Expression of GLUT1 and GLUT3 Glucose Transporters in Endometrial and Breast Cancers

Cancer cells have accelerated metabolism and high glucose requirements. The up-regulation of specific glucose transporters may represent a key mechanism by which malignant cells may achieve increased glucose uptake to support the high rate of glycolysis. In present study we analyzed the mRNA and protein expression of GLUT1 and GLUT3 glucose transporters by quantitative real-time polymerase chain reaction (Q-PCR) and Western blotting technique in 76 cases of endometrial carcinoma and 70 cases of breast carcinoma. SLC2A1 and SLCA2A3 mRNAs expression was found, respectively in 100% and 97.4% samples of endometrial cancers and only in 50% and 40% samples of breast cancers. In endometrial cancers GLUT1 and GLUT3 protein expression was identified in 67.1% and 30.3% of cases. Analogously, in breast cancers in 48.7% and 21% of samples, respectively. The results showed that both endometrial and breast poorly differentiated tumors (grade 2 and 3) had significantly higher GLUT1 and GLUT3 expression than well-differentiated tumors (grade 1). Statistically significant association was found between SLCA2A3 mRNA expression and estrogen and progesterone receptors status in breast cancers. GLUT1 has been reported to be involved in the uptake of glucose by endometrial and breast carcinoma cells earlier and the present study determined that GLUT3 expression is also involved. GLUT1 and GLUT3 seem to be important markers in endometrial and breast tumors differentiation

A study of prognostic factors in Chinese patients with diabetic foot ulcers

Objective: Few studies have identified factors as predictors of clinical prognosis of patients with diabetic foot ulcers (DFUs), especially of Chinese patients. In this study, we assessed the prognostic factors of Chinese patients with DFUs. Methods and materials: This was a retrospective study (January 2009–January 2011) of 194 DFUs conducted in an inpatient population at PLA 454 Hospital in Nanjing, China, to determine the prognostic influential factors of DFUs in Chinese patients. All of the studied patients were grouped into an amputation group, a non-healing group, and a cured group, according to the clinical prognosis. Patient parameters, including gender, age, smoking habits, education level, family history of diabetes mellitus, medical history, duration of foot lesions and complications, ankle-brachial index (ABI), transcutaneous oxygen pressure (TcPO2), urinary albumin/creatinine ratio (Alb/Cr), fundus oculi, electrocardiogram, DFU characteristics, bacterial nature, and neuropathy, were cross-studied among the three groups. Results: Compared with the other two groups, the amputation group showed a higher number of males, older in age, lower ABI and TcPO2 levels, higher Wagner wound grading and size, and significantly higher urinary Alb/Cr ratio, blood urea nitrogen, serum creatinine, white blood cell count, and erythrocyte sedimentation rate. Compared to the cured group (162 patients), more patients with an older age, smoking, family history of diabetes mellitus, medical history of foot ulcerations, lower ABI and TcPO2 levels, higher urine Alb/Cr ratio, and serum creatinine were found in the non-healing group. Regression analysis was used to study the correlation between various factors and clinical prognosis, and the results were as follows: age, Wagner wound classification, and heel ulcerations were negatively correlated to the DFU prognosis, whereas the female population, ABI, and TcPO2 were positively correlated with DFU prognosis. Conclusion: In this retrospective study, we conclude that the DFU prognosis may be related to age, gender, wound location (heel), Wagner wound classification, ABI, and TcPO2 levels in the Chinese population

Performance evaluation of novel fluorescent-based lateral immune flow assay (LIFA) for rapid detection and quantification of total anti-SARS-CoV-2 S-RBD binding antibodies in infected individuals.

The vast majority of the commercially available LFIA is used to detect SARS-CoV-2 antibodies qualitatively. Recently, a novel fluorescence-based LIFA test was developed for quantitative measurement of the total binding antibody units (BAU/mL) against the receptor-binding domain of the SARS-CoV-2 spike protein (S-RBD). To evaluate the performance of the fluorescence LIFA Finecare 2019-nCoV S-RBD test along with its reader (Model No.: FS-113). Plasma from 150 RT-PCR confirmed-positive individuals and 100 pre-pandemic samples were tested by FinCare to access sensitivity and specificity. For qualitative and quantitative validation of the FinCar measurements, the BAU/mL results of FinCare were compared with results of two reference assays: the surrogate virus-neutralizing test (sVNT, GenScript, USA), and the VIDAS®3 automated assay (BioMérieux, France). Finecare showed 92% sensitivity and 100% specificity compared to PCR. Cohen's Kappa statistic denoted moderate and excellent agreement with sVNT and VIDAS®3, ranging from 0.557 (95% CI: 0.32-0.78) to 0.731 (95% CI: 0.51-0.95), respectively. A strong correlation was observed between Finecare/sVNT (r=0.7, p<0.0001) and Finecare/VIDAS®3 (r=0.8, p<0.0001). Finecare is a reliable assay and can be used as a surrogate to assess binding and neutralizing antibody response post-infection or vaccination, particularly in none or small laboratory settings

Effect of the dual endothelin receptor antagonist bosentan on untreatable skin ulcers in a patient with diabetes: a case report

<p>Abstract</p> <p>Introduction</p> <p>Refractory skin ulcers are a major burden in patients with diabetes. Their pathogenesis is multifactorial, and data increasingly implicate endothelin as a mediator of diabetic macro- and microvasculopathy. Here we describe the first reported case of an endothelin receptor antagonist being used to successfully treat refractory skin ulcers in a patient with diabetes.</p> <p>Case presentation</p> <p>An 85-year-old Caucasian man with a 30-year history of type 2 diabetes developed multiple skin ulcerations, including a right heel ulcer. Despite appropriate treatment, the ulcer showed little improvement and the risk of amputation was high. The patient was treated with the dual endothelin receptor antagonist bosentan. After three weeks of treatment, major improvements were observed, and after 21 weeks, all ulcers had healed. No abnormalities were observed during monitoring of blood pressure, erythrocyte sedimentation rate or serum aminotransferase levels.</p> <p>Conclusion</p> <p>In patients with refractory ulceration associated with diabetes, bosentan may be of real benefit, especially in terms of amputation prevention. This case supports the proposed role for endothelin in the pathogenesis of skin ulceration in diabetes and is suggestive of a potential benefit of bosentan in this patient type. This case report is of interest to diabetologists and dermatologists.</p

Neutralizing antibodies against SARS-CoV-2 are higher but decline faster in mRNA vaccinees compared to individuals with natural infection.

Waning protection against emerging SARS-CoV-2 variants by pre-existing antibodies elicited due to current vaccination or natural infection is a global concern. Whether this is due to the waning of immunity to SARS-COV-2 remains unclear. We aimed to investigate the dynamics of antibody isotype responses among vaccinated naïve (VN) and naturally infected (NI) individuals. We followed up antibody levels in COVID-19 mRNA-vaccinated subjects without prior infection (VN, n = 100) in two phases: phase-I (P-I) at ~ 1.4 and phase-II (P-II) at ~ 5.3 months. Antibody levels were compared to those of unvaccinated and naturally infected subjects (NI, n = 40) at ~ 1.7 (P-1) and 5.2 (P-II) months post-infection. Neutralizing antibodies (NTAb), anti-S-RBD-IgG, -IgM, and anti-S-IgA isotypes were measured. The VN group elicited significantly greater antibody responses (p < 0.001) than the NI group at P-I, except for IgM. In the VN group, a significant waning in antibody response was observed in all isotypes. There was about ~ a 4-fold decline in NTAb levels (p < 0.001), anti-S-RBD-IgG (~5-folds, p < 0.001), anti-S-RBD-IgM (~6-folds, p < 0.001), and anti-S1-IgA (2-folds, p < 0.001). In the NI group, a significant but less steady decline was notable in S-RBD-IgM (~2-folds, p < 0.001), and a much smaller but significant difference in NTAb (<2-folds, p < 0.001) anti-S-RBD IgG (<2-folds, p = 0.005). Unlike the VN group, the NI group mounted a lasting anti-S1-IgA response with no significant decline. Anti-S1-IgA, which were ~ 3 folds higher in VN subjects compared to NI in P-1 (p < 0.001), dropped to almost the same levels, with no significant difference observed between the two groups in P-II. While double-dose mRNA vaccination boosted antibody levels, vaccinated individuals' 'boost' was relatively short-lived.This work was made possible by WHO grant numbers COVID-19-22-43 and UREP28–173–3-057 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors

Follow up and comparative assessment of IgG, IgA, and neutralizing antibody responses to SARS-CoV-2 between mRNA-vaccinated naïve and unvaccinated naturally infected individuals over 10 months

BackgroundEvidence on the effectiveness of vaccination-induced immunity compared to SARS-CoV-2 natural immunity is warranted to inform vaccination recommendations. AimIn this study, we aimed to conduct a comparative assessment of antibody responses between vaccinated naïve (VN) and unvaccinated naturally infected individuals (NI) over 10 Months. MethodThe study comprised fully-vaccinated naïve individuals (VN; n = 596) who had no history of SARS-CoV-2 infection, and received two doses of either BNT162b2 or mRNA-1273, and naturally infected individuals who had a documented history of SARS-CoV-2 infection and no vaccination record (NI cohort; n = 218). We measured the levels of neutralizing total antibodies (NtAbs), anti-S-RBD IgG, and anti-S1 IgA titers among VN and NI up to ∼10 months from administration of the first dose, and up to ∼7 months from SARS-CoV-2 infection, respectively. To explore the relationship between the antibody responses and time, Spearman's correlation coefficient was computed. Furthermore, correlations between the levels of NtAbs/anti-S-RBD IgG and NtAbs/anti-S1 IgA were examined through pairwise correlation analysis. ResultsUp to six months, VN individuals had a significantly higher NtAb and anti-S-RBD IgG antibody responses compared to NI individuals. At the 7th month, there was a significant decline in antibody responses among VN individuals, but not NI individuals, with a minimum decrease of 3.7-fold (p < 0.001). Among VN individuals, anti-S1 IgA levels began to decrease significantly (1.4-fold; p = 0.007) after two months, and both NtAb and S-RBD IgG levels began to decline significantly (NtAb: 2.0-fold; p = 0.042, S-RBD IgG: 2.4-fold; p = 0.035) after three months. After 10 months, the most significant decline among VN individuals was observed for S-RBD-IgG (30.0-fold; P < 0.001), followed by NtAb (15.7-fold; P < 0.001) and S-IgA (3.7-fold; P < 0.001) (most stable). Moreover, after 5 months, there was no significant difference in the IgA response between the two groups. ConclusionThese findings have important implications for policymakers in the development of vaccination strategies, particularly in the consideration of booster doses to sustain long-lasting protection against COVID-19.This work was made possible by WHO grant number COVID-19-22-43 and grant number UREP28-173-3-057 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors

CD1a-positive infiltrating-dendritic cell density and 5-year survival from human breast cancer

© Churchill LivingstoneInfiltrating CD1a+ dendritic cells (DCs) have been associated with increased survival in a number of human cancers. This study investigated DC infiltration within breast cancers and the association with survival. Classical established prognostic factors, of tumour size, lymph node status, histological grade, lympho-vascular invasion, the KI-67 (MIB-1) fraction and the Nottingham Prognostic Index (NPI) were also compared. A total of 48 breast cancer patients were followed from the time of surgery and CD1a density analysis for 5 years or until death. Our data set validated previous studies, which show a relationship between survival and the NPI (P<0.001), tumour size (P<0.01) and lymph node status (P<0.05). Although more patients were alive at the 5-year time point in the group with higher CD1a DC density than the lower CD1a DC group, this failed to reach statistical significance at the P=0.05 level. Analysis at 10 years postsurgery is required to investigate the association further.B.J.Coventry and J. Morto

Immunogenic Profiling in Mice of a HIV/AIDS Vaccine Candidate (MVA-B) Expressing Four HIV-1 Antigens and Potentiation by Specific Gene Deletions

BACKGROUND: The immune parameters of HIV/AIDS vaccine candidates that might be relevant in protection against HIV-1 infection are still undefined. The highly attenuated poxvirus strain MVA is one of the most promising vectors to be use as HIV-1 vaccine. We have previously described a recombinant MVA expressing HIV-1 Env, Gag, Pol and Nef antigens from clade B (referred as MVA-B), that induced HIV-1-specific immune responses in different animal models and gene signatures in human dendritic cells (DCs) with immunoregulatory function. METHODOLOGY/PRINCIPAL FINDINGS: In an effort to characterize in more detail the immunogenic profile of MVA-B and to improve its immunogenicity we have generated a new vector lacking two genes (A41L and B16R), known to counteract host immune responses by blocking the action of CC-chemokines and of interleukin 1beta, respectively (referred as MVA-B DeltaA41L/DeltaB16R). A DNA prime/MVA boost immunization protocol was used to compare the adaptive and memory HIV-1 specific immune responses induced in mice by the parental MVA-B and by the double deletion mutant MVA-B DeltaA41L/DeltaB16R. Flow cytometry analysis revealed that both vectors triggered HIV-1-specific CD4(+) and CD8(+) T cells, with the CD8(+) T-cell compartment responsible for >91.9% of the total HIV-1 responses in both immunization groups. However, MVA-B DeltaA41L/DeltaB16R enhanced the magnitude and polyfunctionality of the HIV-1-specific CD4(+) and CD8(+) T-cell immune responses. HIV-1-specific CD4(+) T-cell responses were polyfunctional and preferentially Env-specific in both immunization groups. Significantly, while MVA-B induced preferentially Env-specific CD8(+) T-cell responses, MVA-B DeltaA41L/DeltaB16R induced more GPN-specific CD8(+) T-cell responses, with an enhanced polyfunctional pattern. Both vectors were capable of producing similar levels of antibodies against Env. CONCLUSIONS/SIGNIFICANCE: These findings revealed that MVA-B and MVA-B DeltaA41L/DeltaB16R induced in mice robust, polyfunctional and durable T-cell responses to HIV-1 antigens, but the double deletion mutant showed enhanced magnitude and quality of HIV-1 adaptive and memory responses. Our observations are relevant in the immune evaluation of MVA-B and on improvements of MVA vectors as HIV-1 vaccines

Effect of blood glucose level on standardized uptake value (SUV) in F-18- FDG PET-scan : a systematic review and meta-analysis of 20,807 individual SUV measurements

Objectives To evaluate the effect of pre-scan blood glucose levels (BGL) on standardized uptake value (SUV) in F-18-FDG-PET scan. Methods A literature review was performed in the MEDLINE, Embase, and Cochrane library databases. Multivariate regression analysis was performed on individual datum to investigate the correlation of BGL with SUVmax and SUVmean adjusting for sex, age, body mass index (BMI), diabetes mellitus diagnosis, F-18-FDG injected dose, and time interval. The ANOVA test was done to evaluate differences in SUVmax or SUVmean among five different BGL groups (200 mg/dl). Results Individual data for a total of 20,807 SUVmax and SUVmean measurements from 29 studies with 8380 patients was included in the analysis. Increased BGL is significantly correlated with decreased SUVmax and SUVmean in brain (p <0.001, p <0.001,) and muscle (p <0.001, p <0.001) and increased SUVmax and SUVmean in liver (p = 0.001, p = 0004) and blood pool (p=0.008, p200 mg/dl had significantly lower SUVmax. Conclusion If BGL is lower than 200mg/dl no interventions are needed for lowering BGL, unless the liver is the organ of interest. Future studies are needed to evaluate sensitivity and specificity of FDG-PET scan in diagnosis of malignant lesions in hyperglycemia.Peer reviewe