Thearubigins protected against acetaminophen-induced hepatotoxicity and nephrotoxicity in mice possibly through their antioxidant activity.

Background Forkhead box P3 (Foxp3) functions as a master regulator in the development and function of T-regulatory (Treg) cells. Recent studies have shown that autoimmune diseases including systemic lupus erythematosus (SLE) are associated with an imbalance with the Treg cells and T helper (Th) subtypes. Objectives To evaluate immunohistochemical expression of Foxp3 positive Treg cells in lupus nephritis (LN) and analyze its association with clinicopathologic parameters. Materials and Methods Renal biopsy specimens of 50 patients with LN were studied. Specimens were divided into; group A; 25 LN cases without proliferative activity (Class II and V) and group B: 25 cases with proliferative activity (Class III and IV). Immunohistochemical staining for anti-human Foxp3 antibody and grading from grade 0 to grade 3 was done. Results Foxp3 expression in group A was (grade 0 in 14 [56.0%], grade +1 in 11 [44.0 %]) in comparison to group B (grade +1 in 6 [24.0%], grade +2 in 11 [44.0%] and grade +3 in 8 [32.0%]) (P < 0.001). Foxp3 expression was significantly correlated to National Institutes of Health (NIH) activity and chronicity indices (P < 0.05), as well as serum creatinine (P < 0.01) in both groups A and B and there was a highly significant correlation with proteinuria (P < 0.01) in group B with proliferative LN. Conclusions Immunohistochemical Foxp3 expression in renal tissue was higher in proliferative versus non-proliferative LN and is associated with activity and severity of LN. Further studies are needed to determine its prognostic value in LN.

Background: PD-L1 expression differs from 19 to 92% in various cancer subtypes. Its expression carries a worse prognostic value in various malignancies and could also be used as a predictive marker for immune checkpoint inhibitor response. This study aimed to explore the prevalence of PD-L1 expression in soft tissue sarcomas and the correlation of PD-L1 expression with clinicopathological features.Patients and Methods: The tissue samples of 50 patients with STS were tested for PD-L1 expression using immunohistochemistry (IHC). We followed a 6-step proportional scoring system. The patients were treated at Ain Shams University Hospital from 2011 to 2017. We also explored the correlation of PD-L1 expression with different clinical features of the patients. The chi-square test was used to calculate the differences among variables.Results: Twelve cases (24%) showed positive PD-L1 expression with the highest prevalence in rhabdomyosarcoma and desmoid tumors (2/2 and 2/3 cases, respectively), followed by GIST in 2/4 cases and liposarcoma in 3/11 cases. Patients with positive PD-L1 expression showed a trend for worse survival, with a median overall survival of 11 months vs. 19 months for patients with negative PD-L1 expression (p-value = 0.1) and a mean PFS of 6 months vs. 11 months for patients with negative PD-L1 expression (p-value = 0.1). However, these findings did not reach statistical significance.Conclusion: Although the results did not reach statistical significance due to the small number of cases, PD-L1 expression could represent a prognostic factor for poor outcome. Larger clinical trials are recommended for the validation of PD-L1 as a poor prognostic biomarker.

Background: There is increasing evidence that high-risk human papilloma virus (HPV) is involved in cancers in addition to cervical cancer. Infectious agents are thought to be responsible for approximately 16% of cancers worldwide, however there are mixed reports in the literature regarding the prevalence and potential pathogenicity of viruses in breast cancer. Methods:We screened 30 fresh frozen breast cancer tissue specimens collected immediately postoperative from patients in Ain-Shams University Hospital for the presence of human papilloma virus (HPV) DNA by PCR and Koilocytic changes in the breast cancer tissue. Results:Overall prevalence of HPV in malignant breast tissue was 16.7% In addition, we found that the oncogenic characteristics of HPV associated breast cancer are very similar to HPV-associated cervical cancer. Specifically, that putative koilocytes are present in some HPV associated breast cancers. Conclusion:The above observations indicate a likely causal role for high-risk HPV in human breast cancer and offer the possible role of HPV in breast cancer prognosis.

Background Lupus nephritis (LN) is an ominous manifestation of systemic lupus erythematosus (SLE). Clinical renal affection is present in about 70% of lupus patients, and more patients have histological evidence of renal involvement without clinical manifestations. This study aimed to investigate the potential role of serum interleukin-34 (IL-34) as an early marker for the detection of silent LN. Methods Thirty-three lupus patients with silent LN (group I), 37 patients with clinical LN (group II) and 20 controls were included. The SLE Disease Activity Index (SLEDAI), IL-34, anti-dsDNA antibodies and renal biopsy were assessed in all patients. Results Serum IL-34 levels were significantly higher in all lupus patients compared to healthy controls ( p < 0.001) and showed a significant positive correlation with SLEDAI score. SLE patients with positive anti-dsDNA antibodies had more active disease according to SLEDAI and higher levels of IL-34 than those with negative anti-dsDNA antibodies. In both studied groups, serum IL-34 levels were significantly higher in patients with proliferative LN (class III and class IV) than those with non-proliferative lupus (class II and class V) and controls. Yet, in both groups, IL-34 was not useful in differentiating active from chronic renal affection. Conclusion In lupus patients with insignificant proteinuria, serum levels of IL-34 distinguished the different histological classes of subclinical LN. Serum IL-34 may be used as a surrogate marker for early renal affection in silent LN, especially the proliferative type.

Background: CD117/c-kit, is a powerful stem cell marker for malignant salivary gland tumors in which dysregulation of c-kit is closely associated with impairment of cell adhesion molecules and cancer metastasis. Objective: The main purpose of this work is to evaluate the immunohistochemical expression of c-kit, and claudin-1 and measure the density of lymph vessels (LVD) in common malignant salivary gland tumors by using podoplanin (D2-40) antibody. Materials and Methods: Immunohistochemical staining with streptavidin peroxidase was used to analysis the expression of c-kit, claudin-1 and stained podoplanin (D2-40) lymphatic vessels on fifty archival paraffin blocks of malignant salivary gland tumor (MSGTs) cases included 20 cases of AdCC, 11 cases of MEC, 10 cases of CXPA,              6 cases of AcCC, and 3 cases of PAC. Results: The immunopositivity of c-kit (CD117) was detected in 44/50 (88%) of studied cases, whereas, claudin-1 protein was observed in 35 (70%) of our specimens of MSGTs.  Count down of stained lymph vessels between examined cases was, MEC on the top, followed by CXPA, AdCC, PAC and AcCC. A direct correlation was observed between c-kit and lymphatic density, on the other hand, the inverse correlation was found d between c-kit and cld-1, as well as, between cld-1 and lymphatic density Conclusion: Up regulation of cancer stem cell marker c-kit (CD117) expression is associated with decrease of tight junction protein cld-1 and increase the density of stained lymphatic vessels by podoplanin (D2-40) antibody which confirms the using of c-kit inhibitor to improve treatment strategy of malignant salivary gland tumors.

Introduction: One of the most important regulators of immune response is the programmed death receptor 1 (PD-1) and its interaction with its ligand (PD-L1), which negatively influences the immune response. Objectives: This study aims to clarify PD-L1 expression levels and the associated tumor infiltrating lymphocytes (TILs) in patients with metastatic breast cancer, and to assess their influence on the prognosis of these patients and the association with clinico-pathologic criteria. Patients and Methods: PD-L1 expression was analyzed using immunohistochemistry (IHC) while TILs count was assessed by histopathological examination of the hematoxylin and eosin (H & E) stained full tumor sections from 50 patients diagnosed with stage IV breast cancer at Ain Shams University hospital, Cairo, Egypt. Results: PD-L1 expression was demonstrated on TILs in 21 of 50 specimens, and on tumor cells in 13 of 50 specimens. Triple negative breast cancer (TNBC) and ER-/Her2+ subtypes were significantly associated with TIL infiltration and PD-L1 expression (on TILs and tumor cells). High TIL infiltration was significantly associated with worse overall survival (OS) and progression free survival (PFS) (P=0.0238 [HR 4.7, 95% CI: 1.22-18.11] and P=0.0262 [HR 3.1, 95% CI: 1.14-8.59] respectively). No correlation was found between PD-L1 expression (on tumor or TILs) and the survival of the patients (OS nor PFS). Conclusion: High TIL count infiltrating the breast tumor is associated with worse OS and PFS in patients with metastatic breast cancer. High PD-L1 expression correlated with high counts of TIL levels around the tumor. These findings have major clinical implications in using immune-checkpoint inhibitors in treating breast cancer patients.

Podocyte loss indicated by podocalyxin immunohistochemical expression reflects the degree of activity and severity of LN and the degree of podocyte effacement by E/M.