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BACKGROUND: Among gynaecological malignancies, endometrial cancer (EC) is the most prevalent type of uterine cancer affecting women. This study explored the proteomic profiles of plasma samples obtained from EC patients, those with hyperplasia (Hy), and a control group (CO). A combination of techniques, such as 2D-DIGE, mass spectrometry, and bioinformatics, including pathway analysis, was used to identify proteins with modified expression levels, biomarkers and their associated metabolic pathways in these groups. METHODS: Thirty-four patients, categorized into three groups-10 with EC, 12 with Hy, and 12 CO-between the ages of 46 and 75 years old were included in the study. Untargeted proteomic analysis was carried out using two-dimensional difference in gel electrophoresis (2D-DIGE) coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). RESULTS: In all three groups, 114 proteins that were significantly (p ≤ 0.05 and fold change ≥ 1.5) altered were successfully identified using peptide mass fingerprints (PMFs). Compared with those in the control group (CO), the EC samples had 85 differentially expressed proteins (39 upregulated and 46 downregulated), and in the Hy group, 81 proteins were dysregulated (40 upregulated and 41 downregulated) compared to those in the CO group, while 33 proteins exhibited differential regulation (12 upregulated and 21 downregulated) in the EC plasma samples compared to those in the Hy group. Vitamin D binding protein and complement C3 distinguished Hy and EC from CO with the greatest changes in expression. Among the differentially expressed proteins identified, enzymes with catalytic activity represented the largest group (42.9%). In terms of biological processes, most of the proteins were involved in cellular processes (28.8%), followed by metabolic processes (16.7%). STRING analysis for protein interactions revealed that the significantly differentially abundant proteins in the three groups are involved in three main biological processes: signalling of complement and coagulation cascades, regulation of insulin-like growth factor (IGF) transport and uptake by insulin-like growth factor binding proteins (IGFBPs), and plasma lipoprotein assembly, remodelling, and clearance. CONCLUSION: The identified plasma protein markers have the potential to serve as biomarkers for differentiating between EC and Hy, as well as for early diagnosis and monitoring of cancer progression.
Subject(s)
Biomarkers, Tumor , Endometrial Neoplasms , Proteomics , Humans , Female , Endometrial Neoplasms/blood , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Middle Aged , Aged , Proteomics/methods , Biomarkers, Tumor/blood , Biomarkers, Tumor/metabolism , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Endometrial Hyperplasia/blood , Endometrial Hyperplasia/metabolism , Endometrial Hyperplasia/pathology , Blood Proteins/metabolism , Blood Proteins/analysis , Proteome/metabolismABSTRACT
Uterine cancer is the most prevalent gynecologic malignancy in women worldwide. Endometrial cancer (EC) has an 81% five-year survival rate, depending on disease stage and time of diagnosis. While endometrial cancer is largely treatable when detected early, no established screening techniques are available in clinical practice. As a result, one of the most significant issues in the medical field is the development of novel ways for early cancer identification, which could boost treatment success rates. Liquid chromatography-high-resolution mass spectrometry (LC-HRMS)-based metabolomics was employed to explore the metabolomic markers and pathways unique to this cancer type and link them to the benign endometrial hyperplasia that may progress to cancer in 5% to 25% of patients. The study involved 59 postmenopausal participants, 20 with EC type 1, 20 with benign hyperplasia, and 19 healthy participants. Metabolite distribution changes were analyzed, and 338 of these features were dysregulated and significant. The first two main components, PC1 and PC2, were responsible for 11.5% and 12.2% of the total metabolites, respectively. Compared with the control group (CO), EC samples had 203 differentially expressed metabolites (180 upregulated and 23 downregulated); in hyperplasia (HP), 157 metabolites were dysregulated (127 upregulated and 30 downregulated) compared to the CO group while 21 metabolites exhibited differential regulation (16 upregulated and 5 downregulated) in EC plasma samples compared to the HP group. Hyperplasia samples exhibited similar metabolic changes to those reported in cancer, except for alterations in triglyceride levels, 7a,12 b-dihydroxy-5b-Cholan-24-oic acid, and Hept-2-enedioyl carnitine levels. The metabolites N-heptanoyl glycine and -(Methylthio)-2,3-isopentyl phosphate and formimino glutamic acid can be specific markers for hyperplasia conditions and dimethyl phosphatidyl ethanolamine and 8-isoprostaglandin E2 can be specific markers for EC conditions. Metabolic activities rely on mitochondrial oxidative phosphorylation for energy generation. The changes in metabolites identified in our study indicate that endometrial cancer cells adopt alternative strategies to increase energy production to meet the energy demand, thereby supporting proliferation.
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The incidence and mortality of endometrial cancer (EC) have increased in recent years. There is mounting evidence that diabetes may play a role in the greater incidence of EC. The molecular mechanisms of the interaction between type 2 diabetes and EC are not yet clearly understood yet. The present study was undertaken to investigate the plasma proteomics of EC patients with diabetes in comparison to those of EC patients without diabetes. Plasma samples were obtained from age-matched patients (EC diabetic and EC nondiabetic). Untargeted proteomic analysis was carried out using a two-dimensional differential gel electrophoresis coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Of the 33 proteins identified, which significantly differed in the plasma abundance between groups, 17 were upregulated and 16 were downregulated. The majority of the altered proteins are involved in the acute phase reaction, cholesterol metabolism, scavenging of heme from plasma, and plasma lipoprotein assembly and mobilization. α-2-macroglobulin, Ras association domain-containing protein 3, apolipoprotein A-I, α-1B-glycoprotein, and zinc-α-2-glycoprotein were significantly upregulated. The significantly downregulated proteins included haptoglobin, apolipoprotein A-IV, hemopexin, and α-1-antichymotrypsin. The differential expression of proteins found in patients who had EC and diabetes indicated severe disease and a poor prognosis. The protein interaction analysis showed dysregulation of cholesterol metabolism and heme scavenging pathways in these patients.
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Background: Bethesda III and IV thyroid nodules continue to be difficult to manage. Although molecular testing may assist in decision-making, it is expensive, not widely available, and not without pitfalls. The objective of this study is to assess whether certain thyroid ultrasonographic features may predict the risk of thyroid cancer in patients with Bethesda III and IV thyroid nodules and be used as additional decision-making tools to complement cytopathological results in deciding on diagnostic thyroidectomy. Methods: We retrospectively evaluated the ultrasonographic features of Bethesda categories III and IV thyroid nodules in patients who underwent subsequent thyroidectomy. We used the final histopathological examination of the surgical specimens as the gold-standard test and analyzed individual preoperative ultrasonographic features as predictors of malignancy. Results: Of the 278 patients who were diagnosed with Bethesda III and IV thyroid nodules on fine needle aspiration cytology (FNAC), 111 (39.9%) had thyroid cancer, and 167 (59.9%) exhibited benign nodules. The malignancy rate was higher in patients with Bethesda IV nodules (28/50, 56%) than those with Bethesda III nodules (83/228, 36.4%; p=0.016). In univariate analysis, hypoechogenicity (55.6% in malignant vs. 35.3% in benign, p=0.006) and calcifications (54.5 in malignant vs. 35.4% in benign, p=0.008) were significantly different between the benign and malignant pathology groups, whereas the size of the dominant nodule, number of nodules, irregular borders, taller-than-wide shape, and the presence of lymph nodes were comparable between the two groups. These two ultrasonographic features (hypoechogenicity and calcifications) remained significantly associated with the risk of malignancy in multivariate logistic regression analysis (for hypoechogenicity, p=0.014, odds ratio: 2.1, 95% CI:1.0-3.7 and for calcifications, p=0.019, odds ratio: 1.98, 95% CI:1.12-3.50). The sensitivity, specificity, positive and negative predictive values, and accuracy were 31.5%, 83%, 55.6%,64.7%, and 62.6%, for hypoechogenicity, respectively and 32.4%, 82%, 54.5%, 67.8%, and 62%, for calcification, respectively. Conclusions: Hypoechogenicity and calcifications in Bethesda III and IV thyroid nodules are strong predictors of thyroid cancer and associated with a two-fold increased risk of malignancy.
Subject(s)
Calcinosis , Thyroid Neoplasms , Thyroid Nodule , Humans , Thyroid Nodule/pathology , Retrospective Studies , Thyroid Neoplasms/pathology , Thyroidectomy , Calcinosis/surgeryABSTRACT
OBJECTIVES: This study examined residents' attitudes and practices regarding the relevance of spirituality in psychiatry within Saudi residency training programs; their experiences and comfort levels in addressing patients' spiritual concerns; and their interest and past learning experiences in this area of training and practice. METHODS: This cross-sectional study targeted trainees and recent graduates of residency programs across Saudi Arabia. The study materials consisted of an electronic questionnaire that was adapted with permission. RESULTS: The total number of respondents was 71 out of 180 potential participants (39.44%). Most residents (64.8%) felt that it was appropriate to inquire about the spiritual aspects of patients' lives and that it was essential to address spiritual problems or needs that patients may have within the clinical setting (71.8%). Many participants (40.80%) described themselves as being both religious and spiritual. Most respondents (94.4%) did not receive any training on spirituality and psychiatry, and 80.3% said they would like to learn more about the subject. CONCLUSIONS: Our findings indicate that residents have an overall high level of personal spirituality and that they feel it is relevant in clinical practice. However, they have not had much training in this area and are interested in learning more. Educational initiatives would be beneficial for improving the effectiveness of residents and patient care in this untapped area of spirituality in psychiatry.
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Soft tissue chondromas are rare benign tumors that occur in extraosseous and extra-synovial locations. We report herein a rare presentation of eyelid soft tissue chondroma in a 45-year-old male presented with a 2-year history of a slowly enlarging subcutaneous firm mass on the left upper eyelid, and complete excision of the lesion followed by histopathological examination rendered the diagnosis of soft tissue chondroma.
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Background: Epilepsy is a common global neurological disorder. About 30% of epileptic patients are managed with anti-epileptic Drugs (AEDs). Since 2000, Levetiracetam (LEV) has been marketed around the world as an AED under the brand name Keppra, and recently more generics are found in the Saudi market as cheaper alternatives. The objective of this study is to evaluate the bioequivalence of LEV brand and generics available in the Saudi market in mice. Methods: Pharmacokinetics (PK), liver function test, and behavioral studies were conducted for LEV brand and generic in different groups of Blab/c mice. Results: PK results show a significance difference in PK parameters mostly evidenced with generic 3, then generic 2. The only significant different between Keppra and generic 1 was in T1/2. In addition, Keppra did not significantly increase liver enzymes in comparison to other generics. On the other hand, other generics showed less favorable results in increasing liver enzymes. Keppra reduced the number and intensity of epileptic attacks, had no mortality rate due to epilepsy, and was associated with less sever seizures attacks. Conclusion: Keppra, the brand form of LEV, has better safety and efficacy profiles in mice compared to 3 generics found in the Saudi market. Therefore, we recommend evaluating the same parameters tested in this study in patients utilizing similar generics and brand to establish the existence of bioequivalence between LEV brand and generics.
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INTRODUCTION AND IMPORTANCE: Orbital metastasis from breast cancer may be infrequently noted after the management of the primary lesion. It is rare in such cases to present with unilateral mechanical blepharoptosis without ophthalmoplegia. CASE PRESENTATION: We present a case of unilateral acquired blepharoptosis of the left upper eyelid without ophthalmoplegia or exophthalmos three years after the onset of a suspicious breast mass. The patient did not disclose a history of breast cancer nor any positive family history to the ophthalmologist and anesthesiologist. The radiology images revealed an ill-defined enhanced lesion at the superior medial aspect of the left orbit. The orbital biopsy of the lesion showed poorly differentiated carcinoma as per the initial histopathology report. Vigilant history-taking enabled us to get information about a previous breast lesion and to correlate this with specific histopathological findings. DISCUSSION: Management of orbital lesions might be challenging, and the approach should include detailed history and assessment. Biopsy and radio imaging are further needed to aid in providing the proper diagnosis. The clinicopathological correlation in our case has led to the final diagnosis of orbital metastatic breast cancer. CONCLUSION: Ophthalmologists should be aware of variable ocular presentations of malignancy and adopt a team approach to obtain a carefully detailed history from patients presenting with orbital diseases and communicate adequately with the ocular pathologists who are handling the biopsy. Long-term follow-up and enhancement of patients' awareness of possible late orbital metastasis are recommended in all patients with breast masses.
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Background Triple-negative breast cancer (TNBC) is a highly aggressive disease that lacks therapeutic targets and prognostic biomarkers. Claudin-1 is a well-described tight junction protein with prognostic value in many human cancers. Aims The need for the discovery of biomarkers of TNBC disease was a major reason for this study. Claudin-1 is a tight junction protein that has shown promising results in the prognosis and management of cancer in general. In the breast, claudin-1 expression and significance have shown variable results, especially in TNBC patients. Our study assessed expression of claudin-1 in a group of TNBC patients, and correlated this expression with clinical-pathological parameters, and with the expression of ß-catenin. Materials and methods Tissues from a group of 52 TNBC patients were retrieved from the archives of the community hospital. All related information including demographical, pathologic and clinical data were retrieved. Immunohistochemistry assays of a rabbit polyclonal antibody anti-human claudin-1 were applied using the avidin-biotin peroxidase methodology. Results A statistically significant majority of TNBC cases positively expressed claudin-1 (81%, χ2=13.705; p<0.001). Most TNBC cases had grade 2 ß-catenin expression (77.5%; p<0.001), and positive expression for claudin-1 correlated with that of ß-catenin (χ2= 23.757; p<0.001). Claudin-1 and ß-catenin expressions within tumour cells shared several features including absent or weakness of membranous expression, and redistribution of both proteins to the cytoplasm of tumour cells, and in some cases to the nuclei of these cells. Claudin-1 expression also correlates with adverse survival outcomes, where only four of 20 claudin-1-positive patients who received neo-adjuvant chemotherapy (NAC) achieved pathological complete response (pCR). Conclusions The above presents a complex role of claudin-1 in TNBC patients. In this study, claudin-1 expression was associated with poor prognostic features including invasion, metastases and adverse clinical outcomes. Claudin-1 expression in TNBC correlated with the expression of ß-catenin, an important oncogene and a major contributor to the epithelial mesenchymal transition (EMT) phenomenon. Overall, the above results may serve as an impetus for further mechanistic studies to assess the exact role of claudin-1 in TNBC and its possible use in the management of this subset of breast cancer.
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BACKGROUND In the pediatric age group, middle ear tumors are rare. Rhabdomyosarcoma is considered the most common soft-tissue sarcoma in children. It comprises 5% of all pediatric malignant tumors. It is hypothesized to originate from embryonic mesenchymal cells of striated skeletal muscles. These malignant lesions display an aggressive behavior with local and distant metastasis and can be staged as per the Intergroup Rhabdomyosarcoma Study Group, depending on the organs involved, such as the orbit, head, neck, or genitourinary tract. CASE REPORT In this study, a 2-year-old boy with no medical ailments was presented with a history of ear pain and on/off bleeding from the right ear for 1 year. The patient's case was initially managed medically, for the clinical picture of an ear infection. However, clinical improvement was not seen. Therefore, radiological imaging was done. After further investigations, the diagnosis was confirmed, and a rare case of embryonal rhabdomyosarcoma of the temporal bone was reported. CONCLUSIONS Rhabdomyosarcoma is an uncommon tumor in which delayed diagnosis could cause a significant fatality rate in children. Physicians need a strong index of suspicion to make an early diagnosis. The presented case is of a 2-year-old boy with a clinical picture of a complicated ear infection who was found to have rhabdomyosarcoma of the temporal bone. Early detection and multimodal treatment are critical for a positive outcome.
Subject(s)
Face , Otitis , Child , Humans , Child, Preschool , Temporal Bone/diagnostic imagingABSTRACT
Background: Erlotinib (ERL) and gefitinib (GEF) are extensively metabolized by CYP450 enzymes. Aspartame (ASP), an artificial sweetener, induces CYP2E1 and CYP3A2 enzymes in the brain and could increase liver enzymes. In this work, the influence of ASP on the pharmacokinetics (PK) of ERL and GEF in Wistar rats was evaluated. Methods: The PKs of ERL and GEF were evaluated after receiving 175 mg/kg or 1000 mg/kg of ASP for four weeks using UPLC-MS/MS. Levels of liver enzymes after four weeks of ASP consumption were also evaluated. Results: ASP 175 mg/kg was able to significantly alter levels of Cmax (36% increase for ERL, 38% decrease for GEF), AUC0-72 (205% increase for ERL, 41% increase for GEF), and AUC0-∞ (112% increase for ERL, 14% increase for GEF). Moreover, ASP 175 mg/kg decreased the apparent oral clearance ERL and GEF by 58% and 13%, respectively. ASP 1000 mg/kg increased Cmax of ERL by 159% and decreased GEF's Cmax by and 73%. Both AUC0-72 and AUC0-∞ were increased by ASP 1000 for ERL and decreased for GEF. CL/F decreased by 64% for ERL and increased by 38.8% for GEF. Moreover, data indicated that ASP significantly increased levels of liver enzymes within two weeks of administration. Conclusions: Although ASP 175 and 1000 mg/kg alter ERL and GEF PKs parameters, ASP 1000 mg/kg has the highest impact on most parameters. ASP 1000 mg/kg also can significantly increase activities of liver enzymes indicating the possibility of inducing liver injury. Therefore, it might be of clinical importance to avoid the administration of aspartame containing products while on ERL or GEF therapy.
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BACKGROUND: Locally advanced breast cancer (LABC), the most aggressive form of the disease, is a serious threat for women's health worldwide. The AU-rich RNA-binding factor 1 (AUF1) promotes the formation of chemo-resistant breast cancer stem cells. Thereby, we investigated the power of AUF1 expression, in both cancer cells and their stromal fibroblasts, as predictive biomarker for LABC patients' clinical outcome following neoadjuvant treatment. METHODS: We have used immunohistochemistry to assess the level of AUF1 on formalin-fixed paraffin-embedded tissues. Immunoblotting was utilized to show the effect of AUF1 ectopic expression in breast stromal fibroblasts on the expression of various genes both in vitro and in orthotopic tumor xenografts. Cytotoxicity was evaluated using the WST1 assay, while a label-free real-time setting using the xCELLigence RTCA technology was utilized to assess the proliferative, migratory and invasive abilities of cells. RESULTS: We have shown that high AUF1 immunostaining (≥ 10%) in both cancer cells and their adjacent cancer-associated fibroblasts (CAFs) was significantly associated with higher tumor grade. Kaplan-Meier univariate analysis revealed a strong correlation between high AUF1 level in CAFs and poor patient's survival. This correlation was highly significant in patients with triple negative breast cancer, who showed poor disease-free survival (DFS) and overall survival (OS). High expression of AUF1 in CAFs was also associated with poor OS of ER+/Her2- patients. Similarly, AUF1-positive malignant cells tended to be associated with shorter DFS and OS of ER+/Her2+ patients. Interestingly, neoadjuvant therapy downregulated AUF1 to a level lower than 10% in malignant cells in a significant number of patients, which improved both DFS and OS. In addition, ectopic expression of AUF1 in breast fibroblasts activated these cells and enhanced their capacity to promote, in an IL-6-dependent manner, the epithelial-to-mesenchymal transition and stemness processes. Furthermore, these AUF1-expressing cells enhanced the chemoresistance of breast cancer cells and their growth in orthotopic tumor xenografts. CONCLUSIONS: The present findings show that the CAF-activating factor AUF1 has prognostic/predictive value for breast cancer patients and could represent a great therapeutic target in order to improve the precision of cancer treatment.
Subject(s)
Breast Neoplasms , Heterogeneous-Nuclear Ribonucleoprotein D , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Carcinogenesis/metabolism , Drug Resistance, Neoplasm/genetics , Female , Fibroblasts/metabolism , Heterogeneous Nuclear Ribonucleoprotein D0 , Heterogeneous-Nuclear Ribonucleoprotein D/genetics , Heterogeneous-Nuclear Ribonucleoprotein D/metabolism , Humans , PrognosisABSTRACT
Uterine cancers are among the most prevalent gynecological malignancies, and endometrial cancer (EC) is the most common in this group. This study used tissue-based proteomic profiling analysis in patients with endometrial cancer and hyperplasia, and control patients. Conventional 2D gel electrophoresis, followed by a mass spectrometry approach with bioinformatics, including a network pathway analysis pipeline, was used to identify differentially expressed proteins and associated metabolic pathways between the study groups. Thirty-six patients (twelve with endometrial cancer, twelve with hyperplasia, and twelve controls) were enrolled in this study. The mean age of the participants was 46-75 years. Eighty-seven proteins were significantly differentially expressed between the study groups, of which fifty-three were significantly differentially regulated (twenty-eight upregulated and twenty-five downregulated) in the tissue samples of EC patients compared to the control (Ctrl). Furthermore, 26 proteins were significantly dysregulated (8 upregulated and 18 downregulated) in tissue samples of hyperplasia (HY) patients compared to Ctrl. Thirty-two proteins (nineteen upregulated and thirteen downregulated) including desmin, peptidyl prolyl cis-trans isomerase A, and zinc finger protein 844 were downregulated in the EC group compared to the HY group. Additionally, fructose bisphosphate aldolase A, alpha enolase, and keratin type 1 cytoskeletal 10 were upregulated in the EC group compared to those in the HY group. The proteins identified in this study were known to regulate cellular processes (36%), followed by biological regulation (16%). Ingenuity pathway analysis found that proteins that are differentially expressed between EC and HY are linked to AKT, ACTA2, and other signaling pathways. The panels of protein markers identified in this study could be used as potential biomarkers for distinguishing between EC and HY and early diagnosis and progression of EC from hyperplasia and normal patients.
Subject(s)
Endometrial Neoplasms , Proteomics , Actins , Aged , Electrophoresis, Gel, Two-Dimensional , Endometrial Neoplasms/metabolism , Female , Humans , Hyperplasia , Middle Aged , Proteomics/methodsABSTRACT
Background: Active breast cancer-associated fibroblasts (CAFs) play a leading role in breast carcinogenesis through promoting angiogenesis and resistance to therapy. Consequently, these active stromal cells have significant influence on patient outcome. Therefore, we explored here the role of the DNA methyltransferase 1 (DNMT1) protein in CAF-dependent promotion of angiogenesis as well as the prognostic power of DNMT1 level in both cancer cells and their adjacent CAFs in locally advanced breast cancer patients. Methods: We applied immunohistochemistry to evaluate the level of DNMT1 in breast cancer tissues and their adjacent normal counterparts. Quantitative RT-PCR and immunoblotting were performed to investigate the role of DNMT1 in regulating the expression of pro-angiogenic genes in active CAFs and also their response to the DNMT1 inhibitors decitabine (DAC) as well as eugenol. Results: We have shown that DNMT1 controls the pro-angiogenic potential of CAFs both in vitro and in vivo through positive regulation of the expression/secretion of 2 important pro-angiogenic factors VEGF-A and IL-8 as well as their upstream effectors mTOR and HIF-1α. To confirm this, we have shown that these DNMT1-related pro-angiogenic effects were suppressed by 2 DNMT1 inhibitors decitabine and eugenol. Interestingly, in a cohort of 100 tumors from locally advanced breast cancer patients (LABC), we have shown that high expression of DNMT1 in tumor cells and their adjacent stromal fibroblasts is correlated with poor survival of these patients. Conclusion: DNMT1 upregulation in breast stromal fibroblasts promotes angiogenesis via IL-8/VEGF-A upregulation, and correlates well with poor survival of LABC patients.
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Endometrial cancer (EC) is the most common form of gynecological cancer. Type 2 diabetes mellitus is associated with an increased risk of EC. Currently, no proteomic studies have investigated the role of diabetes in endometrial cancers from clinical samples. The present study aims to elucidate the molecular link between diabetes and EC using a proteomic approach. Endometrial tissue samples were obtained from age-matched patients (EC Diabetic and EC Non-Diabetic) during surgery. Untargeted proteomic analysis of the endometrial tissues was carried out using a two-dimensional difference in gel electrophoresis (2D-DIGE) coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF). A total of 53 proteins were identified, with a significant difference in abundance (analysis of variance (ANOVA) test, p ≤ 0.05; fold-change ≥ 1.5) between the two groups, among which 30 were upregulated and 23 downregulated in the EC Diabetic group compared to EC Non-Diabetic. The significantly upregulated proteins included peroxiredoxin-1, vinculin, endoplasmin, annexin A5, calreticulin, and serotransferrin. The significantly downregulated proteins were myosin regulatory light polypeptide 9, Retinol dehydrogenase 12, protein WWC3, intraflagellar transport protein 88 homolog, superoxide dismutase [Cu-Zn], and retinal dehydrogenase 1. The network pathway was related to connective tissue disorder, developmental disorder, and hereditary disorder, with the identified proteins centered around dysregulation of ERK1/2 and F Actin signaling pathways. Cancer-associated protein alterations such as upregulation of peroxiredoxin-1, annexin 5, and iNOS, and downregulation of RDH12, retinaldehyde dehydrogenase 1, SOD1, and MYL 9, were found in the EC tissues of the diabetic group. Differential expression of proteins linked to cancer metastasis, such as the upregulation of vinculin and endoplasmin and downregulation of WWC3 and IFT88, was seen in the patients with diabetes. Calreticulin and alpha-enolase, which might have a role in the interplay between diabetes and EC, need further investigation.
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INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious with various possible routes of transmission, resulting in high mortality globally. Controversy exists regarding the vertical transmission of the SARS-CoV-2 infection to fetuses of COVID-19-infected women. The aim of this study was to investigate the possibility of the vertical transmission of SARS-CoV-2 from COVID-19-infected mothers to their neonates. MATERIALS AND METHODS: We prospectively collected demographical and clinical characteristics of 31 COVID-19 positive pregnant women and their neonates. All mothers and neonates were tested for SARS-CoV-2 infection using the real-time polymerase chain reaction on nasopharyngeal swabs and breast milk samples. Antenatal and placental abnormalities were ultrasonically and histopathologically examined. In cord blood samples, the immunoglobins (Ig) M and IgG were estimated qualitatively. RESULTS: The women's mean age and gestational age were 31 years and 38 weeks, respectively, with 58% undergoing an elective cesarean section. Gestational diabetes was reported in 29% of cases, 64.5% of women were medically free and only 16.12% were symptomatic. A normal antenatal ultrasound was observed in 77.42% of cases. Nine cord blood samples were positive for IgG. Villous infarction (24%), villous agglutination, and chorangiosis (51%), accelerated villous maturation (21%) and reduced and hypercoiling were reported for 6.97% of the umbilical cords. Three newborns had possible vertical transmission of SARS-CoV-2 infection, of which, two were preterm and IUFD. The third neonate was born full-term, admitted to NICU and later discharged in good health. CONCLUSION: Our findings support the possibility of the direct vertical transmission of the SARS-CoV-2 infection to neonates from infected mothers. Further studies with a larger sample size are required to validate the current findings.
Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Female , Infant, Newborn , Pregnancy , Humans , Adult , SARS-CoV-2 , Cesarean Section , Placenta , Infectious Disease Transmission, Vertical , Immunoglobulin GABSTRACT
Ovarian serous tumors and related lesions are one of the most common conditions of the female genital tract. While ovarian high-grade serous carcinoma carries high mortality and adverse prognosis, most other serous lesions have better clinical behavior. In recent years, significant progress has been made in understanding the nature and histogenesis of these lesions that has contributed to better and more precise clinical management. Most of the high-grade serous carcinomas involve the ovaries and/or peritoneum, although in most cases, their origin seems to be in the fallopian tube. This view is supported by the recognition of precursor lesions in the fallopian tube, such as p53 signature and serous tubular in situ carcinoma. This paper presents salient morphologic, immunohistochemical, and molecular data related to serous tumors and related lesions of the female pelvis and discusses the histogenetic interrelationship among these lesions in light of current knowledge.
Subject(s)
Carcinoma , Fallopian Tube Neoplasms , Ovarian Neoplasms , Carcinoma/pathology , Fallopian Tube Neoplasms/pathology , Fallopian Tubes/pathology , Female , Humans , Ovarian Neoplasms/pathology , Pelvis/pathologyABSTRACT
BACKGROUND: Breast cancer screening is currently predominantly based on mammography, tainted with the occurrence of both false positivity and false negativity, urging for innovative strategies, as effective detection of early-stage breast cancer bears the potential to reduce mortality. Here we report the results of a prospective pilot study on breast cancer detection using blood plasma analyzed by Fourier-transform infrared (FTIR) spectroscopy - a rapid, cost-effective technique with minimal sample volume requirements and potential to aid biomedical diagnostics. FTIR has the capacity to probe health phenotypes via the investigation of the full repertoire of molecular species within a sample at once, within a single measurement in a high-throughput manner. In this study, we take advantage of cross-molecular fingerprinting to probe for breast cancer detection. METHODS: We compare two groups: 26 patients diagnosed with breast cancer to a same-sized group of age-matched healthy, asymptomatic female participants. Training with support-vector machines (SVM), we derive classification models that we test in a repeated 10-fold cross-validation over 10 times. In addition, we investigate spectral information responsible for BC identification using statistical significance testing. RESULTS: Our models to detect breast cancer achieve an average overall performance of 0.79 in terms of area under the curve (AUC) of the receiver operating characteristic (ROC). In addition, we uncover a relationship between the effect size of the measured infrared fingerprints and the tumor progression. CONCLUSION: This pilot study provides the foundation for further extending and evaluating blood-based infrared probing approach as a possible cross-molecular fingerprinting modality to tackle breast cancer detection and thus possibly contribute to the future of cancer screening.
Subject(s)
Breast Neoplasms/blood , Breast Neoplasms/diagnosis , Spectroscopy, Fourier Transform Infrared/methods , Adult , Area Under Curve , Breast Neoplasms/pathology , Case-Control Studies , DNA Fingerprinting , Disease Progression , Early Detection of Cancer/methods , Feasibility Studies , Female , Humans , Liquid Biopsy/methods , Machine Learning , Middle Aged , Pilot Projects , Prospective Studies , ROC Curve , Support Vector MachineABSTRACT
Background and Objectives: Cervical cancer (CC) is the eighth most common cancer among Saudi women of all ages. With limited national data, we aimed to evaluate the public awareness of cervical cancer, CC risk factors, HPV infection, and HPV vaccines in different regions of Saudi Arabia. Materials and Methods: This was a survey-based cross-sectional study that encompassed 564 Saudi women over a period of a month. A self-administrated questionnaire was distributed through different social media platforms. Results: The collected data included sociodemographic variables and questions assessing awareness of CC, and the attitudes toward CC screening and human papillomavirus (HPV) vaccination. Most respondents were aware of CC (84.0%), although their primary source of information was the internet. However, only 45 females (8.0%) had a history of cervical screening. Furthermore, most females did not know that HPV was transmitted sexually (78.9%), or that it caused genital warts (81.7%) and CC (81.9%). Regarding the HPV vaccine, 100 females (17.7%) had heard about it, but only 11 (2.0%) took the vaccine, although more than half of the respondents (54.1%) were willing to take the vaccine after being informed about it. Conclusions: We noticed a remarkable lack of awareness among the respondents regarding HPV's clinical implications; and the HPV vaccine, and its importance and availability. The main source of information for most of the Saudi women in this study was the internet, which may be an unreliable source, or provide misleading information that may delay screening or discourage vaccination. Thus, organized campaigns by the Ministry of Health or other health-advocating agencies, in addition to screening and vaccination programs, are strongly encouraged.
Subject(s)
Alphapapillomavirus , Papillomavirus Infections , Papillomavirus Vaccines , Uterine Cervical Neoplasms , Cross-Sectional Studies , Early Detection of Cancer , Female , Health Knowledge, Attitudes, Practice , Humans , Papillomaviridae , Papillomavirus Infections/epidemiology , Papillomavirus Infections/prevention & control , Saudi Arabia/epidemiology , Surveys and Questionnaires , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/prevention & controlABSTRACT
BACKGROUND Microcystic stromal tumor (MCST) of the ovary is a rare entity with distinct pathological and molecular features. However, a lack of awareness of ovarian MCST can lead to delayed diagnosis or misdiagnosis. We present a case of ovarian MCST and review all previously reported cases and discuss their clinical and pathological characteristics. CASE REPORT A 46-year-old woman with primary infertility due to polycystic ovary syndrome presented with bleeding and pain. Radiological images showed a complex solid and cystic adnexal mass. Microscopically, the tumor was lobulated with cellular regions separated by fibrous plaques and small anastomosing cysts, consistent with an ovarian MCST. The tumor cells showed positive staining for vimentin, CAM 5.2, CD10, ß-Catenin, CD99, and cyclin D1. Genetic sequencing showed a point mutation in the CTNNB1 gene, with no mutations in the APC, BRCA1, and BRCA2 genes. The patient underwent surgery and was disease-free at 24 months after her initial diagnosis. CONCLUSIONS The diagnosis of ovarian MCST should consider the differential diagnosis of cystic tumors of the ovary. Further research is encouraged to elucidate the various molecular pathways involved in the pathogenesis of this tumor and to determine its optimal treatment and long-term prognosis.