Human papillomavirus prevalence and dynamics: Insights from a 5-year population-based study in Jeddah, Kingdom of Saudi Arabia.

OBJECTIVES: To estimate the prevalence and dynamics of human papillomavirus (HPV) infection, over a 5-year period, among Saudi women. METHODS: A 2-phase, population-based study combining cross-sectional and cohort designs was carried out with 5360 ever-married women aged 30-65 from Jeddah, Saudi Arabia, between 2013 and 2018. Participants were enrolled in a designated screening program and screened using the hybrid capture 2 HPV test. Women testing positive for HPV were followed up after one year to estimate the HPV clearance rate, while those testing negative had a follow-up after 5 years to assess new HPV infections. Factors associated with HPV positivity and clearance, including sociodemographic and clinical aspects, were analyzed. RESULTS: Participant's mean age was 44.3 and the average marriage duration was 22.6 years. The initial HPV prevalence was 4.7%. After one year, the HPV clearance rate among initially positive women was 84.3%. The rate of new HPV infections among initially negative women after 5 years was 0.2%, resulting in a cumulative HPV prevalence of 5% over the study period. The incidence rate was estimated at 47 per 100,000 person-years. Parity was the only independent factor inversely associated with HPV positivity, with an odds ratio of 0.93 (95% confidence interval: 0.8 - 0.99). CONCLUSION: The prevalence of HPV in Saudi women was relatively low, suggesting a low transmission rate of HPV. This finding indicates the need for continuous monitoring and tailored prevention strategies.

Overall and progression-free survival in endometrial carcinoma: A single-center retrospective study of patients treated between 2000-2018.

BACKGROUND: Investigating survival in endometrial cancer (EC) is crucial to determine the effectiveness of overall management as it will reflect on the level of care provided among this population. OBJECTIVE: The study was conducted to analyze the overall survival (OS) and progression-free survival (PFS) in treated endometrial carcinoma and to determine the associated predictors. DESIGN: Retrospective SETTING: Department of obstetrics and gynecology in university tertiary hospital PATIENTS AND METHODS: Baseline demographic and clinical data, tumor characteristics and perioperative and outcome data were collected from consecutive patients treated for EC between 2000 and 2018. Kaplan-Meier method and multivariate Cox regression were used to analyze factors and predictors of OS and PFS. MAIN OUTCOME MEASURES: OS, PFS and prognostic factors SAMPLE SIZE: 200 RESULT: Endometrioid type was the most common type accounting for 78.5% of the cases, followed by papillary serous carcinoma (18.5%). At diagnosis, 21.5% were stage III, and 12.0% were stage IV. Invasiveness features showed involvement of the myometrium (96.5%), lymph vessels (36.5%), cervix stroma (18.5%), lower segment (22.0%), and parametrium (7.0%). The majority of patients had open surgery (80.0%), while 11.5% and 7.0% had laparoscopy and robotic surgery, respectively. Staging and debulking were performed in 89.0% of patients, and 12.5% of patients had residual disease of more than 2 cm. The mean OS and PFS were 104.4 (95% CI=91.8-117.0) months and 96.8 (95% CI=83.9-109.7) months, respectively. The 5-year OS and PFS were 62.5% and 46.9%, respectively. The majority of the factors we assessed were significantly associated with OS or PFS. However, reduced OS was independently associated age ≥60 years (hazard ratio [HR]=1.99, P=.010), papillary serous carcinoma (HR=2.35, P=.021), and residual disease (HR=3.84, P=.007); whereas PFS was predicted by age ≥60 years (HR=1.87, P=.014) and residual disease (HR=3.22, P=.040). CONCLUSION: There is a need for a national strategy to tackle the growing burden of EC, by identifying the locally-specific incidence, delayed diagnosis and survival outcome. LIMITATIONS: This was a single-center study conducted at a tertiary center, which may question the generalizability of the findings, as the sample may be biased by overrepresentation with patients who were diagnosed at an advanced stage.

Corrigendum: Human Wharton's Jelly stem cell (hWJSC) extracts inhibit ovarian cancer cell lines OVCAR3 and SKOV3 in vitro by inducing cell cycle arrest and apoptosis.

[This corrects the article DOI: 10.3389/fonc.2018.00592.].

Clinical and pathological patterns of non-epithelial malignant ovarian tumours in Western Saudi Arabia.

Objective: To report a single-center experience in non-epithelial malignant ovarian tumours (NEMOT), by presenting different clinical and pathological characteristics, management and outcomes. Methods: We retrospectively reviewed electronic files of all female patients who underwent surgery for NEMOT at the Gynecology Department of King Abdulaziz University Hospital, Jeddah, Saudi Arabia, from July 2003 to July 2019. We collected baseline demographic, anthropomorphic and clinical data; pathological characteristics; management and follow-up data; and outcomes including residual disease, recurrence and last follow-up status (deceased or alive). Results: Thirty-three women were included; mean (standard deviation) age = 33.24 (17.72) years, range = 4, 86 years. Granulosa cell tumor was the most frequent subtype diagnosed in 17 (51.5%) patients, followed by germ cell tumours 13 (39.4%). The majority of patients were diagnosed at FIGO Stage I (22, 66.7%) and with tumor Grade 1 (23, 69.7%), while 8 (24.2%) were diagnosed with Grade 3 tumors. Granulosa cell and Sertoli-Leydig cell tumours were diagnosed at an older age (mean age = 39.30 vs. 23.92 years) compared to germ cell tumours, respectively (P = 0.012). Two-third of the patients benefited from conservative surgery including oophorectomy + staging, and 16 (48.5%) benefited from chemotherapy with bleomycin, etoposide and platinum being the most common protocol (13, 39.4%) for germ cell tumours. Postoperatively, only 2 (6.1%) patients had residual disease. Recurrence and mortality were reported in one and four patients, respectively, resulting in recurrence rate = 3.0% (95% confidence interval [CI] = 0.01%, 15.8%) and mortality rate = 12.1% (95% CI = 3.4%, 28.2%). Conclusions: The present series of NEMOT was predominated by sex cord-stromal cell tumors, which were diagnosed in patients with older age, while germ cell tumours were underrepresented. Although survival rates were comparable to those reported internationally, more consideration should be given to following up patients regarding fertility outcomes to provide a more comprehensive evaluation of treatment success and quality of care.

The Diagnosis of Cervical Dysplasia in a University Hospital Using Pap Smear and Colposcopy in the Western Region of Saudi Arabia: A Correlational Study.

Objectives To assess the diagnostic performance of Pap smear screening with or without human papillomavirus (HPV) testing and colposcopy in detecting preinvasive lesions of the cervix among women with reference to histopathological findings. Materials and methods We performed a retrospective study in a tertiary care center of the clinical and pathological records of women with evocative symptomatology. The diagnostic performance of Pap smear screening and colposcopy was analyzed. The sensitivity and specificity of Pap smear screening and colposcopy in detecting preinvasive lesions of the cervix were calculated in 388 patients. Results The mean age was 45.12 years, and the most frequent gynecological symptoms included abnormal bleeding (17.2%) and postcoital bleeding (10.9%). Histopathology showed abnormal results in 26.5% of the 388 patients, including cervical intraepithelial neoplasia 1 (CIN 1; 20.4%), CIN 2 (2.8%), CIN 3 (1.3%), and SCC (1.3%). Both Pap smear screening and colposcopy were highly sensitive in detecting CIN 1+ (94.2%vs.93.2%, respectively) and CIN 2+ (100.0% vs.95.8%, respectively) intraepithelial lesions; however, Pap smears had very low specificity in detecting both CIN 1+ (8.1% vs.73.7%, respectively) and CIN 2+ (8.0% vs. 59.3%, respectively) compared with colposcopy. When combined with HPV status, the specificity of Pap smear increased considerably. Conclusion It has become a high priority to improve the efficiency of cervical cancer (CC) screening programs by optimizing the practice of Pap smear screening, increasing the test specificity, and implementing systematic cytology-HPV co-testing.

Interaction Analysis of MRP1 with Anticancer Drugs Used in Ovarian Cancer: In Silico Approach.

Multidrug resistance (MDR) is one of the major therapeutic challenges that limits the efficacy of chemotherapeutic response resulting in poor prognosis of ovarian cancer (OC). The multidrug resistance protein 1 (MRP1) is a membrane-bound ABC transporter involved in cross resistance to many structurally and functionally diverse classes of anticancer drugs including doxorubicin, taxane, and platinum. In this study, we utilize homology modelling and molecular docking analysis to determine the binding affinity and the potential interaction sites of MRP1 with Carboplatin, Gemcitabine, Doxorubicin, Paclitaxel, and Topotecan. We used AutoDock Vina scores to compare the binding affinities of the anticancer drugs against MRP1. Our results depicted Carboplatin < Gemcitabine < Topotecan < Doxorubicin < Paclitaxel as the order of binding affinities. Paclitaxel has shown the highest binding affinity whereas Carboplatin displayed the lowest affinity to MRP1. Interestingly, our data showed that Carboplatin, Paclitaxel, and Topotecan bind specifically to Asn510 residue in the transmembrane domains 1 of the MRP1. Our results suggest that Carboplatin could be an appropriate therapeutic choice against MRP1 in OC as it couples weakly with Carboplatin. Further, our findings also recommend opting Carboplatin with Gemcitabine as a combinatorial chemotherapeutic approach to overcome MDR phenotype associated with recurrent OC.

Survival and prognostic factors in women treated for epithelial ovarian cancer in western region of Saudi Arabia.

OBJECTIVES: To assess survival and prognostic factors among women with epithelial ovarian cancer in Western Saudi Arabia. METHODS: A retrospective cohort study was carried out between October 2000 and May 2018, reviewing clinical and pathology data of all women who underwent staging or debulking surgery for epithelial ovarian cancer. Analysis of disease-free survival (DFS), overall survivals (OS) and the associated factors used Kaplan-Meier method in addition to cox multivariate regression. RESULTS: A total of 144 patients were included (median age=49.5 years), with a median follow-up time was 3.4 years. Majority (59.7%) of the patients were diagnosed at an advanced stage (III or IV). The mean (95% CI) DFS was 82.3 (67.8-96.8) months, OS was 96.2 (81.3-111.2) months, and the 5-year survival rate was estimated as 38.9%. Univariate analysis showed that older age, clear cell or papillary carcinoma subtypes, serous type, advanced International Federation of Gynecology and Obstetrics (FIGO) stage and the presence of residual disease were associated with poorer DFS and OS (log rank <0.05). Cox regression showed FIGO stage and residual disease >1cm as the strongest prognostic factors independently associated with DFS and OS. CONCLUSION: Improving early diagnosis and achieving optimal cytoreduction are the most critical challenges to achieve significant positive impact on survival of women with epithelial ovarian cancer.

Prognostic value of E-Cadherin and its tumor suppressor role in Saudi women with advanced epithelial ovarian cancer.

The extracellular matrix (ECM) disruption and cytoskeleton reorganization are crucial events in tumor proliferation and invasion. E-Cadherin (E-CAD) is a member of cell adhesion molecules involved in cell-cell junctions and ECM stability. The loss of E-CAD expression is associated with cancer progression and metastasis. This retrospective study aimed to assess E-CAD protein expression in ovarian cancer (OC) tissues and to evaluate its prognostic value. PATIENTS AND METHODS: 143 formalin-fixed and paraffin-embedded (FFPE) blocks of primary advanced stages OC were retrieved and used to construct Tissue microarrays. Automated immunohistochemistry technique was performed to evaluate E-CAD protein expression patterns in OC. RESULTS: E-CAD protein expression was significantly correlated with OC histological subtype (p < 0.0001), while borderline significant correlations were observed with both tumor grade (p = 0.06) and stage (p = 0.07). Interestingly, Kaplan-Meier survival analysis showed that OC patients with membranous E-CAD expression survived longer than those with no E-CAD expression mainly those at advanced stages (p < 0.009). Further in silico analysis confirms the key roles of E-CAD in OC molecular functions. CONCLUSION: we reported a prognosis value of membranous E-CAD in advanced stage OC patients. Further validation using larger cohorts is recommended to extract clinically relevant outcomes towards better OC management and individualized oncology.

Assessment of prognostic value of tissue inhibitors of metalloproteinase 3 (TIMP3) protein in ovarian cancer.

Background: TIMP3 is a multifunctional proteolytic enzyme belonging to TIMPs family and acts as a potent inhibitor of matrix metalloproteinases (MMPs). TIMP3 possesses a tumor suppresive function by directly promoting tumor cell apoptosis, preventing angiogenesis and extracellular matrix remodelling. The lower expression of TIMP3 was associated with poor prognosis and overall survival in various cancer types. The aim of this study was to evaluate the association of TIMP3 protein expression with ovarian cancer (OC) clinicopathological features and survival outcomes.Patients and Methods: One hundred forty four of OC FFPE samples were collected from King Abdulaziz University Hospital, Saudi Arabia and constructed in tissue microarray (TMA) slides. Automated Ventana immunostainer platform was used to evaluate TIMP3 protein expression patterns.Results: The study showed that TIMP3 exhibits cytoplasmic localisation. This TIMP3 protein expression was not associated with age, tumor size and the involvement of lymph nodes (p > 0.05). However, it was significantly correlated with tumor stage (p < 0.05) and borderline significant with endpoint status (p = 0.07). Interestingly, the Kaplan-Meier analysis of disease specific survival (DSS) outcomes showed a significant association (p = 0.02, log rank) between OC patients with higher TIMP3 expression compared to those with lower expression. In fact, OC patients with high TIMP3 expression had longer survivals. Multivariate Cox's regression analysis suggests that low TIMP3 protein expression pattern is an independent poor survival marker (p = 0.025).Conclusion: Cytoplasmic TIMP3 protein expression could be used as a good prognosticator to stratify poorly prognostic OC patients in order to personlaize their disease management.

Human Wharton's Jelly Stem Cell Secretions Inhibit Human Leukemic Cell Line K562 in vitro by Inducing Cell Cycle Arrest and Apoptosis.

Emerging resistance to the tyrosine kinase inhibitors that target the BCR-ABL1 oncoprotein has prompted research for novel therapeutics against chronic myeloid leukemia (CML). Herein, we evaluated the tumor inhibitory properties of the human Wharton's jelly stem cells (hWJSCs) co-culture (hWJSC-CC) and their extracts, namely, the hWJSC-conditioned medium (hWJSC-CM; 100%) and hWJSC-lysate (hWJSC-L; 15 µg/ml), on a CML cell line K562 in vitro. The hWJSCs expressed mesenchymal stem cell (MSC)-related cluster of differentiation (CD) markers and demonstrated mesodermal tissue differentiation potential. The cell metabolic activity showed a mean maximal decrease in the K562 cells by 49.12, 41.98, and 68.80% following treatment with the hWJSC-CC, hWJSC-CM, and hWJSC-L, respectively, at 72 h. The sub-G1 population in the cell cycle was decreased by 3.2, 4.5, and 3.8% following treatment with the hWJSC-CC, hWJSC-CM, and hWJSC-L, whereas the G2/M cell population was increased by 13.7 and 12.5% with the hWJSC-CM and hWJSC-L, respectively, at 48 h. Annexin V-allophycocyanin (APC) assay showed an increase in the apoptotic cells by 4.0, 3.9, and 4.5% at 48 h. The expression of pro-apoptotic BAX and CASP3 genes were increased, whereas BIRC5 (Survivin) was decreased compared with the control. The pro-inflammation-related genes, namely, IFN-γ, TNF-α, IL-1ß, IL-6, IL-8, and IL-12A, were decreased, whereas the anti-inflammatory genes, namely, IL-4 and IL-10, were increased following treatment with the hWJSC-CC, hWJSC-CM, and hWJSC-L at 48 h. Multiplex bead-based cytokine assay also demonstrated decreases in the pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1ß, IL-6, and IL-12) and an increase in the anti-inflammatory cytokine (IL-10) compared with the control. The pro-inflammatory cytokine IL-8 showed an increase with the hWJSC-CC and decreases with both the hWJSC-CM and the hWJSC-L. The hWJSCs and their extracts inhibited the K562 cells by causing cell cycle arrest and inducing apoptosis via the soluble cellular factors. However, an in vivo evaluation is necessary to unravel the true potential of the hWJSCs and their extracts before its use in CML inhibition.

Decoding the Role of Astrocytes in the Entorhinal Cortex in Alzheimer's Disease Using High-Dimensional Single-Nucleus RNA Sequencing Data and Next-Generation Knowledge Discovery Methodologies: Focus on Drugs and Natural Product Remedies for Dementia.

Introduction: Alzheimer's disease (AD) is a major cause of the development of cognitive decline and dementia. AD and associated dementias (ADRD) are the major contributors to the enormous burden of morbidity and mortality worldwide. To date, there are no robust therapies to alleviate or cure this debilitating disease. Most drug treatments focus on restoring the normal function of neurons and the cells that cause inflammation, such as microglia in the brain. However, the role of astrocytes, the brain's housekeeping cells, in the development of AD and the initiation of dementia is still not well understood. Objective: To decipher the role of astrocytes in the entorhinal cortex of AD patients using single nuclear RNA sequencing (snRNASeq) datasets from the Single Cell RNA-seq Database for Alzheimer's Disease (scREAD). The datasets were originally derived from astrocytes, isolated from the entorhinal cortex of AD brain and healthy brain to decipher disease-specific signaling pathways as well as drugs and natural products that reverse AD-specific signatures in astrocytes. Methods: We used snRNASeq datasets from the scREAD database originally derived from astrocytes isolated from the entorhinal cortex of AD and healthy brains from the Gene Expression Omnibus (GEO) (GSE138852 and GSE147528) and analyzed them using next-generation knowledge discovery (NGKD) platforms. scREAD is a user-friendly open-source interface available at https://bmbls.bmi.osumc.edu/scread/that enables more discovery-oriented strategies. snRNASeq data and metadata can also be visualized and downloaded via an interactive web application at adsn.ddnetbio.com. Differentially expressed genes (DEGs) for each snRNASeq dataset were analyzed using iPathwayGuide to compare and derive disease-specific pathways, gene ontologies, and in silico predictions of drugs and natural products that regulate AD -specific signatures in astrocytes. In addition, DEGs were analyzed using the L1000FWD and L1000CDS2 signature search programming interfaces (APIs) to identify additional drugs and natural products that mimic or reverse AD-specific gene signatures in astrocytes. Results: We found that PI3K/AKT signaling, Wnt signaling, neuroactive ligand-receptor interaction pathways, neurodegeneration pathways, etc. were significantly impaired in astrocytes from the entorhinal cortex of AD patients. Biological processes such as glutamate receptor signaling pathway, regulation of synapse organization, cell-cell adhesion via plasma membrane adhesion molecules, and chylomicrons were negatively enriched in the astrocytes from the entorhinal cortex of AD patients. Gene sets involved in cellular components such as postsynaptic membrane, synaptic membrane, postsynapse, and synapse part were negatively enriched (p < 0.01). Moreover, molecular functions such as glutamate receptor activity, neurotransmitter receptor activity, and extracellular ligand-gated ion channels were negatively regulated in the astrocytes of the entorhinal cortex of AD patients (p < 0.01). Moreover, the application of NGKD platforms revealed that antirheumatic drugs, vitamin-E, emetine, narciclasine, cephaeline, trichostatin A, withaferin A, dasatinib, etc. can potentially reverse gene signatures associated with AD. Conclusions: The present study highlights an innovative approach to use NGKD platforms to find unique disease-associated signaling pathways and specific synthetic drugs and natural products that can potentially reverse AD and ADRD-associated gene signatures.

MDR1 Gene Polymorphisms and Its Association With Expression as a Clinical Relevance in Terms of Response to Chemotherapy and Prognosis in Ovarian Cancer.

In spite of the significant advancements in the treatment modalities, 30% of advanced stage ovarian cancer (OC) patients do not respond to the standard chemotherapeutic regimen and most of the responders finally relapse over time due to the escalation of multidrug resistance (MDR) Phenomenon. Our present study evaluated chemotherapeutic sensitivity response among 47 ovarian tumor patients of which we found 37 (78.8%) sensitive and remaining 10 (21.2%) resistant. Among the resistant, seven tumor samples were found to be platinum resistant or refractory to platinum (CB/TX), one to carboplatin, and two to 5FU. Notably, all these resistant cases were observed in the disease recurrence group of patients identified at stage III or IV. The stage III resistant cases revealed heterozygous mutation (C/T) in exon 12 (C1236T) and 26 (C3435T) and increased level of mRNA, whereas homozygous mutation (T/T) was found at stage IV tumor patients. The genotypic difference was found to be significant (p = 0.03) for exon 12, and p = 0.003 for exon 26 mutant genotypes. No significant association between genotypes of different exons with tumor stages and tumor grade was observed (p > 0.05). However, a significant association was observed between the genotype of exon-12 and histopathology of tumor tissue (p = 0.028). Statistically, the chemotherapy response was found to be significantly associated with the tumor stage (p = 0.019). We also observed a significant difference in PFS (P = 0.019) and OS (P = 0.047) between tumor grades 1 and 3. Notably, the highest mRNA expression was observed in resistant tumor sample T-32, where interestingly we found homozygosity TT in all of the exons 12, 21, and 26. Thus, we suggest that exons 12 (C1236T) and exon 26 (C3435T) polymorphism may play a role in inducing drug resistance by altering the expression level of the MDR1 gene. To summarize, we suggest that the expression of MDR1 in OC is influenced by tumor stage and genotype variants as well as by chemotherapeutic drugs. Thus our findings suggest that inter individual variability in platinum based therapy may be anticipated by MDR1 genotypes. Further studies on a large number of samples shall eventually lead to provide beneficial information for the individualized chemotherapy.

Indicators of survival and prognostic factors in women treated for cervical cancer at a tertiary care center in Saudi Arabia.

BACKGROUND: Investigating survival in cervical cancer at the local level is crucial to determine the effectiveness of overall management, as it reflects the level of care provided and awareness among the population about screening and early diagnosis. OBJECTIVES: Analyze overall survival (OS) and disease-free survival (DFS) among patients treated for cervical cancer and to investigate clinical, management- and outcome-related independent factors associated with survival. DESIGN: A retrospective medical record review. SETTING: Gynecology oncology unit in a tertiary care center. PATIENTS AND METHODS: All women with cervical cancer who were treated and followed up between January 1999 and December 2017. Baseline demographic and clinical data, tumor characteristics, treatment options and outcomes including recurrence were collected and analyzed as factors and predictors of survival. MAIN OUTCOME MEASURES: OS and DFS among patients treated for cervical cancer. SAMPLE SIZE: 190 patients. RESULTS: The 190 patients had a mean (SD) age of 54.2 (13.1) years (median 52.0, interquartile range, 46-62), and median (IQR) follow-up time was 37.0 (12.0-69.0) months. Tumor characteristics showed FIGO stage (I [19.0%], II [48.9%], III [18.4%], IV [13.6%]), grade (I [15.8%], II [46.8%], III [35.8%]) and the most frequent histological type was squamous cell carcinoma (77.4%). Patients received initial radiotherapy with concurrent chemotherapy (53.2%), initial radical hysterectomy (24.7%), systemic chemotherapy (6.3%) and palliative care (4.7%). Mean OS and DFS were 97.1 (82.2, 111.9) and 85.2 (70.4, 100.0) months, respectively. Recurrence and mortality rates were 25.8% and 46.8%, occurring after a median (IQR) time=13.0 (6.0-28.0) and 20.0 (9.0-45.0) months, respectively. Survival was independently associated with grade II (hazard ratio [HR]=3.6, 95%CI: 1.3-9.7, P=.012), grade III (HR=4.5, 95%CI:1.6-12.6, P=.004), number of regional organs involved (1-3 organs: HR=7.8, 95%CI: 1.2, 49.1, P=.030), and recurrence (HR=2.23, P=.001). CONCLUSION: Survival was about 8 years in our institution, which is predicted by the tumor grade, regional organs involved and recurrence. Remarkably, this study found a high percentage of patients diagnosed at an advanced stage, which probably impacts survival and stresses the need for improving early detection. LIMITATIONS: Retrospective design, resulting in recall bias and missing data. CONFLICT OF INTEREST: None.

Appropriate Management of Subcutaneous Tissue of Midline Abdominal Incisions.

Objectives To identify the optimal method for subcutaneous tissue management following midline abdominal incisions among patients with high thickness of subcutaneous fat (TSF). Methods A single-center prospective controlled trial among women undergoing elective gynecologic surgery by midline incision with TSF ≥ 3 cm. Incision was managed by suture approximation of Camper's fascia (group 1), closed suction drainage (group 2), or no intervention (control). Groups were compared for the incidence of four-week postop wound complications including surgical site infection (SSI), superficial wound dehiscence (SWD), and seroma; and baseline and perioperative factors were analyzed using multivariate regression. Results Among 145 patients included (43.4% suture, 29.7% drain, 26.9% control), the overall incidence of wound complications was 15.2% (SSI 8.3%, SWD 0.7%, seroma 6.2%). The incidence of SSI was higher with suture (14.3%) versus drain (4.7%) and control (2.6%), while seroma was more frequent in drain (11.6%) versus suture (3.2%) and control (5.1%); however, both results were not statistically significant. Wound complication was independently associated with hemoglobin level (OR = 0.58, p = 0.019) and the occurrence of intraoperative complications (OR = 8.67, p = 0.048). Conclusion There is no statistical evidence about the optimal method of wound closure in the study population. Specific risk profiles can be constructed with an emphasis on preoperative anemia and intraoperative complications.

Molecular docking analysis of HER-2 inhibitor from the ZINC database as anticancer agents.

The human epidermal growth factor (HER2) is a transmembrane receptor that is highly expressed in breast cancer and in different other cancers. Therefore, it is of interest to identify the new HER2 inhibitors from a selected 300 compounds in the ZINC database. The top two hit compounds (ZINC000014780728 (-11.0 kcal/mol) and ZINC000014762512 (-10.8 kcal/mol)) showed a high affinity with HER2 relative to the reference compound (lapatinib (-10.2 kcal/mol)) for further consideration.

Genetic diversity and phylogenetic analysis of HPV 16 & 18 variants isolated from cervical specimens of women in Saudi Arabia.

Human papillomavirus (HPV) are well known to be associated with the development of cervical cancer. HPV16 and HPV 18 are known as high-risk types and reported to be predominantly associated with cervical cancer. The prevalence and genetic diversity of HPV have been well documented globally but, in the Kingdom of Saudi Arabia, data on HPV genetic diversity are lacking. In this study, we have analyzed the genetic diversity of both HPV16 and HPV18 based on their L1 gene sequence because L1 gene is a major capsid protein gene and has been utilized to develop a prophylactic vaccine. In January 2011-2012, a total of forty samples from cervical specimens of women in Saudi Arabia were collected. The association of HPV16, HPV18 was detected by polymerase chain reaction, sequenced and submitted to GenBank. The sequences identity matrix and the phylogenetic relationship were analyzed with selected HPVs. The highest sequence identity (99.5%) for HPV16 and (99.3%) for HPV was observed with selected HPVs. The phylogenetic analysis results showed that HPVs from Saudi Arabia formed a closed cluster with African, Asian, East Asian as well as American HPVs distributed into multiple linages from various geographical locations. The results provided the valuable information about genetic diversity, but there is an urgent need to generate full genome sequence information which will provide a clearer picture of the genetic diversity and evolution of HPVs in Saudi Arabia. In conclusion, the generated data will be highly beneficial for developing molecular diagnostic tools, analyzing and correlating the epidemiological data to determine the risk of cervical cancer and finally to develop a vaccine for Saudi Arabian population.

Structure-based virtual screening and molecular docking for the identification of potential novel EGFRkinase inhibitors against ovarian cancer.

Epidermal Growth Factor Receptor (EGFR) is, for the most part, deregulated and over-communicated in ovarian disease, which is legitimately connected with STAT3 enactment that prompts the collection of hostile to apoptotic occasions and along these lines, docetaxel medicate obstruction happens. As to, expanding of docetaxel medicate affectability by focusing on EGFR receptor alongside docetaxel drugs is one of the real techniques in ovarian disease treatment. In this specific circumstance, utilizing atomic recreation considers, the present examination depicted the auxiliary and pragmatic properties of IBS Database mixes as a potential inhibitor of EGFR tyrosine kinase, and furthermore ADMET had researched its Pharmacokinetic profile. As indicated by the outcomes, STOCK1N-98911, STOCK1N- 98869, and STOCK1N-98896 have appeared tremendous restricting vitality by associating with critical build ups in the dynamic site. Natural movement range forecast of these mixes indicated potential anticancer properties by demonstrating important collaboration with EGFR tyrosine kinase. Besides, the investigation is likewise valuable for further clinical based examinations and furthermore for the approval of toxicological and pharmacokinetic contemplate.

Growing teratoma syndrome with porta hepatis involvement - a case report.

Growing teratoma syndrome is a rare entity of tumors, it arises seldomly from ovarian and testicular carcinoma. It presents with disseminating masses of mature teratoma during or following chemotherapy of malignant germ cell tumors. We are reporting a 19-year old presented with recurrent left ovarian mass and supra renal large mass close to the porta hepatis was seen on magnetic resonance imaging. This patient was treated 3 years ago for stage I immature teratoma with left ovarian cystectomy and chemotherapy. Surgical excision of the left ovary and the abdominal mass required meticulous dissection, and the mass was shaved off the porta hepatis with no intraoperative or postoperative complications. Pathology showed mature teratoma. She has no recurrent 5 years after treatment. To the best of our knowledge, this is the first case report describing close relation of growing teratoma syndrome to the porta hepatis, no such case report like this has been reported in our region.

Cytokines secreted by human Wharton's jelly stem cells inhibit the proliferation of ovarian cancer (OVCAR3) cells in vitro.

Cytokines enhance tumour cell recognition via cytotoxic effector cells and are therefore effectively used in cancer immunotherapy. Mesenchymal stem cells have efficient homing potential and have been used to target and inhibit various types of cancer mediated by the release of soluble/bioactive factors. Initial evaluation of the human Wharton's jelly stem cell conditioned medium (hWJSC-CM) and cell lysate (hWJSC-CL) against an ovarian cancer cell line (OVCAR3) demonstrated their inhibitory effect in vitro. The secreted cytokine profile was then studied to understand whether the OVCAR3 inhibitory effect was mediated by the cytokines. Expression of cytokines in OVCAR3 following 48 h treatment with hWJSC extracts, namely the hWJSC-CM (50%) and hWJSC-CL (10 µg/ml), was evaluated using multiplex cytokine assay. Paclitaxel (5 nM) was used as a positive control. Cytokines tumour necrosis factor α, interleukin (IL)-4, IL-6, IL-8, IL-10, IL-13, IL-17, IL-1ß and granulocyte colony-stimulating factor, reported to be involved in tumour growth, invasion and migration, were significantly decreased. Cytokines with antitumour effects, namely IL-1 receptor antagonist (IL-1RA), IL-2, IL-2 receptor, IL-5, IL-7, IL-12, IL-15, interferon (IFN)-α and IFN-γ, were mildly increased or decreased. Only the increases in IL-1RA (with paclitaxel, hWJSC-CM and hWJSC-CL) and granulocyte-macrophage colony-stimulating factor (with hWJSC-CL) were statistically significant. The chemokines monocyte chemoattractant protein 1, macrophage inflammatory protein (MIP)-1α, MIP-1ß and Regulated Upon Activation, Normally T-Expressed, and Secreted were significantly decreased while monokine induced by IFN-γ, IFN-γ induced protein 10 and Eotaxin demonstrated mild decreases. The growth factors basic fibroblast growth factor, vascular endothelial growth factor and hepatocyte growth factor were significantly decreased. Heatmaps demonstrated differential fold changes in cytokines and hierarchical cluster analysis revealed 3 major and 7 minor sub-clusters of associated cytokines, chemokines and growth factors. In conclusion, the hWJSC extracts decreased the expression of oncogenic cytokines, chemokines and growth factors, which mediated the inhibition of OVCAR3 cells in vitro.

Human Wharton's Jelly Stem Cell (hWJSC) Extracts Inhibit Ovarian Cancer Cell Lines OVCAR3 and SKOV3 in vitro by Inducing Cell Cycle Arrest and Apoptosis.

Ovarian cancer is a highly lethal and the second highest in mortality among gynecological cancers. Stem cells either naïve or engineered are reported to inhibit various human cancers in both in-vitro and in-vivo. Herein we report the cancer inhibitory properties of human Wharton's jelly stem cell (hWJSC) extracts, namely its conditioned medium (hWJSC-CM) and cell lysate (hWJSC-CL) against two ovarian cancer cell lines (OVCAR3 and SKOV3) in-vitro. Cell metabolic activity assay of OVCAR3 and SKOV3 cells treated with hWJSC-CM (12.5, 25, 50, 75, 100%) and hWJSC-CL (5, 10, 15, 30, and 50 µg/ml) demonstrated concentration dependent inhibition at 24-72 h. Morphological analysis of OVCAR3 and SKOV3 cells treated with hWJSC-CM (50, 75, 100%) and hWJSC-CL (15, 30, and 50 µg/ml) for 24-72 h showed cell shrinkage, membrane damage/blebbings and cell death. Cell cycle assay demonstrated an increase in the sub-G1 and G2M phases of cell cycle following treatment with hWJSC-CM (50, 75, 100%) and hWJSC-CL (10, 15, and 30 µg/ml) at 48 h. Both OVCAR3 and SKOV3 cells demonstrated mild positive expression of activated caspase 3 following treatment with hWJSC-CM (50%) and hWJSC-CL (15 µg/ml) for 24 h. Cell migration of OVCAR3 and SKOV3 cells were inhibited following treatment with hWJSC-CM (50%) and hWJSC-CL (15 µg/ml) for 48 h. Tumor spheres (TS) of OVCAR3 and SKOV3 treated with hWJSC-CM (50, 75, 100%) and hWJSC-CL (10, 15, 30 µg/ml) for 48 h showed altered surface changes including vacuolations and reduction in size of TS. TS of OVCAR3 and SKOV3 also showed the presence of few ovarian cancer stem cells (CSCs) in minimal numbers following treatment with hWJSC-CM (50%) or hWJSC-CL (15 µg/ml) for 48 h. Real-time gene expression analysis of OVCAR3 and SKOV3 treated with hWJSC-CM (50%) or hWJSC-CL (15 µg/ml) for 48 h demonstrated decreased expression of cell cycle regulatory genes (cyclin A2, Cyclin E1), prostaglandin receptor signaling genes (EP2, EP4) and the pro-inflmmatory genes (IL-6, TNF-α) compared to untreated controls. The results indicate that hWJSC-CM and hWJSC-CL inhibit ovarian cancer cells at mild to moderate levels by inducing cellular changes, cell cycle arrest, apoptosis, decreasing the expression of CSC markers and related genes regulation. Therefore, the stem cell factors in hWJSCs extracts can be useful in cancer management.