G801A Polymorphism of Human Stromal Cell–Derived Factor 1 Gene Raises No Susceptibility to Neoplastic Lesions of Uterine Cervix

2012 ◽  
Vol 22 (8) ◽  
pp. 1297-1302 ◽  
Author(s):  
Yi-Torng Tee ◽  
Shun-Fa Yang ◽  
Po-Hui Wang ◽  
Hsiu-Ting Tsai ◽  
Long-Yau Lin ◽  
...  
Keyword(s):  
Uterine Cervix ◽  
Gene Polymorphisms ◽  
Stromal Cell ◽  
Cervical Neoplasia ◽  
Low Grade ◽  
Significant Difference ◽  
Neoplastic Lesions ◽  
Polymerase Chain ◽  
Stromal Cell Derived Factor ◽  
Increased Susceptibility

ObjectiveThis study aimed to investigate the association of stromal cell–derived factor 1 (SDF-1) gene polymorphisms with the neoplastic lesions of uterine cervix in Mid-Taiwan women.Materials and MethodsFour hundred ninety-eight blood samples were collected from 161 patients with neoplasia of uterine cervix, including 76 cancer patients, 61 patients with high-grade dysplasia, and 24 with low-grade dysplasia, and 337 healthy controls who lived in Mid-Taiwan. Polymorphism of the SDF-1 gene was examined using polymerase chain reaction–restriction fragment length polymorphism.ResultsFor SDF-1 gene polymorphisms, the wild-type homozygous alleles (G/G) yielded 100- and 193-bp products, the heterozygous alleles (G/A) yielded 100-, 193- and 293-bp products, whereas the mutated-type homozygous alleles (A/A) yielded a 293-bp product. We found no significant difference in genotypes or alleles distribution of SDF-1 polymorphisms between patients with cervical neoplasia and healthy women (P = 0.530). Compared with the homozygous GG subgroup, GA and AA subgroups do not increase the risk of cervical neoplasia.ConclusionsAlthough the expression of SDF-1 was reported to be significantly increased in cervical carcinogenesis in previous studies, our results, however, show that SDF-1 gene polymorphism could not be considered as a factor related to an increased susceptibility to cervical neoplasia.

Stromal cell–derived factor-1 and macrophage-derived chemokine: 2 chemokines that activate platelets

Blood ◽  
2000 ◽  
Vol 96 (1) ◽  
pp. 50-57 ◽  
Author(s):  
M. Anna Kowalska ◽  
Mariusz Z. Ratajczak ◽  
Marcin Majka ◽  
Jianguo Jin ◽  
Satya Kunapuli ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Stromal Cell ◽  
Platelet Rich Plasma ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Creatine Phosphate ◽  
Polymerase Chain ◽  
Stromal Cell Derived Factor ◽  
Induced Aggregation ◽  
Second Wave

Platelets play roles in both thrombosis and inflammation, and chemokines that are released at sites of inflammation could potentially activate platelets. Among the chemokine receptors expressed on platelets, the CXCR4 is the receptor for chemokine stromal cell-derived factor-1 (SDF-1), and the CCR4 is the receptor for macrophage-derived chemokine (MDC). Of the chemokines tested, SDF-1 and MDC were the only 2 that activated platelets. Both are weak agonists, but they enhanced response to low-dose adenosine 5′-diphosphate (ADP), epinephrine, or serotonin. When SDF-1 and MDC were added together, full and brisk platelet aggregation occurred. Platelet activation by these 2 chemokines appears to involve distinct pathways: SDF-1 inhibited an increase in cyclic adenosine monophosphate (cAMP) following prostaglandin (PG) I2, while MDC had no effect. In contrast, MDC, but not SDF-1, lead to Ca++mobilization by platelets. Further, second-wave aggregation induced by MDC in platelet-rich plasma was inhibited by aspirin, ADP scavenger creatine phosphate/creative phosphokinase (CP/CPK), and ARL-66096, an antagonist of the ADP P2TAC receptor involved in adenylyl cyclase inhibition. But the aggregation was not affected by A3P5PS, an inhibitor of the ADP P2Y receptor. SDF-1–induced aggregation was inhibited by aspirin, but it was only slightly affected by CP/CPK, ARL-66096, or A3P5PS. Finally, the presence of chemokines in platelets was determined. Reverse transcriptase–polymerase chain reaction studies with platelet RNA did not detect the presence of SDF-1 or MDC. In summary, SDF-1 and MDC are platelet agonists that activate distinct intracellular pathways. Their importance in the development of thrombosis at sites of inflammation needs to be further evaluated.

scholarly journals Multiple HPV infection as possible marker of neoplastic progression

2020 ◽  
Author(s):  
Maria Teresa Bruno ◽  
Guido Scalia ◽  
Nazario Cassaro ◽  
Sara Boemi
Keyword(s):  
Prognostic Factor ◽  
Uterine Cervix ◽  
Hpv Infection ◽  
Multiple Infections ◽  
Neoplastic Progression ◽  
Hpv 16 ◽  
Cervical Biopsy ◽  
Neoplastic Lesions ◽  
Polymerase Chain

Abstract Background : Some studies in the literature suggest a possible role of multiple HPV infections as a prognostic factor in the development and progression of cervical neoplasia. we studied the cases of single and multiple HPV infection and analyzed the correlation with negative cases, and preneoplastic and neoplastic lesions of the uterine cervix with the aim of making a contribution to the prognostic factor under discussion Methods: 921 women with clinical HPV manifestations were enrolled. Inclusion criteria were: positive at the cytology for HPV lesions, presence of preneoplastic and neoplastic lesions of the uterine cervix diagnosed by the histology examination All the patients underwent colposcopy and cervical biopsy with viral genotyping. The search for viral DNA was carried out using polymerase chain reaction. Genotype 16 is correlated with the majority of CIN2+; we divided the multiple HPV16 infections into “infections with 16 as the first genotype” (16mHPV) (e.g. HPV 16 , 31, 52) and into “ infections containing 16” (m16HPV) (e.g. HPV 31, 16 , 52), we then divided them based on the number of genotypes present: infections with 2 strains, 3 strains, 4 strains, and > 4 strains. Results: We analyzed the differences between single and multiple infections with HPV16, the patients with single infections had a higher incidence of CIN2+ (83.3%) with respect to those with multiple infections (71.4%). The 16mHPV infection was significative for CIN2/CIN3. When the prevalence of the combinations between the genotypes was studied, we found that in 16mHPV infection HPV16, 18 and HPV 16, 31 were the most common combinations of mHPV infection (50%) and the most frequent in CIN2/CIN3 The 16mHPV infection with 2 genotypes, with respect to the infections with 3 or more genotypes, was significative with an OR= 7.94 (IC% 2.55-24.73). Conclusions: Our results suggest that single HPV infections give a higher risk of SCC development with respect to multiple HPV infections. Among multiple infections, only 16mHPV infection with 2 genotypes is associated with CIN2/CIN3 in a significative way and it presents an 8 times greater risk of developing a high grade lesion.

Mre11 Expression in Atypical Adenomatous Hyperplasia and Adenocarcinoma of the Lung

2006 ◽  
Vol 130 (9) ◽  
pp. 1330-1334
Author(s):  
Kuniaki Nakanishi ◽  
Fumiyuki Kumaki ◽  
Sadayuki Hiroi ◽  
Makio Mukai ◽  
Eiji Ikeda ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Reverse Transcription ◽  
Telomere Maintenance ◽  
Low Grade ◽  
High Grade ◽  
Atypical Adenomatous Hyperplasia ◽  
Adenomatous Hyperplasia ◽  
Chain Reaction ◽  
Significant Difference ◽  
Polymerase Chain

Abstract Context.—The Mre11-Rad50-NBS1 complex plays an important role in telomere maintenance. Recently, it has been proposed that alterations in Mre11 function may be contributing factors in the development of some tumors. Moreover, mutations of Mre11 have been demonstrated to cause reduced Mre11 immunostaining. Objective.—To investigate Mre11 in atypical adenomatous hyperplasia (AAH) and nonmucinous bronchioloalveolar carcinoma (NMBAC), an issue not previously explored. Design.—We examined (1) the expression of Mre11 protein in 27 AAHs (9 lesions interpreted as low-grade AAH and 18 as high-grade AAH) and 40 NMBACs (using immunohistochemistry) and (2) Mre11 mRNA expression in 1 high-grade AAH and 6 NMBACs (using reverse transcription polymerase chain reaction). For the analysis of immunoreactivity, the intensity and extent of staining were each scored from 0 to 3. These 2 scores were summed to give in each case a final score of 0 to 6. Results.—Scores for Mre11 expression were 5.0 ± 2.1 for low-grade AAH, 5.4 ± 1.2 for high-grade AAH, and 5.5 ± 0.9 for NMBAC, and there was no statistically significant difference among these 3 types of lesions. In the reverse transcription polymerase chain reaction for Mre11 mRNA, polymerase chain reaction products were detected in all samples. Conclusions.—On this basis, we suggest that the part played by Mre11 in telomere maintenance may not be important for the progression of the adenoma–carcinoma (AAH–NMBAC) sequence in the lung, although some role for it in carcinogenesis cannot be completely ruled out.

scholarly journals Effects of Stromal Cell-Derived Factor-1α Secreted in Degenerative Intervertebral Disc on Activation and Recruitment of Nucleus Pulposus-Derived Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Jinwei Ying ◽  
Zhihua Han ◽  
Shishen Pei ◽  
Linghao Su ◽  
Dike Ruan
Keyword(s):  
Stem Cells ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Stromal Cell ◽  
Ex Vivo ◽  
Systemic Delivery ◽  
Proinflammatory Mediators ◽  
Significant Difference ◽  
Stromal Cell Derived Factor

Stromal cell-derived factor-1α (SDF-1α) plays a significant role in mobilizing and recruiting mesenchymal stem cells (MSCs) to the sites of injury. This study investigated the potential of SDF-1α released in the degenerative intervertebral disc (IVD) to activate and recruit endogenous nucleus pulposus-derived stem cells (NPSCs) for regeneration in situ. We found SDF-1α was highly expressed and secreted by the native disc cells when cultured in the proinflammatory mediators in vitro mimicking the degenerative settings. Immunohistochemical staining also showed that the expression level of SDF-1α was significantly higher in the degenerative group compared to that in the normal group. In addition to enhancement of viability, SDF-1α significantly increased the number of NPSCs migrating into the center of the nucleotomized bovine IVD ex vivo. After the systemic delivery of exogenous PKH26-labelled NPSCs into the rats in vivo, there was a significant difference in the distribution of the migrated cells between the normal and the degenerative IVDs, which might be caused by the different expression levels of SDF-1α. However, blocking CXC chemokine receptor 4 (CXCR4) with AMD3100 effectively abrogated SDF-1α-stimulated proliferation and migration. Taken together, SDF-1α may be a key chemoattractant that is highly produced in response to the degenerative changes, which can be used to enhance the proliferation and recruitment of endogenous stem cells into the IVDs. These findings may be of importance for understanding IVD regenerative mechanisms and development of regenerative strategies in situ for IVD degeneration.

scholarly journals Association between NLPR1, NLPR3, and P2X7R Gene Polymorphisms with Partial Seizures

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Haidong Wang ◽  
Pengfei Xu ◽  
Dehua Liao ◽  
Ruili Dang ◽  
Xin He ◽  
...  
Keyword(s):  
Gene Polymorphisms ◽  
Purinergic Receptor ◽  
Partial Seizures ◽  
Chain Reaction ◽  
Chinese Han ◽  
Significant Difference ◽  
Inflammatory Processes ◽  
Polymerase Chain ◽  
The Brain

Objectives. Clinical and experimental evidence has clarified that the inflammatory processes within the brain play a pivotal role in the pathophysiology of seizures and epilepsy. Inflammasomes and P2X7 purinergic receptor (P2X7R) are important mediators during the inflammatory process. Therefore, we investigated the possible association between partial seizures and inflammasomes NLPR1, NLRP3, and P2X7R gene polymorphisms in the present study. Method. A total of 163 patients and 201 health controls were enrolled in this study and polymorphisms of NLPR1, NLRP3, and P2X7R genes were detected using polymerase chain reaction- (PCR-) ligase detection reaction method. Result. The frequency of rs878329 (G>C) genotype with C (CG + CC) was significantly lower among patients with partial seizures relative to controls (OR = 2.033, 95% CI = 1.290–3.204, p=0.002 for GC + CC versus GG). Intriguingly, we found that the significant difference of rs878329 (G>C) genotype and allele frequency only existed among males (OR = 2.542, 95% CI = 1.344–4.810, p=0.004 for GC + CC versus GG), while there was no statistically significant difference among females. However, no significant results were presented for the genotype distributions of rs8079034, rs4612666, rs10754558, rs2027432, rs3751143, and rs208294 polymorphisms between patients and controls. Conclusion. Our study demonstrated the potentially significant role of NLRP1 rs878329 (G>C) in developing susceptibility to the partial seizures in a Chinese Han population.

scholarly journals Gene Polymorphisms in FAS (Rs3740286 and Rs4064) Are Involved in Endometriosis Development in Brazilian Women, but not those in CASP8 (rs13416436 and rs2037815)

2018 ◽  
Vol 40 (08) ◽  
pp. 450-457 ◽  
Author(s):  
Cristina Pissetti ◽  
Sarah Tanaka ◽  
Andrezza Hortolani ◽  
Alessandra Marqui
Keyword(s):  
Gene Polymorphisms ◽  
Death Receptor ◽  
Control Group ◽  
Allelic Frequencies ◽  
Significant Difference ◽  
Chi Squared ◽  
Thermo Fisher Scientific ◽  
Polymerase Chain ◽  
Control Study ◽  
Fisher Scientific

Objective The present study aims to investigate the association between caspase-8 (CASP8) (rs13416436 and rs2037815) and Fas cell surface death receptor (FAS) (rs3740286 and rs4064) polymorphisms with endometriosis in Brazilian women. Methods In the present case-control study, 45 women with a diagnosis of endometriosis and 78 normal healthy women as a control group were included. The genotyping was determined by real-time polymerase chain reaction (PCR) with Taqman hydrolysis probes (Thermo Fisher Scientific, Darmstadt, Germany). Genotypic and allelic frequencies were analyzed using Chi-squared (χ2) test. In order to determine the inheritance models and haplotypes ,SNPStats (Institut Català d'Oncologia, Barcelona, Spain) was used. Levels of 5% (p = 0.05) were considered statistically significant. Results No significant difference was observed in genotypic or allelic frequencies between control and endometriosis groups for rs13416436 and rs2037815 (CASP8 gene). On the other hand, a significant difference between rs3740286 and rs4064 (FAS gene) was found. Regarding polymorphisms in the FAS gene, a statistically significant difference was found in co-dominant and dominant models. Only the haplotype containing the rs3740286A and rs4064G alleles in the FAS gene were statistically significant. Conclusion The polymorphisms in the CASP8 gene were not associated with endometriosis. The results indicate an association between FAS gene polymorphisms and the risk of developing endometriosis.

MT1-MMP Plays a Critical Role In the Modulation of Hematopoiesis.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3851-3851
Author(s):  
Chiemi Nishida ◽  
Beate Heissig ◽  
Yoshihiko Tashiro ◽  
Motoharu Seiki ◽  
Hiromitsu Nakauchi ◽  
...  
Keyword(s):  
Stromal Cell ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Critical Role ◽  
Cancer Drug ◽  
Hematopoietic Stem ◽  
Kit Ligand ◽  
Significant Difference ◽  
Stromal Cell Derived Factor

Abstract Abstract 3851 Specific niches, in which hematopoietic stem cells (HSCs) reside control the balance between HSC quiescence and self-renewal, yet little is known about the extrinsic signals provided by the niche and how these niche signals regulate such a balance. In the recent study, activation of the fibrinolytic pathway via matrix metalloproteinases (MMPs) including MMP-9 resulted in the release of kit ligand (KitL) in the BM niche. Membrane type 1-MMP (MT1-MMP) can activate MMP-9 in the process of mutual activation of MMP. It has already known that BM myeloablation with irradiation or anti-cancer drug induces MT1-MMP expression, but the role of MT1-MMP in hematopoiesis is not well-understood. We examined MT1-MMP deficient mice (MT1-MMP-/-) 12 days after birth. MT1-MMP-/- were suffering from pancytopenia, and are reduced numbers of bone marrow mononuclear cells (BMMCs), splenocytes and number of hematopoietic progenitor cells in the BM although the number of HSCs in BM showed no significant difference. BM cytospins from MT1-MMP-/- mice showed mild erythropoietic disturbance and severer impairment of myelopoiesis. Interestingly, a powerful hematopoietic factor, Kit-ligand (KitL) levels were significantly lower in MT1-MMP-/- mice than wild type. MT1-MMP knockdown by shRNA or/and siRNA impaired KitL expression and secretion in transfected stroma cells compared to Mock controls, demonstrating that reduced KitL plasma levels were due to impaired release/production and not due to reduced numbers of stromal cells in MT1-MMP-/-. Similarly, impaired proliferation and differentiation of MT1-MMP-/- BMMCs in vitro could be restored by exogenous sKitL. Others and we reported that BM ablation induces the production of stromal cell-derived factor-1 (SDF-1; CXCL12), which plays a key role in stem cell homing and B-cell lymphopoiesis. Reduced SDF-1 expression was observed in BMMCs of MT1-MMP-/- mice and genetic knockdown of MT1-MMP resulted in lower SDF-1 expression both on a transcriptional and protein level. BMMCs of MT1-MMP-/- showed a decrease in the percentage of mature B cells compare to controls. Knocking down of MT1-MMP in stromal cell reduced the number of adherent hematopoietic cells, but addition of rec. SDF-1 could reverse the phenotype. These results suggested stromal-derived MT1-MMP was functionally important to maintain HSC function in long-term cultures of WT HSCs. Thus, MT1-MMP is a critical modulator of hematopoiesis, as it alters the growth factor output of niche cells. Disclosures: No relevant conflicts of interest to declare.

Stromal cell–derived factor-1 and macrophage-derived chemokine: 2 chemokines that activate platelets

Blood ◽  
2000 ◽  
Vol 96 (1) ◽  
pp. 50-57 ◽  
Author(s):  
M. Anna Kowalska ◽  
Mariusz Z. Ratajczak ◽  
Marcin Majka ◽  
Jianguo Jin ◽  
Satya Kunapuli ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Stromal Cell ◽  
Platelet Rich Plasma ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Creatine Phosphate ◽  
Polymerase Chain ◽  
Stromal Cell Derived Factor ◽  
Induced Aggregation ◽  
Second Wave

Abstract Platelets play roles in both thrombosis and inflammation, and chemokines that are released at sites of inflammation could potentially activate platelets. Among the chemokine receptors expressed on platelets, the CXCR4 is the receptor for chemokine stromal cell-derived factor-1 (SDF-1), and the CCR4 is the receptor for macrophage-derived chemokine (MDC). Of the chemokines tested, SDF-1 and MDC were the only 2 that activated platelets. Both are weak agonists, but they enhanced response to low-dose adenosine 5′-diphosphate (ADP), epinephrine, or serotonin. When SDF-1 and MDC were added together, full and brisk platelet aggregation occurred. Platelet activation by these 2 chemokines appears to involve distinct pathways: SDF-1 inhibited an increase in cyclic adenosine monophosphate (cAMP) following prostaglandin (PG) I2, while MDC had no effect. In contrast, MDC, but not SDF-1, lead to Ca++mobilization by platelets. Further, second-wave aggregation induced by MDC in platelet-rich plasma was inhibited by aspirin, ADP scavenger creatine phosphate/creative phosphokinase (CP/CPK), and ARL-66096, an antagonist of the ADP P2TAC receptor involved in adenylyl cyclase inhibition. But the aggregation was not affected by A3P5PS, an inhibitor of the ADP P2Y receptor. SDF-1–induced aggregation was inhibited by aspirin, but it was only slightly affected by CP/CPK, ARL-66096, or A3P5PS. Finally, the presence of chemokines in platelets was determined. Reverse transcriptase–polymerase chain reaction studies with platelet RNA did not detect the presence of SDF-1 or MDC. In summary, SDF-1 and MDC are platelet agonists that activate distinct intracellular pathways. Their importance in the development of thrombosis at sites of inflammation needs to be further evaluated.

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