ABSTRACT
The oxidation of ß-NiAl at high temperatures leads to the preferential formation of metastable alumina, such as θ-Al2O3, which exhibits a significantly faster growth rate compared to stable α-Al2O3. However, our recent research has shown that through the use of the surface-dispersing nanoparticles (NPs) of metal oxides with a hexagonal closed pack (hcp), such as α-Al2O3, the thermal growth of α-Al2O3 can be facilitated. The present study employed laser additive manufacturing (LAM) to develop an integrated α-Al2O3 NPs surface-seeded two-phase intermetallic alloy comprising brittle ß-NiAl and tougher γ'-Ni3Al, which demonstrated better comprehensive mechanical properties. It was found that seeding the α-Al2O3 NPs promoted the early stage growth of α-Al2O3 on both ß and γ' phases during oxidation in air at 1000 °C. This led to a decrease in the oxidation rate but an enhancement in adhesion of the formed alumina scale in comparison to the naked ß/γ' two-phase alloy. The reasons for this result were interpreted.
ABSTRACT
BACKGROUND: The locally advanced cervical cancer (LACC) of FIGO stage IB3-IIA2 is characterized by large local mass, poor prognosis and survival rate. Tumor response to neoadjuvant chemotherapy for LACC, utilized as a surrogate endpoint, is urgently needed to improve. Given that the antitumor immune response can be suppressed by programed death-1 axis, the treatment paradigm of neoadjuvant chemotherapy combined with immunotherapy has been explored as one of the prognostic treatments in a variety of solid carcinoma. So far, the application of sintilimab, a domestic immune checkpoint inhibitor, combined with neoadjuvant chemotherapy is still limited in LACC, especially in large lesions. CASE DESCRIPTION: We present three postmenopausal women diagnosed with FIGO stage IB3-IIA2 cervical squamous cell carcinoma with lesions larger than 5 cm. Demographic, clinical, histopathological, laboratory and imaging data were record. At the completion of the neoadjuvant therapy with paclitaxel plus carboplatin combined with sintilimab, all patients underwent hysterectomy. After neoadjuvant treatment, a pathologic complete response in case 1 and partial responses in case 2 and case 3 were achieved, and neither patient showed any relapse during the follow-up period of 16 to 22 months. CONCLUSIONS: This report provide evidence to support the combination of sintilimab with neoadjuvant chemotherapy in cervical cancer, which has yet to be validated in prospective studies. More clinical data are needed to verify the effectiveness of the combined regimens. This literature review also collected studies involving potential predictors of response to NACT and immunotherapy, which would be helpful in stratifying patients for future trials.
Subject(s)
Carcinoma, Squamous Cell , Uterine Cervical Neoplasms , Humans , Female , Neoadjuvant Therapy/methods , Carcinoma, Squamous Cell/drug therapy , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/pathology , Prospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/pathology , Paclitaxel/therapeutic use , Carboplatin/therapeutic use , Neoplasm Staging , Chemotherapy, Adjuvant/methods , Hysterectomy/methodsABSTRACT
Trichomonas vaginalis (T. vaginalis) infection is one of the most common sexually transmitted infections worldwide and is associated with several complications. However, the paucity of research regarding the prevalence of T. vaginalis infection in the Tibetan area limits control efforts. We aimed to evaluate the prevalence of T. vaginalis infection in the Tibetan area by a comparison with the prevalence of T. vaginalis in Wuhan city and to unveil the potential risk factors in the Tibetan area. This descriptive, cross-sectional study was conducted among adult women attending gynecology outpatient clinics in two public hospitals (one in Shannan city of Tibet and one in Wuhan city) in China in 2020. Data were retrieved from the medical record system and laboratory information management system, including T. vaginalis infection, bacterial vaginosis, and vulvovaginal candidiasis by wet mount microscopy or nucleic acid hybridization of vaginal secretions from patients. The associations of variables associated with T. vaginalis prevalence were quantified by odds ratios with 95% confidence intervals. The overall prevalence rates of T. vaginalis infection in the Tibetan area and Wuhan city were 20.94% and 2.84%, respectively. The statistically significant factors for the higher prevalence of T. vaginalis infection in the Tibetan area included tertiary educational status (AOR: 0.36 [95% CI: 0.16-0.81]), yearly family income > ¥100,000 (AOR: 0.48 [95% CI: 0.26-0.91]), clinical symptoms (AOR: 4.58[95% CI: 2.32-9.04]), and III-IV grade vaginal cleanliness (AOR: 29.71 [95% CI: 3.95-223.56]) in the multivariate logistic analysis. Interventions targeting improved living standards as well as women's educational level and promoting reproductive hygiene habits are recommended to contribute to the reduction in T. vaginalis infection in the Tibetan area.
Subject(s)
Trichomonas Infections , Trichomonas Vaginitis , Trichomonas vaginalis , Adult , Humans , Female , Tibet/epidemiology , Prevalence , Cross-Sectional Studies , Trichomonas Infections/epidemiology , Risk Factors , Trichomonas Vaginitis/epidemiology , Trichomonas Vaginitis/diagnosisABSTRACT
BACKGROUND: To investigate the survival of cervical cancer patients undergoing laparoscopic radical hysterectomy (LRH) in a minimally invasive gynecology center. METHODS: A consecutive series of patients undergoing first LRH for cervical cancer from May 2008 to December 2017 at a national laparoscopic training center was retrospectively analyzed. The overall survival (OS) and progression-free survival (PFS) were compared between groups. RESULTS: In total, 1316 women with FIGO (2009) stage IA-IIB cervical cancer received LRH. Among them, 1114 (84.7%) were followed up for 3 months or longer; the median follow-up period was 48 months (range 3-144 months). In patients with stage IA, IB1 (≤ 2 cm), IB1 (> 2 cm), IB2, IIA1 and IIA2-IIB tumors, the 4-year PFS rates were 98.6, 94.5, 87.4, 65.6, 80.0 and 67.4%, respectively, and the 4-year OS rates were 98.6, 96.8, 91.1, 77.4, 85.6 and 76.2%, respectively. The 4-year PFS and OS were as high as 96.2 and 97.5%, respectively, in patients with squamous cell carcinoma of 2 cm or smaller in diameter. A stable high 4-year OS and PFS was achieved after completing 100 LRHs. In patients operated on by the same surgeon, an improvement in survival was observed after 40 LRHs. CONCLUSION: Favorable oncologic outcomes can be achieved in patients with IA-IB1 cervical cancer after LRH in a center with a high surgery volume.
Subject(s)
Laparoscopy , Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/pathology , Retrospective Studies , Neoplasm Staging , Hysterectomy , China , Disease-Free SurvivalABSTRACT
AIM: To share our experiences of resuming the treatments for gynecologic patients after lifting the lockdown in a hotspot area for the Coronavirus Disease 2019 (COVID-19) pandemic. METHODS: The triage process used to resume medical activities for gynecologic patients at the Wuhan Union Hospital after a 76-day lockdown of the city is described, and its effectiveness in preventing COVID-19 nosocomial transmission is shown. RESULTS: Nonemergency patients were pretriaged based on their contact history and body temperature at an outpatient clinic, and negative COVID-19 screening test results were required for admission to the buffering rooms at the gynecologic department. The buffering lasted at least 3 days for symptom monitoring, and a second round of COVID-19 testing was required before patients could be transferred to the regular gynecologic wards. For patients who needed emergency surgery, the first screening was completed at the isolation wards after surgery, followed by buffering at the gynecologic department. We received 19 298 outpatient visits, admitted 326 patients, and performed 223 operations in the first 2 months after the lockdown was lifted. No COVID-19 cases occurred in the hospitalized patients, while the proportion of potentially high-risk patients with cancer and severe anemia was increased in comparison to that observed during the same period in 2019 and the first 2 months of 2020 before the lockdown. CONCLUSIONS: We provide an effective triage system with buffering at two levels to guarantee safe and timely treatment for non-COVID-19 gynecologic patients in the postlockdown phase.
Subject(s)
COVID-19 , Triage , COVID-19 Testing , Communicable Disease Control , Female , Humans , Lifting , SARS-CoV-2ABSTRACT
The utility of placental growth factor (PlGF) and its receptor VEGFR-1 (Flt-1) as biomarkers for cervical cancer has not been clarified yet. To address this issue, we investigated the levels of soluble PlGF (sPlGF) and soluble Flt-1 (sFlt-1) in the serum from patients with early cervical cancer, cervical intraepithelial neoplasia (CIN) and controls in this study. sPlGF and sFlt-1 were detected in 44 preoperative patients with cervical cancer, 18 cases with CIN, and 20 controls by ELISA. It was found that both sPlGF and sFlt-1 were significantly increased in the cervical cancer group as compared with those in CIN and control groups. sPlGF presented a high diagnostic ability of cervical cancer, with a sensitivity of 61.36% and a specificity of 89.47%; and sFlt-1 with a sensitivity of 50.00% and a specificity of 92.11%. Importantly, the combined use of sPlGF and sFlt-1 could increase the diagnostic rate of cervical cancer, with a sensitivity of 70.45% and a specificity of 92.11%. These results indicated that both sPlGF and sFlt-1 in circulation can serve as possible valuable diagnostic biomarkers for cervical cancer, and the combined use of them can be more valuable to diagnose the patients with early cervical cancer.
Subject(s)
Early Detection of Cancer , Placenta Growth Factor/blood , Uterine Cervical Neoplasms/blood , Vascular Endothelial Growth Factor Receptor-1/blood , Adult , Aged , Biomarkers, Tumor/blood , Female , Humans , Membrane Proteins , Middle Aged , Neoplastic Cells, Circulating/pathology , Pregnancy , Uterine Cervical Neoplasms/pathology , Young AdultABSTRACT
From a large medical center in Wuhan, the epicenter of the 2019 novel coronavirus disease (COVID-19), we report clinical features and prognosis for three women diagnosed with COVID-19 after gynecologic oncology surgery and hospitalized in January 2020. The incidence of COVID-19 was 0.77% (3 of 389) of total hospitalizations and 1.59% (3 of 189) of patients undergoing surgeries in the ward. The infection of severe acute respiratory syndrome coronavirus 2 may be related to the older age, comorbidities, malignant tumor, and surgery in gynecologic hospitalizations. By February 20, 2020, only two of the three patients had met the clinical discharge criteria. Given the long and uncertain incubation period of COVID-19, screening for the virus infection should be carried out for all patients, both preoperatively and postoperatively. Postponement of scheduled gynecologic surgery for patients in the epidemic area should be considered.
Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Genital Neoplasms, Female/surgery , Gynecologic Surgical Procedures/adverse effects , Pneumonia, Viral/diagnosis , Postoperative Complications/diagnosis , Adult , COVID-19 , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Female , Hospitalization/statistics & numerical data , Humans , Incidence , Male , Mass Screening/standards , Medical Records/statistics & numerical data , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Postoperative Complications/epidemiology , Postoperative Complications/virology , Retrospective Studies , SARS-CoV-2ABSTRACT
Persistent activation of IGF1R/mTOR signaling pathway plays crucial role in the development of hepatocellular carcinoma (HCC). Therefore, our goal was to elucidate microRNAs (miRNAs) targeting IGF1R/mTOR and the therapeutic potential of single or dual miRNA on HCC development. In this study, we found that miR-497 and miR-99a that target the 3'-UTR of both IGF1R and mTOR were down-regulated in HCC human tissues and cell lines. Functional assay revealed that ectopic expression of miR-497 or miR-99a in HCC cells resulted in a significant inhibition on tumor growth and invasiveness in vitro and tumor development in vivo via repressing the expression of IGF1R and mTOR. Such inhibitory effect on tumor growth is reversed by application of IGF1 ((IGF1R ligand) or MHY1485 (mTOR agonist) in vitro. Furthermore, we found that simultaneous over-expression of both miR-497 and miR-99a exhibited much stronger inhibitory effects on tumor growth than their individual effect, which is still correlated with significantly stronger repression of IGF1R and mTOR. Overall, our results suggest that miR-497 and miR-99a both function as tumor-suppressive miRNAs by suppressing IGF1R/mTOR signaling pathway. The synergistic actions of these two miRNAs partly correlated with IGF1R and mTOR levels, which may represent new strategies for the molecular treatment of HCC.
Subject(s)
Carcinoma, Hepatocellular/genetics , Gene Expression Regulation, Neoplastic , Liver Neoplasms/genetics , MicroRNAs/genetics , Receptors, Somatomedin/genetics , TOR Serine-Threonine Kinases/genetics , 3' Untranslated Regions , Carcinoma, Hepatocellular/metabolism , Cell Cycle/genetics , Cell Line, Tumor , Cell Proliferation , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Humans , Liver Neoplasms/metabolism , RNA Interference , Receptor, IGF Type 1 , Receptors, Somatomedin/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolismABSTRACT
OBJECTIVES: Angiopoietins have been found to play essential roles in tumor angiogenesis. The present study was aimed at investigating the diagnostic and prognostic values of serum angiopoietin 1 and 2 (sAng-1 and sAng-2) in cervical cancer. METHODS: The sAng-1 and sAng-2 concentrations were analyzed in 77 women with cervical cancer, 44 women with cervical intraepithelial neoplasia (CIN) and 43 women without cervical lesions by enzyme-linked immunosorbent assay. The diagnostic values of sAng-1, sAng-2 and sAng-1/sAng-2 were evaluated by receiver operating characteristic (ROC) curves. The Ang-1 and Ang-2 expression in cervical cancer tissues as well as microvessel density (MVD), were assessed by immunohistochemistry. RESULTS: The concentration of sAng-2 gradually increased and the sAng-1/Ang-2 ratio was gradually decreased from normal control to CIN, then to squamous cell cancer, and the sAng-1/sAng-2 ratio was also significantly decreased in adenocarcinoma. The area under ROC curves of sAng-2 and sAng-1/sAng-2 ratio for discriminating cervical cancer from normal were 0.744 and 0.705, respectively. Decreased sAng-1/sAng-2 was significantly associated with advanced tumor stage, poor differentiation, lymph-vascular space invasion and high MVD. sAng-2 was positively correlated with the Ang-2 expression in cervix epithelia. A high sAng-1/sAng-2 ratio was associated with a longer progression-free survival and a longer overall survival in cervical cancer patients. CONCLUSIONS: These findings suggest that sAng-2 and the sAng-1/sAng-2 ratio may be valuable diagnostic and prognostic biomarkers for cervical cancer.
ABSTRACT
There is no consensus on the syntheses concerning the impact of BRCA mutation on ovarian cancer survival. A systematic review and meta-analysis of observational studies was conducted that evaluated the impact of BRCA mutations on the survival outcomes of patients with ovarian cancer. The primary outcome measure was overall survival (OS) and secondary outcome was progression-free survival (PFS). We presented data with hazard ratios (HRs) and 95% confidence interval (CI) and pooled them using the random-effects models. From 2,624 unique records, 34 eligible studies including 18,396 patients were identified. BRCA1/2 mutations demonstrated both OS and PFS benefits in patients with ovarian cancer (OS: HR = 0.67, 95% CI, 0.57 to 0.78, I2 = 76.5%, P <0.001; PFS: HR = 0.62, 95% CI, 0.53 to 0.73, I2 = 18.1%, P = 0.261). For BRCA1 mutation carriers, the HRs for OS and PFS benefits were 0.73 (95% CI, 0.63 to 0.86) and 0.68 (95% CI, 0.52 to 0.89), respectively. For BRCA2 mutation carriers, the HRs for OS and PFS benefits were 0.57 (95% CI, 0.45 to 0.73) and 0.48 (95% CI, 0.30 to 0.75), respectively. The results of subgroup analyses for OS stratified by study quality, tumor stage, study design, sample size, number of research center, duration of follow-up, baseline characteristics adjusted and tumor histology were mostly constant across BRCA1/2, BRCA1 and BRCA2 mutation subtypes. In summary, for patients with ovarian cancer, BRCA mutations were associated with improved OS and PFS. Further large-scale prospective cohort studies should be conducted to test its benefits in specific patients.
Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Ovarian Neoplasms/genetics , Ovarian Neoplasms/mortality , Disease-Free Survival , Female , Humans , Mutation , Neoplasm Staging , Ovarian Neoplasms/pathology , Prognosis , Survival Analysis , Tumor BurdenABSTRACT
AIMS: DOG1 has proven to be a useful marker of gastrointestinal stromal tumors (GISTs). Recently, DOG1 expression has also been reported in some non-GIST malignant tumors, but the details related to DOG1 expression in breast tissue remain unclear. The aim of this study was to detect the expression of DOG1 in the human breast and to evaluate the feasibility of using DOG1 to discriminate between invasive breast carcinoma and noninvasive breast lesions. METHODS AND RESULTS: A total of 210 cases, including both invasive and noninvasive breast lesions, were collected to assess DOG1 expression immunohistochemically. DOG1 expression was consistently positive in breast myoepithelial cells (MECs), which was similar to the results obtained for three other MEC markers: calponin, smooth muscle myosin heavy chain (SMMHC), and P63 (P > 0.05 in all). Importantly, DOG1 was useful in discriminating invasive breast carcinoma from noninvasive breast lesions (P < 0.05). CONCLUSIONS: DOG1 is a useful marker of breast MECs, and adding DOG1 to the MEC identification panel will provide more sophisticated information when diagnosing uncertain cases in the breast.
Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms/diagnosis , Carcinoma, Intraductal, Noninfiltrating/diagnosis , Chloride Channels/metabolism , Neoplasm Proteins/metabolism , Adult , Aged , Anoctamin-1 , Breast Neoplasms/metabolism , Carcinoma, Intraductal, Noninfiltrating/metabolism , Diagnosis, Differential , Epithelial Cells/metabolism , Female , Humans , Middle Aged , Neoplasm Invasiveness , Young AdultABSTRACT
Epithelial-mesenchymal transition (EMT) is a critical process in the promotion of epithelial tumor progression and metastasis. The present study aimed to investigate the role of Ras homolog gene family, member C (RhoC) guanosine triphosphatase (GTPase) in transforming growth factor (TGF)-ß1 induced EMT. EMT occurred in human cervical carcinoma SiHa cells following TGF-ß1 stimulation for 4 days, as demonstrated by the appearance of mesenchymal morphology, reorganization of the actin cytoskeleton, reduced E-cadherin expression and increased Vimentin expression, which was associated with increased RhoC expression and activity. However, EMT was not observed in cells that were pretreated with RhoC siRNA prior to TGF-ß1 stimulation. Downregulation of RhoC 4 days following TGF-ß1 stimulation was not able to reverse the existing EMT. In addition, TGF-ß1 promoted the invasion of the control SiHa cells but not that of the cells in which RhoC was downregulated. In conclusion, RhoC expression is activated by TGF-ß1, and sufficient RhoC expression levels are essential for TGF-ß1-induced EMT.
ABSTRACT
OBJECTIVE: To investigate soluble neuropilin-1 (sNRP-1) in circulating and NRP-1 protein in cervical tissues from patients with cervical cancer or cervical intraepithelial neoplasia (CIN). METHODS: sNRP-1 was measured in 64 preoperative patients and 20 controls. NRP-1 protein in cervical tissue was detected in 56 patients and 20 controls. RESULTS: Both sNRP-1 and NRP-1 proteins were correlated with stage. sNRP-1 presented a high diagnostic ability of cervical cancer and CIN, with a sensitivity of 70.97% and a specificity of 73.68%. CONCLUSIONS: sNRP-1 in circulating can serve as a possible valuable diagnostic biomarker for cervical cancer and CIN.
Subject(s)
Biomarkers, Tumor/blood , Neuropilin-1/blood , Uterine Cervical Dysplasia/blood , Uterine Cervical Neoplasms/blood , Adult , Aged , Case-Control Studies , Female , Humans , Middle Aged , Uterine Cervical Neoplasms/pathology , Uterine Cervical Dysplasia/pathologyABSTRACT
The most common way for cervical cancer to spread is through the lymphatic system. Tumor-associated lymphatic endothelial cell (TLEC) has been considered to play a crucial role in metastasis of certain cancers. The aim of this study was to isolate TLEC from human cervical cancers and explore its involvement in metastasis-associated behaviors in vitro. Lymphatic vessels in 62 cervix tissue specimens ranging from cervical intraepithelial neoplasia (CIN) to advanced invasive cancer were detected using immunochemical staining with D2-40 antibody. Relation of lymphatic vessel density (LVD) to clinicopathological characters was analyzed. Primary TLECs were isolated by LYVE-1 immuno-magnetic beads from cervical cancer tissues and verified through expression of LEC markers Prox-1 and D2-40, and then cultured in vitro. Invasiveness and viability of cells were assessed by transwell assay and typan blue exclusion, respectively. Our results showed that higher LVD was significantly associated with advanced FIGO stage, pelvic lymphatic nodal metastasis (LNM), and poorer cell differentiation. TLECs were successfully primarily isolated and cultured in vitro. Supernatant of TLEC enhanced invasiveness of Hela cell, but did not significantly affect cell viability. In conclusion, TLECs might actively promote lymphatic metastasis of cervical cancer. Further studies are needed to demonstrate the underlying mechanisms.
Subject(s)
Cervix Uteri/pathology , Endothelial Cells/pathology , Lymphatic Vessels/pathology , Uterine Cervical Dysplasia/pathology , Uterine Cervical Neoplasms/pathology , Adult , Aged , Antibodies, Monoclonal, Murine-Derived/immunology , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Cell Survival , Female , HeLa Cells , Homeodomain Proteins/biosynthesis , Humans , Lymphatic Metastasis , Middle Aged , Neoplasm Invasiveness , Tumor Suppressor Proteins/biosynthesis , Young AdultABSTRACT
Tumor-associated lymphatic endothelial cells (TLEC) could play a key role in the process of tumor metastasis. The aim of this study was to investigate the effect of TLECs that were isolated from human epithelial ovarian tumor (EOT) on ovarian cancer cell line CAOV-3 in vitro. First, TLECs in EOT were detected by immunochemistry and flow cytometry, then marked by lymphatic endothelial cell (LEC) marker LYVE-1, isolated by magnetic beads, and cultured in vitro. The cells were identified by immunostaining of LEC markers LYVE-1, Prox-1, Podoplanin, VEGFR-3, and pan-endothelial cell marker CD31. TLECs from EOT can be detected, cultured, and identified in vitro successfully. The effects of TLECs on invasion and migration of CAOV-3 cells were investigated by 12-well Boyden chamber; the proliferation effect was studied by counting the Trypan blue exclusion cell number. Furthermore, changes in MMP-2/9 secreted by CAOV-3 cells treated with TLEC were shown using real-time PCR and zymography, and TIMP-1/2 was detected by real-time PCR. In vitro, TLECs can enhance invasion and migration of CAOV-3 cells, but have no significant effect on proliferation. It was clear that the expression of MMP-9 increased and TIMP-2 decreased in CAOV-3 cells treated by TLECs, and the increasing of MMP-9 was confirmed by zymography. TLECs from EOT can enhance migration and invasion of human ovarian carcinoma cell line in vitro, and the possible mechanism was through activation of MMP-9/TIMP-2.
Subject(s)
Endothelial Cells/physiology , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/pathology , Adolescent , Adult , Cell Line, Tumor , Cell Movement , Cell Proliferation , Female , Humans , Middle Aged , Neoplasm Invasiveness , Neoplasm Metastasis , Tissue Inhibitor of Metalloproteinase-2/genetics , Vesicular Transport Proteins/analysisABSTRACT
Most vascular endothelial growth factors (VEGF) have been shown to be associated with lymphangiogenesis and angiogenesis in various cancers. However, whether placental growth factor (PlGF), a rarely mentioned VEGF member, is involved in the pathogenesis of uterine cervical lesions remains unclear. To address this issue, we examined the relationship between PlGF expression and clinicopathologic variables in patients with pre-invasive and invasive lesions of uterine cervix. Sixty-two cervical specimens were immunostained with PlGF polyclonal antibody to define PlGF expression, and monoclonal antibodies D2-40 and CD34 to evaluate the lymphatic vessel density (LVD) and blood vessel density (BVD) of the lesions. PlGF mRNA level was detected by RT-PCR in all lesions from fresh tissues. We found that the levels of PlGF protein and mRNA expression were related to clinical stages (p < 0.05), but not to other clinicopathologic variables. No significant difference in PlGF expression was observed between squamous carcinoma and adenocarcinoma. Increased LVD and BVD were all associated with advanced stages (p < 0.001). Although LVD was strongly correlated with BVD, only high LVD was associated with pelvic lymphatic metastasis. Moreover, the level of PlGF expression was associated with both BVD(r = 0.715, p < 0.001) and LVD(r = 0.321, p < 0.05). Together, our study suggests that PlGF may participate in both tumor-associated angiogenesis and lymphangiogenesis of cervical carcinogenesis.
Subject(s)
Adenocarcinoma/immunology , Carcinoma, Squamous Cell/immunology , Gene Expression Regulation, Neoplastic/immunology , Lymphangiogenesis/immunology , Neovascularization, Pathologic/immunology , Pregnancy Proteins/immunology , Uterine Cervical Neoplasms/immunology , Adenocarcinoma/genetics , Adult , Aged , Carcinoma, Squamous Cell/genetics , Female , Humans , Immunohistochemistry , Middle Aged , Neovascularization, Pathologic/genetics , Placenta Growth Factor , Pregnancy Proteins/genetics , RNA, Neoplasm/chemistry , RNA, Neoplasm/genetics , Reverse Transcriptase Polymerase Chain Reaction , Uterine Cervical Neoplasms/geneticsABSTRACT
BACKGROUND: Tumor cells need large energy and nucleic acids to proliferate and grow. For most of their energy needs, cancer cells depend more on glycolysis. For most of their nucleic acids needs, cancer cells depend more on the nonoxidative pathway of the pentose phosphate pathway. Transketolase(TKT) is a crucial enzyme in the nonoxidative pathway of the PPP. METHODS: The real-time quantity PCR was used to determine the expression of transketolase gene family in uterine cervix cancer. Transketolase activity of cell was determined by using enzyme-linked method. Cell proliferation was detected by using MTT. RESULTS: The TKTL1 mRNA was specifically over-expressed in uterine cervix cancer cells(HeLa cell line) compare with normal human endocervical epithelial cells(End1/E6E7 cell line)(P < 0.05), whereas the expression of TKT and transketolase-like gene 2(TKTL2) have no significant differences between the two cell lines(P > 0.05). Moreover, we found that total transketolase activity was significantly reduced, and cell proliferation was remarkably inhibited after anti-TKTL1 siRNA treatment in HeLa cells. The total transketolase activity and cell proliferation have no significant differences after anti-TKTL1 siRNA treatment in End1/E6E7 cells. CONCLUSION: These results indicate that TKTL1 plays an important role in total transketolase activity and cells proliferation in uterine cervix cancer.
Subject(s)
Gene Expression Regulation, Enzymologic/genetics , Transketolase/metabolism , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation , Cervix Uteri/enzymology , Epithelial Cells/enzymology , Female , Health , Humans , RNA, Small Interfering/genetics , Transketolase/genetics , Uterine Cervical Neoplasms/geneticsABSTRACT
OBJECTIVE: To assess roles of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) in the mechanisms of lymphangiogenesis in epithelial ovarian carcinoma. METHODS: (1) Expression of Prox1, a newly described lymphatic endothelial cell nucleus marker, VEGF-A, VEGF-C, VEGF-D and PDGF-A, PDGF-B, PDGF-C, PDGF-D were detected by RT-PCR in SKOV3 cell line and in 90 ovarian tissue samples, included 15 benign tumors, 10 borderline tumors, 45 malignant tumors and 20 normal ovarian samples. (2) Expression levels of Prox1, VEGF-A, -C, -D and PDGF-A, -B, -C, -D were detected in 90 ovarian tissue sample mentioned above by real-time quantitative PCR (RTQ-PCR). RESULTS: (1) Prox1 was expressed in ovarian samples mentioned above, while not detected in SKOV3 cell. VEGF-A, -C, -D and PDGF-A, -B, -C, -D were found in SKOV3 cell and various ovarian tissues. (2) Expression levels of Prox1 (2.2 +/- 1.3, P < 0.01), VEGF-A (3.5 +/- 1.5, P < 0.01), VEGF-C (19 +/- 14, P < 0.01), VEGF-D (3.0 +/- 1.8, P < 0.01) and PDGF-A (3.3 +/- 3.3, P < 0.05), PDGF-C (6.9 +/- 4.6, P < 0.01) in malignant group were found to be significantly higher than those in borderline group and benign group. (3) The expression levels of Prox1, VEGF-A and PDGF-A were significantly greater in samples from the patients with lymph node metastasis (Prox1: 3.0 +/- 1.4, VEGF-A: 4.1 +/- 1.7, PDGF-A: 4.9 +/- 4.1), peritoneum metastasis (Prox1: 2.8 +/- 0.9, VEGF-A: 4.0 +/- 1.8, PDGF-A: 4.5 +/- 4.0) and in stage III - IV (Prox1: 2.6 +/- 1.3, VEGF-A: 4.0 +/- 1.4, PDGF-A: 4.1 +/- 3.7) than those without lymph node metastasis, without peritoneum metastasis and in stage I - II. There was a significant increased in the degree of VEGF-C and VEGF-D expression in positive lymph node metastasis group (VEGF-C: 24 +/- 13, VEGF-D: 3.9 +/- 2.0) compared with negative group (P < 0.05). (4) There were significant positive correlations between the expression levels of Prox1 and VEGF-D (r = 0.62, P < 0.01), PDGF-C (r = 0.91, P < 0.01) or PDGF-D (r = 0.61, P < 0.01). CONCLUSIONS: VEGF-A, VEGF-C and PDGF-A may promote lymphatic metastasis in epithelial ovarian carcinoma through else mechanisms other than lymphangiogenesis. VEGF-D may facilitate lymphangiogenesis and lymph node metastasis in epithelial ovarian cancer. There is no significant correlation between the expression of PDGF-B and lymphangiogenesis and lymph node metastasis. PCGF-C and PDGF-D may motivate lymphangiogenesis, but could not participate in lymph node metastasis in ovarian carcinoma.