Immune Checkpoints Receptors Expression of Macrophage/Monocytes in Response to Acute Viral Respiratory Infection.

Background: We aimed to monitor the phenotypic changes in macrophages and their polarization in patients with acute viral respiratory diseases, including coronavirus disease diagnosis, focusing on the variations in the percentages of macrophages and monocytes and their sub-populations in those patients compared to healthy control. Moreover, we defined the correlation between macrophage subtypes and some inflammatory indices. Methods: Twenty-seven patients with clinical and radiologic diagnosis of acute viral respiratory infection admitted in Al-Azhar and Assiut University hospitals were recruited. Fresh peripheral blood samples were collected from all patients and healthy controls for flow cytometric analysis using BD FACSCanto II analyzer equipped with three lasers. Results: Compared to healthy controls, accumulation of cluster of differentiation (CD)11B+CD68+ macrophages (M) (P = 0.018), CD274+ M1 (P = 0.01), CD274+ M2 (P < 0.001), and CD80-CD206+ M2 (P = 0.001) was more evident in patients. Moreover, CD273+ M2 (P = 0.03), CD80+CD206- M1 (P = 0.002), and CD80+CD86+ M1 (P = 0.002) were highly expressed in controls compared with patients. Conclusion: The examination of clinical specimens obtained from patients with signs of acute respiratory viral infection showed the role of the macrophage in the immune response. Dysfunction in macrophages results in heightened immune activity and inflammation, which plays a role in the progression of viral diseases and the emergence of accompanying health issues. This malfunction in macrophages is a common characteristic seen in various viruses, making it a promising focus for antiviral therapies with broad applicability. The immune checkpoint could be a target for immune modulation in patients with severe symptoms.

Memes Adoption in Basic Medical Science Education as a Successful Learning Model: A Mixed Method Quasi-Experimental Study.

Purpose: Basic medical sciences are of a solid abstract nature. Pharmacology is a challenging discipline delivered in all healthcare-related curricula with different aims and goals. Memes are one of aiding instructional designs proved to surge students' performance and satisfaction with the educational process. Apart from assessing medical students' and faculty's perception of meme use in pharmacology learning, the current study aimed to explore the criteria of preferences and factors associated with successful memes' adoption in this discipline as one of the most challenging basic medical sciences. Methods: A biphasic study was conducted among second-year undergraduate medical students and faculty members. The study involved assessing the perceptions of staff and students, and thematic content analysis was performed on the narrative responses of the participants to explore factors contributing to the success of learning memes. Additionally, students' performance was also analyzed. Results: The use of memes in pharmacology was well perceived by medical students, with a mean satisfaction rating of 4.5/5 for high-achieving students and 4.33 for low-achieving students. Memes were associated with a performance surge (p = 0.022). Six themes emerged as criteria for a successful learning experience of meme use: previous scientific background on the meme topic, scenario context of the meme, learning concepts tackled by memes, the simplicity of meme's message, the relevance of meme's message to practice, and the modality of meme's use in the topic of education. Regarding the perception of meme use in pharmacology learning, four themes emerged: the mode and engagement of learning experience mode, the feasibility of meme use in pharmacology learning, students' attitudes towards further meme inclusion in their study, and the perceived impact of memes on students' cognitive skills. Conclusion: The use of memes in pharmacology yields positive learning outcomes. A careful selection of memes is required to ensure a successful learning experience.

Metformin Loaded Zein Polymeric Nanoparticles to Augment Antitumor Activity against Ehrlich Carcinoma via Activation of AMPK Pathway: D-Optimal Design Optimization, In Vitro Characterization, and In Vivo Study.

Metformin (MET), an antidiabetic drug, is emerging as a promising anticancer agent. This study was initiated to investigate the antitumor effects and potential molecular targets of MET in mice bearing solid Ehrlich carcinoma (SEC) as a model of breast cancer (BC) and to explore the potential of zein nanoparticles (ZNs) as a carrier for improving the anticancer effect of MET. ZNs were fabricated through ethanol injection followed by probe sonication method. The optimum ZN formulation (ZN8) was spherical and contained 5 mg zein and 30 mg sodium deoxycholate with a small particle size and high entrapment efficiency percentage and zeta potential. A stability study showed that ZN8 was stable for up to three months. In vitro release profiles proved the sustained effect of ZN8 compared to the MET solution. Treatment of SEC-bearing mice with ZN8 produced a more pronounced anticancer effect which was mediated by upregulation of P53 and miRNA-543 as well as downregulation of NF-κB and miRNA-191-5p gene expression. Furthermore, ZN8 produced a marked elevation in pAMPK and caspase-3 levels as well as a significant decrease in cyclin D1, COX-2, and PGE2 levels. The acquired findings verified the potency of MET-loaded ZNs as a treatment approach for BC.

Memory T Cells Discrepancies in COVID-19 Patients.

The immune response implicated in Coronavirus disease 2019 (COVID-19) pathogenesis remains to be fully understood. The present study aimed to clarify the alterations in CD4+ and CD8+ memory T cells' compartments in SARS-CoV-2-infected patients, with an emphasis on various comorbidities affecting COVID-19 patients. Peripheral blood samples were collected from 35 COVID-19 patients, 16 recovered individuals, and 25 healthy controls, and analyzed using flow cytometry. Significant alterations were detected in the percentage of CD8+ T cells and effector memory-expressing CD45RA CD8+ T cells (TEMRA) in COVID-19 patients compared to healthy controls. Interestingly, altered percentages of CD4+ T cells, CD8+ T cells, T effector (TEff), T naïve cells (TNs), T central memory (TCM), T effector memory (TEM), T stem cell memory (TSCM), and TEMRA T cells were significantly associated with the disease severity. Male patients had more CD8+ TSCMs and CD4+ TNs cells, while female patients had a significantly higher percentage of effector CD8+CD45RA+ T cells. Moreover, altered percentages of CD8+ TNs and memory CD8+CD45RO+ T cells were detected in diabetic and non-diabetic COVID-19 patients, respectively. In summary, this study identified alterations in memory T cells among COVID-19 patients, revealing a sex bias in the percentage of memory T cells. Moreover, COVID-19 severity and comorbidities have been linked to specific subsets of T memory cells which could be used as therapeutic, diagnostic, and protective targets for severe COVID-19.

Applying a neoscore in locally advanced rectal cancer is beneficial in predicting local recurrences after surgery.

BACKGROUND AND AIM: The current study was undertaken to provide more detailed prognostic models for early prediction of local recurrences and local recurrence free survival (RFS) using different radiologic and pathologic features of locally advanced rectal carcinomas treated with neoadjuvant chemoradiation (CRT). METHODS: One hundred patients with locally advanced rectal carcinomas decided to receive neoadjuvant CRT were retrospectively recruited, Hazard ratios (HR) were determined in the two cox regression models and only significant ratios were considered for pointing, Models were built to determine their important effects of different predictors including: pathologic T (T), pathologic N (N), grade (G), clinical stage (cTNM), site (S), perineural invasion (PNI), and response to CRT (R) on 3-year RFS, goodness of performance of each model was measured by Harrell's C index. RESULTS: HR of 1st group of models: T+N, T+N+G, T+N+G+S, T+N+G+S+PNI, and T+N+G+S+PNI+R were summated and categorized into scores, these scores were significantly correlated with the risk of recurrence (Somer's D = 0.5, p<0.0001) & Harrell's C index = 0.751, (Somer's D = 0.6, p<0.0001) & its Harrell's C index = 0.794, (Somer's D = 0.7, p<0.0001) & C index = 0.826, Somer's D = 0.7, p<0.0001) & C index = 0.827, and (Somer's D = 0.7, p<0.0001) & C index = 0.843 respectively. The 2nd group of models including: cTNM stage, cTNM+G, cTNM+G+S, cTNM+G+S+PNI, cTNM+G+S+PNI+R scores which were significantly correlated with the HR of LRR (Somer's D = 0.2, 0.5, 0.6, 0.6, & 0.6 respectively), (p = 0.006, <0.0001, <0.0001, <0.0001, <0.0001 respectively), the corresponding Harrell's C indices were 0.595, 0.743, 0.782, 0.795, & 0.813 respectively. CONCLUSION: We propose that the addition of biologic factors to staging of rectal cancer provide precise stratification and association with local recurrences in patients received preoperative CRT.

Peripheral Mononuclear Cells Surface Markers Evaluation in Different Stages of Hepatocellular Carcinoma; in a Trial for Early and Accurate Diagnosis in Patients with Post-Hepatitis Liver Cirrhosis and Unremarkable Raised AFP.

Introduction: HCC is frequently diagnosed late, when only palliative treatment is available. So, we try to use different immunological markers to identify early HCC in patients with unremarkable raised AFP. Methods: This study was conducted on 112 participants divided into two equal groups: Group I, 56 patients with liver cirrhosis and different stages of HCC; Group II, 56 patients with liver cirrhosis. The diagnosis of HCC was based on AASLD guidelines. TNM and BCLC classification systems are used for staging of HCC. Results: A significant reduction in the median percentage of lymphocyte subset (CD3+, CD4+, CD8+, CD19+) and NK cell percentage (CD56+) has been detected in HCC patients (all P < 0.001). In the HCC group the median monocyte subpopulations CD14+ CD16- Classical, CD14++ CD16+ Intermediate, and CD14-+ CD16++ Non-Classical were 11.7, 4.0, and 3.5, respectively, with marked reduction compared with liver cirrhosis group (all P < 0.001). Patients with advanced stages (BCLC C and D) were more likely to have significantly higher median CD33+ than patients with early stages (BCLC A and B) (P = 0.05); also, the median levels of HLA DR+ lymphocytes % in the HCC case group were 21.8 in patients with advanced disease (BCLC C and D) and 13.1 in patients with early stages of the disease (P = 0.04). Patients with late stage (TNM III) were more likely to have significantly higher median CD14+ CD16- Classical monocyte subset, CD36+ HLA DR+, and CD36+ CD16- than patients with early stages (TNM I and II). Conclusion: Patients with HCC with unremarkable raised AFP showed marked reduction in lymphocytes, natural killer cells, and all monocyte subpopulations. In addition, patients with advanced HCC showed increased CD33+ and HLA DR+ lymphocytes %, CD14+ CD16- Classical monocyte subset, CD36+ HLA DR+, and CD36+ CD16- compared with patients with early stages of HCC.

The dogma of cetuximab in advanced squamous cell carcinoma of the head and neck after failure of surgery and radiotherapy: is it true among patients in upper Egypt?

Background and aim: We aimed from the current study to explore the treatment results of cetuximab in combination with a weekly carboplatin and paclitaxel regimen in advanced squamous cell carcinoma of head and neck (HNSCC) after failure of radiotherapy and chemotherapy. Methods: This study was a non-randomised, single arm, phase 2 efficacy study conducted in two oncology centres in upper Egypt, we recruited 31 patients with recurrent HNSCC previously treated with concurrent chemoradiation ± surgery to receive weekly cetuximab, carboplatin and paclitaxel for 18 weeks followed by maintenance cetuximab every 2 weeks for 12 months. All patients underwent intention to treat analysis. Results: The current study revealed a significant reduction of the size of recurrent primary lesion (p < 0.001), without comparable significant reduction of regional lymph nodes (LNs) (p = 0.06), the current overall response rate (ORR) was 83.9%, ≥1-year progression-free survival (PFS) was 58.1%, also surgical intervention was succeeded to salvage 32.3% who did not achieve complete response to the current protocol, the median PFS was 12 months which was significantly affected by tumour site (p = 0.012), programmed death ligand-1 (PDL-1) expression (p = 0.01) and overall response rate (ORR) (p < 0.001). Conclusion: Based on favourable treatment outcomes, including high ORR and disease control rate, improved median PFS and tolerable toxicity profile, the current weekly cetuximab, carboplatin and paclitaxel with 1 year maintenance cetuximab in responding patients is considered a feasible and effective regimen.

COVID-19 Infection in Patients with Comorbidities: Clinical and Immunological Insight.

AIM: Our study's objectives were to study the clinical and laboratory characteristics that may serve as biomarkers for predicting disease severity, IL-10 levels, and frequencies of different T cell subsets in comorbid COVID-19 patients. METHODS: Sixty-two hospitalized COVID-19 patients with comorbidities were assessed clinically and radiologically. Blood samples were collected to assess the T lymphocyte subsets by flow cytometry and IL-10 levels by ELISA. RESULTS: The most common comorbidities observed in COVID-19 patients were diabetes mellitus (DM), hypertension, and malignancies. Common symptoms and signs included fever, cough, dyspnea, fatigue, myalgia, and sore throat. CRP, ferritin, D dimer, LDH, urea, creatinine, and direct bilirubin were significantly increased in patients than controls. Lymphocyte count and CD4+ and CD8+ T-cells were significantly decreased in comorbid COVID-19 patients, and CD25 and CD45RA expression were increased. CD4+ and CD8+ regulatory T cells (Tregs) and IL-10 levels were significantly decreased in patients. CONCLUSIONS: Many parameters were found to be predictive of severity in the comorbid patients in our study. Significant reductions in the levels and activation of CD4+ and CD8+ T-cells were found. In addition, CD4+ and CD8+ Tregs were significant decreased in patients, probably pointing to a prominent role of CD8+ Tregs in dampening CD4+ T-cell activation.

Eye metastasis in breast cancer: case report and review of literature.

The paradigm of breast cancer management has been revolutionised, resulting in prolonged survival that echoes an increasing incidence of metastasis in uncommon sites. With orbital metastases - despite being rare - the incidence scales up to 13% of breast cancer cases with no specific management guidelines. We report a case of a 31-year-old luminal B breast cancer patient who initially presented with T2N2M0 disease and received six cycles of adjuvant chemotherapy (5-Fluorouracil (5-FU) 600 mg/m2 IV, Doxorubicin 60 mg/m2 IV, Cyclophosphamide 600 mg/m2 IV), followed by radiotherapy (RTH) and adjuvant Tamoxifen. Two years later, the patient experienced successive bone metastasis, so she received several lines of endocrine therapy as Fulvestrant and aromatase inhibitors in combination with luteinizing hormone-releasing hormone (LHRH) analogues. Later on, she presented with right eye ptosis and magnetic resonance imaging (MRI) showed a soft tissue mass in the superior and lateral rectus muscles. The patient received six cycles of chemotherapy with no improvement. Further disease progression occurred 3 months later, so the patient received palliative RTH resulting in no response. One month later, the patient was deceased, secondary to progressive disease. With the rising incidence of ocular metastasis due to breast cancer, oncologists should be aware of symptoms and use the proper diagnostic modalities. Here we provide a literature review on similar cases and discuss possible treatment modalities for those patients. The main concern is to evaluate the need for chemotherapy in such cases in the presence of highly effective endocrinal treatment.

Overexpression of PD-1 and CD39 in tumor-infiltrating lymphocytes compared with peripheral blood lymphocytes in triple-negative breast cancer.

BACKGROUND AND AIM: Growing evidence highlighted the primary role of the immune system in the disease course of triple-negative breast cancer (TNBC). The study aim was to investigate the expression of PD-1 and CD39 on CD4+ and CD8+ cells infiltrating tumor tissue compared to their counterparts in peripheral blood and explore its association with tumor characteristics, disease progression, and prognosis in females with TNBC. PATIENTS AND METHODS: The study included 30 TNBC patients and 20 healthy controls. Cancer and normal breast tissue and peripheral blood samples were collected for evaluation of the expression of PD-1 and CD39 on CD4+ and CD8+T cells by flow cytometry. RESULTS: A marked reduction in the percentage of CD8+ T lymphocytes and a significant increase in the frequencies of CD4+ T lymphocytes and CD4+ and CD8+ T lymphocytes expressing PD1 and CD39 were evident in tumor tissue in comparison with the normal breast tissue. The DFS was inversely related to the cancer tissue PD1+CD8+ and CD39+CD8+ T lymphocytes. Almost all studied cells were significantly increased in the tumor tissue than in peripheral blood. Positive correlations were detected among peripheral PD1+CD4+T lymphocytes and each of cancer tissue PD1+CD4+, PD1+CD8+and CD39+CD8+T cells, and among peripheral and cancer tissue CD39+CD4+and CD39+CD8+ T cells. CONCLUSIONS: The CD39 and PD1 inhibitory pathways are synergistically utilized by TNBC cells to evade host immune response causing poor survival. Hence, combinational immunotherapy blocking these pathways might be a promising treatment strategy in this type of cancer.

Prognostic Role of Monocytic Myeloid-Derived Suppressor Cells in Advanced Non-Small-Cell Lung Cancer: Relation to Different Hematologic Indices.

METHODS: We recruited 40 cases of advanced NSCLC, stages III and IV, aged > 18-<70 years old, and eligible to receive chemotherapy with or without radiotherapy, along with 20 healthy controls of comparable age and sex; after diagnosis and staging of patients, blood samples were collected for flow cytometric detection of Mo-MDSCs. RESULTS: Significant accumulation of Mo-MDSCs in patients compared to their controls (p < 0.0001). Furthermore, these cells accumulated significantly in stage IV compared to stage III (p = 0.006) and correlated negatively with overall survival (r = -0.471, p = 0.002), lymphocyte to monocyte ratio (r = -0.446, p = 0.004), and mean platelet volume to platelet count ratio (MPV/PC) (r = -0.464, p = 0.003), patients with Mo-MDSCs < 13% had significantly better survival than those with Mo-MDSCs ≥ 13% (p = 0.041). CONCLUSION: Mo-MDSCs represent one of the key mechanisms in the immunosuppressive tumor microenvironment (TME) to play major roles not only in the carcinogenesis of lung cancer but also in disease progression and prognosis and, in addition, predict the efficacy of immune checkpoint inhibitors; our results provided some support to target Mo-MDSCs and needed to be augmented by further studies.

Microparticles and PD1 interplay added a prognostic impact in treatment outcomes of patients with multiple myeloma.

Although multiple myeloma (MM) is still considered as an incurable disease by current standards, the development of several combination therapies, and immunotherapy approaches has raised the hope towards transforming MM into an indolent, chronic disease, and possibly achieving a cure. We tried to shed light on the expression of PD1 and different Microparticles (MPs) in MM and their interplay as a mechanism of resistance to standardized treatments, in addition, find their associations with prognostic factors of symptomatic MM. Thirty patients with newly diagnosed and chemotherapy naïve active MM, along with 19 healthy participants of comparable age and sex were recruited, after diagnosis of MM; blood samples were collected from both patients and controls for flow cytometric detection of CD4+, CD8+, CD4+PD1+, and CD8+PD1+T cells, total MPs, CD138+ MPs, and platelet MPs. MM patients had statistically significant higher levels of TMPs, CD138+ MPs compared to their controls, while PMPs exhibited no significant difference between both groups. Statistically significant higher percentages of CD8+, PD1CD8+, PD1CD4+T cells were detected in patients compared to controls, while the latter group had a significantly higher percentage of CD4+T cells than MM patients, patients who did not achieve complete response, had significantly higher percentages of PMPs, CD138+MPs, PD1+CD8+, PD1+CD4+, and CD8+T cells (cutoff values = 61, 10.6, 13.5, 11.3 and 20.1 respectively), (p-values = 0.002, 0.003, 0.017, 0.001 and 0.008 respectively). Microparticles and PD1 expressions were associated with proliferative potential and resistance to Bortezomib-based treatments, our results suggested that they played a crucial role in myeloma progression.

Accumulation of Regulatory T Cells in Triple Negative Breast Cancer Can Boost Immune Disruption.

BACKGROUND AND AIM: The present study was conducted to evaluate the number of Tregs in triple negative breast cancer (TNBC), in normal breast parenchyma and in the peripheral blood of these patients and controls, in addition to their correlations with the clinico-pathologic features and the outcomes of TNBC. METHODS: Thirty adult treatment-naïve women with non-metastatic TNBC were recruited. In addition, 20 ages matched healthy females participated as a control group. Peripheral blood samples were collected from all participants in tubes containing heparin, fresh tumor tissues were also obtained from all patients undergoing surgery, and 20 normal breast tissue samples were obtained from the same patients' areas adjacent to the safety margins; all these samples were taken for flow cytometric detection of Tregs. RESULTS: The mean percentages of CD4+CD25+highT cells and Tregs were higher in TNBC peripheral blood than healthy controls and in malignant tissue than normal tissue. Moreover, the frequencies of tumor-infiltrating CD4+T cells and Tregs were exceeding those in the peripheral blood of cancer patients. Only tumor-infiltrating Tregs have shown increasing levels with the increase in the tumor size and were significantly higher in patients with local recurrences than those without recurrence. In addition, Tregs showed significant inverse relation with DFS and direct relation with the level of the peripheral Tregs. CONCLUSION: The findings of the current study support the possibility that TNBC microenvironment conveys specific characteristics on Tregs distinguishing them from those in normal breast tissue or Tregs in peripheral blood, improving the capabilities of tumor-infiltrating Tregs to enhance tumor growth, local recurrence and reduce the DFS.

Increase in polymorphonuclear myeloid-derived suppressor cells and regulatory T-cells in children with B-cell acute lymphoblastic leukemia.

Our study aimed to evaluate the levels of MDSCs and Tregs in pediatric B-cell acute lymphoblastic leukemia (B-ALL), their relation to patients' clinical and laboratory features, and the impact of these cells on the induction response. This study included 31 pediatric B-ALL patients and 27 healthy controls. All patients were treated according to the protocols of the modified St. Jude Children's Research Hospital total therapy study XIIIB for ALL. Levels of MDSCs and Tregs were analyzed using flow cytometry. We observed a reduction in the levels of CD4 + T-cells and an increase in both the polymorphonuclear MDSCs (PMN-MDSCs) and Tregs. The frequencies of PMN-MDSCs and Tregs were directly related to the levels of peripheral and bone marrow blast cells and CD34 + cells. Complete postinduction remission was associated with reduced percentages of PMN-MDSCs and Tregs, with the level of PMN-MDCs in this subpopulation approaching that of healthy controls. PMN-MDSCs and Tregs jointly play a critical role in maintaining an immune-suppressive state suitable for B-ALL tumor progression. Thereby, they could be independent predictors of B-ALL progress, and finely targeting both PMN-MDSCs and Tregs may be a promising approach for the treatment of B-ALL.

Circulating microparticles and activated platelets as novel prognostic biomarkers in COVID-19; relation to cancer.

BACKGROUND AND AIM: The study aimed to determine whether the MPs levels and platelet activation are affected by the COVID-19 infection in both malignant and non-malignant patients compared to healthy individuals and define their contribution to the COVID-19 associated coagulopathy and the relation of these MPs to other hematologic parameters. PATIENTS AND METHODS: We recruited 23 malignant patients with reverse transcription polymerase chain reaction (RT-PCR) positive COVID-19, also, 19 COVID-19 non-malignant patients, and 20 healthy volunteers were also enrolled for comparison. Blood samples were collected from patients and healthy donors into 5 mL vacutainer tube containing 3.5% buffered sodium citrate solution for measurement of total microparticles (TMPs), platelet microparticles (PMPs), endothelial microparticles (EMPs), CD62 activated platelets, and CD41 platelet marker. RESULTS: COVID-19 malignant patients had significantly lower hemoglobin and platelets compared to COVID non-malignant ones, while they had significantly higher C-reactive protein, LDH, AST, Albunim, creatinine, and prognostic index (PI) compared to COVID-19 non-malignant patients. significant accumulations of TMPs, PMPs, EMPs, and activated platelets in COVID-19 affected patients compared to healthy controls. TMPs, and EMPs were significantly accumulated in COVID-19 malignant compared to COVID-19 non-malignant patients with no significant difference in PMPs between both. CONCLUSION: Circulating MPs and activated platelets may be promising novel prognostic biomarkers capable of identifying potentially severe COVID-19 patients who require immediate care especially in cancer patients.

Reviving up dendritic cells can run cancer immune wheel in non-small cell lung cancer: a prospective two-arm study.

BACKGROUND AND AIM: Lung cancer is the number one cause of cancer-related deaths. Dendritic cells (DCs) are heterogeneous components of innate immunity that play a crucial role in the anti-tumor T cell immunity and may represent a promising approach for tumor immunotherapy. In this study, we aimed to evaluate the frequency of the two major subsets of DCs; plasmacytoid dendritic cells (pDCs) and monocytic dendritic cells (mDCs) in non-small cell lung cancer (NCSLC) and correlating them with different clinicopathologic features and survival outcomes. PATIENTS AND METHODS: This study was a case-controlled one, included 50 patients with denovo pathologically confirmed NSCLC and 20 healthy controls of comparable age and gender. After diagnosis and staging of patients, the frequency of DCs was evaluated using flow cytometry. RESULTS: We unveiled significantly reduced levels of pDCs (P = 0.024), and mDCs (P = 0.013) in NSCLC patients compared to controls. Furthermore, there was a significant accumulation of pDCs in non-metastatic patients compared to metastatic ones (P < 0.0001), while there was no significant (P = 0.6) differences in mDCs, and mDCs/pDCs ratio (P = 0.9). There was a Significant negative correlation (r = - 0.3, P = 0.04) between OS and mDCs. On the other hand, there was a significantly higher OS with pDCs ≥ 0.82 compared to patients with pDCs < 0.82, log rank Ch2 = 12.128, P < 0.0001. CONCLUSION: Despite the controversy about the prognostic role of pDCs not only in NSCLC but also in other solid tumors, our study sheds light on the possible prognostic impact of pDCs and mDCs on treatment outcomes of NSCLC patients.

Hypofractionated radiation therapy with temozolomide versus standard chemoradiation in patients with glioblastoma multiforme (GBM): A prospective, single institution experience.

BACKGROUND AND AIM: the study aimed to determine whether hypofractionated radiotherapy (HFRT) with simultaneous and adjuvant temozolomide (TMZ) was feasible and could provide adequate disease control in primary GBM patients with poor prognostic factors including large tumor size, poor performance status, unresectable or multifocal lesions, poor imaging and inflammatory indices. PATIENTS AND METHODS: A total of 93 patients with glioblastoma multiforme were collected and distributed randomly as 1:1.7 of cases to controls; cases or arm (I) received HFRT with 45 Gy in 15 fractions over 3 weeks concurrently with TMZ. Controls or arm (II) received standard conventional fractionation radiotherapy of 60 Gy in 30 fractions over 6 weeks concurrently with TMZ. RESULTS: 35 patients were recruited in arm I while 58 patients in arm II with significant difference in site of GBM, pattern of enhancement, type of surgery, and neutrophil to lymphocyte ratio, while no significant differences in tumor size, focality, responses, progression free survival, and overall survival (OS), only the type of surgery was an independent predictor for OS, no significant difference in the type and degree of toxicity between both arms. CONCLUSION: Our results showed that HFRT with concurrent TMZ is a feasible therapeutic approach in patients with GBM, especially those with poor prognostic factors, assuring high treatment compliance and low toxicity rates. Dose escalation and reduction in overall treatment time are clear advantages of HFRT, while at least the same survival rates as conventional fractionated RT are maintained.

Role of pretreatment inflammatory indicators in pediatric acute leukemias; where do we stand? A prospective cohort study.

BACKGROUND AND AIM: There is a limited data at the moment regarding the clinical value of inflammatory indices and malnutrition markers in children with acute leukemias. We have examined the usefulness of prognostic nutritional index (PNI), Glasgow prognostic score (GPS), Prognostic Index (PI), monocyte to lymphocyte (MLR), neutrophil to lymphocyte (NLR), and platelet to lymphocyte (PLR) ratios to stratify patients as regards the response to induction therapy correlating them to different prognostic factors. PATIENTS AND METHODS: Children with acute leukemia and without microbial-induced inflammation at the time of diagnosis were prospectively recruited. Preliminary total and differential CBC, c-reactive protein (CRP), serum albumin (ALB) were used to calculate different inflammatory indicators including NLR, MLR, PLR, PNI, GPS, and PI. RESULTS: Higher PNI was significantly more associated to children who achieved remission as compared to those without remission (p< 0.0001). Patients without remission had GPS 1 or 2 compared to GPS 0 or 1 in those who entered remission (p= 0.001). NLR was significantly lower in patients in remission than in those without remission (p= 0.005). Similarly, complete remission was significantly associated to MLR ⩽ 0.45 as compared to MLR > 0.45 (p< 0.0001). CONCLUSION: Pretreatment PNI, GPS, CRP, serum albumin, NLR, MLR, and PLR are remission promising prognostic markers in pediatric acute leukemias, which deserve to be further investigated in large-scale studies.

Genetic polymorphisms in XRCC1, OGG1, and XRCC3 DNA repair genes and DNA damage in radiotherapy workers.

DNA damage may develop at any dose of ionizing radiation. DNA damage activates pathways that regulate cell growth and division or coordinate its replication and repair. The repair pathways, base excision repair (BER) and single-strand break repair (SSBR), can repair such damages efficiently and maintain genome integrity. Loss of this repair process or alteration of its control will be associated with serious outcomes for cells and individuals. This study aimed to determine the relationship between XRCC1 (Arg194Trp, Arg280His, and Arg399Gln), OGG1 (Ser326Cys), and XRCC3 (Thr241Met) SNPs and DNA damage and to identify high-risk individuals with reduced DNA repair capacity. This case-control study was conducted on 80 subjects; 50 subjects working in Clinical Oncology and Nuclear Medicine Department in Assiut University Hospital along with 30 controls. A total of 1 mL blood samples were collected for Single-Cell Gel Electrophoresis Technique (Comet Assay) for detection of DNA damage in those subjects. A total of 3 mL fresh blood samples were collected and analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based technique. DNA damage detected by comet test was significantly high in IR-exposed workers than control. Statistically high significant difference was found in exposed subjects versus control subjects regarding the frequencies of the variant alleles of hOGG1326, XRCC1280 & 399, and XRCC3241. The level of DNA damage was not affected by OGG1326 SNPs when comparing subjects of wild genotype with those of (pooled) variants either in the exposed staff or in the control group while XRCC1280, 399 and XRCC3241 variant alleles had an influence on the studied DNA damage biomarker. Moreover, genotyping distribution pattern was highly variable in relation to gender. The present study indicated a relationship between DNA damage detected by comet test and single nucleotide polymorphisms in genes coding for DNA certain repair enzymes. Individuals occupationally exposed to low doses of ionizing radiation could be at great risk and more susceptible to the increased DNA damage if they have inherited genetic polymorphism.

Prognostic Significance of Circulating CD28 Negative Suppressor T Cells and Memory B Cells in Patients with Breast Cancer.

BACKGROUND: It has been suggested that routine assessment and quantification of different lymphocyte subsets can provide clinically meaningful prognostic information in breast cancer (BC). OBJECTIVE: To determine the relationship between peripheral blood lymphocyte subsets and pathological parameters and response to therapy in patients with BC. METHODS: Thirty patients with operable breast cancer treated surgically with either modified radical mastectomy or breast conservative surgery, and 20 healthy controls were included. For detection of lymphocyte subsets in peripheral blood; Fluorochrome-labeled monoclonal antibodies were used andcells were analyzed by flow cytometry. Patients were treated with chemotherapy, radiotherapy and hormonal treatment, and followed up to determine relapse and recurrence-free survival (RFS). RESULTS: Significant differences were found in the frequencies of B, T, NK, NKT, and CD28‒T cells between patients with BC and controls. Moreover, a significant difference was found in the percentage of CD8+CD28‒ T cells between patients with different pathologic subtypes of BC and negative correlations were observed between the frequency of CD8+CD28‒T cells and memory B cells, and RFS. Also, a significant difference in the frequency of naïve B cells was found in patients with different tumor grades and a negative correlation was found between the frequencies of B cells and NKT cells. CONCLUSION: NK, NKT, lymphocytes, and CD28‒ T cells significantly differed between healthy controls and BC patients. Also, memory B cells were associated with good response to treatment while CD28‒ T cells were associated with shorter RFS.