Immunolocalization of neurokinin 1 receptor in WHO grade 4 astrocytomas, oral squamous cell and urothelial carcinoma

Neurokinin-1 receptor (NK-1R) induces inflammatory reactions in peripheral tissues but its regulatory effects in target tissues is dependent on receptor signalling. Substance P (SP) has a high affinity for the NK-1R, to which it binds preferentially. We aimed to investigate the expression of NK-1R in World Health Organization (WHO) grade 4 astrocytomas as well as in oral squamous cell carcinoma (OSCC) and urothelial carcinoma, and its association with disease progression.The study included tissue samples from 19 brain astrocytomas, 40 OSCCs and 10 urothelial carcinomas. NK-1R expression was quantitatively assessed in the tumour cells using immunohistochemistry. The relationship between NK-1R expression in astrocytomas and recurrence-free interval has been explored.The results showed that the NK-1R was intensely expressed in patients with WHO grade 4 astrocytoma, OSCC and urothelial carcinoma. However, cases clinically diagnosed as a low-grade cancer showed reduced NK-1R expression.NK-1R is overexpressed in all cases of WHO grade 4 astrocytoma, OSCC and urothelial carcinoma. The ubi-quitous presence of SP/NK-1R complex during tumour development and progression suggests a possible therapeutic key strategy to use NK-1R antagonist as an adjuvant therapy in the future

Stress Could be a Major Contributing Factor in the Pathopenesis & Prognosis of COVID-19 in the Medical Team Professionals

The world with COVID-19 is in greatly challenging circumstances that can lead to stress for many reasons including the feeling of uncertainty and the worry about family members and friends. Chronic stress affects both humoral and cellular immunity. The role of government and public support for the health teams is demanded to help the health professionals overcome these stressors and therefore defeat the infection.</p

Hospital-Based Study of Epithelial Malignancies of Endometrial Cancer Frequency in Lahore, Pakistan, and Common Diagnostic Pitfalls

The current study was conducted to see the frequency of epithelial malignancies of endometrium with focus on the common diagnostic pitfalls and identify morphological and immunohistochemical markers helpful in the differential diagnosis between different subtypes. It is a retrospective descriptive study carried out on 52 specimens of endometrial tumors received in Fatima Memorial Hospital, Lahore, Pakistan, during three years (2010–2012). Patients were divided into 5 age groups: <40, 41–50, 51–60, 61–70, and >70 yrs. Tissues were fixed in 10% formalin and processed and stained with haematoxylin-eosin. Stained slides were examined to determine the histological types by WHO classification, and immunohistochemistry for WT1, p53, ER/PR, and MIB1 was done in cases where morphology alone was not helpful in making a confirmed diagnosis. 80% of specimens were of endometrioid adenocarcinomas, 11% of serous tumors, 4% of clear cell carcinoma, and 4% of squamous cell carcinomas involving both cervix and endometrium. Most of the patients (28.84%) with endometrial carcinomas fall in the age range of 51–60 yrs. Endometrioid adenocarcinoma is the most common type of epithelial endometrial malignancies. Morphology is the keystone in the evaluation of these tumors, but immunohistochemistry can also be helpful in establishing the correct diagnosis

Enhanced Neurokinin-1 Receptor Expression Is Associated with Human Dental Pulp Inflammation and Pain Severity

Substance P (SP) is a peptide involved in many biological processes, including nociception and inflammation. SP has a high affinity for its receptor neurokinin-1 (NK-1R). SP/NK-1R complex plays a major role in the interactions going on during the onset of dental pain and inflammation. Objective. To identify the expression of NK-1R in healthy and inflamed human dental pulp, as well as to identify any association with severity of dental pain. Methods. This case-control study included ten irreversibly inflamed samples of dental pulp, which were extirpated from patients presenting with chief complaint of dental pain due to caries. Ten healthy pulps, extirpated from those teeth which were indicated for extraction due to orthodontic reasons, were used as the control group. Visual analog scale (VAS) and modified McGill Pain Questionnaire were used to assess the characteristic and severity of pain. Immunohistochemical study was performed using monoclonal antibodies against NK-1R. Results. The results showed that the NK-1R was expressed intensely in patients with higher pain score. The mean pain score in cases was 7.0±2.0. The healthy dental pulps had negative or mild NK-1R staining of +1 intensity. The NK-1R score in cases was 2.4±0.516 and 0.2±0.4216 in controls. There was significant difference in NK-1R score between both groups (p value <0.05). There was a strong positive correlation between the pain score and NK-1R expression score. As the pain increased, the NK-1R expression score was also increased (0.95∗∗, p value 0.000). Conclusions. NK-1R is overexpressed in inflamed dental pulp. SP/NK-1R modulation may provide a novel approach for the treatment of pulpal inflammation and pain

DNA methylation signatures of breast cancer in peripheral T-cells

Abstract Background Immune surveillance acts as a defense mechanism in cancer, and its disruption is involved in cancer progression. DNA methylation reflects the phenotypic identity of cells and recent data suggested that DNA methylation profiles of T cells and peripheral blood mononuclear cells (PBMC) are altered in cancer progression. Methods We enrolled 19 females with stage 1 and 2, nine with stage 3 and 4 and 9 age matched healthy women. T cells were isolated from peripheral blood and extracted DNA was subjected to Illumina 450 K DNA methylation array analysis. Raw data was analyzed by BMIQ, ChAMP and ComBat followed by validation of identified genes by pyrosequencing. Results Analysis of data revealed ~ 10,000 sites that correlated with breast cancer progression and established a list of 89 CG sites that were highly correlated (p  0.7, r < − 0.7) with breast cancer progression. The vast majority of these sites were hypomethylated and enriched in genes with functions in the immune system. Conclusions The study points to the possibility of using DNA methylation signatures as a noninvasive method for early detection of breast cancer and its progression which need to be tested in clinical studies

Additional file 1: of DNA methylation signatures of breast cancer in peripheral T-cells

Table S1. Clinical table of normal individuals and cancer patients. Table S2. Primer sequences. Table S3. List of CpG probes, whose DNA methylation changes correlate with progression in t-cells of breast cancer patients. Table S4. List of top 89 CpG probes (r > 0.7, r < − 0.7, p < 0.01), whose DNA methylation changes correlate with progression in t-cells of breast cancer patients. Table S5. Differentially methylated probes in t-cells of breast cancer patients. Table S6. Differentially methylated probes in t-cells of breast cancer patients (stages 1 and 2). Table S7. Differentially methylated probes in t-cells of breast cancer patients (stages 3 and 4). Table S8. List of overlapped differentially methylated probes between stages 1,2 and stages 3 and 4 in t-cells of breast cancer patients. Table S9. Ingenuity Canonical Pathways of differentially methylated genes in T cells of breast cancer. Table S10. Upstream regulators of differentially methylated genes in T cells of breast cancer. Table S11. Overlap CpG probes, whose DNA methylation changes correlate with progression in t-cells of breast cancer patients and differentially methylated probes in DCIS, mixed and invasive breast from dataset GSE60185. Table S12. Canonical Pathways of genes whose DNA methylation changes with breat cancer progression in T cells and overlapped with differentially methylated genes in DCIS, mixed and invasive breast cancer. Table S13. Upstream regulators of genes whose DNA methylation changes with breat cancer progression in T cells and overlapped with differentially methylated genes in DCIS, mixed and invasive breast cancer. (XLSX 6740 kb

The value of open-source clinical science in pandemic response: lessons from ISARIC

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