SMARCA4­deficient uterine adnexal tumor with ascites: A case report and literature review.

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SMARCA4)-deficient tumors are rare and highly aggressive tumors characterized by a loss of SMARCA4 expression, and SMARCA4-deficient tumors in the adnexal area of the uterus are particularly rare. The present study describes the case of a 64-year-old woman who was admitted to Weifang People's Hospital (Weifang, China) with abdominal distension, and was observed to have a mass with ascites in the adnexal area of the uterus. Based on clinical, imaging and pathological findings, the patient was diagnosed with a SMARCA4-deficient adnexal tumor with ascites. Biopsy of the left and right adnexal lesions was performed, and the patient was administered chemotherapy. After one cycle of bevacizumab, sindilizumab and carboplatin, no further treatment was administered. After biopsy and chemotherapy, the abdominal distension was alleviated and the general condition of the patient was satisfactory. The patient was followed up and died 3 months after treatment. Notably, it is important to avoid misdiagnosing this tumor as other types of adnexal uterine tumors, and morphological and immunohistochemical features may be useful for diagnosing primary SMARCA4-deficient tumors in the adnexal area of the uterus.

[Expression Changes of Hypoxia-Inducible Factor-1α in G-CSF Induced Hematopoietic Stem Cell Mobilization].

OBJECTIVE: To investigate the expression and its relative mechanism of hypoxia-inducible factor-1α(HIF-1α) in bone marrow(BM) of mice during G-CSF mobilization of hematopoietic stem cells (HSC) . METHODS: Flow cytometry was used to detect the proportion of Lin-Sca-1+ c-kit+ (LSK) cells in peripheral blood of C57BL/6J mice before and after G-CSF mobilization. And the expression of HIF-1α and osteocalcin (OCN) mRNA and protein were detected by RQ-PCR and immunohistochemistry. The number of osteoblasts in bone marrow specimens of mice was counted under the microscope. RESULTS: The proportion of LSK cells in peripheral blood began to increase at day 4 of G-CSF mobilization, and reached the peak at day 5, which was significantly higher than that of control group (P<0.05). There was no distinct difference in the expression of HIF-1α mRNA between bone marrow nucleated cells and osteoblasts of steady-state mice (P=0.073), while OCN mRNA was mainly expressed in osteoblasts, which was higher than that in bone marrow nucleated cells (P=0.034). After mobilization, the expression level of HIF-1α increased, but OCN decreased, and the number of endosteum osteoblasts decreased. The change of HIF-1α expression was later than that of OCN and was consistent with the proportion of LSK cells in peripheral blood. CONCLUSION: The expression of HIF-1α in bone marrow was increased during the mobilization of HSC mediated by G-CSF, and one of the mechanisms may be related to the peripheral migration of HSC induced by osteoblasts inhibition.

Five-year remission without disease progression in a patient with relapsed/refractory multiple myeloma with extramedullary disease treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study: a case report.

BACKGROUND: Multiple myeloma remains incurable despite treatment advancements over the last 20 years. LCAR-B38M Cells in Treating Relapsed/Refractory Multiple Myeloma was a phase 1, first-in-human, investigator-initiated study in relapsed/refractory multiple myeloma conducted at four sites in China. The study used LCAR-B38M chimeric antigen receptor-T cells expressing two B-cell maturation antigen-targeting single-domain antibodies designed to confer avidity, and a CD3ζ signaling domain with a 4-1BB costimulatory domain to optimize T-cell activation and proliferation. This chimeric antigen receptor construct is identical to ciltacabtagene autoleucel. In the LEGEND-2 study (n = 57, Xi'an site), overall response rate was 88%; median (95% CI) progression-free survival and overall survival were 19.9 (9.6-31.0) and 36.1 (26.4-not evaluable) months, respectively; and median follow-up was 25 months. This case study reports on a patient with relapsed/refractory multiple myeloma (λ light chain type) who was treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study (Xi'an site); he had received five prior lines of treatment and had extensive extramedullary lesions. CASE PRESENTATION: The patient, a 56-year-old Asian male, received cyclophosphamide (500 mg daily × 3 days) as lymphodepletion therapy and a total dose of 0.5 × 106 chimeric antigen receptor + T cells/kg split into three infusions (days 1, 24, and 84 from June to August 2016). He experienced grade 2 cytokine release syndrome after the first infusion; all symptoms resolved with treatment. No cytokine release syndrome occurred following the second and third infusions. His λ light chain levels decreased and normalized 20 days after the first infusion, and extramedullary lesions were healed as of January 2018. He has sustained remission for 5 years and received no other multiple myeloma treatments after LCAR-B38M chimeric antigen receptor T cell infusion. As of 30 October 2020, the patient is still progression-free and has maintained minimal residual disease-negative (10-4) complete response status for 52 months. CONCLUSIONS: This case provides support that treatment with LCAR-B38M chimeric antigen receptor T cells can result in long-term disease remission of 5 or more years without disease progression in a heavily pretreated patient with extensive extramedullary disease and no other treatment options.

Characteristics of Retained Foreign Bodies in the Tongue: A Retrospective Study of 35 Cases.

PURPOSE: There are only a few case reports of foreign bodies (FBs) in the tongue. Delayed diagnosis or misdiagnosis is commonly reported. The purpose of this study was to identify the demographic, clinical, and radiological features that might facilitate the diagnosis of retained FBs in the tongue. METHODS: A retrospective case series was performed. Clinical and imaging data of patients with FBs in the tongue at Wuhan University Hospital of Stomatology were reviewed. The outcome variable was a preliminary, radiological, intraoperative, or pathological diagnosis. Covariates included age, sex, FB-related history, symptoms and signs, duration, and computed tomography (CT) imaging features. Descriptive statistics were computed for each study variable. RESULTS: Thirty-five patients were included. The sample's mean age was 54.5 ± 11.2 years, included 19 males (54.3%). Eighty percent of the patients reported FB-related history with a mean duration of 4 weeks. More than 70% of the patients presented with tongue swelling. Approximately half of the 35 cases were preliminarily misdiagnosed, and 15 of them were initially suspected to be tumors. After CT examinations, 33 of the 35 cases were diagnosed as FB. Characteristic CT imaging feature of the FB was a radiopaque line. Most FBs were located at the anterior two-thirds and marginal area of the tongue and in an oblique direction. The depth of FB was 0.61 ± 0.42 cm. The superficial ends of most FBs were close to the surface of the dorsum and the tongue margin. CONCLUSIONS: The possibility of a retained FB should be included in the differential diagnosis of a nonhealing wound or tongue enlargement when a radiopaque line is present on CT images of patients presenting with or without FB-related history. It may be easier to detect a FB in the tongue when a CT imaging postprocessing protocol, including thin-slice reconstruction and multiplanar reformation visualization and careful interpretation, is used.

Identification of high expression profiles of miR-31-5p and its vital role in lung squamous cell carcinoma: a survey based on qRT-PCR and bioinformatics analysis.

BACKGROUND: The function of miR-31-5p in lung squamous cell carcinoma (LUSC) remains unclear, therefore, a systematic study was performed for the clinical significance and molecular mechanism of miR-31-5p in LUSC. METHODS: Quantitative real-time reverse transcription PCR (qRT-PCR) was utilized to test the expression level of miR-31-5p in 88 LUSC tissue samples and their matching normal tissues. Data from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were also utilized to confirm the expression level and clinical value of miR-31-5p in LUSC. The potential target genes of miR-31-5p were predicted by several online predicted software. Gene ontology (GO), protein-protein interaction (PPI) and pathway analysis were utilized to investigate the underlying molecular mechanism of miR-31-5p in LUSC. RESULTS: The result from qRT-PCR found that there was significant difference of miR-31-5p between LUSC and normal tissues (P<0.001). Meanwhile, Data from TCGA also showed a higher expression of miR-31-5p in LUSC tissues than that in the normal tissues (P<0.001). on the basis of the data of GEO database, five GEO datasets indicated that the expression of miR-31-5p in LUSC tissues was significantly higher than that in normal lung tissues, include GSE51858 (P=0.025), GSE74190 (P<0.000), GSE16025 (P=0.031), GSE25508 (P=0.0.01), and GSE47525 (P=0.049). Moreover, in consideration of the meta-analysis, 1,012 clinical specimens were systematically analyzed via meta-analysis, clinical specimens were systematically analyzed via meta-analysis, and the results showed that the expression of miR-31-5p in LUSC was significantly higher than in the adjacent lung tissues (SMD =0, CI: 1.08-1.45, Z=13.30, P=0.000). In addition, result from GO and pathway analyses showed that potential target genes of miR-31-5p were significantly associated with 20 GO terms and 5 pathways, such as signal transduction, transmembrane receptor protein tyrosine kinase activity, plasma membrane and Rap1 signaling pathway. Meanwhile, we also found thatmiR-31-5p target genes were related to the Rap1 signaling pathway, Oxytocin signaling pathway and Proteoglycans in cancer. Furthermore, six hub genes were identified from PPI and three hub genes, including ADCY6, ADCY9 and EGFR, proved to coexist in the Rap1 signaling pathway, oxytocin signaling pathway and Melanogenesis simultaneously. CONCLUSIONS: According to what has been discussed above, we speculated that miR-31-5p may play a vital role in the occurrence and development of LUSC.

A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma.

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM). METHODS: This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m2. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 106 cells/kg [range, 0.07 to 2.1 × 106]) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group. RESULTS: At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval [CI], 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached. CONCLUSIONS: LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered.

Role of miR-452-5p in the tumorigenesis of prostate cancer: A study based on the Cancer Genome Atl(TCGA), Gene Expression Omnibus (GEO), and bioinformatics analysis.

BACKGROUND: MiR-452-5p has been reported to be down-regulated in prostate cancer, affecting the development of this type of cancer. However, the molecular mechanism of miR-452-5p in prostate cancer remains unclear. Therefore, we investigated the network of target genes of miR-452-5p in prostate cancer using bioinformatics analyses. MATERIALS AND METHODS: We first analyzed the expression profiles and prognostic value of miR-452-5p in prostate cancer tissues from a public database. Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), PANTHER pathway analyses, and a disease ontology (DG) analysis were performed to find the molecular functions of the target genes from GSE datasets and miRWalk. Finally, we validated hub genes from the protein-protein interaction (PPI) networks of the target genes in the Human Protein Atlas (HPA) database and Gene Expression Profiling Interactive Analysis (GEPIA). Narrowing down the optimal target genes was conducted by seeking the common parts of up-regulated genes from GEPIA, down-regulated genes from GSE datasets, and predicted genes in miRWalk. RESULTS: Based on mining of GEO and ArrayExpress microarray chips and miRNA-Seq data in the TCGA database, which includes 1007 prostate cancer samples and 387 non-cancer samples, miR-452-5p is shown to be down-regulated in prostate cancer. GO, KEGG, and PANTHER pathway analyses suggested that the target genes might participate in important biological processes, such as transforming growth factor beta signaling and the positive regulation of brown fat cell differentiation and mesenchymal cell differentiation, as well as the Ras signaling pathway and pathways regulating the pluripotency of stem cells and arrhythmogenic right ventricular cardiomyopathy (ARVC). Nine genes-GABBR, PNISR, NTSR1, DOCK1, EREG, SFRP1, PTGS2, LEF1, and BMP2-were defined as hub genes in the PPI network. Three genes-FAM174B, SLC30A4, and SLIT1-were jointly shared by GEPIA, the GSE datasets, and miRWalk. CONCLUSIONS: Down-regulated miR-452-5p might play an essential role in the tumorigenesis of prostate cancer.

Submucosal tunnelling endoscopic resection (STER) for the treatment of a case of huge esophageal tumor arising in the muscularis propria: a case report and review of literature.

BACKGROUND AND AIMS: Endoscopic Interventional Treatment is of little trauma and less complications in the treatment of esophageal tumor and leads to faster recovery and fewer days of hospitalization. This study was aimed to investigate the safety and efficacy of endoscopic interventional therapy for huge esophageal tumor arising in the muscularis propria. METHODS: The patient was treated by submucosal tunneling endoscopic resection (STER). RESULTS: The huge esophageal tumor was resected completely by STER technique, with little trauma and less complications. The size of the resected tumor was 5.5×3.5×3.0 cm. CONCLUSION: Submucosal tunneling endoscopic resection is a safe and efficient technique for treating Huge Esophageal Tumor originating from muscularis propria layer.

Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice.

AIM: To evaluate the efficacy of ursodeoxycholic acid (UDCA) as a chemotherapeutic agent for the treatment of hepatocellular carcinoma (HCC). METHODS: BALB/c nude mice were randomized into four groups 24 h before subcutaneous injection of hepatocarcinoma BEL7402 cells suspended in phosphate buffered saline (PBS) into the right flank. The control group (n = 10) was fed a standard diet while treatment groups (n = 10 each) were fed a standard daily diet supplemented with different concentrations of UDCA (30, 50 and 70 mg/kg per day) for 21 d. Tumor growth was measured once each week, and tumor volume (V) was calculated with the following equation: V = (L × W(2)) × 0.52, where L is the length and W is the width of the xenograft. After 21 d, mice were killed under ether anesthesia, and tumors were excised and weighed. Apoptosis was evaluated through detection of DNA fragmentation with gel electrophoresis and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the expression of apoptosis-related proteins BAX, BCL2, APAF1, cleaved caspase-9, and cleaved caspase-3. RESULTS: UDCA suppressed tumor growth relative to controls. The mean tumor volumes were the following: control, 1090 ± 89 mm(3); 30 mg/kg per day, 612 ± 46 mm(3); 50 mg/kg per day, 563 ± 38 mm(3); and 70 mg/kg per day, 221 ± 26 mm(3). Decreased tumor volumes reached statistical significance relative to control xenografts (30 mg/kg per day, P < 0.05; 50 mg/kg per day, P < 0.05; 70 mg/kg per day, P < 0.01). Increasing concentrations of UDCA led to increased DNA fragmentation observed on gel electrophoresis and in the TUNEL assay (control, 1.6% ± 0.3%; 30 mg/kg per day, 2.9% ± 0.5%; 50 mg/kg per day, 3.15% ± 0.7%, and 70 mg/kg per day, 4.86% ± 0.9%). Western blot analysis revealed increased expression of BAX, APAF1, cleaved-caspase-9 and cleaved-caspase-3 proteins, which induce apoptosis, but decreased expression of BCL2 protein, which is an inhibitor of apoptosis, following administration of UDCA. CONCLUSION: UDCA suppresses growth of BEL7402 hepatocellular carcinoma cells in vivo, in part through apoptosis induction, and is thus a candidate for therapeutic treatment of HCC.

Caspase-8 Mediates Amyloid-ß-induced Apoptosis in Differentiated PC12 Cells.

The pathogenesis of Alzheimer's disease (AD) is very complex and there are currently no significant treatments for the disease. Caspase-8 is known to be involved in neuronal apoptosis. To explore a possible molecular mechanisms involved in AD pathology, this study investigated the effect of caspase-8 knockdown on amyloid-ß 1-40 (Aß1-40)-induced apoptosis in PC12 cells. The proliferation of PC12 cells was significantly inhibited in Aß-treated cells, and a high fraction of the cells underwent apoptosis in a dose- and time-dependent manner. Transfection of caspase-8 small interfering RNA (siRNA) resulted in reduced apoptosis following Aß1-40 treatment. The activation of caspase-3, caspase-8, and caspase-9 was stimulated by Aß1-40, an effect that was also significantly reduced by caspase-8 siRNA. Knockdown of caspase-8 increased the phosphorylation of the signaling molecules AKT and ERK1/2 relative to cells treated with Aß1-40 alone. Caspase-8 is an important effector molecule involved in apoptosis induced by Aß1-40 and is likely involved in AD pathology. This study suggests that targeted inhibition of caspase-8 may be a new therapeutic for preventing neuronal apoptosis and inhibiting the progression of AD.

Spect-guidance to reduce radioactive dose to functioning lung for stage III non-small cell lung cancer.

OBJECTIVE: To investigate the treatment effect of additional information obtained by single photon emission computed tomography (SPECT) lung perfusion imaging (LPI) in the radiotherapy planning process for patients with stage III non-small cell lung cancer (NSCLC). METHODS: 39 patients with stage III NSCLC were enrolled. Gross tumor volume (GTV) was outlined by SPECT/CT images, SPECT-LPIs being used to define functional lung (FL) and non-functional lung (NFL) regions. Two sets of IMRT plans were designed to deliver 64Gy to PTV. One was a regular IMRT plan using CT images only (Plan 1), and the other was a corresponding IMRT plan using co-registered images (Plan 2). FLVx (the % volume of functional lung receiving ≥x Gy) and WLVx (% volume of whole lung to receive ≥x Gy) were compared by paired Student's t test. Kendalls correlation was used to analyze the factor (s) related with the FLV20 decrease. RESULTS: Compared with plan 1, both WLVx and FLVx were decreased in plan 2. WLV10, WLV15, WLV20, WLV25, WLV30 and WLV35 decreased 9.7%, 13.8%, 17.2%, 12.9%, 9.8% and 9.8%, and FLV10, FLV15, FLV20, FLV25, FLV30 and FLV35 decreased 10.8%, 14.6%, 17.3%, 14.5%, 14.5% and 10.5%. FLVx decreased significantly compared with WLVx. There were significant differences in WLV10, WLV15, WLV20, WLV25, WLV3 and FLV10, FLV15, FLV20, FLV25, FLV30 between plan 1 and plan 2 (P=0.002, 0.000, 0.000, 0.005, 0.027 and 0.002, 0.000, 0.000, 0.006, 0.010). According to Kendall correlation analysis, NFL had a negative relation with the percentage FLV20 decrease (r=-0.559, P<0.01), while the distance of PTV and NFL center had a significantly positive relation with the percentage of FLV20 decrease (r=0.768, P<0.01). CONCLUSION: Routine use of SPECT-LPI for patients undergoing radiotherapy planning for stage III NSCLC appears warranted.

[Value of intraoperative GeneSearch(TM) BLN assay to detect breast cancer metastases in sentinel lymph nodes].

OBJECTIVE: To evaluate the value of GeneSearch(TM) BLN assay as an intraoperative diagnostic method of sentinel lymph node metastases in breast cancer patients. METHODS: Ninety consecutive patients were involved in this study. SLNs were intraoperatively identified and dissected, and then sectioned vertically to the long axis into multiple blocks. The odd blocks were tested by BLN assay and even ones prepared for frozen sectioning (FS), while all blocks were evaluated by touch imprint cytology (TIC). Post-operatively, residual tissues of the even blocks were assessed by histopathologic examination (4 - 6 µm thick serial sectioning permanent H&E slides were performed every 150 µm and one block made 6 slides). RESULTS: BLN assay could be performed within less than 35 min after learning curve of 10 cases. A correlation was found between cycle time values of mammaglobin or cytokeratin-19 and size of metastases, with Spearman correlation coefficients of 0.67 and 0.71, respectively. The accuracy, sensitivity, specificity, positive predict value (PPV) and negative predict value (NPV) of the assay were 95.6%, 93.3%, 96.7%, 93.3% and 96.7%, While FS had the sensitivity, specificity, PPV, NPV of 76.7%, 100%, 100%, 89.6%, and TIC of 73.3%, 100%, 100%, 88.2%, respectively. The sensitivity of the assay was higher than that of FS (P = 0.07), and was significantly higher than that of FS (P = 0.04). When assessing patients with micro-metastases, the assay had a sensitivity of 85.7%, which was significantly higher than that of FS and TIC (P = 0.03). CONCLUSION: GeneSearch(TM) BLN Assay can replace FS and TIC for the intraoperative assessment of SLN.

[Mechanism of recombinant adenovirus-mediated mutations of hypoxia inducible factor 1alpha in modulation of cell apoptosis].

OBJECTIVE: To investigate the mechanism by which recombinant adenovirus (Ad)-mediated mutations of hypoxia inducible factor 1alpha (Ad-HIF-1alpha-Ala564-Ala803) regulates cell apoptosis. METHODS: LoVo cells were infected with recombinant Ad-HIF-1alpha-Ala564-Ala803 and control virus Ad-lacZ under normoxia condition. Real-time PCR was used to detect HIF-1alpha and p21WAF1/CIP1 mRNA expressions at different time points. Western blotting was employed to verify HIF-1alpha and p21WAF1/CIP1 protein expression. Hoechst 33342 flourescein staining was performed to observe the ratio of apoptotic LoVo cells. RESULTS: The expression levels of HIF-1alpha mRNA and protein increased after infection with Ad-HIF-1alpha- Ala564-Ala803, accompanied by an increase in p21WAF1/CIP1 mRNA and protein expressions. The apoptotic ratio was significantly higher in LoVo cells infected with recombinant Ad-HIF-1alpha-Ala564-Ala803 (16.2%) than in the control cells (5.5%, P=0.00). CONCLUSION: HIF-1alpha may induce cell cycle arrest by up-regulating p21WAF1/CIP1 expressions to promote LoVo cell apoptosis.

Melanoma differentiation-associated gene-7/interleukin 24 inhibits invasion and migration of human cervical cancer cells in vitro.

OBJECTIVE: In this study, we used an adenoviral vector -melanoma differentiation-associated gene-7 (Ad-mda7) to examine the effect of the ectopic production of MDA-7/IL-24 on cell migration and invasion by human cervical cancer cells. METHODS: The study took place in the Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing, China, between April 2006 and November 2006. The change of metastasis of cervical cancer cells (CaSki) cells were detected by Cell Migration Assay and Cell Invasion Assay after treated with Ad-mda7. The production of proteins associated with cell migration and invasion were detected by western blot. RESULTS: Cervical cancer cells treated in vitro with Ad-mda7 migrated and invaded less than cells treated with phosphate-buffered saline (PBS) or Ad-Luc (vector control). Melanoma differentiation-associated gene-7 /IL-24 inhibited migration and invasion by down-regulating the production of matrix metalloproteinase-2 (MMP-2) and by up-regulating the production of p38 mitogen-activated protein kinase. relative to PBS and Ad-Luc. CONCLUSION: These results show that MDA-7/IL-24 inhibits invasion and migration by cervical cancer cells by down- or up- regulating proteins associated with these processes, resulting in reduced metastasis. Thus, Ad-mda7 should be considered a therapeutic agent that can inhibit primary tumor growth and prevent metastasis.