Comparison of the effectiveness and duration of anti-RBD SARS-CoV-2 IgG antibody response between different types of vaccines: Implications for vaccine strategies.

BACKGROUND AND OBJECTIVES: Little is known about the efficacy and durability of anti-RBD IgG antibodies induced by certain SARS-CoV-2 vaccines. It has been shown that neutralizing antibodies are associated with the protection against re-infection. This study aims to compare the mean titers, duration, and efficacy of generating protective anti-RBD IgG antibody response among recipients of Pfizer/BioNTech, AstraZeneca, Sputnik V, Johnson & Johnson, Moderna, and Sinopharm COVID-19 vaccines. In addition, we aimed to compare the susceptibility of getting COVID-19 breakthrough infections after various types of vaccines. MATERIALS AND METHODS: Samples from 2065 blood bank donors and healthcare workers at King Hussein Cancer Center (KHCC) were collected between February and September 2021. Anti-Spike/RBD IgG levels were measured using Chemiluminescent microparticle-immunoassay (CMIA) (ARCHITECT IgG II Quant test, Abbott, USA). RESULTS: The mean titer of anti-RBD IgG levels was significantly diverse among different types of vaccines. The highest titer level was seen in participants who took a third booster vaccine shot, followed by Pfizer/BioNTech, AstraZeneca, and Sinopharm vaccine. The mean titer levels of anti-RBD IgG antibodies in the Pfizer vaccinated group was the highest after vaccination but started to drop after 60 days from vaccination unlike AstraZeneca and Sinopharm vaccine-induced antibodies where the mean titers continued to be stable until 120 days but their levels were significantly lower. Most of the breakthrough infections were among the Sinopharm vaccinated group and these breakthroughs happened at random times for the three main types of vaccines. CONCLUSIONS: Our data demonstrate that the mean-titer of anti-RBD IgG levels drop after four months which is the best time to take the additional booster shot from a more potent vaccine type such as mRNA vaccines that might be needed in Jordan and worldwide.

Clinical Significance of Circulatory miRNA-21 as an Efficient Non-Invasive Biomarker for the Screening of Lung Cancer Patients

Dysregulation in the miRNA-21 expression has been previously observed in a number of malignancies and not only in the tumor cell itself but also in the body fluids of the cancer patients. The present study aimed to find out the clinical significance of cell-free circulating miRNA-21 as an efficient non-invasive biomarker for the screening of lung cancer patients. The present case-control study included plasma samples from 80 lung cancer patients and 80 healthy controls. Magnetic bead technology was used for efficient miRNA isolation and advanced TaqMan miRNA assays were used for the quantification of miRNA-21 level in the plasma of the lung cancer patients and healthy individuals.The overall mean relative expression level of plasma miRNA-21 among lung cancer patients (2.32±1.7) was higher when compared to healthy individuals (0.715 ± 0.48) and it showed a significant difference of p<0.0001. The area under ROC curve was 0.8913 [95% confidence interval (CI): 0.8394 to 0.9431, p< 0.0001] and the sensitivity and specificity were both 80.0% when the cut-off value was 1.207. In conclusion, plasma miRNA-21 can be efficiently extracted by the magnetic bead technology and quantified by the advanced TaqMan miRNA assay. Plasma miRNA-21 showed a high ability to distinguish between lung cancer patients and healthy individuals, therefore can be used as an efficient non-invasive biomarker for the screening of Lung cancer patients.

Frequency of t(14;18) in follicular lymphoma patients: geographical or technical variation.

The t(14;18) translocation is the most distinguishing molecular finding in follicular lymphoma (FL). However, the reported frequencies of t(14;18) in FL show significant variation, which is often attributed to geographical and/or methodological factors. The methods used to detect t(14;18) include Southern blotting, conventional cytogenetics, fluorescent in situ hybridization, and polymerized chain reaction (PCR). Because of its practicality and superior sensitivity, PCR is becoming the more commonly used method in clinical laboratories. The identification of the main breakpoint regions on chromosome 18, including the major breakpoint region (MBR), the minor cluster region (mcr), and the newly defined intermediate cluster region (icr), increased the detection frequency of PCR. In our study, using a highly sensitive nested PCR strategy with primers for MBR, mcr and icr regions, we were able to detect t(14;18) in 95% of FL patients, which is one of the highest reported frequencies using PCR. We screened 58 FL patient samples collected retrospectively from different hospitals in Jordan. DNA was extracted from archival paraffin-embedded samples, some of which were >10 years old. The respective breakpoint distributions were, 47 for MBR (81%), two for mcr (3.5%) and six for icr (10.3%). In this report, we analyze this high frequency of t(14;18) detection in a general review of the recent literature, in an attempt to assess the geographical vs. methodological influences on the reported frequencies.

The transforming mutation E17K/AKT1 is not a major event in B-cell-derived lymphoid leukaemias.

Despite the major role of the AKT/PKB family of proteins in the regulation of many growth and survival mechanisms in the cell, and the increasing evidence suggesting that AKT disruption could play a key role in many human malignancies, no major mutations of AKT genes had been reported, until very recently when Carpten et al reported a novel transforming mutation (E17K) in the pleckstrin homology domain of the AKT1 gene in solid tumours. Several laboratories are now screening for this mutation in different malignancies, and, recently, the mutation was described by Malanga et al in 1.9% of lung cancer patients. Considering the importance of the PI3K/AKT pathway in mediating survival and antiapoptotic signals in the B-cell types of chronic lymphocytic leukaemia (CLL) and acute lymphoblastic leukaemia (ALL), we sequenced the AKT1 exon 3 for the above mentioned mutation in 87 specimens, representing 45 CLLs, 38 ALLs and 4 prolymphocytic leukaemia (PLL) cases, which are all of B-cell origin. Our results show that the mutation E17K/AKT1 was not detected in the pleckstrin homology domain of AKT1 of the investigated cases. We conclude that this mutation is not a major event in B-cell-derived lymphoid leukaemias.

Inhibition of tumor growth by DT-A expressed under the control of IGF2 P3 and P4 promoter sequences.

The human IGF2 P3 and P4 promoters are highly active in a variety of human cancers. We here present an approach for patient oriented therapy of TCC bladder carcinoma by driving the diphtheria toxin A-chain (DT-A) expression under the control of the IGF2 P3 and P4 promoter regulatory sequences. High levels of IGF2 mRNA expression from P3, P4 or both promoters were detected in 18 TCC samples (n = 29) by ISH or RT-PCR. Normal bladder samples (n = 4) showed no expression from either promoter. The activity and specificity of the IGF2 P3 and P4 regulatory sequences were established in human carcinoma cell lines by means of luciferase reporter gene assay. These sequences were used to design DT-A expressing, therapeutic vectors (P3-DT-A and P4-DT-A). The activity of both was determined in cell lines (in vitro) and the activity of P3-DT-A was determined in a heterotopic animal model (in vivo). The treated cell lines highly responded to the treatment in a dose-response manner, and the growth rate of the developed tumors in vivo was highly inhibited (70%) after intratumoraly injection with P3-DT-A compared to non-treated tumors (P < 0.0002) or tumors treated by luciferase gene expressing LucP3 vector (P < 0.002).

Use of transcriptional regulatory sequences of telomerase (hTER and hTERT) for selective killing of cancer cells.

Telomerase (hTER and hTERT) plays a crucial role in cellular immortalization and carcinogenesis. Telomerase activity can be detected in about 85% of different malignant tumors, but is absent in most normal cells. In situ hybridization analysis showed that high levels of hTER and hTERT expression are present in bladder cancer, while no signal was detected in normal tissue. Therefore, in this work we propose to use hTER and hTERT transcriptional regulatory sequences to control the expression of a cytotoxic gene in bladder tumor cells, resulting in the selective destruction of this cell population. Expression vectors containing the diphtheria toxin A-chain (DT-A) gene were linked to hTER and hTERT transcriptional regulatory sequences, respectively. Inhibition of protein synthesis occurred in bladder and hepatocellular carcinoma cells transfected with the plasmids containing the DT-A gene under the control of the hTER or hTERT promoters in correlation with their activity. These studies support the feasibility of using hTER and hTERT transcriptional regulatory sequences for targeted patient-oriented gene therapy of human cancer.

Fatty acid composition of human milk in Kuwaiti mothers.

Kuwaiti diet is exceptionally rich in fat, carbohydrates and proteins. In addition, subjects in Kuwait are exposed to extreme heat and sun light. Fatty acid profiles of human milk obtained from 19 full breast feeding Kuwaiti mothers were analyzed. Dietary patterns for individual mothers were determined by 24 h dietary recall and food frequency questionnaire. The fatty acid content of human milk was affected by the diet consumed by the lactating mother. The content of long chain polyunsaturated fatty acids (LCP) in human milk lipids did not correlate with their parent fatty acids like linoleic and alpha-linolenic acids. However the human milk LCP were related to the of content of LCP in the maternal diet. Mothers reporting a high fish consumption showed significant amounts of C22:6, omega 3 and C20:5, omega 3 fatty acids. As a general conclusion, breast milk produced by a well nourished mother is better suited to meet the lipid requirements of infants.

Pathologic review of consecutive radical prostatectomy specimens. Nerve sparing versus nonnerve sparing.

Retrospective pathologic analysis was conducted of specimens from 88 radical retropubic prostatectomy operations performed between 1982 and 1987 inclusive. The median age of patients was sixty years (range, 46 to 73 years). Of the 88 radical prostatectomies performed, 51 were nerve-sparing (40 bilateral) and 37 were nonnerve-sparing (11 unilateral) procedures. Preoperative clinical staging was similar in both groups. Thirty-five of 37 patients (95%) in nonnerve-staging group and 51 of 51 patients (100%) in nerve-sparing group had clinical Stage B2 disease or less. Pathologic staging in both groups was also similar. In 26 of 37 patients (70%) in nonnerve-sparing group and in 35 of 51 patients (69%) in nerve-sparing group, disease remained localized to the prostate. Both groups were analyzed retrospectively to determine whether or not the incidences of microinvasion of capsule and of extraprostatic disease differed. Review of the apical and lateral margins of the specimens revealed no statistically significant difference in either the degree of microinvasion of capsule or the incidence of extraprostatic disease between the groups.