Effects Of Cervical Cancer Research Articles

SMYD2 suppresses p53 activity to promote glucose metabolism in cervical cancer

Reprogrammed energy metabolism, especially the Warburg effect, is emerged as a hallmark of cancer. The protein lysine methyltransferase SMYD2 functions as an oncogene and is implicated in various malignant phenotypes of human cancers. However, the role of SMYD2 in tumor metabolism is still largely unknown. Here, we report that SMYD2 is highly expressed in human cervical cancer and its aberrant expression is linked to a poor prognosis. Bioinformatic analysis revealed a novel link between SMYD2 expression and aerobic glycolysis. Through loss-of-function experiments, we demonstrated that SMYD2 knockdown or inhibition induced a metabolic shift from aerobic glycolysis to oxidative phosphorylation, as evidenced by glucose uptake, lactate production, extracellular acidification, and the oxygen consumption rate. In contrast, SMYD2 overexpression promoted glycolytic metabolism in cervical cancer cells. Moreover, SMYD2 was required for tumor growth in cervical cancer and this oncogenic activity was largely glycolysis-dependent. Mechanistically, SMYD2 altered the methylation status of p53 and inhibited its transcriptional activity. Genetic silencing of p53 largely abrogated the effects of SMYD2 in promoting aerobic glycolysis. Taken together, our findings reveal a novel function of SMYD2 in regulating the Warburg effect in cervical cancer.

Circular RNA ZNF609 functions as a competing endogenous RNA in regulating E2F transcription factor 6 through competitively binding to microRNA-197-3p to promote the progression of cervical cancer progression

ABSTRACT Countless studies have demonstrated that Circular RNAs (circRNAs) exert vital effects in regulating tumorigenesis of various cancers. CircRNA ZNF609 (circ-ZNF609) has been reported as an oncogene in various human cancers. Nevertheless, its regulating effect in cervical cancer (CC) remains to be further explored. RT-qPCR was adopted to measure circ-ZNF609, miR-197-3p and E2F6 levels. CC cell proliferation, migration and invasion were analyzed via CCK-8 and transwell assays. Dual-luciferase reporter assay was adopted to confirm the interaction between miR-197-3p and circ-ZNF609 or E2F6. In the present study, it was found that circ-ZNF609 was elevated in CC tissues and cell lines, and circ-ZNF609 deletion repressed cell viability, migration and invasion in CC. Moreover, circ-ZNF609 was identified to negatively regulate miR-197-3p expression in CC cells. The inhibition of miR-197-3p abrogated the inhibitory effect on CC cell proliferation, migration and invasion induced by circ-ZNF609 knockdown. Additionally, we further demonstrated that circ-ZNF609 upregulated E2F6 by interacting with miR-197-3p. Finally, rescue assays indicated that E2F6 overexpression upended the suppression of CC progression induced by circ-ZNF609 deletion. In conclusion, circ-ZNF609 promoted CC progression through modulating the miR-197-3p/E2F6 axis as an oncogene. This finding offers a unique insight into CC molecular mechanism and suggests a potential target for CC therapy.

Endostar Rebuilding Vascular Homeostasis and Enhancing Chemotherapy Efficacy in Cervical Cancer Treatment.

BackgroundThe incidence rate of cervical cancer is the highest in the reproductive tract and is not sensitive to chemotherapy. An appropriate amount of anti-angiogenic agents can reconstruct tumor blood vessels in a short period of time and form vascular homeostasis, increase the function of blood vessel perfusion and reverse the multidrug resistance of chemotherapy, which is also called “vascular normalization.” Endostar (a recombinant human endostatin) was developed by China and as a multi-target anti-angiogenesis agent. Many reports about endostar involved the treatment of non-small cell lung cancer, fewer reports are on cervical cancer.PurposeTo determine whether endostar can rebuild tumor vascular homeostasis and enhance chemotherapy effects for patients with cervical cancer.MethodsIn this study, the patients with cervical cancer within stage IIB2 were selected, endostar combined with cisplatin+paclitaxel neoadjuvant chemotherapy (NACT) before radical surgical operation was adopted, patients outcome and adverse reaction were followed up. The changes of tumor vascular structure and perfusion function before and after endostar given were evaluated by histopathology and dynamic contrast-enhanced magnetic resonance imaging (DEC-MRI). VEGF-Notch signal pathway was detected for the regulating mechanism of vascular proliferation in different groups. GraphPad Prism 6 software was used for statistical analysis of the study results.ResultsEndostar enhanced the short-term (2 year) overall survival (OS), progression-free survival (PFS) rates for cervical cancer patients. All the same, endostar increased long-term (5 year) OS for cervical cancer patients. Endostar therapy exhibited with mild adverse reaction. MRI showed endostar+NACT further reduce tumor volume than NACT alone. The parameters of Ktrans, Ve for DEC-MRI in endostar group exhibited obviously increase than NACT group. Tumor vascular maturation index α-SMA/CD31 in endostar group increased obviously than NACT group, correspondingly Ki67 staining for tumor proliferative rates, lymphovascular space invasion in endostar group further declined than NACT group. The genes and proteins expression of VEGFR2, Notch1, Notch4, Dll4, Jag1 were obviously downregulated in endostar group comparing to NACT group.ConclusionEndostar restored vascular homeostasis in cervical cancer temporarily, enhanced chemotherapeutic agents effects in cervical cancer, increased patient OS ratio. Endostar+NACT treatment may provide a new target therapy for cervical cancer.

Priming the Abscopal Effect in Cervical Cancer

Current treatment options for advanced cervical cancer are limited, especially for patients in low-resource settings. The purpose of this study is to investigate a potential therapeutic approach by priming the abscopal effect, leading to regression of both locally treated and distant untreated tumors. We hypothesize that radiotherapy combined with locally delivered anti-CD40 will boost the abscopal effect, with initial investigation in mice. Naïve healthy female mice C57BL/6 were injected with mice cervical cancer cells TC-1 subcutaneously on contralateral flanks, mimicking primary and metastatic tumors. The animals were then randomized into different cohorts. In the treatment cohort, only the primary tumor was treated and response of both tumors was monitored. The treatment consisted of image-guided radiotherapy (IGRT) with a single 6 Gy dose with 10x10 mm2 field size using the Small Animal Radiation Research Platform (SARRP), followed by intratumoral injection of 20 μg anti-CD40. The study was repeated while also varying different treatment parameters including radiotherapy dose (6 Gy, 10 Gy, and 15 Gy) and dosing schedule (one versus three times administration over 2 weeks) of immunoadjuvant anti-CD40. For each study, the size of both treated and untreated tumors was measured with a caliper and SARRP computed tomography imaging and responses compared to those in appropriate control cohorts. Statistical analyses for tumor volume and Kaplan–Meier survival assay were achieved using ANOVA and Log-rank test. The results consistently showed that one 6 Gy compared to 10 Gy or 15 Gy fraction doses of RT with a single dose of agonistic anti-CD40 can generate highly effective abscopal responses after 14 days, with a significant increase in animal survival (p = 0.0004). 60% of the mice treated with this combination showed long term survival with complete tumor regression, where tumors of mice in other cohorts continued to grow (see Table below). Moreover, re-challenged responders to the treatment developed vitiligo suggesting developed immune memory for this cancer. The findings corroborate the hypothesis and show that a single RT fraction dose optimized at 6 Gy in combination with locally delivered anti-CD40 can generate effective abscopal responses. Further investigations to optimize and advance mechanistic understanding of the abscopal effect associated with cervical cancer could lead to innovative treatment methods offering a new more accessible therapy option for cervical cancer care, with a major potential impact, especially in resource-poor settings.Tabled 1Abstract 3022; TableGroupsShrinkage Rate: Treated Tumors [responders/mice in group]Shrinkage Rate: Untreated Tumors: [responders/mice in groups]Complete Tumors Regression [%]Control0/150/1506 Gy2/100/100mAb (1 dose)1/102/100mAb (3 doses)1/51/506 Gy + mAb10/159/156010 Gy + mAb2/51/5015 Gy + mAb4/51/506 Gy + mAb (3 doses)3/53/50 Open table in a new tab

SP1-induced lncRNA FOXD3-AS1 contributes to tumorigenesis of cervical cancer by modulating the miR-296-5p/HMGA1 pathway.

Long noncoding RNAs (lncRNAs) have drawn growing attention due to their regulatory roles in various diseases, including tumors. Recently, lncRNA FOXD3 antisense RNA 1 (FOXD3-AS1) was shown to be overexpressed in colon adenocarcinoma and glioma, exerting oncogenic functions. However, its expression and effects in cervical cancer (CC) remained unknown. In this research, our group first reported that the levels of FOXD3-AS1 were distinctly elevated in CC samples and cell lines. The distinct upregulation of FOXD3-AS1 was associated with lymphatic invasion, distant metastasis, and International Federation of Gynecology and Obstetrics stage, and also predicted poor clinical results of CC patients. Next, transcription factor SP1 was demonstrated to resulting in the upregulation of FOXD3-AS1 in CC. Functional assays indicated that knockdown of FOXD3-AS1 distinctly suppressed CC progression via affecting cell proliferation, cell apoptosis, and metastasis. Moreover, mechanistic studies suggested that FOXD3-AS1 acted as an endogenous sponge by directly binding miR-296-5p, resulting in the suppression of miR-296-5p. In addition, we also reported that high mobility group A, a direct target of miR-296-5p, could mediate the tumor-promotive effects that FOXD3-AS1 displayed. Overall, our present study might help to lead a better understanding of the pathogenesis of CC, provide a novel possible tumor biomarker, and probe the feasibility of lncRNA-directed treatments for CC.

Abstract 6000: eIF3A regulate the Warburg effect via ENO1 in cervical cancer cells

Abstract Eukaryotic translation initiation factor 3A (eIF3A) is one of the core subunits of the translation initiation complex eIF3. eIF3A is critical for ribosomal subunit joining and recruiting mRNA to the ribosome, as well as for the regulation of various gene products. However, the function of eif3A have not been reported in cervical cancer (CC). Here we reported that Eif3A protein was overexpressed in CC tissues and the higher expression of Eif3A predicted a worse prognosis. Further experiments showed that eIF3A knockdown inhibited CC cells' proliferation and migration and promoted apoptosis in vitro and in vivo. eIF3A silencing accelerated acidification of the culture medium of CC cells. Seahorse results showed that the decreased expression of eIF3A significantly reduced glycolysis flux in CC cells. Mass spectrometry suggested that eIF3A knockdown could significantly repressed the expression of ENO1, which is a famous glycolytic protein. Western blot assay indicated that eIF3A silencing significant decreased the expression of ENO1. Therefore, our results indicated that eIF3A could enhance the warburg effect in cervical cancer by regulating ENO1. Citation Format: Pengfei Xu, Dake Li. eIF3A regulate the Warburg effect via ENO1 in cervical cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6000.

CFTR Regulates the Proliferation, Migration and Invasion of Cervical Cancer Cells by Inhibiting the NF-κB Signalling Pathway.

BackgroundThe cystic fibrosis transmembrane conductance regulator (CFTR) and nuclear factor κB (NF-κB) signalling pathways are currently regarded as co-regulators of the occurrence of cervical cancer. However, the detailed mechanism of CFTR- and NF-κB-mediated effects in cervical cancer remains to be elucidated. This study aimed to investigate the mechanism by which CFTR and NF-κB influence the development of cervical cancer.Patients and MethodsCFTR ΔF508 mutation and CFTR promoter methylation were detected in cervical tissue samples. NF-κB p65 and IκBα protein levels were tested in HeLa cells with CFTR overexpression and knockdown by Western blotting. The effects of CFTR on cell proliferation, migration, and invasion were examined in HeLa cells by WST-1 and soft agar assays, cell wound scratch assay, and Matrigel invasion assays, respectively. The protein–protein interaction (PPI) network was constructed by using GeneMANIA. GeneCoDis3 was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis on genes in the PPI network.ResultsCFTR mutation and CFTR promoter methylation were not associated with the occurrence of cervical cancer. NF-κB p65 protein levels were decreased in CFTR overexpression lines and increased in CFTR knockdown lines, and IκBα levels were affected in the opposite manner, indicating that CFTR inhibited the NF-κB signalling pathway. CFTR also regulated the cell proliferation, migration, and invasion ability of cervical cancer cells. When CFTR was overexpressed, cell proliferation, migration, and invasion ability were decreased. There were 20 genes that interacted with CFTR. KEGG pathway analysis showed enrichment in the gastric acid secretion, chemokine signalling, bile secretion and apoptosis pathways.ConclusionCFTR plays an important role in cancer cell proliferation, migration and invasion by inhibiting the NF-κB signalling pathway in cervical cancer.

Effect of the oral CXCR4 inhibitor X4-136 on tumor control and side effects in cervical cancer treated with radiotherapy and concurrent chemotherapy.

e18010 Background: Cervical cancer is a global health problem. Despite scale up of prevention programs, there will be an ongoing need to improve the effectiveness of radiotherapy/cisplatin (RTCT) for women with established, locally advanced disease. We have shown that RTCT with the CXCR4 inhibitor plerixafor improves tumor control, reduces metastases and reduces RT-related side effects compared to RTCT alone. X4-136 is an oral CXCR4 inhibitor that is better suited to long-term, once daily use. In this study we examined: 1. The efficacy of RTCT and X4-136 in cervical cancer; 2. Biomarkers of response to RTCT and X4-136; and 3. Effects of RTCT and X4-136 on intestinal toxicity, an important dose-limiting RT side effect in these patients. Methods: Orthotopic cervical cancer xenografts derived from our patients were treated with RT (30 Gy; 2 Gy/day) and cisplatin (4 mg/kg/week ip) with or without concurrent X4-136 (100 mg/kg/day orally) for 3 weeks. Mice were sacrificed immediately after treatment for biomarker assessment. In separate experiments, mice had CT imaging weekly after treatment to evaluate tumor response. Acute and late intestinal toxicity was assessed histologically 3.5 and 90 days after treatment respectively. Results: RTCT alone increased CXCL12/CXCR4 signaling, intratumoral accumulation of myeloid cells and PD-L1 expression. The addition of X4-136 during RTCT abrogated these effects and improved tumor response in 2 cervical cancer models. Furthermore, the addition of X4-136 increased the proportion of surviving intestinal crypt cells in keeping with a reduction in acute RT toxicity, and reduced late histologic changes of late RT toxicity. Conclusions: The addition of X4-136 blunts RTCT-induced upregulation of the CXCL12/CXCR4 pathway, reduces intratumoral myeloid cells, improves tumor control and reduces side effects in cervical cancer. Few if any pharmacologic strategies have been identified previously that expand the therapeutic window with RT in this way. The combination of RTCT and CXCR4 inhibition warrants testing in clinical trials to validate these findings. These benefits may apply to other tumors where RTCT plays a curative role.

<p>Regulations of miR-183-5p and Snail-Mediated Shikonin-Reduced Epithelial-Mesenchymal Transition in Cervical Cancer Cells</p>

BackgroundShikonin, the main ingredient of Lithospermum erythrorhizon, has been reported to have antitumor effects via multiple targets and signaling pathways. However, the detailed mechanism underlying the effects in cervical cancer still remained unknown.MethodsMTT, wound-healing, transwell assays and flow cytometry experiments were used to measure cell growth, migration, invasion, and cell cycle analysis. Western blot was used to examine protein levels of Snail, Vimentin and E-cadherin. The expression level of miR-183-5p was measured via qRT-PCR. The E-cadherin promoter activity was detected via Secrete-PairTM Dual Luminescence Assay Kit. The transient transfection experiments were used for silencing of E-cadherin and overexpression of Snail genes. Tumor xenograft and bioluminescent imaging experiments were carried out to confirm the in vitro findings.ResultsWe showed that shikonin inhibited cell viability, migration and invasion, and induced cell cycle arrest in a dose-dependent manner in cervical cancer Hela and C33a cells. Mechanistically, we found that shikonin increased miR-183-5p expression and inhibited expression of transcription factor Snail protein. The mimics of miR-183-5p reduced, while the inhibitors of miR-183-5p reversed shikonin-inhibited Snail protein expression. In addition, shikonin decreased Vimentin, increased E-cadherin protein expressions and E-cadherin promoter activity, the latter was reversed in cells transfected with exogenous Snail overexpression vectors. Moreover, silencing of E-cadherin significantly abolished shikonin-inhibited cervical cancer cell growth. Similar findings were also observed in vivo using one xenograft mouse model.ConclusionOur results show that shikonin inhibits EMT through inhibition of Snail and stimulation of miR-183-5p expressions, which resulted in induction of E-cadherin expression. Thus, blockade of EMT could be a novel mechanism underlying the anti-cervical cancer effects of shikonin.

Identification of autophagy related antitumor effect in cervical cancer

Objective: AMP-activated protein kinase (AMPK) is a highly conserved serine/threonine protein kinase and an essential mediator in maintaining cellular energy homeostasis. Recent studies suggested that AMPK is crucial for the activation of autophagy, which is an emerging target for the prevention and treatment of various cancers. The aim of this study was to explore the antitumor effects of AMPK-inducing agents in human cervical cancer cells.

Assessment of the false negative rate of preoperative imaging in cervical cancer patients undergoing primary radical surgery

Objective: Patient selection for primary radical surgery is paramount to avoid the use of adjuvant radiation treatment and its associated adverse effects in cervical cancer. The use of preoperative imaging could help identify those best suited for surgery versus primary radiation; however, no standard of care has been identified. We aim to describe the false negative rate and false positive rate of preoperative imaging at a single institution prior to radical surgery for cervical cancer.

Assessment of the false negative rate of preoperative imaging in cervical cancer patients undergoing primary radical surgery

Objectives: Patient selection for primary radical surgery is paramount to avoid the use of adjuvant radiation treatment and its associated adverse effects in cervical cancer. The use of preoperative imaging could help identify those best suited for surgery versus primary radiation; however, no standard of care has been identified. We aim to describe the false negative rate and false positive rate of preoperative imaging at a single institution prior to radical surgery for cervical cancer.

CKD-602, a topoisomerase I inhibitor, induces apoptosis and cell-cycle arrest and inhibits invasion in cervical cancer

BackgroundCervical cancer is the third most common gynecological malignancy. Conventional treatment options are known to be ineffective for the majority of patients with advanced or recurrent cervical cancer. Therefore, novel therapeutic agents for cervical cancer are necessary. In this study, the effects of CKD-602 in cervical cancer were investigated.MethodsThree established human, immortalized, cervical cancer cell lines (CaSki, HeLa and SiHa) were used in this study. Following treatment with CKD-602, apoptosis was quantified using fluorescein isothiocyanate Annexin V-FITC and propidium iodide (PI) detection kit and cell cycle analysis was analyzed using fluorescence activated cell sorting (FACS). Transwell chambers were used for invasion assays. Western blot assay was performed to analyze proteomics. CaSki cells were subcutaneously injected into BALB/c-nude mice and cervical cancer xenograft model was established to elucidate the antitumor effect of CKD-602 in vivo.ResultsTreatment with CKD-602 induced apoptosis and increased expression of the enzyme PARP, cleaved PARP, and BAX. In addition, expression of phosphorylated p53 increased. Cell cycle arrest at G2/M phase and inhibition of invasion were detected after treatment with CKD-602. A significant decrease in cervical cancer tumor volume was observed in this in vivo model, following treatment with CKD-602.ConclusionsThis is the first report of CKD-602 having an antitumor effect in cervical cancer in both an in vitro and in vivo models. The results of this study indicate that CKD-602 may be a novel potential drug, targeting cervical cancer, providing new opportunities in the development of new therapeutic strategies.

Effects and possible mechanism of a picosecond pulsed electric field on angiogenesis in cervical cancer in vitro.

Picosecond pulsed electric field (psPEF) is an athermal, minimally invasive and local ablative biomedical engineering technique used in cancer therapy. However, to the best of our knowledge, the effect of psPEF on angiogenesis in cervical cancer is unknown. Therefore, the aim of the current study was to investigate the effects and possible mechanism of psPEF on angiogenesis in cervical cancer in vitro. HeLa cell and human umbilical vein endothelial cell (HUVEC) suspensions were exposed to psPEF with an increasing gradient of electric field intensity (0, 200, 400 and 600 kV/cm). A Cell Counting kit-8 assay and flow cytometry were used to investigate the effect of psPEF on the proliferation and apoptosis of HUVECs. The invasion, migration and tube formation capabilities of HUVECs following psPEF treatment were investigated by Transwell invasion assay, scratch test and lumen formation assay, respectively. Changes in the protein and mRNA levels of angiogenesis-associated factors in HeLa cells were detected by western blot analysis and reverse transcription-quantitative polymerase chain reaction. psPEF was identified to inhibit proliferation and tube formation, and induce apoptosis and necrosis of HUVECs in a dose-dependent manner. psPEF was revealed to decrease the protein and mRNA expression levels of vascular endothelial growth factor and hypoxia-inducible factor 1α in HeLa cells. In summary, psPEF exhibited anti-angiogenic effects in cervical cancer in vitro by exerting direct effects on HUVECs and indirect effects on angiogenesis-associated factors in HeLa cells.

MicroRNA-454-3p inhibits cervical cancer cell invasion and migration by targeting c-Met.

Increasing evidence has demonstrated that microRNAs (miRNAs) have a crucial role in the initiation and progression of tumors. The present study aimed to investigate the expression and the role of miRNA-454-3p in human cervical cancer. Human cervical cancer cells were transfected with miRNA-454-3p mimics or negative control miRNA. MTT, Transwell and wound healing assays were performed to investigate the effects of miRNA-454-3p overexpression on cell proliferation, invasion and migration, respectively. The results indicated that miRNA-454-3p was down-regulated in human cervical cancer cell lines, while its ectopic overexpression significantly inhibited their proliferation, migration and invasion. Furthermore, a luciferase reporter assay confirmed that c-met was a novel target of miRNA-454-3p in HeLa cells. In conclusion, the results of the present study suggested that miRNA-454-3p exhibits significant tumor-suppressive effects in cervical cancer by targeting c-met, and may be a potential means of treating cervical cancer.

Chitosan-based zinc oxide nanoparticle for enhanced anticancer effect in cervical cancer: A physicochemical and biological perspective

In this study, chitosan-assembled zinc oxide nanoparticle (CZNP) was successfully prepared for evaluated for its anticancer efficacy against cervical cancer cells. The CZNP particles were nanosized and spherical in shape. The zinc oxide nanoparticle (ZNP) and CZNP showed significant cytotoxicity in cervical cancer cells in a concentration-dependent manner. Results showed that the enhanced cytotoxicity was mainly attributed to the reactive oxygen species (ROS) generation in the cancer cells. The apoptosis assay further revealed that apoptosis was the main reason behind the cell killing effect of the zinc oxide nanoparticles. The apoptosis was further confirmed by the nuclear chromatin assay. Live dead assay showed increased red fluorescent cell for CZNP treated cancer cells. Overall, metal oxide present in nanoparticulate dimensions will be advantageous in imparting the cytotoxicity to cervical cancer cell.

Association of bladder dose with late urinary side effects in cervical cancer high-dose-rate brachytherapy

PurposeThe purpose of this work was to study the association between specific urinary sequelae and locally accumulated dose to the bladder wall and bladder neck in the treatment of cervical cancer with multifraction high-dose-rate (HDR) brachytherapy. Methods and MaterialsA cohort of 60 cervical cancer patients, treated with both external beam and five HDR brachytherapy insertions between 2008 and 2014 at the BC Cancer Agency, was identified. The accumulated dose received over five brachytherapy sessions was evaluated for the bladder wall and bladder neck of each patient using dosimetric parameters calculated from deformably registered image data sets. These parameters were examined as potential predictors of urinary sequelae including hematuria, frequency, urgency, incontinence, stream, nocturia, and dysuria. Two different dichotomization schemes were evaluated for grouping patients into Case and Control groups. The two-sample Student's t test was used for normally distributed samples and the Mann–Whitney nonparametric U test for non-normal distributions. ResultsA strong association between dose to the bladder neck and incontinence was found (p = 0.001). A statistically significant association (p < 0.05) was also observed between urgency and certain bladder-wall parameters. ConclusionsLocalized dose to the bladder neck is a potential predictor of urinary incontinence, whereas weaker associations were observed between urgency and some bladder-wall parameters.

LincRNA-p21 knockdown enhances radiosensitivity of hypoxic tumor cells by reducing autophagy through HIF-1/Akt/mTOR/P70S6K pathway

Hypoxic conditions are common in solid tumors and have a significant effect on tumor progression, therapeutic and prognosis. Long noncoding RNAs (lncRNAs) are longer than 200 nucleotides and cannot be translated into proteins, which play important roles in some diseases including cancer. Although previous analysis have showed that long intergenic non-coding RNA (lincRNA)-p21 is hypoxia-responsive and functions as a new regulator of cell cycle, apoptosis and warburg effect in cervical cancer, its biological roles in hypoxic hepatoma and glioma are unknown. In this work, we found that X-ray irradiation or hypoxia treatment elevated lincRNA-p21 expression in SMMC7721 hepatoma and U251MG glioma cells. Knockdown of lincRNA-p21 induced G2/M phase arrest, promoted apoptosis, decreased cell proliferation and motility, and reduced autophagy through HIF-1/Akt/mTOR/P70S6K pathway in hypoxic tumor cells. Our results delineated a novel mechanism of lincRNA-p21 in enhancing hypoxic tumor cell radiosensitivity, which might provide valuable targets for radiation therapy for solid tumors, such as hepatoma and glioma.

PERAN KELUARGA DAN KUALITAS HIDUP PASIEN KANKER SERVIKS

Introduction. Cervical cancer diagnosis has been a major burden both for patients and their family. For patients, cervical cancer obliterated some of their role as a wife and a mother. Most patients with advance cancer have low score of quality of life indicating they have problems. Family must take care of their beloved ones dealing with the diagnosis, treatment, and side effects of cervical cancer. Family as a caregiver might be ill prepared to undertake that role. The objective of this research was to identify the correlation of family health task on quality of life in patients with cervical cancer. Methods. This research employed cross-sectional design. Population in this research was all patients with cervical cancer in gynecology ward Dr Soetomo Hospital in Surabaya. Participant for this research were patients with cervical cancer and their family. Data were taken by structured interview using Fact Cx for Quality of life and family health task question form. Linear regression analysis was applied with level of significance ≤0.05. Results. Most family had moderate level of family health task while most patients also have moderate level of quality of life. Unfortunately there are no significance correlations of family health task on quality of life in patients with cervical cancer. Discussion. Quality of life in patient with cervical cancer was not affected directly by their family health task. Nonetheless patient gratefully thanks family for their support during their cancer treatments. Keywords: family health task, fact cx, family support, quality of life, cervical cancer

1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D&lt;sub&gt;3&lt;/sub&gt;对宫颈癌作用的研究进展

宫颈癌是目前常见的妇科恶性肿瘤之一，近年来由于人乳头瘤病毒(HPV)感染率的上升、人类生存环境的不断恶化等原因，宫颈癌的发病率呈现快速增高趋势，早期宫颈癌多采用手术治疗，晚期患者多采用手术联合放化疗等治疗方案。但是目前临床上用的化疗药物多具有较严重的毒性，限制了其临床应用。因此寻找新的、副作用小的药物是肿瘤研究的方向之一。近年来研究发现1,25(OH)2D3具有明显的抗肿瘤作用，现将其抗肿瘤效应及在宫颈癌方面的应用作一综述，为宫颈恶性肿瘤的临床治疗提供新的思路和理论依据。 Cervical cancer is one of common gynecological malignancies. In recent years, due to the rise of human papillomavirus (HPV) infection rates, the worsening of the human environment and other reasons, the incidence of cervical cancer showed a rapid increasing trend. Early cervical cancer is usually treated by surgery, while patients of advanced disease use surgery combining with radiotherapy and chemotherapy and other treatment options. But the chemotherapy drugs currently used in clinical practice have more serious toxicity, limiting its clinical application. Therefore, the search for drugs of new and few side effects is one of the directions of cancer research. Recent studies have found that 1,25(OH)2D3 has significant anti-tumor effect, and now its anti-tumor effects in cervical cancer and its application are reviewed, to provide new ideas and theoretical basis for the clinical treatment of cervical cancer.