IntRoduCtIonLung cancer ranks the first in the incidence and mortality rates amongst all malignancies worldwide. Non-small cell lung cancer (NSCLC) constitutes 80% -85% of all diagnosed cases and more than 70% of NSCLC are diagnosed as an advanced or late disease (1).Recognition of tumor antigens by t cells leads to activation of anti-tumor immune reaction mainly by cytotoxic CD+8 tumor infiltrating lymphocytes (tiLs), but malignant cells may have many pathways to evade the immunological destruction. PD-1 is a co-stimulatory molecule on t-cells that inhibits t cell activation. PD-1, which is a 288-amino acid cell-surface protein, can bind two ligands, PD-L1 and PD-L2, which negatively control the immune response. tumor cells express PD-L1 can inhibit t cell-mediated immune response and can progress to distant metastasis (2,3). CD8 marker is expressed on cytotoxic t cells, natural killer, and dendritic cells. CD8+ t cells are a major component of the cell-mediated immune system against malignant cells. CD8+ t cells undergo differentiation to effector cytotoxic t cells. Then the effector CD8+ cells undergo apoptosis leaving memory cells when a pathogenic response is resolved. Memory t cells and cytotoxic t cells are associated with a more favorable prognosis in NSCLC (4).PD-L1 over-expression has been proved to be a poor prognostic marker in many human cancers (5). PD-1/ PD-L1 interaction suppresses CD8+ tiLs survival and proliferation and leads to apoptosis of tumor-infiltrating lymphocytes. PD-L1 over-expression in tumor cells in a syngeneic transplant model of tumor cells makes them evade from cytotoxic tiLs (6). AbStRACtObjective: Programmed cell death ligand-1 interacts with the immune receptors on the surface of CD8+ tumor infiltrating lymphocytes and PD-1, thereby blocking its anti-tumor activity. therapeutics suppression of this interaction will show a promise in the treatment of non-small cell lung cancer by restoring the functional anti-tumor t-cell activity. We aimed to evaluate the association between the immunohistochemical expression of PD-L1, stromal CD8+ tumor infiltrating lymphocytes and p53 with the clinicopathological characteristics, response to chemotherapy, progression-free-survival, and overall survival. Material and Method:We examined the immunohistochemical expression of PD-L1, stromal CD8+ tiLs, and p53 expression in 50 patients with advanced stage (iii&iV) non-small cell lung cancer.Results: PD-L1 was expressed in 56% of the studied cases. PD-L1 expression was related to unfavorable response to the therapy without significant difference. PD-L1 expression was significantly associated with disease progression, poor progression-free-survival & overall survival. CD8+ tiLs were high in 32% of the cases. tumors with high CD8+ tiLs showed a partial response to therapy and had a better progression-free-survival and overall survival. p53 expressed in 82% of the studied cases. there was a significant negative association between PD-L1 and CD8+ tiLs (p=0.009), while a non-significant association wa...
Objective: tumor stem cells have been found in a variety of neoplasms and stated to have a role in tumor progression. This study aimed to evaluate the prognostic significance of biomarkers which are said to be related to these cells, i.e., EZH2, ALDH1 and Ki-67, and their correlation with each other in astrocytic gliomas. Material and Method:Formalin-fixed, paraffin-embedded tissue specimens of 40 patients with astrocytic glioma who underwent initial surgery during the period from December 2011 to May 2014 at Zagazig University Hospitals were enrolled in the study. Consecutive 4-μm thick sections from formalin-fixed, paraffin-embedded tissue blocks were prepared and stained with hematoxylin and eosin for histopathological evaluation. immunohistochemical analysis using ALDH1, EZH2 and Ki-67 antibodies were performed to examine the cases.Results: A total of forty patients; 22 males and 18 females were studied. The lesions were classified as follows: 14 cases of low-grade astrocytoma (WHO grade i or ii), 11 cases of anaplastic astrocytoma (WHO grade iii), and 15 glioblastomas (WHO grade iV). There was a significant increase in ALDH1 immunoreactivity with increasing the grade of astrocytoma (mean ±SD = 0.2 ±0.4, 0.5 ±0.6, 1.1 ±1.3 and 2.95 ±2.97 in grade i to iV astrocytic gliomas, respectively). This expression was significantly correlated with overall survival (OS) and progression-free survival (pFS) (p=0.004). EZH2 expression was also significantly associated with advanced grades (mean ±SD =1.35 ±0.4, 3.1 ±2.6, 7.2 ±3.5 and 9.9 ±4.1, in grade i to iV astrocytic gliomas, respectively). EZH2 and Ki-67 expressions were found to be correlated with OS and pFS (p < 0.001).Conclusion: increased expression of ALDH1, EZH2 and Ki67 are found to be associated with unfavourable prognosis in patients with astrocytic gliomas and may predict therapeutic modalities.
Introduction: Toxoplasma gondii is an intracellular protozoan that may disrupt the traditional cell barriers against cancer, allowing the accumulation of oncogenic mutations over time. Our research aimed to explore the relationship between T. gondii infection and tumor development. Methodology: The anti-T. gondii IgG and IgM antibodies were tested for156 patients with tumors (51 with breast cancer, 20 with hepatoma, 20 with larynx carcinoma, 20 with squamous cell carcinoma of bone, 16 with lymphoma, 13 with brain tumor, 4 with bladder cancer and 12 with benign uterine tumor) and 90 healthy controls by using electrochemiluminescence immunoassay. Tissue specimens were collected from T. gondii seropositive cases for histological and immunohistochemistry (IHC) examinations. Results: The seroprevalence of human toxoplasmosis in the Sharkia Governorate, Egypt is significantly correlated with various types of tumors: breast cancer in 49 subjects (96.1%), and squamous cell carcinoma of bone in 16 subjects (80%). It was also present in nine cases of brain tumors. Anti-Toxoplasma IgG was detected in seven cases of liver tumors and one-quarter of bladder cancer. The anti- Toxoplasma IgM was present in three patients with benign uterine tumors, one patient with a bone tumor and two patients with breast cancer. Toxoplasma cysts were detected in immunostained brain sections. Conclusion: The correlation between T. gondii infection and tumors was established by this study indicating a significant emerging role of human toxoplasmosis in the etiology or existence of particular types of tumors.
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