Serum Levels Of Antigen Research Articles

Study on Early Prostate Cancer Antigen (EPCA) and existent risk factors of prostate cancer, Sudan: A case-control study

Background: Early prostate cancer antigen (EPCA), a nuclear matrix protein, has recently been recommended as a hopeful biomarker for early prostate carcinogenesis. Objectives: To evaluate the validity of serum early prostate cancer antigen (EPCA) in the early detection of prostate cancer (PCa) and the characteristics of Sudanese patients diagnosed with prostate cancer. Method: In this study, seventy men were considered as a case subject, who were diagnosed as cancer prostate at Gezira Hospital for Renal Disease and Surgery (GHRDS), Sudan during the period February 2018 to July 2019. Randomly selected sixty patients of BPH patients and forty-five apparently healthy men as controls group. EPCA, and PSA estimations were performed from serum samples using the principle of Enzyme Linked Immunosorbent Assay (ELISA). Results: There was significant association between age, family history, residence, unhealthy habits, education, BMI, occupations and prostate cancer, results also revealed a significant elevation between the means of the serum levels of both early prostate cancer antigen and prostate specific antigen of the patients with prostate cancer when compared with the control groups. EPCA biomarker offered the best performance statically (P= 0.00) and highest specificity (81%) and sensitivity (94%) in prostate cancer detection in Sudanese males over PSA biomarker. Conclusions: Cases of studied prostate cancer linked to many risk factors. Serum levels of early prostate cancer antigen and prostate specific antigen were significantly increased in patients with prostate cancer, however, our data proposed that EPCA has higher power statistical value, so could be utilized as a prostate cancer specific and sensitive biomarker for early detection of prostate cancer.

Targeting HMGB1/PI3K/Akt and NF-κB/Nrf-2 signaling pathways by vildagliptin mitigates testosterone-induced benign prostate hyperplasia in rats

Benign prostatic hyperplasia (BPH) is a prevalent illness in older adults. It is well-recognized that testosterone is essential in the onset of BPH. Vildagliptin (Vilda), a dipeptidyl peptidase-IV inhibitor, has been shown to have anti-inflammatory and antioxidant effects. In this study, we studied the effects of vildagliptin on testosterone-induced BPH in rats and its underlying mechanisms. Forty male Wistar rats were allocated into four groups (n = 10): CTRL, Vilda, BPH, and BPH + Vilda groups. Our results revealed that vildagliptin treatment considerably lessened the prostate weight, prostate index, serum levels of prostate-specific antigen, 5α-reductase activity, and DHT levels compared to the testosterone group. Furthermore, vildagliptin treatment inhibited the expression of HMGB1, PI3K/Akt/NF-κB, and TNF-α signaling pathways in the prostate tissue of diseased rats. Additionally, vildagliptin treatment increased the expression of Nrf-2 and HO-1, reduced GSH levels, and lowered MDA levels. Besides, vildagliptin noticeably scaled up the level of cleaved caspase-3 enzyme and, conversely, the protein expression of proliferating cell nuclear antigen (PCNA). Correspondingly, vildagliptin counteracts testosterone-induced histological irregularities in rats' prostates. These findings suggest that vildagliptin may be a potential prophylactic approach to avoid BPH.

Serum levels and significance of soluble B-cell maturation antigen in childhood-onset systemic lupus erythematosus with renal involvement.

The aim of this study was to investigate serum levels of soluble B-cell maturation antigen (sBCMA) in childhood-onset systemic lupus erythematous (cSLE) patients with renal involvement, and to elucidate their association with clinical characteristics. 116 cases of cSLE patients with renal involvement (84 females and 32 males; median age 11.6 (10.1, 12.9) years) hospitalized in Department of Pediatric Nephrology and Rheumatology, the First Affiliated Hospital, Sun Yat-sen University and 31 healthy controls (HCs) were enrolled. Serum concentrations of sBCMA were determined using enzyme-linked immunosorbent assay (ELISA). Clinical and laboratory information of cSLE patients were retrospectively analyzed. Serum sBCMA levels were significantly increased in primary cSLE when compared with treated cSLE patients and HCs, whereas there was no significant difference between treated cSLE patients and HCs. Patients with high disease activity displayed higher serum sBCMA levels compared with those with no or mild to moderate disease activity. Positive correlation was observed between serum sBCMA levels and systemic lupus erythematosus disease activity index-2K (SLEDAI-2K), antinuclear antibody titers, anti-double-stranded DNA titers, erythrocyte sedimentation rate, and immunoglobulin G levels, while sBCMA levels were negatively correlated with blood white blood cell count, hemoglobin, platelet count, complement C3 and C4 levels. Serum sBCMA levels decreased as disease ameliorated after treatments among 11 cases with follow-up examinations. In cSLE patients with renal involvement, serum sBCMA levels correlated significantly with disease activity, immunological, and hematological parameters, but not with renal parameters. Our results suggest the potential and significance of serum sBCMA as a biomarker in cSLE patients.

Hepatitis B core-related antigen serum levels may be a predictor of acute flare of chronic hepatitis B among pregnant women in the immune-tolerant phase of chronic HBV infection after short-course antiviral therapy

ABSTRACT Background Studies have shown acute flares of chronic hepatitis B (CHB) might be related to immunologic changes that occur during pregnancy. However, the indicators for predicting acute flares of CHB among pregnant women still need further study. We aimed to distinguish the relevance between serum levels of HBcrAg and acute flares of CHB in pregnant women in the immune-tolerant phase of chronic HBV infection after short-course antiviral therapy. Methods A total of 172 chronic HBV-infected pregnant women who were judged to be in the immune-tolerant phase were recruited in our research. All patients received short-course antiviral therapy with TDF. The biochemical, serological, and virological parameters were measured using standard laboratory procedures. The serum levels of HBcrAg were tested by ELISA. Results Fifty-two (30.2%) out of 172 patients had acute flares of CHB. At postpartum week 12 (TDF cessation), serum HBcrAg (OR, 4.52; 95% CI, 2.58–7.92) and HBsAg (OR, 2.52; 95% CI, 1.13–5.65) were associated with acute flares of CHB. The serum HBcrAg levels were beneficial for confirmation of patients with acute flares of CHB, with an area under the ROC curve of 0.84 (95% CI, 0.78–0.91). Conclusions For pregnant women with chronic HBV infection in the immune-tolerant phase, serum HBcrAg and HBsAg levels at postpartum week 12 were associated with acute flares of CHB after short-course antiviral therapy with TDF. The serum HBcrAg level can correctly identify acute flares of CHB and may be a predictor of the need for continuing antiviral therapy after 12 weeks postpartum.

Diagnostic Value of SMARCE1 and CRISP3 Combined with Tumor Markers in Cervical Cancer

Background: To investigate the diagnostic value of SMARCE1, cysteine-rich secreted protein 3 (CRISP3) combined with tumor markers in the diagnosis of cervical cancer. Methods: A total of 80 patients with cervical lesions who were diagnosed and treated in our hospital from January 2020 to March 2022 were selected and divided into control group (chronic cervicitis, n = 30) and observation group (cervical cancer, n = 50). Immunohistochemistry was used to detect the expression levels of SMARCE1 and CRISP3 in cervical tissue of the two groups of subjects, and the relationship between the expression of SMARCE1 and CRISP3 in cervical cancer tissue and the clinicopathological data of the patients was analyzed. In addition, the serum tumor marker levels of the two groups of subjects were detected, and the diagnostic value of SMARCE1 and CRISP3 combined with tumor markers in cervical cancer was analyzed. The female sexual function index (FSFI) and the functional assessment of cancer therapy-general (FACT-G) score were used to evaluate female sexual function and quality of life. Results: The positive expression rates of SMARCE1 and CRISP3 in the observation group were significantly higher than those in the control group (p < 0.05). There was no significant difference in the positive expression of SMARCE1 and CRISP3 among cervical cancer patients with age, lymph node metastasis and tumor node metastasis (TNM) classification stage (p > 0.05), and the lower the degree of tumor differentiation, the higher the positive expression rate of SMARCE1 and CRISP3 proteins (p < 0.05). The serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125 and CA153 in the observation group were significantly higher than those in the control group (p < 0.05). The results of the receiver operating characteristic (ROC) curve analysis showed that the area under curve (AUC) values of SMARCE1, SMARCE1 + tumor markers, CRISP3, CRISP3 + tumor markers, SMARCE1, CRISP3 combined with tumor markers for the diagnosis of cervical cancer were 0.760, 0.851, 0.739, 0.810, and 0.944, respectively. Conclusions: SMARCE1 and CRISP3 are expressed in patients with cervical cancer, and CEA, CA125, and CA153 are expressed at high levels in the serum of patients with cervical cancer. The combined detection of SMARCE1 and CRISP3 combined with tumor markers has high clinical diagnostic value for cervical cancer.

Anti-Tumor Activity of Orally Administered Gefitinib-Loaded Nanosized Cubosomes against Colon Cancer

Gefitinib (GFT) is a tyrosine kinase inhibitor drug used as a first-line treatment for patients with advanced or metastatic non-small cell lung, colon, and breast cancer. GFT exhibits low solubility and hence low oral bioavailability, which restricts its clinical application. One of the most important trends in overcoming such problems is the use of a vesicular system. Cubosomes are considered one of the most important vesicular systems used to improve solubility and oral bioavailability. In this study, GFT cubosomal nanoparticles (GFT-CNPs) were prepared by the emulsification method. The selected formulation variables were analyzed and optimized by full factorial design and response surface methodology. Drug entrapment efficiency (EE%), transmission electron microscopy, particle size, polydispersity index, in vitro release and its kinetics, and the effect of storage studies were estimated. The chosen GFT-CNPs were subjected to further investigations as gene expression levels of tissue inhibitors of metalloproteinases-1 (TIMP-1) and matrix metalloproteinases-7 (MMP-7), colon biomarkers, and histopathological examination of colon tissues. The prepared GFT-CNPs were semi-cubic in shape, with high EE%, smaller vesicle size, and higher zeta potential values. The in vivo data showed a significant decrease in the serum level of embryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), and gene expression level of TIMP-1 and MMP-7. Histopathological examination showed enhancement in cancer tissue and highly decreased focal infiltration in the lamina propria after treatment with GFT-CNPs.

Serum Level of Soluble Human Leukocyte Antigen G in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis.

This study aimed to evaluate the serum level of human leukocyte antigen G [HLA-G] in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) compared to healthy controls; moreover, it attempted to assess its relationship with SLE and RA disease activity indices. This descriptive study was conducted on 31 SLE patients (17 cases with a recent diagnosis and 14 cases with a previous diagnosis), 21 RA patients (7 cases with a recent diagnosis and 14 cases with a previous diagnosis), and 18 healthy controls who visited Ghaem Hospital affiliated to Mashhad University of Medical Sciences, Mahhad, Iran. SLE and RA activity indices were measured and recorded. Furthemore, soluble isoforms, including shed HLA-G1 and HLA-G5, were measured in serum samples via the ELISA method. A comparison of the five groups showed no significant differences in the serum level of sHLA-G. However, sHLA-G serum level was significantly higher in SLE and RA patients compared to healthy controls (P<0.05). sHLA-G level showed no correlation with disease duration and activity in SLE and RA patients (P>0.05). However, a strong positive correlation was observed between the serum level of sHLA-G and 24-h urine protein in the previously diagnosed SLE group (r=0.83, P=0.01). It seems that the serum level of sHLA-G is higher in RA and SLE patients compared to healthy controls. Furthermore, a strong correlation was found between sHLA-G serum levels and 24-h urine protein in cases with a previous diagnosis of SLE.

Understanding the Mechanism of the Disproportionately Reduced C1-Esterase Inhibitor (C1-INH) Levels in Hereditary Angioedema (HAE)

HAE is an autosomal dominant disorder caused by defects in the SERPING1 gene. HAE patients maintain one functional wild-type SERPING1 allele, therefore at least 50% of the normal C1-INH value is expected. However, serum antigen levels of C1-INH in HAE patients are usually 5-30% of normal. We hypothesize that the type of SERPING1 mutations and their impact on C1-INH protein structure and function lead to the variable degrees of C1-INH level in HAE patients.

Marine Natural Products with Activities against Prostate Cancer: Recent Discoveries.

Prostate cancer is the most common cancer in men, with over 52,000 new cases diagnosed every year. Diagnostics and early treatment are potentially hindered by variations in screening protocols, still largely reliant on serum levels of acid phosphatase and prostate-specific antigen, with tumour diagnosis and grading relying on histopathological examination. Current treatment interventions vary in terms of efficacy, cost and severity of side effects, and relapse can be aggressive and resistant to the current standard of care. For these reasons, the scientific community is looking for new chemotherapeutic agents. This review reports compounds and extracts derived from marine organisms as a potential source of new drugs against prostate cancer. Whilst there are several marine-derived compounds against other cancers, such as multiple myeloma, leukemia, breast and lung cancer, already available in the market, the presently collated findings show how the marine environment can be considered to hold potential as a new drug source for prostate cancer, as well. This review presents information on compounds presently in clinical trials, as well as new compounds/extracts that may enter trials in the future. We summarise information regarding mechanisms of action and active concentrations.

A preoperative magnetic resonance imaging-based model to predict biochemical failure after radical prostatectomy

To investigate if a magnetic resonance imaging (MRI)-based model reduced postoperative biochemical failure (BF) incidence in patients with prostate cancer (PCa). From June 2018 to January 2020, we retrospectively analyzed 967 patients who underwent prostate bi-parametric MRI and radical prostatectomy (RP). After inclusion criteria were applied, 446 patients were randomized into research (n = 335) and validation cohorts (n = 111) at a 3:1 ratio. In addition to clinical variables, MRI models also included MRI parameters. The area under the curve (AUC) of receiver operating characteristic and decision curves were analyzed. The risk of postoperative BF, defined as persistently high or re-elevated prostate serum antigen (PSA) levels in patients with PCa with no clinical recurrence. In the research (age 69 [63–74] years) and validation cohorts (age 69 [64–74] years), the postoperative BF incidence was 22.39% and 27.02%, respectively. In the research cohort, the AUC of baseline and MRI models was 0.780 and 0.857, respectively, with a significant difference (P < 0.05). Validation cohort results were consistent (0.753 vs. 0.865, P < 0.05). At a 20% risk threshold, the false positive rate in the MRI model was lower when compared with the baseline model (31% [95% confidence interval (CI): 9–39%] vs. 44% [95% CI: 15–64%]), with the true positive rate only decreasing by a little (83% [95% CI: 63–94%] vs. 87% [95% CI: 75–100%]). 32 of 100 RPs can been performed, with no raise in quantity of patients with missed BF. We developed and verified a MRI-based model to predict BF incidence in patients after RP using preoperative clinical and MRI-related variables. This model could be used in clinical settings.

Preoperative evaluation of prostate cancer by 68Ga-PMSA positron emission tomography/computed tomography: comparison with magnetic resonance imaging and with histopathological findings.

To evaluate the accuracy of preoperative positron emission tomography/computed tomography with 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA PET/CT) for staging prostate cancer and compare it with magnetic resonance imaging (MRI) using histopathology of surgical specimens as the gold standard. In this retrospective study, 65 patients with prostate cancer were analyzed. The accuracy of 68Ga-PSMA PET/CT for tumor detection was 95%, and that of MRI was 91%. There was no difference between 68Ga-PSMA PET/CT and MRI regarding localization of the lesion. The sensitivity of 68Ga-PSMA PET/CT for detecting extraprostatic extension was quite low (14%). For detection of seminal vesicle invasion, 68Ga-PSMA PET/CT showed a sensitivity of 57% and accuracy of 91%. There was a moderate correlation between the maximum standardized uptake value (SUVmax) and the serum level of prostate-specific antigen (p < 0.01; ρ = 0.368) and between the SUVmax and the International Society of Urological Pathology (ISUP) grade (p < 0.01; ρ = 0.513). 68Ga-PSMA PET/CT is a promising tool for detecting and evaluating the primary tumor, which can alter the staging and management of the disease.

Neoadjuvant Chemotherapy Efficacy and Safety in Borderline Resectable Pancreatic Cancer

The current study was designed to investigate the safety and effectiveness of neoadjuvant therapy in patients with borderline resectable pancreatic cancer. The study was a retrospective case control with propensity score similarity. From January 2017 to June 2022, data regarding 70 patients who had received radical resection of pancreatic cancer at the department of hepatobiliary and pancreatic surgery of first affiliated hospital of Huzhou university was acquired. The neoadjuvant therapy group consisted of 35 patients who underwent neoadjuvant therapy before surgery. Patients who received extensive surgical resection were included in the control group directly. The effect of the neoadjuvant therapy group was evaluated before the operation and serum tumor markers carcinoembryonic antigen, cancer antigen 125 and cancer antigen 19-9 levels were compared before and after neoadjuvant therapy. Comparative analyses of perioperative surgical variables, postoperative pathological symptoms and postoperative complications were performed between both groups. Among the patients without complete remission or progressive disease after neoadjuvant therapy, 13 cases (37.14 %) were evaluated as partial response and 22 cases (62.86 %) were assessed as stable disease. After neoadjuvant therapy, serum levels of cancer antigen 19-9, cancer antigen 125 and carcinoembryonic antigen indexes revealed a significant (all p<0.05) downward trend. There were no statistically significant differences (all p>0.05) between the two groups regarding surgery type, operation duration, intraoperative blood loss, number of cases requiring blood transfusion, or postoperative hospital stay. Neoadjuvant treatment patient’s tumor diameters and the number of removed lymph nodes were significantly less (p<0.05) than those of the control group and their R0 resection rates were significantly greater (p<0.05) than those of the control group. There was no substantial variation in the frequency of complications between both groups (p>0.05). Preoperative neoadjuvant therapy for patients with minimally resectable pancreatic cancer can lower tumor marker levels. Moreover, it can produce a specific curative impact without raising surgical risk levels and boosting the R0 resection rate, which is safe and appropriate.

Discovery of a first-in-class orally available HBV cccDNA inhibitor

The persistence of covalently closed circular DNA (cccDNA) in infected hepatocytes is the major barrier preventing viral eradication with existing therapies in patients with chronic hepatitis B. Therapeutic agents that can eliminate cccDNA are urgently needed to achieve viral eradication and thus HBV cure. A phenotypic assay with HBV-infected primary human hepatocytes (PHHs) was employed to screen for novel cccDNA inhibitors. A HBVcircle mouse model and a uPA-SCID (urokinase-type plasminogen activator-severe combined immunodeficiency) humanized liver mouse model were used to evaluate the anti-HBV efficacy of the discovered cccDNA inhibitors. Potent and dose-dependent reductions in extracellular HBV DNA, HBsAg, and HBeAg levels were achieved upon the initiation of ccc_R08 treatment two days after the HBV infection of PHHs. More importantly, the level of cccDNA was specifically reduced by ccc_R08, while it did not obviously affect mitochondrial DNA. Additionally, ccc_R08 showed no significant cytotoxicity in PHHs or in multiple proliferating cell lines. The twice daily oral administration of ccc_R08 to HBVcircle model mice, which contained surrogate cccDNA molecules, significantly decreased the serum levels of HBV DNA and antigens, and these effects were sustained during the off-treatment follow-up period. Moreover, at the end of follow-up, the levels of surrogate cccDNA molecules in the livers of ccc_R08-treated HBVcircle mice were reduced to below the lower limit of quantification. We have discovered a small-molecule cccDNA inhibitor that reduces HBV cccDNA levels. cccDNA inhibitors potentially represent a new approach to completely cure patients chronically infected with HBV. Covalently closed circular DNA (cccDNA) persistence in HBV-infected hepatocytes is the root cause of chronic hepatitis B. We discovered a novel small-molecule cccDNA inhibitor that can specifically reduce cccDNA levels in HBV-infected hepatocytes. This type of molecule could offer a new approach to completely cure patients chronically infected with HBV.

Assessment of Prostate Carcinoma Aggressiveness: Relation to 68Ga-PSMA-11-PET/MRI and Gleason Score.

To test the correlation of 68Ga-PSMA-11 uptake and the expression of PSMA (prostatic specific membrane antigen) with the Gleason score, apparent diffusion coefficient (ADC) and pharmacokinetic parameters obtained from dynamic contrast agent-enhanced MRI/PET. Forty newly diagnosed, therapy naïve patients with prostatic carcinoma (PC) (mean age of 56.7, range=34-79), who were referred for 68Ga-PSMA-11-PET/MRI for primary staging and had undergone radical prostatectomy (RAPE) were included in this prospective study. Their blood samples were tested for serum levels of prostate-specific antigen (PSA) and proPSA. The patients' prostates were evaluated using whole-mount sections, which helped determine the extent and grade of the tumor; tests were performed to determine immunohistochemical PSMA expression. A correlation between PSMA expression and the accumulation of 68Ga-PSMA-11 was found using the Spearman correlation coefficient (p=0.0011). A stronger correlation was found between Gleason patterns 3 or 4 and PSMA expression (p=0.06). Furthermore, the correlation of Gleason score with the overall 68Ga-PSMA-11 accumulation within the tumor or non-tumor tissue was found to be significant (p=0.0157). A significant relation was found only with the Kep elimination rate constant, which was stronger in Gleason pattern 4 than in Gleason pattern 3. A weaker correlation was found between the accumulation of 68Ga-PSMA-11 and Ktrans in Gleason pattern 4: the most significant relation being between ADCmin and Gleason pattern 3 and 4 (p=0.0074). The total size of the tumor correlated with levels of proPSA (p<0.0001), and its extra prostatic extension correlated with levels of proPSA (p<0.0001). 68Ga-PSMA-11 correlates well with the expression of PSMA. Gleason pattern 3 and 4 had a higher correlation with 68Ga-PSMA-11 levels than did Gleason pattern 5. Either no correlation, or a weak correlation, was established with pharmacokinetics.

Biparametric MRI-based radiomics classifiers for the detection of prostate cancer in patients with PSA serum levels of 4∼10 ng/mL.

To investigate the predictive performance of the combined model by integrating clinical variables and radiomic features for the accurate detection of prostate cancer (PCa) in patients with prostate-specific antigen (PSA) serum levels of 4-10 ng/mL. A retrospective study of 136 males (mean age, 67.3 ± 8.4 years) with Prostate Imaging-Reporting and Data System (PI-RADS) v2.1 category ≤3 lesions and PSA serum levels of 4-10 ng/mL were performed. All patients underwent multiparametric MRI at 3.0T and transrectal ultrasound-guided systematic prostate biopsy in their clinical workup. Radiomic features were extracted from axial T2-weighted images (T2WI) and apparent diffusion coefficient (ADC) maps of each patient using PyRadiomics. Pearson correlation coefficient (PCC) and recursive feature elimination (RFE) were implemented to identify the most significant radiomic features. Independent clinic-radiological factors were identified via univariate and multivariate regression analyses. Seven machine-learning algorithms were compared to construct a single-layered radiomic score (ie, radscore) and multivariate regression analysis was applied to construct the fusion radscore. Finally, the radiomic nomogram was further developed by integrating useful clinic-radiological factors and fusion radscore using multivariate regression analysis. The discriminative power of the nomogram was evaluated by area under the curve (AUC), DeLong test, calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC). The transitional zone-specific antigen density was identified as the only independent clinic-radiological factor, which yielded an AUC of 0.592 (95% confidence interval [CI]: 0.527-0.657). The ADC radscore based on six features and Naive Bayes achieved an AUC of 0.779 (95%CI: 0.730-0.828); the T2WI radscore based on 13 features and Support Vector Machine yielded an AUC of 0.808 (95%CI: 0.761-0.855). The fusion radscore obtained an improved AUC of 0.844 (95%CI: 0.801-0.887), which was higher than the single-layered radscores (both P<0.05). The radiomic nomogram achieved the highest value among all models (all P<0.05), with an AUC of 0.872 (95%CI: 0.835-0.909). Calibration curve showed good agreement and DCA together with CIC confirmed the clinical benefits of the radiomic nomogram. The radiomic nomogram holds the potential for accurate and noninvasive identification of PCa in patients with PI-RADS ≤3 lesions and PSA of 4-10 ng/mL, which could reduce unnecessary biopsy.

Investigation of the relationship between endothelial nitric oxide synthase T786C polymorphism and PSA, PSA derivatives, and prostate cancer in the Turkish population.

Prostate cancer is a slowly progressing cancer. However, it has remained a major medical problem for affected men. Risk factors of prostate cancer include age, race, and prostate cancer family history. Prostate cancer may occur at different frequencies between ethnic populations and countries. Currently, studies on genetic risk factors in prostate cancer aetiology have been increasing. Due to the importance of changes in endothelial nitric oxide synthase in carcinogenesis, we aimed to reveal whether eNOS T786C polymorphism is associated with prostate cancer. Archival samples included in this study were whole blood samples taken from patients who were grouped according to prostate biopsy pathology results (BPH, n: 42; PCa, n: 48) and from healthy participants (controls, n:27). DNA was isolated from these whole blood samples and real-time polymerase chain reaction analysis was performed for endothelial nitric oxide synthase T786C polymorphism with LightCycler 480 II. Measured free and total prostate-specific antigen serum levels were evaluated retrospectively. There was a statistical difference between patient-healthy control and control-healthy control groups regarding genotype distributions for eNOS T786C hism. Controls were more likely to have TC and CC genotypes and C alleles than the other two groups. Compared to other groups, the percentage of the eNOS786C allele in the control group was found to be higher. As a result of these data, it can be thought that carrying the allele may be protective against the disease.

Association between interleuleukin-1β polymorphism (rs16944) and biomarkers levels in Iraqi patients with prostate cancer.

Prostate cancer (PCa) is the second-leading cause of mortality in men and the most commonly diagnosed non-cutaneous male malignancy. Host genetic factors, and inflammation-induced cytokines, play a key role in prostate oncogenesis. Single Nucleotide Polymorphisms (SNP) in cytokine genes were suggested to increase the susceptibility for PCa development and progression. This study aimed to investigate the association between the SNP (rs16944) in the interleukin-1 β (IL-1β) gene and the serum levels of Prostate Specific Antigen (PSA) Prolactine (PRL), testosterone, and IL-1β in Iraqi PCa patients versus healthy controls. Taqman Real Time-PCR, was performed to investigate the IL-1β (rs16944) polymorphism in 100 Iraqi PCa patients and 50 age-matched healthy controls in a case-control study. Serum levels of PSA, PRL, and testosterone were determined by ELISA and FIA, and associated with the IL-1β serum level as well as with the SNP (rs 16944). The association between the clinico-pathological parameters and the genotype distribution of PCa patients was also studied. There level of IL-1β was significant increased in the serum of PCa patients compared to controls (P = 8.19 10-7). Serum levels for other biomarkers such as PSA, PRL and testosterone were also significantly elevated in patients compared to controls (P < 0.0001). No differences were seen for genotype and allele distribution between PCa patients and controls. Nevertheless, in the group of controls, we found that 36% carried the GG genotype against only 26% in the patients group.This suggests that this could be a protective genotype (OR 0.62, P = 0.254). In addition, we found that the GA genotype is slightly more frequent in patients as compared to controls (OR 1.22, P = 0.605). Interestingly, serum levels of IL-1β, PSA, PRL and testosterone were significantly higher in PCa patients carrying the GA genotype, and the GA and AA genotypes are strongly associated with the aggressive behavior of the disease such as advanced TNM, and high Gleason score. Our data suggest that both serum IL-1β level and IL-1β SNP (rs16944) may be considered as candidate biomarkers for PCa. Moreover, the GA, and AA genotypes carriers along with high sera levels of IL-1β, PSA and PRL, have an increased risk for PCa with aggressive behavior in Iraqi men.

A Case of Acute Disseminated Histoplasmosis of the Liver in a Patient Receiving Amphotericin-B Therapy

Abstract Introduction/Objective Acute disseminated histoplasmosis (DH), caused by Histoplasma Capsulatum (HC), occurs primarily in immunocompromised hosts. It is characterized by an abrupt onset of symptoms (fever, malaise, hepatosplenomegaly, lymphadenopathy, anemia, leucopenia and thrombocytopenia) and a lack of granulomatous inflammatory response. If left untreated, death occurs within three months of the disease. The treatment of choice is a two-week course of Amphotericin-B (AmpB-Tx). Studies show a drop in fungal load in 85% of blood cultures and a drop of 1.6 U and 2.1 U in serum and urine antigen levels of histoplasmosis respectively, within 14 days of treatment thereby making it unlikely to see liver failure secondary to acute DH in a patient receiving AmpB-Tx. Methods/Case Report We present a case of a 41-year-old male, newly diagnosed with HIV (CD4=44; viral load=5,350,000) and DH on AmpB-Tx. At presentation, his liver function tests (LFT’s) were mildly elevated (Bilirubin =2.7mg/dL; ALP=259U/L; AST=271U/L; ALT=71U/L). On Day-9 of AmpB-Tx, he became somnolent and jaundiced with hepatosplenomegaly and ascites. His LFTs were markedly raised, showing an obstructive pattern (Bilirubin=16mg/dL; ALP=1578U/L; AST=261U/L; ALT=213U/L). On Day-11 of treatment, we received a liver biopsy for HIV cholangiopathy versus drug induced hepatotoxicity. The clinicians considered DH to be a less likely cause since the patient was already on AmpB-Tx. The liver biopsy showed hepatocytes with cholestasis, minimal acute portal inflammation and numerous portal tract and parenchymal macrophages laden with fungal organisms. Gomori-Methenamine-Silver stain confirmed the fungal organisms as being HC. This diagnosis prompted the continuation of AmpB-Tx past 14 days. The patient’s LFT’s reached maximum values of Bilirubin=18mg/dL; ALP=1680U/L; AST=355U/L; ALT=324U/L. After 25 days of AmpB-Tx, his LFT’s trended downwards with a resolution of his hepatic encephalopathy and jaundice. While a 14 day course was initially intended, AmpB-Tx was continued for a total of 28 days until a resolution of symptoms was achieved. Results (if a Case Study enter NA) NA. Conclusion Our case identifies a patient with progressive hepatic histoplasmosis in spite of AmpB-Tx. Keeping in mind and identifying such cases on pathology can alter the course of treatment for patients.

Inflammatory Mediators (CA125, CRP) and Uric Acid in Association with Severity of Preeclampsia in North Kordofan State, Western Sudan

Introduction: Inflammatory mediators could be laboratory markers of preeclampsia, as the induction of an inflammatory process within the placenta may trigger the expression of cancer antigen 125(CA125), C-reactive protein (CRP) and uric acid (UA). Regarding the pathophysiology of pre-eclampsia, there is defective trophoblastic invasion of uteroplacental blood vessels that leads to placental ischemia, and induction of an inflammatory process within the placenta.&#x0D; Objective: To evaluate the association of serum levels of cancer antigen (CA125), C-reactive protein (CRP) and serum uric acid with the Severity of Preeclampsia.&#x0D; Materials and Methods: The study recruited 200 singleton Sudanese pregnant women. These participants were divided into two groups: control (n = 100) and cases (n = 100). The cases were further subdivided into; mild preeclampsia (n =46), and severe preeclampsia (n = 54). The study groups were well-matched in maternal age, gestational age and body mass index. Blood samples were taken for measurement of serum cancer antigen-CA125, uric acid and C - reactive protein using immune- assay and enzymatic automated chemical analysis.&#x0D; Results: The mean levels of cancer antigen-CA125 in mild and severe preeclampsia groups were; 21.94±5.08 (IU/ml) and 40.77±9.82 (IU/ml) respectively, which were significantly higher, (P&lt;0.001) in comparison with the control group (16.88±7.36 (IU/ml). The mean levels of C-reactive protein in mild and severe preeclampsia were; 15.17±5.35 (mg/L), 31.49±12.56 (mg/L) respectively. There was significant difference in their levels, compared to the control group (4.79±1.78 (mg/L), (P&lt;0.01). Also, the mean levels of uric acid in mild and severe cases were; 6.44±1.98 and 7.37±2.00 which was significantly higher, in comparison with the control (4.00±0.61); (P&lt;0.001). The level of uric acid also, showed significant difference within the case (severe and mild) group (P&lt;0.05). CA125, CRP and UA level‎s correlated positively with Mean Arterial blood pressure (MAP), (r&gt;0.7; P &lt; 0.001). ROC curve validate the utility of these biomarker for the detection of preeclampsia severity (AUC&gt;0. 8; P &lt; 0.001).&#x0D; Conclusion: Serum cancer antigen 125(CA125), C- reactive protein and uric acid in studied preeclampsia groups were found to be significantly higher compared with the control group, and the rises were directly associated with the severity of preeclampsia.

Prognostic significance of combined α-fetoprotein and CA19-9 for hepatocellular carcinoma after hepatectomy

BackgroundThe prognosis of hepatocellular carcinoma (HCC) varies considerably among patients with the same disease stage and characteristics, and only about two thirds show high levels of α-fetoprotein (AFP), a common prognostic indicator for HCC. Here, we assessed whether the combination of presurgical serum levels of AFP and carbohydrate antigen 19-9 (CA19-9) can predict the prognosis of HCC patients after hepatectomy.MethodsThe clinicopathological characteristics and post-hepatectomy outcomes of 711 HCC patients were retrospectively reviewed. The patients were classified into three groups based on whether their preoperative serum levels of both AFP and CA19-9 were higher than the respective cut-offs of 400 ng/ml and 37 U/ml [double positive (DP)], the level of only one marker was higher than the cut-off [single positive (SP)], or neither level was higher than the cut-off [negative (N)]. The overall survival (OS) and recurrence-free survival (RFS) rates were estimated using Kaplan–Meier curves. Univariate and multivariate survival analyses were performed to identify the clinicopathological factors significantly associated with HCC prognosis.ResultsThe 1-year, 3-year, and 5-year RFS and OS rates in the N group were significantly higher than those in the SP group, while the DP group showed the lowest rates. Multivariate Cox regression analysis showed that large tumor size (> 5 cm), multiple tumors (≥ 2), incomplete tumor capsule, positive microvascular invasion, Barcelona Clinic Liver Cancer C stage, and CA19-9 level > 37 U/mL were independent risk factors for RFS and OS in HCC patients. Moreover, aspartate aminotransferase levels > 40 U/L proved to be an independent prognostic factor for OS.ConclusionThe combination of serum AFP and CA19-9 levels may be a useful prognostic marker for HCC patients after hepatectomy.