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1.
J Infect Dev Ctries ; 17(8): 1160-1167, 2023 08 31.
Article in English | MEDLINE | ID: mdl-37699101

ABSTRACT

INTRODUCTION: Trichomoniasis is the most common non-viral sexually transmitted infection that increases the risk of cervical cancer. Trichomonas vaginalis (T. vaginalis) can regulate the pro-inflammatory cytokine production in the host cells. Toll-like receptors (TLRs) are a family of the pattern recognition receptors (PRRs) of mammalian cells, expressed in various host cells and have an important role in recognizing pathogens, and pro-inflammatory responses. The aim of the present study is to investigate the role of TLR5 in cervical cancer cells (HeLa) and human vaginal epithelial cells (HVECs) exposed to T. vaginalis. METHODOLOGY: First, the cells and parasites were cultured in RPMI and trypticase yeast extract maltose (TYM), respectively. After adaption of parasite and epithelial cells by RPMI-TYM medium co-culture (9:1 vol/vol), HVECs and HeLa cells were stimulated with T. vaginalis trophozoites (24-hour incubation at 37 °C, 5% CO2). Following RNA extraction and cDNA synthesis, the gene expression levels of TLR5, IRAK1, and NF-κB were assessed using real-time PCR. Besides, the protein levels were measured using western blotting. All tests and controls were normalized using ß-actin as a housekeeping control. RESULTS: Real-time PCR results showed an increased gene expression of TLR5, IRAK1, and NF-κB in T. vaginalis exposed HVECs and HeLa cells compared to the control group (p < 0.05). Additionally, western blot analysis showed a statistically significant increase in TLR5, and NF-κB proteins in both groups after exposure to the parasite (p < 0.05). CONCLUSIONS: These findings provide insight into the host-parasite interaction, and the results indicated that T. vaginalis could stimulate TLR5 and activate related pathways.


Subject(s)
Trichomonas vaginalis , Uterine Cervical Neoplasms , Animals , Female , Humans , Epithelial Cells , HeLa Cells , Interleukin-1 Receptor-Associated Kinases , NF-kappa B , Toll-Like Receptor 5 , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/parasitology
2.
Parasit Vectors ; 14(1): 603, 2021 Dec 11.
Article in English | MEDLINE | ID: mdl-34895315

ABSTRACT

BACKGROUND: Trichomonas vaginalis causes lesions on the cervicovaginal mucosa in women; however, its pathogenesis remains unclear. We have investigated the involvement of the endoplasmic reticulum (ER) in the induction of apoptosis by T. vaginalis and its molecular mechanisms in human cervical cancer SiHa cells. METHODS: Apoptosis, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), ER stress response and Bcl-2 family protein expression were evaluated using immunocytochemistry, flow cytometry, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide dye staining and western blotting. RESULTS: Trichomonas vaginalis induced mitochondrial ROS production, apoptosis, the ER stress response and mitochondrial dysfunction, such as MMP depolarization and an imbalance in Bcl-2 family proteins, in SiHa cells in a parasite burden- and infection time-dependent manner. Pretreatment with N-acetyl cysteine (ROS scavenger) or 4-phenylbutyric acid (4-PBA; ER stress inhibitor) significantly alleviated apoptosis, mitochondrial ROS production, mitochondrial dysfunction and ER stress response in a dose-dependent manner. In addition, T. vaginalis induced the phosphorylation of apoptosis signal regulating kinase 1 (ASK1) and c-Jun N-terminal kinases (JNK) in SiHa cells, whereas 4-PBA or SP600125 (JNK inhibitor) pretreatment significantly attenuated ASK1/JNK phosphorylation, mitochondrial dysfunction, apoptosis and ER stress response in SiHa cells, in a dose-dependent manner. Furthermore, T. vaginalis excretory/secretory products also induced mitochondrial ROS production, apoptosis and the ER stress response in SiHa cells, in a time-dependent manner. CONCLUSIONS: Trichomonas vaginalis induces apoptosis through mitochondrial ROS and ER stress responses, and also promotes ER stress-mediated mitochondrial apoptosis via the IRE1/ASK1/JNK/Bcl-2 family protein pathways in SiHa cells. These data suggest that T. vaginalis-induced apoptosis is affected by ROS and ER stress response via ER-mitochondria crosstalk.


Subject(s)
Apoptosis , Endoplasmic Reticulum Stress , Reactive Oxygen Species/metabolism , Signal Transduction , Trichomonas vaginalis/physiology , Uterine Cervical Neoplasms/parasitology , Cell Line, Tumor , Endoplasmic Reticulum/metabolism , Female , Humans , Membrane Potential, Mitochondrial , Mitochondria/metabolism
3.
BMC Infect Dis ; 21(1): 691, 2021 Jul 17.
Article in English | MEDLINE | ID: mdl-34273957

ABSTRACT

BACKGROUND: Female genital schistosomiasis (FGS) is a neglected tropical gynaecological disease that affects millions of women in sub-Saharan Africa (SSA). FGS is caused by Schistosoma haematobium, a parasitic carcinogen involved in the pathogenesis of squamous cell carcinoma of the bladder. Cervical cancer incidence and mortality are highest in SSA, where pre-cancerous cervical dysplasia is often detected on screening with visual inspection with acetic acid (VIA). There are no studies evaluating the association between VIA positivity and FGS diagnosed by genital PCR. METHODS: Women were recruited from the Bilharzia and HIV (BILHIV) study in Zambia a community-based study comparing genital self-sampling to provider obtained cervicovaginal-lavage for the diagnosis of FGS in women aged 18-31. FGS was defined as positive Schistosoma DNA from any genital PCR. Urogenital schistosomiasis diagnostics included urine circulating anodic antigen, urine microscopy and portable colposcopy. Participants were offered cervical cancer screening using VIA at Livingstone Central Hospital. Associations of PCR confirmed FGS and other diagnostics with VIA positivity were assessed using multivariable logistic regression. RESULTS: VIA results were available from 237 BILHIV participants. A positive Schistosoma PCR in any genital specimen was detected in 14 women (5.9%), 28.6% (4/14) of these women had positive VIA compared to 9.0% without PCR evidence of schistosome infection (20/223). Schistosoma PCR positivity in any genital specimen was strongly associated with VIA positivity (OR: 6.08, 95% CI: 1.58-23.37, P = 0.02). CONCLUSIONS: This is the first study to find an association between FGS and positive VIA, a relationship that may be causal. Further longitudinal studies are needed.


Subject(s)
Schistosomiasis haematobia/epidemiology , Uterine Cervical Dysplasia/epidemiology , Adolescent , Adult , Animals , Colposcopy/methods , Diagnostic Tests, Routine/methods , Early Detection of Cancer/methods , Female , Genitalia, Female/parasitology , Genitalia, Female/pathology , Humans , Incidence , Microscopy/methods , Polymerase Chain Reaction , Schistosoma haematobium/genetics , Schistosoma haematobium/isolation & purification , Schistosomiasis haematobia/diagnosis , Schistosomiasis haematobia/parasitology , Specimen Handling , Urinalysis/methods , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Dysplasia/parasitology , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/parasitology , Young Adult , Zambia/epidemiology
4.
Pathol Res Pract ; 216(12): 153234, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33075741

ABSTRACT

Gardnerella vaginalis (GV) and Trichomonas vaginalis (TV) infections have been proposed as risk factors for persistence or progression of low-grade precancerous cervical lesions (CIN1/L-SIL). However, their role is still undefined. We aimed to assess if GV and TV infections affect the risk of persistence/progression of CIN1/L-SIL. A retrospective cohort study was performed to assess the risk of CIN1/L-SIL persistence or progression, persistence alone and progression alone in patients with GV and/or TV infections (GV + and/or TV+), only GV (GV+), only TV (TV+), or GV and TV coinfections compared to patients without these infections. Relative risk (RR) with 95 % confidence intervals (CI) was adopted (significant p-value>0.05). Two hundred and seventy patients were included. RR for CIN1/L-SIL persistence or progression was 1.63 in GV + and/or TV+ (p = 0.02), 1.99 in GV+ (p = 0.0008), 0.25 in TV+ (p = 0.32), 1.78 in coinfection (p = 0.26). RR for persistence was 1.55 in GV + and/or TV+ (p = 0.1), 2.179 in GV+ (p = 0.0013), 0.32 in TV+ (p = 0.41), 0.45 in coinfection (p = 0.55). RR for progression was 1.92 in GV + and/or TV+ (p = 0.22), 1.34 in GV+ (p = 0.68), 1.16 in TV+ (p = 0.91), 8.39 in coinfection (p = 0.0002). In conclusion, GV infection may be a risk factor for CIN1/L-SIL persistence. TV infection alone does not significantly affect the risk of persistence or progression of such lesions, while it may greatly increase the risk of progression when associated with GV infection.


Subject(s)
Gardnerella vaginalis/pathogenicity , Gram-Positive Bacterial Infections/microbiology , Trichomonas Vaginitis/parasitology , Trichomonas vaginalis/pathogenicity , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Vaginosis, Bacterial/microbiology , Adult , Disease Progression , Female , Gram-Positive Bacterial Infections/diagnosis , Humans , Middle Aged , Neoplasm Grading , Retrospective Studies , Risk Assessment , Risk Factors , Trichomonas Vaginitis/diagnosis , Uterine Cervical Neoplasms/microbiology , Uterine Cervical Neoplasms/parasitology , Uterine Cervical Neoplasms/pathology , Vaginosis, Bacterial/diagnosis , Uterine Cervical Dysplasia/microbiology , Uterine Cervical Dysplasia/parasitology , Uterine Cervical Dysplasia/pathology
5.
Parasitol Res ; 119(8): 2649-2657, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32583161

ABSTRACT

Trichomonas vaginalis is the most common nonviral sexually transmitted infection. According to the 2019 WHO cancer report, cervical cancer is the fourth most frequent cancer in women. However, previous research, which has not included a large-scale study to date, has revealed that Trichomonas vaginalis increases cervical cancer risk. In this study, we investigated a group of Asian females in Taiwan to determine the association between trichomoniasis and the risk of developing cervical lesions, including cancer, neoplasm, and dysplasia. We conducted a nested case-control study by using the National Health Insurance (NHI) program database in Taiwan. The International Classification of Diseases, 9th Revision classifications (ICD-9-CM) was used to categorize all of the medical conditions for each patient in the case and control groups. The adjusted odds ratio (AOR) and 95% confidence interval (CI) for the association between trichomoniasis and cervical lesions were estimated using multivariable conditional logistic regression to adjust for all comorbidities and variables. In total, 54,003 individuals were enrolled in the case group and 216,012 were enrolled in the control group. Trichomonas vaginalis exposure had a significant association with cervical lesions (AOR 2.656, 95% CI = 1.411-5.353, p = 0.003), especially cervical cancer (AOR 3.684, 95% CI = 1.622-6.094, p = 0.001). In patients with both trichomoniasis and depression, the relative risk increased 7.480-fold compared to those without trichomoniasis or depression. In conclusion, female patients with Trichomonas vaginalis exposure had a significantly higher risk of developing cervical lesions (especially cervical cancer) than those without exposure.


Subject(s)
Trichomonas Infections/complications , Trichomonas vaginalis/pathogenicity , Uterine Cervical Diseases/pathology , Uterine Cervical Diseases/parasitology , Adult , Case-Control Studies , Depression/complications , Depression/epidemiology , Female , Humans , Middle Aged , Odds Ratio , Taiwan/epidemiology , Trichomonas Infections/epidemiology , Uterine Cervical Diseases/epidemiology , Uterine Cervical Diseases/psychology , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/parasitology , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/psychology
6.
Arch Gynecol Obstet ; 302(3): 649-655, 2020 09.
Article in English | MEDLINE | ID: mdl-32488400

ABSTRACT

PURPOSE: To evaluate the prevalence of cervical pre-malignancies in the cervical cytology of female renal transplant recipients (RTR) and compare to immunocompetent patients. METHODS: A prospective case-control study of 165 RTR (cases) and 372 immunocompetent women (controls) was carried out from May 2015 to August 2016. The participants completed a questionnaire with demographic characteristics, habits, reproductive history, and information about the renal transplant. Cervical cytology samples were collected at their visit for cervical cancer screening. Relevant medical history was obtained from medical records and previous cervical cytology results were retrieved: from the time of kidney transplantation to the beginning of this study for RTR and all collected throughout life for controls. RESULTS: The mean age was similar between groups (42.6 ± 11.4 vs. 41.8.2 ± 11.1 years, p = 0.447). Considering cervical cytology collected since the kidney transplant, RTR had three times higher rates of abnormal cervical cytology test (24.8% of RTR vs. 6.3% for controls), and the abnormalities were more frequent (p < 0.001) for low squamous intraepithelial lesion (LSIL) (n = 23, 13.9%) and high squamous intraepithelial lesion (HSIL) (n = 9, 5.5%). Cervical cytology collected during the study had normal results in 152 RTR (92.1%) vs. 326 controls (93.9%) (p > 0.05). When the altered results were broken down, a higher frequency of LSIL could be seen in RTR (3.6% vs 0.0%, p = 0.008). CONCLUSION: RTR had significantly higher rates of cervical cytology abnormalities comparing to the control group and most of it was composed of LSIL.


Subject(s)
Cervix Uteri/pathology , Immunocompromised Host , Kidney Transplantation/adverse effects , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Neoplasms/diagnosis , Vaginal Smears/methods , Adult , Brazil , Case-Control Studies , Early Detection of Cancer , Female , Humans , Immunocompetence , Middle Aged , Papillomaviridae , Papillomavirus Infections , Prospective Studies , Uterine Cervical Neoplasms/parasitology , Vagina/pathology , Young Adult , Uterine Cervical Dysplasia/pathology
7.
Sci Rep ; 8(1): 11547, 2018 08 01.
Article in English | MEDLINE | ID: mdl-30069018

ABSTRACT

Persistent infection with human papillomavirus (HPV) is responsible for nearly all new cervical cancer cases worldwide. In low- and middle-income countries (LMIC), infection with helminths has been linked to increased HPV prevalence. As the incidence of cervical cancer rises in helminth endemic regions, it is critical to understand the interaction between exposure to helminths and the progression of cervical cancer. Here we make use of several cervical cancer cell lines to demonstrate that exposure to antigens from the hookworm N. brasiliensis significantly reduces cervical cancer cell migration and global expression of vimentin and N-cadherin. Importantly, N. brasiliensis antigen significantly reduced expression of cell-surface vimentin, while decreasing HPV type 16 (HPV16) pseudovirion internalization. In vivo infection with N. brasiliensis significantly reduced vimentin expression within the female genital tract, confirming the relevance of these in vitro findings. Together, these findings demonstrate that infection with the hookworm-like parasite N. brasiliensis can systemically alter genital tract mesenchymal markers in a way that may impair cervical cancer cell progression. These findings reveal a possible late-stage treatment for reducing cervical cancer progression using helminth antigens.


Subject(s)
Ancylostomatoidea/growth & development , Cell Movement , Epithelial Cells/parasitology , Epithelial Cells/virology , Human papillomavirus 16/growth & development , Uterine Cervical Neoplasms/parasitology , Uterine Cervical Neoplasms/virology , Animals , Antigens, CD/analysis , Cadherins/analysis , Disease Models, Animal , Epithelial-Mesenchymal Transition , Female , Gene Expression Profiling , Genitalia, Female/pathology , HeLa Cells , Humans , Models, Biological , Uterine Cervical Neoplasms/pathology , Vimentin/analysis
8.
Eur J Obstet Gynecol Reprod Biol ; 228: 166-173, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29980111

ABSTRACT

Trichomoniasis, caused by the extracellular eukaryotic parasite trichomonas vaginalis, is one of the most common non-viral sexually transmitted infections worldwide. The correlation between trichomoniasis and cervical cancer was ambiguous. This meta-analysis was carried out to determine the relevance between trichomoniasis and cervical cancer. Relevant data from 1985 to 2016 were identified through an extensive search of Medline, Cochrane database, Google Scholar, EMBASE, China National Knowledge Infrastructure. Finally 17 eligible articles covered 7715 individuals with cervical lesions and 67,598 controls were included. Meta-analysis of total eligible studies showed that odds ratio of retrospective studies was 2.06, with 95% confidence interval (95% CI) of 1.77 to 2.39, prospective studies with adjusted relative risk of 1.94 (95% CI = 1.19 to 3.15) and 2.84 (95% CI = 1.32 to 6.12) respectively, and the combined relative risk was 2.03 (95% CI = 1.35 to 3.06). Subgroup analysis indicated that there were significant regional and racial differences in the correlation between trichomoniasis and cervical cancer. Odds ratio of Africa and Europe are 2.43 (95% CI = 1.15 to 5.13) and 1.82 (95% CI = 1.67 to 2.62) respectively. Odds ratio of mixed population is 2.87 (95% CI = 2.00 to 4.12), followed by black and white, Asian with the lowest odds ratio of 1.91 (95% CI = 1.32 to 2.77). In conclusion, our data demonstrate that individuals infected with trichomonas vaginalis have a higher risk of cervical cancer, especially co-infected with Human Papilloma Virus. Besides, there is significant regional and racial variation in the correlation between trichomonas vaginalis infection and risk of cervical cancer.


Subject(s)
Carcinoma/parasitology , Trichomonas Infections/complications , Trichomonas vaginalis , Uterine Cervical Neoplasms/parasitology , Case-Control Studies , Cohort Studies , Female , Humans , Risk
9.
Clin Cancer Res ; 24(20): 5028-5036, 2018 10 15.
Article in English | MEDLINE | ID: mdl-29959140

ABSTRACT

Purpose: This study investigates the association between body composition change during concurrent chemoradiotherapy (CCRT) and outcome in patients with locally advanced cervical cancer (LACC).Experimental Design: Pre- and posttreatment CT images of 245 patients with LACC who were treated between 2004 and 2015 were analyzed. Skeletal muscle index (SMI) and density (SMD), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) were measured from two sets of CT images at the level of the L3 vertebra. Sarcopenia and a low SMD were defined using published cut-off points. Predictors of overall survival (OS) and cancer-specific survival (CSS) were analyzed using Cox regression models.Results: The median follow-up was 62.7 (range, 7.3-152.3) months. Among the 245 patients, 127 (51.8%) had pretreatment sarcopenia, and 154 (62.9%) had a low SMD. SMI did not decrease significantly during CCRT, 0.6%/150 days [95% confidence interval (CI), -1.8-0.6; P = 0.35]. However, SMI loss during CCRT of >10.0%/150 days was independently associated with poorer OS (HR, 6.02; 95% CI, 3.04-11.93; P < 0.001) and CSS (HR, 3.49; 95% CI, 1.44-8.42; P = 0.006) when adjusted for FIGO stage, pathology, and treatment. Pretreatment sarcopenia and change of SMD, SATI, and VATI during CCRT were not associated with survival.Conclusions: Skeletal muscle measurements could be imaging biomarkers to predict outcomes for patients with LACC in clinical practice. Further studies are needed to determine whether multimodal interventions can preserve skeletal muscle mass and thereby improve survival. Clin Cancer Res; 24(20); 5028-36. ©2018 AACR.


Subject(s)
Diagnostic Imaging , Muscle, Skeletal/diagnostic imaging , Muscle, Skeletal/pathology , Muscular Atrophy/diagnosis , Muscular Atrophy/etiology , Uterine Cervical Neoplasms/complications , Uterine Cervical Neoplasms/parasitology , Aged , Biomarkers , Body Composition , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Middle Aged , Muscle, Skeletal/metabolism , Muscular Atrophy/metabolism , Neoplasm Metastasis , Neoplasm Staging , Prognosis , Proportional Hazards Models , Sarcopenia/diagnosis , Sarcopenia/etiology , Sarcopenia/metabolism , Tomography, X-Ray Computed , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/therapy
10.
Acta Cytol ; 62(1): 28-33, 2018.
Article in English | MEDLINE | ID: mdl-29130974

ABSTRACT

OBJECTIVE: The aim of this study was to assess the correlation between atypical squamous cells (ASC) and inflammatory infiltrate and vaginal microbiota using cervical liquid-based cytological (SurePath®) and high-risk human papillomavirus (HR-HPV) tests. STUDY DESIGN: A cross-sectional study was conducted using a 6-year database from a laboratory in Fortaleza (Brazil). Files from 1,346 ASC cases were divided into subgroups and results concerning inflammation and vaginal microorganisms diagnosed by cytology were compared with HR-HPV test results. RESULTS: An absence of specific microorganisms (ASM) was the most frequent finding (ASC of undetermined significance, ASC-US = 74%; ASC - cannot exclude high-grade squamous intraepithelial lesion, ASC-H = 68%), followed by bacterial vaginosis (ASC-US = 20%; ASC- H = 25%) and Candida spp. (ASC-US = 6%; ASC-H = 5%). Leukocyte infiltrate was present in 71% of ASC-US and 85% of ASC-H (p = 0.0040), and in these specific cases HR-HPV tests were positive for 65 and 64%, respectively. A positive HR-HPV test was relatively more frequent when a specific microorganism was present, and Candida spp. was associated with HR-HPV-positive results (p = 0.0156), while an ASM was associated with negative HR-HPV results (p = 0.0370). CONCLUSION: ASC-US is associated with an absence of inflammation or vaginosis, while ASC-H smears are associated with Trichomonas vaginalis and inflammatory infiltrate. A positive HR-HPV is associated with Candida spp. in ASC cytology.


Subject(s)
Atypical Squamous Cells of the Cervix/pathology , Human Papillomavirus DNA Tests , Microbiological Techniques , Papillomaviridae/genetics , Papillomavirus Infections/virology , RNA, Viral/genetics , Squamous Intraepithelial Lesions of the Cervix/pathology , Uterine Cervical Neoplasms/pathology , Vaginitis/pathology , Adult , Atypical Squamous Cells of the Cervix/microbiology , Atypical Squamous Cells of the Cervix/parasitology , Atypical Squamous Cells of the Cervix/virology , Brazil , Candida/isolation & purification , Candidiasis, Vulvovaginal/microbiology , Candidiasis, Vulvovaginal/pathology , Cross-Sectional Studies , Databases, Factual , Female , Humans , Leukocytes/pathology , Liquid Biopsy , Middle Aged , Papillomaviridae/isolation & purification , Papillomavirus Infections/pathology , Predictive Value of Tests , RNA, Viral/isolation & purification , Risk Factors , Squamous Intraepithelial Lesions of the Cervix/microbiology , Squamous Intraepithelial Lesions of the Cervix/parasitology , Squamous Intraepithelial Lesions of the Cervix/virology , Trichomonas Vaginitis/parasitology , Trichomonas Vaginitis/pathology , Trichomonas vaginalis/isolation & purification , Uterine Cervical Neoplasms/microbiology , Uterine Cervical Neoplasms/parasitology , Uterine Cervical Neoplasms/virology , Vaginal Smears , Vaginitis/microbiology , Vaginitis/parasitology , Young Adult
11.
Tumour Biol ; 37(7): 8931-40, 2016 Jul.
Article in English | MEDLINE | ID: mdl-26753959

ABSTRACT

Our previous studies have demonstrated overexpression of Mcl-1 in cervical cancer tumorigenesis. However, the molecular mechanism of its overexpression remains not elucidated. MiR-320 has been reported to be down-regulated in various types of cancer, and bioinformatics prediction indicated that it may regulate the expression of Mcl-1. The aim of this study is to investigate the role of miR-320 and its target gene Mcl-1 in cervical cancer progression and to assess their clinical significance. miR-320 and Mcl-1 expressions in human cervical cancer tissues were investigated by qRT-PCR, in situ hybridization, and immunohistochemical staining, respectively. The clinicopathological implications of these molecules were analyzed. Bioinformatic prediction and luciferase assays were employed to identify the predicted microRNA (miRNA) which regulates Mcl-1. The apoptosis, proliferation, migration, and invasion assays were performed to investigate the effect of miR-320 on the cervical cancer cells. MiR-320 expression is significantly down-regulated versus Mcl-1 expression is up-regulated in cervical cancer tissues compared with normal controls with a negative correlation between them. Luciferase assay showed that miR-320 negatively regulates Mcl-1 expression. In addition, miR-320 induces apoptosis via down-regulation of Mcl-1 and activation of caspase-3 but inhibits cell proliferation, migration, invasion, and tumorigenesis in cervical cancer cells. Our studies show that miR-320 expression is decreased in cervical cancer, and its expression is negatively correlated with Mcl-1 expression in cervical cancer. In addition, miR-320 inhibits cervical cancer progression by down-regulation of Mcl-1. These results indicate that miR-320 may be an important biomarker and target for diagnosis and treatment of cervical cancer patient.


Subject(s)
Apoptosis/genetics , Down-Regulation/genetics , MicroRNAs/genetics , Myeloid Cell Leukemia Sequence 1 Protein/genetics , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/parasitology , Animals , Carcinogenesis/genetics , Carcinogenesis/pathology , Caspase 3/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Disease Progression , Female , Gene Expression Regulation, Neoplastic/genetics , HeLa Cells , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Up-Regulation/genetics
12.
Gynecol Obstet Invest ; 81(4): 339-45, 2016.
Article in English | MEDLINE | ID: mdl-26580917

ABSTRACT

BACKGROUND: Pretreatment prognostic information is lacking for patients with cervical cancer International Federation of Gynecology and Obstetrics (FIGO) stage IB1 disease. Thus, we attempted to identify a high-risk subgroup among them prior to treatment. METHODS: Cervical cancer FIGO stage IB1 patients who had received curative treatment with various modalities in our institute between January 2004 and December 2010 were enrolled. Pretreatment clinical parameters including age, squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen, hemoglobin (Hb) level, platelet count, histological type, and treatment modality were analyzed for treatment outcomes. RESULTS: One hundred ninety-seven patients were included with a median follow-up of 66 months (range 6-119 months). In Cox regression analysis, only SCC histology (HR 0.457, 95% CI 0.241-0.967, p = 0.017) was an independent factor predicting better disease-free survival (DFS). Among SCC histology, patients with an Hb level less than 12 g/dl and a SCC-Ag level more than 3 ng/ml had worse treatment outcomes. The 5-year DFS rates were 89.2, 69.3, and 44.4% for the patients at low-risk (SCC, Hb >12 g/dl, SCC-Ag ≤3 ng/ml), intermediate-risk (non-SCC), and high-risk (SCC, Hb ≤12 g/dl, SCC-Ag >3 ng/ml), respectively (p < 0.001). CONCLUSION: Non-SCC and SCC histology with both anemia and high pretreatment SCC-Ag level were associated with recurrence. Further validation studies are warranted for clarification.


Subject(s)
Neoplasm Recurrence, Local/radiotherapy , Neoplasm Recurrence, Local/surgery , Uterine Cervical Neoplasms/radiotherapy , Uterine Cervical Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm/analysis , Carcinoma, Squamous Cell/pathology , Disease-Free Survival , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Retrospective Studies , Risk Factors , Serpins/analysis , Treatment Outcome , Uterine Cervical Neoplasms/parasitology
13.
Femina ; 42(3): 129-134, maio-jun. 2014. ilus
Article in Portuguese | LILACS | ID: lil-749129

ABSTRACT

Trichomonas vaginalis é um agente infectante da microbiota vaginal que vem sendo correlacionado ao câncer cervical. Um receptor denominado alectina-1 (Gal 1) pode ser expresso em células epiteliais cervicais humanas se ligando à glicofosfolipídica (LPG) de T. vaginalis. A interação de T. vaginalis com as células epiteliais é mediada por cadeias galactose e N-acetilglucosamina (LacNac). Gal 1 se liga aos sítios poly-LacNAC e está relacionada com a aderência de T. vaginalis à célula humana. A sinalização ocorre por intermédio de sítios da proteína Src (SH2) que se associam, ocorrendo sob os domínios de PI3K que fosforilam a membrana de lípides fosfatidilinositol (PIP e PIP2). Aderindo-se às membranas citoplasmáticas e secretando enzimas, T. vaginalis pode ocasionar a ruptura do envoltório celular podendo fagocitar células epiteliais em meio vaginal. O núcleo N-acetilactosamina de Gal 1 pode mediar a regulação do crescimento celular com a ajuda da proteína GRB2; entretanto, Gal 1 pode contribuir para a supressão da inflamação por meio da indução de apoptose pelas células T ativadas. (AU)


Trichomonas vaginalis is an infectious agent of the vaginal flora which has been associated with cervical cancer. Galectin-1 (Gal 1) is a cell receptor expressed in cervical epithelial cells binding T. vaginalis? lipophosphoglican (LPG). Interaction between T. vaginalis and the epithelial cell is mediated by poly-LacNac domains (galactoside and acetil-lactosamin) and is related to cell adherence as well. Cell signaling occurs by the time Src (SH2) domains are correlated with this interaction and PI3K phosphorilation brings up phosphatidil inositol lipid membranes (PIP and PIP2). T. vaginalis adheres to cytoplasm membrane and secrets specific enzymes that probably lead to membrane rupture. Moreover this parasite may phagocyte epithelial cells in vaginal discharge. Gal 1 nucleus called N-acetil-lactosamin can mediate growth development through GRB2 protein and may contribute to inflammation suppression owing to apoptosis induction of activated T cells.(AU)


Subject(s)
Humans , Female , Trichomonas vaginalis/cytology , Trichomonas vaginalis/physiology , Trichomonas vaginalis/pathogenicity , Signal Transduction , Uterine Cervical Neoplasms/parasitology , Galectin 1 , Platelet-Derived Growth Factor , Epidemiologic Factors , Apoptosis , Fas Ligand Protein
14.
Exp Parasitol ; 131(3): 267-73, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22525014

ABSTRACT

The protozoan Trichomonas vaginalis a sexually transmitted protozoan parasite causes vaginitis, urethritis and cervicitis in humans. The present study highlights phenotypic 'variant' forms of trophozoites isolated from patients suffering from cervical neoplasia condition. The growth curve of 10 isolates i.e., four non-cervical neoplasia (NCN) isolates (NCN1-NCN4) and six cervical neoplasia (CN) isolates (CN1-CN6) showed two distinct and different in vitro growth profiles. The parasite count and growth rates were significantly higher in trophozoites from CN isolates in cultures of day 2 up to day 8 (p<0.05, Mann-Whitney test). The average generation time was 1.84±0.40 and 3.38±0.55h for NCN and CN isolates respectively. The nucleus of trophozoites in CN isolates using acridine orange and DAPI showed more intense staining revealing higher nuclear content. The FITC-labeled Concanavalin A stained stronger green fluorescence with surface of trophozoites in CN isolates showing more rough and creased surface with numerous deep micropores. Transmission electron microscopy studies revealed that there was higher numbers of vacuoles and hydrogenosomes in these forms. The study mounted staining techniques, growth profiles, morphology, morphometry studies using scanning and transmission electron microscopy and confirms that the trophozoites from cervical neoplasia proliferates at a higher rate, shows higher FITC-labeled Concanavalin A binding with rough and creased surface implying that these are virulent forms which can aggravate or exacerbate cervical neoplasia conditions. The large numbers of hyrogenosomes and vacuoles implies that these forms are active and implicates a possible role in such conditions.


Subject(s)
Trichomonas Vaginitis/parasitology , Trichomonas vaginalis/growth & development , Uterine Cervical Neoplasms/parasitology , Case-Control Studies , Female , Histocytochemistry , Humans , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Phenotype , Trichomonas Vaginitis/complications , Trichomonas vaginalis/isolation & purification , Trichomonas vaginalis/ultrastructure , Uterine Cervical Neoplasms/complications , Vaginal Smears
16.
Rom J Morphol Embryol ; 52(1): 45-51, 2011.
Article in English | MEDLINE | ID: mdl-21424031

ABSTRACT

At European level, Romania unfortunately comes first as far as mortality due to cervical cancer is concerned, mortality rate recording a continuous increase due to disease detection in advanced stages. In this context, we followed an assessment of women's cognitive and attitudinal fund in relation to early detection of cervical cancer, through the application of a questionnaire on a batch of 617 women with ages from 18 to 75-year-old, with various levels of education, residents of Craiova City and communes from Dolj County. Statistic processing of their answers indicates that 43.3% of the inquired subjects have not had a routine gynecological exam for at least seven years (or even never), which is more often found in the subgroup of women from the rural environment, with ages over 35 years and with an elementary educational level (p<0.001). 65.8% of the women have not done a Babes-Papanicolau test for seven years or even never, residence area, age and education level being once again discrimination factors between the subgroups. The reasons usually put forward as a justification for the failure to do the cytological test for the past three years are negligence (23.8%), the lack of information on the existence of such an investigation (18.2%), the absence of a genital pathology (12.8%) or of a medical recommendation (11.8%). Results suggest the need to provide uniform accessibility of the population to health services, by developing and implementing new strategies of educational and sanitary intervention mainly in rural communities.


Subject(s)
Early Detection of Cancer , Health Knowledge, Attitudes, Practice , Uterine Cervical Neoplasms/diagnosis , Adolescent , Adult , Aged , Female , Humans , Logistic Models , Middle Aged , Papillomaviridae/physiology , Time Factors , Trichomonas/physiology , Uterine Cervical Neoplasms/parasitology , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/virology , Vaginal Smears , Young Adult
17.
Acta Cytol ; 54(2): 205-8, 2010.
Article in English | MEDLINE | ID: mdl-20391981

ABSTRACT

BACKGROUND: The association between Schistosoma haematobium and cervical cancer has been reported for a long time. However, recently human papillomavirus, a cofactor in the genesis of cervical cancer, has been confirmed. A case of squamous intraepithelial lesion after S haematobium infection is presented, and the relation between schistosomiasis, human papillomavirus and squamous intraepithelial lesion, with long-term follow-up by Papanicolaou smear, is discussed. CASE: A 33-year-old, normal, healthy woman with a history of Copper intrauterine device (IUD) use for 3.9 years presented for her annual contraceptive follow-up. Her Pap smear revealed inflammation with a S haematobium egg. She was followed up with Pap smears for 4 years. Retrospective contraceptive history revealed use ofa copper IUD on 5 occasions with a total duration of 13 years and 1 month. Similarly, annual follow-up of Pap smears for the past 13 years showed mild inflammation with bacterial vaginitis and monilial infection. Subsequent smears showed an Actinomyces-like organism and then human papillomavirus infection with atypical squamous cells of undetermined significance followed by human papillomavirus-associated low/high grade squamous intraepithelial lesion. CONCLUSION: Caution is required while screening routine Pap smears. Apart from nuclear abnormalities, one can observe unusual findings. Long-term followup by Pap smear following detection of S haematobium revealed that in the absence of human papillomavirus, S haematobium alone is not the causative agent for the abnormal proliferation of squamous epithelium of the cervix. Genital Schistosomia acts as a cofactor by traumatizing the genital epithelium or immune suppression to favor human papillomavirus infection.


Subject(s)
Papillomavirus Infections/pathology , Schistosomiasis haematobia/pathology , Uterine Cervical Dysplasia/pathology , Uterine Cervical Neoplasms/pathology , Adult , Alphapapillomavirus/isolation & purification , Animals , Female , Humans , Papanicolaou Test , Papillomavirus Infections/virology , Schistosoma haematobium/isolation & purification , Schistosomiasis haematobia/parasitology , Uterine Cervical Neoplasms/parasitology , Uterine Cervical Neoplasms/virology , Vaginal Smears , Uterine Cervical Dysplasia/parasitology , Uterine Cervical Dysplasia/virology
18.
Acta Cytol ; 54(1): 43-9, 2010.
Article in English | MEDLINE | ID: mdl-20306987

ABSTRACT

OBJECTIVE: To describe recent trends in the prevalence of cytologic patterns of the vaginal flora (koilocytosis, Trichomonas, dys-bacteriosis, Candida, Gardnerella, Actinomyces, Chlamydia trachomatis) over the last decade. STUDY DESIGN: From 1996 to 2005 > 500,000 cervical smears were screened in the context of the Dutch national screening program on a 5-year basis. Data from the first screening period were compared with those of the second screening period. RESULTS: Prevalences differed from 34.8 for dysbacteriosis to 0.2 for C trachomatis. Bacterial imbalance (dysbacteriosis, unequivocal Gardnerella and Trichomonas) showed a decline in all age groups. Cases of human papillomavirus (HPV)-related koilocytosis have dramatically increased among young women (30 and 35 years). CONCLUSION: Bacterial imbalance of the vaginal flora has significantly decreased during the past decade in all age cohorts. Campaigns on consciousness of vaginal hygiene might have contributed to this amazing effect. We ought to be concerned about the increase in HPV-related koilocytosis.


Subject(s)
Inflammation/microbiology , Uterine Cervical Neoplasms/microbiology , Uterine Cervical Neoplasms/parasitology , Vagina/microbiology , Adult , Female , Humans , Inflammation/parasitology , Inflammation/pathology , Mass Screening , Middle Aged , Uterine Cervical Neoplasms/pathology , Vagina/parasitology , Vagina/pathology , Vaginal Smears
19.
Rev Salud Publica (Bogota) ; 9(3): 327-41, 2007.
Article in Spanish | MEDLINE | ID: mdl-18026598

ABSTRACT

OBJECTIVE: Describing the use of the Papanicolau (Pap) test and the main factors related to using screening amongst Colombian women aged 25 to 69 years. METHODS: Information was taken from the 2005 National Health and Demography Survey. The variable "pap test during the last three years" was calculated; coverage and related factors were described using simple percentages and multivariate analysis using conditional logistic regression. RESULTS: Recent Pap test coverage in Colombian women aged 25 to 69 years was 76.5 %. Factors associated with the absence of recent exam included non-affiliation to the health system, affiliation to the susbsidiary regimen, having no live-born children and no recent medical consultation. Factors associated with recent coverage were income level, being aged 35 to 44, a higher educational level and being pregnant. CONCLUSIONS: Results indicated the need for efforts at increasing coverage amongst the poorer population as well as amongst women from the subsidiary regimen and those having no affiliation. Persistence of high mortality in spite of acceptable coverage suggested the need for more efforts regarding definitive diagnosis and opportune treatment.


Subject(s)
Health Services/history , Vaginal Smears/economics , Colombia , Female , History, 21st Century , Humans , Surveys and Questionnaires , Uterine Cervical Neoplasms/parasitology , Uterine Cervical Neoplasms/prevention & control
20.
Gynecol Oncol ; 107(3): 590-1, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17963828

ABSTRACT

BACKGROUND: Vesicovaginal fistulae are well-recognized complications of radiotherapy for the treatment of cervical cancer. These patients often require some form of urinary diversion. Small bowel is often utilized for these purposes. CASE: A patient with stage IIB cervical cancer presented with a vesicovaginal fistula 6 years post-radiotherapy. An ileal conduit was performed. On day 9 post-surgery breakdown of the small bowel anastomosis was suspected. At laparotomy small bowel anastomotic breakdown was confirmed with round worms at the anastomotic site. CONCLUSION: Perforation of small bowel by round worm has been previously described in a patient with Meckel' s diverticulum. This report describes an unusual cause of small bowel anastomotic breakdown following urinary diversion.


Subject(s)
Anastomosis, Surgical , Ascariasis/complications , Ileum/parasitology , Postoperative Complications/parasitology , Urinary Diversion , Uterine Cervical Neoplasms/surgery , Vesicovaginal Fistula/surgery , Animals , Ascariasis/pathology , Ascaris lumbricoides/isolation & purification , Female , Humans , Ileum/surgery , Middle Aged , Uterine Cervical Neoplasms/parasitology , Uterine Cervical Neoplasms/radiotherapy , Vesicovaginal Fistula/parasitology
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