Metastasis Of Cervical Carcinoma Research Articles

High M2-TAM Infiltration and STAT3/NF-κB Signaling Pathway as a Predictive Factor for Tumor Progression and Death in Cervical Cancer

Introduction: The tumor microenvironment (TME) plays a crucial role in the progression, invasion, and metastasis of cervical carcinoma (CC). Tumor-associated macrophages (TAMs) are significant components of the CC TME, but studies on their correlation with CC progression are still controversial. This study aimed to investigate the relationship between TAM infiltration, the STAT3/NF-κB signaling pathway, and Overall Survival (OS) in CC patients. Methods: In a retrospective study, 691 CC patients who had received a definitive histopathologic diagnosis of CC scored by the FIGO staging system and not undergone preoperative treatment were selected from a database. The effect of TAM infiltration on tumor progression biomarkers using Tissue Microarray (TMA) and immunohistochemistry was evaluated. Furthermore, the impact of the expression of these biomarkers and clinical–pathological parameters on recurrence-free (RF) and OS using Kaplan–Meier and multivariable Cox regression methods was also analyzed. Results: High stromal CD163 + 204 + TAMs density and via STAT3 and NF-κB pathways was relevant to the expression of E-cadherin, Vimentin, MMP9, VEGFα, Bcl-2, Ki-67, CD25, MIF, FOXP3, and IL-17 (all p < 0.0001). In addition, elevated TNM staging IV had a strong association correlation with STAT3 and NF-κB pathways (p < 0.0001), CD25 (p < 0.001), VEGFα (p < 0.001), MIF (p < 0.0001), and Ki-67 (p < 0.0001). On the other hand, overall and recurrence survival was shown to be strongly influenced by the expression of SNAIL (HR = 1.52), E-cadherin (HR = 1.78), and Ki-67 (HR = 1.44). Conclusion: M2-TAM and via STAT3/NF-κB pathways had a strong effect on CC tumor progression which reverberated in the severity of clinicopathological findings, becoming an important factor of poor prognosis.

Step-by-step guided photo-chemotherapy nanoplatforms for efficiently suppressing cervical carcinoma metastasis by hijacking intracellular metabolism

Intracellular energy metabolism, particularly in the mitochondria, can effectively modulate the epithelial to mesenchymal transition (EMT) to promote cervical carcinoma metastasis, which contributes to a much worse prognosis in the clinic. Notably, mitochondria are more vulnerable to hyperthermia and oxidative damage, thereby mitochondria-targeting photothermal therapy (PTT) and photodynamic therapy (PDT) appear to be promising strategies against EMT. Herein, we developed step-by-step guided photo-chemotherapy nanoplatforms (CS@ATO/CHC/T780 NPs) to reprogram intracellular metabolism for efficiently suppressing cervical carcinoma metastasis. Mechanistically, chondroitin sulfate (CS) and triphenylphosphine (TPP)-tailored phototherapeutic agent IR780 (T780) achieved step-by-step delivery to cancer cells and mitochondria, respectively. Subsequently, the atovaquone (ATO) disturbed mitochondrial electron transport chain complex III to efficiently induce mitochondrial dysfunction, which reversed the thermo-resistance associated with PTT by the down-regulation of ATP-dependent heat shock protein 70 (HSP 70) expression. Simultaneously, α-cyano-4-hydroxycinnamate (CHC) efficiently reduced the internalization of lactate (LA) to conserve oxygen consumption for enhancing PDT efficacy. Furthermore, the decrease in intracellular LA also inhibited the process of EMT. As expected, the enhanced phototherapy significantly induced mitochondrial impairment to suppress the proliferation and metastasis of cervical cancer in vitro and in vivo, offering a promising strategy for the treatment of cervical cancer by hijacking intracellular metabolism.

Abstract 14138: A Rare Encounter With Unusual Metastasis: Metastatic Right Ventricular Tumor Secondary to Cervical Cancer

Background: Metastasis of cervical carcinoma to the heart is a rare and uncommon phenomenon. Cervical cancer most commonly metastasizes to the lungs, liver, bones, and lymph nodes in four ways: 1) hematogenous spread, 2) lymphatic spread, 3) transvenous extension, and 4) direct extension. We present a case of a patient with cardiac metastasis from cervical cancer who initially suffered nonspecific symptoms thought to be secondary to a pulmonary embolism. Case presentation: A 41-year-old African American woman with a history of stage IIIB squamous cell carcinoma (SCC) of the cervix was being evaluated in the hospital for exertional dyspnea and chest pain. She was tachycardic and lung auscultation revealed decreased breath sounds bilaterally. Laboratory results were unremarkable. Initially, there was concern for pulmonary embolism (PE), computed tomography angiography with contrast demonstrated no evidence of PE but a hypoenhancing defect within the right ventricle (RV) with multiple diffuse bilateral pulmonary nodules. Echocardiography revealed RV mass vs thrombus. A cardiac MRI revealed a large infiltrative irregular mass. These findings favored evidence of a tumor rather than a thrombus. Imaging findings are illustrated in Figure 1. The patient subsequently underwent a biopsy of the right lower lobe lung nodule. The biopsy revealed metastatic SCC positive for p16, p40, and PD-L1. The patient was being treated but the prognosis was poor. Conclusion: Metastasis from cardiac tumors with primary cervical cancer is uncommon with a poor prognosis and average life expectancy of less than 6 months when diagnosed. Only 4% of cases of cardiac metastasis from cervical cancer are diagnosed as antemortem. A multimodality approach with prompt diagnosis is necessary for improving prognosis.

Virtual Screening, Molecular Docking, and Dynamic Simulations Revealed TGF-β1 Potential Inhibitors to Curtail Cervical Cancer Progression.

Cervical cancer is one of the main causes of cancer death in women globally, and its epidemiology is similar to that of a low-infectious venereal illness. Many sexual partners and early age at first intercourse have been demonstrated to have a significant influence on risk. TGF-β1 is a multifunctional cytokine that is required for cervical carcinoma metastasis, tumor development, progression, and invasion. The TGF-β1 signaling system plays a paradoxical function in cancer formation, suppressing early-stage tumor growth while increasing tumor progression and metastasis. Importantly, TGF-β1 and TGF-β receptor 1 (TGF-βR1), two components of the TGF-β signaling system, are substantially expressed in a range of cancers, including breast cancer, colon cancer, gastric cancer, and hepatocellular carcinoma. The current study aims to investigate possible inhibitors targeting TGF-β1 using molecular docking and dynamic simulations. To target TGF-β1, we used anti-cancer drugs and small molecules. MVD was utilized for virtual screening, and the highest scoring compound was then subjected to MD simulations using Schrodinger software package v2017-1 (Maestro v11.1) to identify the most favorable lead interactions against TGF-β1. The Nilotinib compound has shown the least XP Gscore of -2.581kcal/mol, 30ns MD simulations revealing that the Nilotinib- TGF-β1 complex possesses the lowest energy of -77784.917kcal/mol. Multiple parameters, including Root Mean Square Deviation, Root Mean Square Fluctuation, and Intermolecular Interactions, were used to analyze the simulation trajectory. Based on the results; we conclude that the ligand nilotinib appears to be a promising prospective TGF-β1inhibitor for reducing TGF-β1 expression ad halting cervical cancer progression.

Matrix metalloproteinase-induced cervical extracellular matrix remodelling in pregnancy and cervical cancer.

Graphical abstract The phenomenal extracellular matrix (ECM) remodelling of the cervix that precedes the myometrial contraction of labour at term or preterm appears to share some common mechanisms with the occurrence, growth, invasion and metastasis of cervical carcinoma. Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are pivotal to the complex extracellular tissue modulation that includes degradation, remodelling and exchange of ECM components, which contribute to homeostasis under normal physiological conditions such as cervical remodelling during pregnancy and puerperium. However, in cancer such as that of the uterine cervix, this extensive network of extracellular tissue modulation is altered leading to disrupted cell–cell and cell–basement membrane adhesion, abnormal tissue growth, neovascularization and metastasis that disrupt homeostasis. Cervical ECM remodelling during pregnancy and puerperium could be a physiological albeit benign neoplasm. In this review, we examined the pathophysiologic differences and similarities in the role of MMPs in cervical remodelling and cervical carcinoma.Lay summaryDuring pregnancy and childbirth, the cervix, which is the barrel-shaped lower portion of the womb that connects to the vagina, gradually softens, shortens and opens to allow birth of the baby. This process requires structural and biochemical changes in the cervix that are stimulated by enzymes known as matrix metalloproteinases. Interestingly, these enzymes also affect the structural and biochemical framework of the cervix during cervical cancer, although cervical cancers usually occur after infection by human papillomavirus. This review is intended to identify and explain the similarities and differences between the structural and chemical changes in the cervix during pregnancy and childbirth and the changes seen in cervical cancer.

Radiological evaluation of metastatic lymph nodes in carcinoma cervix with emphasis on their infiltrative pattern

Background & objectives:Imaging has been added to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging system of cervical carcinoma. This study was performed to assess the impact of imaging in staging and to ascertain the prevalence and pattern of nodal metastasis on contrast-enhanced computed tomography (CECT) in patients with cervical carcinoma who were treated based on FIGO 2009 staging system.Methods:This retrospective study was conducted to evaluate all patients with biopsy-proven cervical carcinoma who underwent CECT of abdomen at a tertiary cancer centre in north India from April 2017 to April 2019 and for whom either baseline or follow up scans were available. In patients with enlarged or necrotic lymph nodes, the location, size and pattern of infiltration of adjacent organs were recorded.Results:A total of 602 patients of cervical carcinoma had undergone CT during the study period, of whom 138 (22.9%) underwent CT at baseline and 464 (77.1%) patients during follow up. The FIGO (2009) stage distribution at the time of presentation was stage IB: 109 (18.1%); stage IIA: 14 (2.3%), stage IIB: 118 (19.6%), stage IIIA: 12 (2%), stage IIIB: 277 (46%), stage IVA: 20 (3.3%) and stage IVB: 52 (8.6%). Ninety of the 138 (65.22%) patients underwent a stage shift according to the FIGO 2018 because of the presence of enlarged lymph nodes at baseline scan. Sixteen (2.7%) patients had infiltrative nodal masses most commonly involving the blood vessels (n=14) followed by ureter (n=8), bones (n=5), muscle and bowel (n=3, each). The majority (14/16) of these patients presented with vague abdominal pain, discomfort and vomiting, while two had bone pain.Interpretation & conclusions:CECT at baseline helps in accurately assessing the stage in cervical carcinoma. It helps in the identification of lymph node metastasis in cervical carcinoma, which is crucial for guiding accurate management.

The correlation between tumor-associated macrophage infiltration and progression in cervical carcinoma.

Tumor microenvironment (TME) plays a particularly important role in the progression, invasion and metastasis of cervical carcinoma (CC). Tumor-associated macrophages (TAMs) are significant components of the tumor microenvironment in CC. However, the results of studies on the correlation between TAMs and progression in CC are still controversial. This research aimed to investigate the relationship between TAMs infiltration and progression in CC. A total of 100 patients with CC were included in the study. The correlation between TAMs and clinicopathologic features was studied. Besides, a systematic literature search was conducted from legitimate electronic databases to specifically evaluate the role of TAMs in TME of cervical carcinoma. In the meta-analysis, high stromal CD68+ TAMs density was relevant to lymph node metastasis (WMD = 11.89, 95% CI: 5.30–18.47). At the same time, CD163+ M2 TAM density was associated with lymph node metastasis (OR = 2.42, 95% CI: 1.09–5.37; WMD = 39.37, 95% CI: 28.25–50.49) and FIGO stage (WMD = -33.60, 95% CI: -45.04 to -22.16). This was further confirmed in the experimental study of 100 tissues of cervical cancer. It supported a critical role of TAMs as a prospective predictor of cervical cancer. In conclusion, CD68+ TAM and CD163+ M2 TAM infiltration in CC were associated with tumor progression. And CD163+ M2 TAM infiltration was associated with more advanced FIGO stage and lymph node metastasis in CC.

Uterine Cervical Carcinoma: Evaluation Using Non-Gaussian Diffusion Kurtosis Imaging and Its Correlation With Histopathological Findings.

The aim of the study was to assess non-Gaussian diffusion kurtosis imaging (DKI)'s usefulness as a noninvasive method to evaluate tumor invasion depth, histological grade, and lymph node metastasis in cervical carcinoma (CC) patients. Twenty-two consecutive patients with histologically confirmed CC were examined by 1.5-T MRI and non-Gaussian DKI with 4 b values of 0, 500, 1000, and 2000 s/mm2. Kurtosis (K), diffusivity (D), and apparent diffusion coefficient (ADC) maps were compared with histopathological findings. Kurtosis maps revealed the fibrous stroma as a distinct high K zone (1.442 ± 0.373) that was significantly different from values of the cervical mucosa, outer stroma, and parametrium (0.648 ± 0.083, 0.715 ± 0.113, and 0.504 ± 0.060, respectively, P < 0.0001). Kurtosis (1.189 ± 0.228) and D (0.961 ± 0.198 × 10-3 mm2/s) values of all CCs were significantly different from those of all uterine cervical wall layers. Kurtosis and D values were significantly correlated with histological grades of CCs (r = 0.934, P < 0.0001, and r = -0.925, P < 0.0001, respectively), whereas no significant differences were found in ADC values between grades 2 and 3 CCs (P = 0.787). Metastatic and nonmetastatic lymph nodes showed significantly different K (P < 0.0001) and D (P < 0.0001) values; however, their ADC values did not show significant differences (P = 0.437). For differentiating grade 3 CCs from grade 1 or 2 CCs, the areas under the curve for K (0.991, P = 0.0375) and D (0.982, P = 0.0337) values were significantly higher than those for ADC values (0.759). For differentiating metastatic and nonmetastatic lymph nodes, the areas under the curve for K (0.974, P = 0.0028) and D (0.968, P = 0.0018) values were significantly higher than those for ADC (0.596). Non-Gaussian DKI may be clinically useful for noninvasive evaluation of tumor invasion depth, histological grade, and lymph node metastasis in CC patients.

MicroRNA-455-5p exerts inhibitory effect in cervical carcinoma through targeting S1PR1 and blocking mTOR pathway.

MicroRNAs (miRNAs) have been increasingly exploited in human malignancies. The regulation of microRNA-455-5p (miR-455-5p) has been shown in several cancers, except for cervical carcinoma. Therefore, the role of miR-455-5p was exploited in cervical carcinoma. The qRT-PCR experiment was used to assess miR-455-5p and S1PR1 expression levels. We explored the function of miR-455-5p through MTT and Transwell assays. The mTOR pathway and cell apoptosis were detected by Western blot assays. The relationship between miR-455-5p and S1PR1 was testified by dual-luciferase reporter assay. MiR-455-5p expression was decreased in cervical carcinoma, which was related to poor clinical outcome in cervical carcinoma patients. MiR-455-5p inhibited cell viability and metastasis in cervical carcinoma. Further, S1PR1 is a direct target of miR-455-5p. S1PR1 recovered the inhibition of cell viability and metastasis induced by miR-455-5p in cervical carcinoma. In addition, miR-455-5p induced cell apoptosis and inactivated the mTOR pathway in cervical carcinoma. MiR-455-5p exerts inhibitory effect in cervical carcinoma through targeting S1PR1 and blocking the mTOR pathway.

Prognostic value of lymphovascular space invasion in patients with early stage cervical cancer in Jilin, China: A retrospective study.

The metastasis of cervical carcinoma is associated with the lymphovascular spread. The primary objective of the present study was to determine the prognostic value of lymphovascular space invasion (LVSI) in patients with early-stage cervical cancer in Jilin, China.In this retrospective cohort study, patients with early-stage cervical cancer (stage IB-IIA) at the Second Hospital of Jilin University from February 2014 to December 2016 were included in the analysis. All included participants underwent radical hysterectomy with pelvic lymphadenectomy. LVSI was identified by hematoxylin and eosin (H&E) staining. The primary outcomes are overall survival (OS) and progression-free survival (PFS). Kaplan-Meier curves were used to calculate the patient's survival. Survival was compared using the log-rank test, while risk factors for the prognosis were assessed by Cox regression analysis.The incidence of LVSI was positively associated with the depth of stromal invasion (P = .009) and lymph node metastasis (LNM, P < .001). LVSI is an independent factor that affects OS (P = .009) and PFS (P = .006) in patients with early stage cervical cancer. LNM status is an independent factor that affects postoperative OS (P = .005).The incidence of lymphatic vessel infiltration is positively associated with the depth of stromal invasion and LNM. LVSI is an independent risk factor for the prognosis of early cervical cancer. The results suggest that further large-scale studies are needed to improve the treatment for patients with LVSI.

A case of cutaneous metastatic adenosquamous carcinoma of the cervix

Introduction:Cutaneous metastasis of cervical carcinoma is very rare, with a reported incidence of .1 to 2%. The adenosquamous carcinoma subtype has been reported the least.3-5 We present a case report of ulceronodular cutaneous metastasis of adenosquamous carcinoma of the cervix.Case Description:A 50-year-old African American female with an eleven-year history of metastatic adenosquamous carcinoma of the cervix presented to the emergency department with an asymptomatic rash in her groin for one-month duration. On physical exam, there were hyperpigmented to violaceous papulonodules across the mons pubis and three ulcerated plaques of the left mons pubis. Punch biopsy was consistent with metastases of cervical adenosquamous carcinoma. No disease specific interventions were taken, and the patient passed away five weeks later.Discussion:Cervical cancer rarely metastasizes to the skin, with a reported incidence of .1 to 2%. Among the subtypes, cutaneous metastasis of cervical adenosquamous carcinoma has been reported the least. In a review of 1185 cases of cervical cancer, Imachi et al found that only 15 cases spread cutaneously, none of which were adenosquamous carcinoma.5 Cutaneous metastases of cervical carcinoma predict a poor prognosis, with an average length of survival of three months.6Our patient developed cutaneous metastases eleven years after diagnosis, which is to our knowledge the longest reported interval from initial diagnosis to development of cutaneous metastases. Although rare, it is important to recognize cutaneous metastases of adenosquamous carcinoma of the cervix as it predicts a poor prognosis and treatment has not been shown to improve outcomes.

Bone involvement in patients with cervical carcinoma: a single-institution cohort study

CITATION: Butt, J. L. & Botha, M. H. 2019. Bone involvement in patients with cervical carcinoma: a single-institution cohort study. Southern African Journal of Gynaecological Oncology, 11(2): 31-37. doi:10.1080/20742835.2019.1702299

MiR-199a-5p promotes proliferation and metastasis and epithelial-mesenchymal transition through targeting PIAS3 in cervical carcinoma.

Cervical carcinoma is the second most frequent gynecological malignancies in females worldwide. The objective of this study was to investigate the role of miR-199a-5p and protein inhibitor of activated signal transducer and activators of transcription 3 (PIAS3) in cervical carcinoma. Quantitative reverse transcription polymerase chain reaction was utilized to detect miR-199a-5p and PIAS3 expression in cervical carcinoma tissues and cells. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide Kit, transwell assay were used to explore the biological functions of miR-199a-5p in cervical carcinoma. Western blot analysis was applied to determine the expression level of epithelial-mesenchymal transition (EMT)-associated proteins and PIAS3 expression. The relationship between miR-199a-5p and PIAS3 was verified by luciferase activity reporter assay. We found that miR-199a-5p was upregulated in cervical carcinoma tissues and cell lines, and overexpression of miR-199a-5p promoted cell proliferation and metastasis in cervical carcinoma. In addition, Western blot analysis indicated that the enforced upregulation of miR-199a-5p enhanced mesenchymal markers vimentin and N-cadherin expressions, whereas reduced epithelial marker E-cadherin expressions. miR-199a-5p directly targeted PIAS3 and negatively regulated PIAS3 level in cervical carcinoma cells. And upregulation of PIAS3 reversed the effects of miR-199a-5p in cervical carcinoma. Collectively, our data provide evidence for miR-199a-5p function in cervical carcinoma growth, EMT, and metastasis; it may be act as a therapeutic strategy target for patients with cervical carcinoma.

CTHRC1 overexpression promotes cervical carcinoma progression by activating the Wnt/PCP signaling pathway.

The tumorigenesis and metastasis of tumors are associated with human collagen triple helix repeats containing 1 (CTHRC1). To study the effects and possible impacting mechanisms of CTHRC1 on human cervical carcinoma development, samples of paraffin-embedded cervical carcinoma and HeLa cells were examined. Immunofluorescence, cell wound scratch assay, western blot analysis and Transwell invasion assay were used to evaluate HeLa cells in response to silencing of the CTHRC1 gene in cervical carcinoma. The expression levels of gap-associated proteins of the Wnt/PCP pathway in paraffin-embedded cervical carcinoma samples were also evaluated by immunohistochemical staining. CTHRC1 promoted the migration and invasion of HeLa cells in vitro, downregulated Ror2 and p-c-Jun and activated the Wnt/PCP pathway. Furthermore, the expression of p-c-Jun, Ror2 and Wnt5a was increased after overexpression of CTHRC1 as revealed in HeLa cells compared to control group. The present experiments revealed that CTHRC1 promoted HeLa cell progression by activating the Wnt/PCP signaling pathway and may play a key role in the invasion and metastasis of cervical carcinoma.

Iliopsoas Muscle Metastasis from Cervical Carcinoma

Introduction: Isolated metastasis of cervical carcinoma to iliopsoas region might be infrequent and its occurrence is a diagnostic challenge. The aim of this study was to report a case of iliopsoas muscle metastasis from cervical carcinoma. Case Presentation: A 52-year-old multiparous females complaining about post menopause bleeding was referred to the researcher’s oncology department. Gynecological examination revealed cervical mass with involved parameters and biopsy confirming squamous cell carcinoma. In addition, the patient had a large cystic mass on the lateral side of pelvic area and abdomen. Investigations detected solid ovarian mass associated with a rise of tumor marker CA-125 and CEA levels. Magnetic resonance imaging (MRI) and CT scan reports suggested possible hematoma in iliopsoas muscle. Imaging-guided biopsy detected metastatic squamous cell carcinoma in iliopsoas muscle mass. Based on diagnosis of advance stage cervical cancer, the patient received chemotherapy following adjuvant radiation therapy. Conclusions: Metastasis of squamous cell carcinoma of the cervix to iliopsoas muscle is considered as a rare event. It is recommended to keep this unusual manifestation in mind.

RASSF1A promoter methylation was associated with the development, progression and metastasis of cervical carcinoma: a meta-analysis with trial sequential analysis.

RASSF1A promoter methylation has been reported in cervical cancer. However, clinical effect of RASSF1A promoter methylation in cervical cancer remains unclear. This meta-analysis was conducted to assess the correlation between RASSF1A promoter methylation and cervical cancer and the association of RASSF1A promoter methylation with clinicopathological features. Electronic databases were searched to identify eligible publications. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Trial sequential analysis (TSA) was performed to assess the required study population information. Twenty-six papers published from 2001 to 2017 were analyzed in the meta-analysis, including a total of 1820 patients with cervical cancer, 507 patients with cervical intraepithelial neoplasia (CIN) lesions and 894 nonmalignant controls. RASSF1A promoter methylation was significantly increased in cervical cancer than in CIN lesions and nonmalignant tissue samples. In addition, RASSF1A promoter methylation was correlated with cervical cancer among two studies of blood and cytology samples (cancer vs nonmalignant controls). No correlation was found between RASSF1A promoter methylation and age factor, human papillomavirus (HPV) subtypes or clinical stage. RASSF1A promoter methylation was associated with tumor grade (grade 3-4 vs 1-2: OR 2.31, 95% CI 1.12-4.77, P=0.023), lymph node metastasis (yes vs no: OR 2.97, 95% CI 1.60-5.52, P=0.001), tumor histology (squamous cell carcinoma vs adenocarcinoma: OR 0.49, 95% CI 0.22-1.08, P=0.076), and HPV infection (positive vs negative: OR 0.45, 95% CI 0.28-0.73, P=0.001). TSA showed that the cumulative Z-curve did not cross the trial sequential monitoring boundary for significant results. RASSF1A promoter methylation may be associated with cervical cancer development, progression and metastasis. Methylated RASSF1A may be a noninvasive blood or cytology biomarker. Based on TSA, more studies are essential in the future.

An Unusual Presentation of Cervical Carcinoma Metastasis as Mediastinal Adenopathy

An Unusual Presentation of Cervical Carcinoma Metastasis as Mediastinal Adenopathy

Prevalence of synchronous bilateral tonsil squamous cell carcinoma: A retrospective study.

The prevalence of synchronous bilateral tonsil cancer remains unexplored. To date, only 38 cases have been described in the literature. With an aim to substantiate the Danish recommendation of performing bilateral tonsillectomy in patients with suspected or proven tonsil cancer and in patients with cervical carcinoma metastasis from an unknown primary tumour, this study was undertaken to determine the prevalence of synchronous bilateral tonsil cancer. A retrospective review of all patients diagnosed with tonsil cancer in the period 2000-2015, Aarhus University Hospital, Denmark, was performed. Seven of 211 (3.3%) consecutive patients with tonsil cancer, who had undergone bilateral tonsillectomy (n = 180) or unilateral tonsillectomy (clinically normal side) combined with contralateral tonsil biopsy (side with suspected cancer) (n = 31), had synchronous bilateral tonsil cancer. Furthermore, dysplasia was found in the contralateral tonsil in two patients with unilateral tonsil cancer. Four of 171 (2.3%) patients with suspected unilateral tonsillar cancer had additional contralateral tonsil cancer. Three of 34 (8.8%) patients without clinical signs of tonsillar malignancy on any side (32 patients with carcinoma of unknown primary) had synchronous bilateral tonsil cancer. In none of the patients were bilateral tonsil cancer suspected. Patients with unilateral vs synchronous bilateral tonsil cancer had similar clinical and tumour characteristics. Knowledge on additional contralateral synchronous tonsil cancer is crucial for avoidance of early recurrence of oropharyngeal cancer in patients with tonsil cancer. Based on our findings, we recommend bilateral tonsillectomy in all patients with suspected or proven tonsil cancer and carcinoma of unknown primary.

The Bidirectional Regulation between MYL5 and HIF-1α Promotes Cervical Carcinoma Metastasis.

Myosin light chains (MLC) serve important regulatory functions in a wide range of cellular and physiological processes. Recent research found that MLC are also chromatin-associated nuclear proteins which regulate gene transcription. In this study, the MLC member myosin regulatory light chain 5 (MYL5) expression was upregulated in late stage cervical cancer patients, positively correlated with pelvic lymph node metastasis, and identified as a poor survival indicator. MYL5 overexpression promoted metastasis in cervical cancer in vitro and in vivo models, whereas MYL5 silencing had the converse effect. We demonstrated a bidirectional regulation between MYL5 and hypoxia inducible factor-1α (HIF-1α). HIF-1α activates MYL5 via binding to the hypoxia response element (HRE) in the promoter of MYL5, and MYL5 could sustain HIF-1α expression by tethering to recognition sequence AGCTCC in the HIF-1α promoter region. Clinical data confirmed a positive correlation between MYL5 and HIF-1α. In summary, our data show that MYL5 may act as a prognosis predictive factor in cervical carcinoma, and strategies that inhibit the interaction of MYL5 and HIF-1α may benefit the cervical carcinoma patients with metastasis.

Blocking Modification of Eukaryotic Initiation 5A2 Antagonizes Cervical Carcinoma via Inhibition of RhoA/ROCK Signal Transduction Pathway.

Cervical carcinoma is one of the leading causes of cancer-related death for female worldwide. Eukaryotic initiation factor 5A2 belongs to the eukaryotic initiation factor 5A family and is proposed to be a key factor involved in the development of diverse cancers. In the current study, a series of in vivo and in vitro investigations were performed to characterize the role of eukaryotic initiation factor 5A2 in oncogenesis and metastasis of cervical carcinoma. The expression status of eukaryotic initiation factor 5A2 in 15 cervical carcinoma patients was quantified. Then, the effect of eukaryotic initiation factor 5A2 knockdown on in vivo tumorigenicity ability, cell proliferation, cell cycle distribution, and cell mobility of HeLa cells was measured. To uncover the mechanism driving the function of eukaryotic initiation factor 5A2 in cervical carcinoma, expression of members within RhoA/ROCK pathway was detected, and the results were further verified with an RhoA overexpression modification. The level of eukaryotic initiation factor 5A2 in cervical carcinoma samples was significantly higher than that in paired paratumor tissues ( P < .05). And the in vivo tumorigenic ability of HeLa cells was reduced by inhibition of eukaryotic initiation factor 5A2. Knockdown of eukaryotic initiation factor 5A2 in HeLa cells decreased the cell viability compared with normal cells and induced G1 phase cell cycle arrest ( P < .05). Moreover, the cell migration ability of eukaryotic initiation factor 5A2 knockdown cells was dramatically inhibited. Associated with alterations in phenotypes, RhoA, ROCK I, and ROCK II were downregulated. The above-mentioned changes in eukaryotic initiation factor 5A2 knockdown cells were alleviated by the overexpression of RhoA. The major findings outlined in the current study confirmed the potential of eukaryotic initiation factor 5A2 as a promising prognosis predictor and therapeutic target for cervical carcinoma treatment. Also, our data inferred that eukaryotic initiation factor 5A2 might function in carcinogenesis of cervical carcinoma through an RhoA/ROCK-dependent manner.