Genetic Predisposition and Chemotherapeutic Approaches Including Oncolytic Virus for the Treatment of Prostatic Adenocarcinoma

Among the leading causes of cancer mortality, prostatic adenocarcinoma (PaC) is at second to lung carcinoma, but it is the most commonly happening non-cutaneous malignancy in elderly men in the world. Therapeutic options for PaC depend on age, growth & stage of malignancy, the desired outcomes and shortcomings of available treatment, estimated cost and patient compliance. Patients older than 60 years with a sluggish localized tumor may be placed on active surveillance, otherwise go with transurethral resection of the prostate (TURP), prostate artery embolization (PAE) and pelvic lymphadenectomy with/without radiation therapy. For metastatic PC androgen-deprivation therapy is an option with or without surgery. These agents decline the body’s testosterone production or block its activity by gonadotropin- releasing hormone (GnRH) analogues including leuprolide acetate and goserelin acetate implant. The hormone’s activity can be stopped by androgens antagonist such as flutamide, bicalutamide and nilutamide along with chemotherapeutic agents, such as taxanes (e.g., docetaxel, paclitaxel) but after all the disease relapses in 20-30% of patients. So, new immunological or vaccine-based therapeutic moieties have been investigated to meet the objective of providing selectivity to cancerous cells and desired therapeutic outcomes with less/no harmful effects to normal cells. The chimeric version, oncolytic poliovirus and human rhinovirus i.e. PVSRIPO is most promising feature in cancer therapeutics and activate innate immunity by neutrophils infiltration via PAMP & DAMP pathways while Sipuleucel-T expresses major histocompatibility complex (MHC) which can stimulate CD4+ helper T-cells and CD8+ cytotoxic T-cells and ultimately activate the acquired immunity against cancer cells. In this article, we have discussed the role of genetic predisposition and chemotherapeutic approaches including oncolytic poliovirus for the treatment of PaC in order to better understanding of tumor biology and mechanisms involved in chemotherapeutic drugs based resistance.

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The abscopal effect of radiation therapy

Future Oncology ◽

10.2217/fon-2020-0994 ◽

2021 ◽

Vol 17 (13) ◽

pp. 1683-1694

Author(s):

Daniel J Craig ◽

Nisha S Nanavaty ◽

Monika Devanaboyina ◽

Laura Stanbery ◽

Danae Hamouda ◽

...

Keyword(s):

T Cells ◽

Radiation Therapy ◽

Cytotoxic T Cells ◽

Cell Activity ◽

The Body ◽

Abscopal Effect ◽

Sting Pathway ◽

And Migration ◽

Anticancer Response

Radiation therapy (RT) in some cases results in a systemic anticancer response known as the abscopal effect. Multiple hypotheses support the role of immune activation initiated by RT-induced DNA damage. Optimal radiation dose is necessary to promote the cGAS-STING pathway in response to radiation and initiate an IFN-1 signaling cascade that promotes the maturation and migration of dendritic cells to facilitate antigen presentation and stimulation of cytotoxic T cells. T cells then exert a targeted response throughout the body at areas not subjected to RT. These effects are further augmented through the use of immunotherapeutic drugs resulting in increased T-cell activity. Tumor-infiltrating lymphocyte presence and TREX1, KPNA2 and p53 signal expression are being explored as prognostic biomarkers.

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Predicting and Quantifying Antagonistic Effects of Natural Compounds Given with Chemotherapeutic Agents: Applications for High-Throughput Screening

Cancers ◽

10.3390/cancers12123714 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3714

Author(s):

G. Lavender Hackman ◽

Meghan Collins ◽

Xiyuan Lu ◽

Alessia Lodi ◽

John DiGiovanni ◽

...

Keyword(s):

Natural Products ◽

High Throughput ◽

High Throughput Screening ◽

Cancer Therapeutics ◽

Chemotherapeutic Agents ◽

The Body ◽

Cancer Drug ◽

Therapeutic Effects ◽

Cancer Drugs ◽

Antagonistic Effects

Natural products have been used for centuries to treat various human ailments. In recent decades, multi-drug combinations that utilize natural products to synergistically enhance the therapeutic effects of cancer drugs have been identified and have shown success in improving treatment outcomes. While drug synergy research is a burgeoning field, there are disagreements on the definitions and mathematical parameters that prevent the standardization and proper usage of the terms synergy, antagonism, and additivity. This contributes to the relatively small amount of data on the antagonistic effects of natural products on cancer drugs that can diminish their therapeutic efficacy and prevent cancer regression. The ability of natural products to potentially degrade or reverse the molecular activity of cancer therapeutics represents an important but highly under-emphasized area of research that is often overlooked in both pre-clinical and clinical studies. This review aims to evaluate the body of work surrounding the antagonistic interactions between natural products and cancer therapeutics and highlight applications for high-throughput screening (HTS) and deep learning techniques for the identification of natural products that antagonize cancer drug efficacy.

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Correlation between Platelet to Lymphocyte Ratio with C-Reactive Protein in COVID-19 Patients

INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY ◽

10.24293/ijcpml.v28i1.1750 ◽

2021 ◽

Vol 28 (1) ◽

pp. 17

Author(s):

Novianti Anggie Lestari ◽

Dwi Retnoningrum

Keyword(s):

Immune Response ◽

T Cells ◽

Cytotoxic T Cells ◽

The Body ◽

Cross Sectional ◽

Reactive Protein ◽

A Value ◽

Infected Cells ◽

Spearman Test ◽

Moderate Positive Correlation

Coronavirus 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Inflammation occurs when the body is infected with the virus. Platelets play a role in immune response and immunomodulation by activating P-Selectin Glycoprotein (PSGL) to the site of inflammation. Lymphocytes play a role through CD4 T-cells, B-cells producing specific viral antibodies, and CD8 cytotoxic T-cells by directly killing the virus in infected cells. This study aimed to prove the correlation between PLR and CRP as inflammation markers in COVID-19 patients. This study was a retrospective observational study with the cross-sectional approach at Dr. Kariadi Hospital, Semarang, for the period March-August 2020. Spearman test performed for analyzing data with p<0.05 was significant. Thirty-three confirmed COVID-19 patients with median value of PLR 218 (103-1609) and CRP 15.94 (1.24-200) mg/L were tested for correlation with a value of p=0.013 and r=0.427. The increase of PLR and CRP in COVID-19 patients was caused by an inflammatory process mediated by the immune response. High values in the blood were associated with disease severity and poor prognosis. There was a statistically significant moderate positive correlation between PLR and CRP in COVID-19 patients.

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Pathophysiology of Autoimmune Thrombocytopenia: Current Insight with a Focus on Thrombopoiesis

Hämostaseologie ◽

10.1055/s-0039-1678732 ◽

2019 ◽

Vol 39 (03) ◽

pp. 227-237 ◽

Cited By ~ 7

Author(s):

Irene Marini ◽

Tamam Bakchoul

Keyword(s):

T Cells ◽

Cytotoxic T Cells ◽

The Body ◽

Additional Contribution ◽

Autoimmune Thrombocytopenia ◽

Platelet Destruction ◽

Platelet Production ◽

Low Platelet Count ◽

Underlying Mechanisms ◽

The Impact

AbstractImmune thrombocytopenia (ITP) is an autoimmune disease characterized by a significant reduction in the number of circulating platelets which is frequently associated with bleeding. The total count of platelets in the body is finely regulated by the balance between platelet production and destruction. Although the pathogenesis of ITP is still not completely elucidated, it is largely recognized that the low platelet count observed in ITP patients is due to alterations of both mechanisms. An abnormal proliferation of autoreactive T cells leading to the breakdown of immune tolerance to platelet antigens is suggested to be responsible for the up-regulated proliferation of autoantibody producing B cells. Consequently, the immune response induces enhanced T cell-mediated cytotoxicity and antibody-mediated platelet destruction through phagocytosis, complement activation and apoptosis. An additional contribution to the pathophysiology of ITP is given by alterations of thrombopoiesis caused by platelet-reactive autoantibodies or cytotoxic T cells leading to impaired megakaryocyte differentiation and platelet production. All these processes involved in ITP pathophysiology account for the complexity and heterogeneity in the clinical manifestation and therapy responsiveness of this disorder. For this reason, a better understanding of the different underlying mechanisms in ITP is necessary to develop more efficient therapeutic treatments in the future. In this review, we will provide an update on the pathophysiology of ITP with a particular focus on the impact of impaired thrombopoiesis.

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Effects of a Low Dose of T-2 Toxin on the Percentage of T and B Lymphocytes and Cytokine Secretion in the Porcine Ileal Wall

Toxins ◽

10.3390/toxins13040277 ◽

2021 ◽

Vol 13 (4) ◽

pp. 277

Author(s):

Paweł Wojtacha ◽

Wojciech Trybowski ◽

Piotr Podlasz ◽

Magdalena Żmigrodzka ◽

Józef Tyburski ◽

...

Keyword(s):

T Cells ◽

Cellular Response ◽

Cytotoxic T Cells ◽

Fusarium Species ◽

The Body ◽

Double Positive ◽

Plant Materials ◽

Food Antigens ◽

Anti Inflammatory ◽

Materials Used

Plant materials used in the production of pig feed are frequently contaminated with mycotoxins. T-2 toxin is a secondary metabolite of selected Fusarium species, and it can exert a harmful influence on living organisms. Most mycotoxins enter the body via the gastrointestinal tract, and they can modulate the gut-associated lymphoid tissue (GALT) function. However, little is known about the influence of low T-2 toxin doses on GALT. Therefore, the aim of this study was to evaluate the effect of T-2 toxin administered at 50% of the lowest-observed-adverse-effect level (LOAEL) on the percentage of CD2+ T cells, CD4+ T helper cells, CD8+ cytotoxic T cells, CD4+CD8+ double-positive T cells, TCRγδ+ cells, CD5+CD8- B1 cells, and CD21+ B2 cells, and the secretion of proinflammatory (IFN-γ, IL-1β, IL-2, IL-12/23p40, IL-17A), anti-inflammatory, and regulatory (IL-4, IL-10, TGF-β) cytokines in the porcine ileal wall. The results of the study revealed that T-2 toxin disrupts the development of tolerance to food antigens by enhancing the secretion of proinflammatory and regulatory cytokines and decreasing the production of anti-inflammatory TGF-β. T-2 toxin triggered the cellular response, which was manifested by an increase in the percentage of CD8+ T cells and a decrease in the percentage of B2 and Tγδ lymphocytes.

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