two barrier membranes for the reconstruction of critical-size bone defects. Materials & methods: 3D-printed scaffolds of biodegradable calcium phosphate and bioinert titanium were loaded with rhBMP-2 bone marrow aspirate, wrapped by a collagen membrane or a periosteum transplant and implanted into the greater omentum of miniature pigs. Results: Histological evaluation demonstrated significant bone formation within the first 8 weeks in both scaffolds. The periosteum transplant led to enhanced bone formation and a homogenous distribution in the scaffolds. The omentum tissue grew out a robust vascular supply. Conclusion: Endocultivation using 3D-printed scaffolds in the greater omentum is a very promising approach in defect-specific bone tissue regeneration.

scholarly journals Treatment of HIV-associated facial lipoatrophy: impact on infection progression assessed by viral load and CD4 count

2013 ◽  
Vol 88 (4) ◽  
pp. 570-577 ◽  
Author(s):  
Flávia Machado Gonçalves Soares ◽  
Izelda Maria Carvalho Costa
Keyword(s):  
Viral Load ◽  
Disease Progression ◽  
Statistical Significance ◽  
Undetectable Viral Load ◽  
Fat Distribution ◽  
Cd4 Count ◽  
Before And After ◽  
Facial Lipoatrophy ◽  
A Prospective Study ◽  
The Impact

BACKGROUND: HIV/AIDS-Associated Lipodystrophy Syndrome includes changes in body fat distribution, with or without metabolic changes. The loss of fat from the face, called facial lipoatrophy, is one of the most stigmatizing signs of the syndrome.OBJECTIVES:To evaluate the effect of FL treatment using polymethylmethacrylate (PMMA) implants on disease progression, assessed by viral load and CD4 cell count.METHODS: This was a prospective study of 44 patients treated from July 2009 to December 2010. Male and female patients, aged over 18 years, with clinically detectable FL and who had never been treated were included in the study. PMMA implantation was done to fill atrophic areas. Laboratory tests were conducted to measure viral load and CD4 count before and after treatment.RESULTS: Of the 44 patients, 72.72% were male and 27.27% female, mean age of 44.38 years. Before treatment, 82% of patients had undetectable viral load, which increased to 88.6% after treatment, but without statistical significance (p = 0.67). CD4 count before treatment ranged from 209 to 1293, averaging 493.97. After treatment, the average increased to 548.61. The increase in CD4 count after treatment was statistically significant with p = 0.02.CONCLUSION: The treatment of FL with PMMA implants showed a statistically significant increase in CD4 count after treatment, revealing the impact of FL treatment on disease progression. Viral load before and after treatment did not vary significantly.

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