scholarly journals Omics Derived Biomarkers and Novel Drug Targets for Improved Intervention in Advanced Prostate Cancer

Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 658
Author(s):  
Maria Frantzi ◽  
Marie C. Hupe ◽  
Axel S. Merseburger ◽  
Joost P. Schanstra ◽  
Harald Mischak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Survival Rates ◽  
Initial Therapy ◽  
Clinical Settings ◽  
Recommended Treatment ◽  
Novel Drug

Prostate cancer (PCa) is one of the most frequently diagnosed malignancies, and the fifth leading cause of cancer related mortality in men. For advanced PCa, radical prostatectomy, radiotherapy, and/or long-term androgen deprivation therapy are the recommended treatment options. However, subsequent progression to metastatic disease after initial therapy results in low 5-year survival rates (29%). Omics technologies enable the acquisition of high-resolution large datasets that can provide insights into molecular mechanisms underlying PCa pathology. For the purpose of this article, a systematic literature search was conducted through the Web of Science Database to critically evaluate recent omics-driven studies that were performed towards: (a) Biomarker development and (b) characterization of novel molecular-based therapeutic targets. The results indicate that multiple omics-based biomarkers with prognostic and predictive value have been validated in the context of PCa, with several of those being also available for commercial use. At the same time, omics-driven potential drug targets have been investigated in pre-clinical settings and even in clinical trials, holding the promise for improved clinical management of advanced PCa, as part of personalized medicine pipelines.

Új lehetőségek a refrakter és relabált Hodgkin-lymphomás betegek kezelésében

2015 ◽  
Vol 156 (45) ◽  
pp. 1824-1833 ◽  
Author(s):  
Árpád Illés ◽  
Ádám Jóna ◽  
Zsófia Simon ◽  
Miklós Udvardy ◽  
Zsófia Miltényi
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Relapse Free Survival ◽  
Term Survival ◽  
Free Survival ◽  
Novel Treatment ◽  
Refractory Hodgkin Lymphoma

Introduction: Hodgkin lymphoma is a curable lymphoma with an 80–90% long-term survival, however, 30% of the patients develop relapse. Only half of relapsed patients can be cured with autologous stem cell transplantation. Aim: The aim of the authors was to analyze survival rates and incidence of relapses among Hodgkin lymphoma patients who were treated between January 1, 1980 and December 31, 2014. Novel therapeutic options are also summarized. Method: Retrospective analysis of data was performed. Results: A total of 715 patients were treated (382 men and 333 women; median age at the time of diagnosis was 38 years). During the studied period the frequency of relapsed patients was reduced from 24.87% to 8.04%. The numbers of autologous stem cell transplantations was increased among refracter/relapsed patients, and 75% of the patients underwent transplantation since 2000. The 5-year overall survival improved significantly (between 1980 and 1989 64.4%, between 1990 and 1999 82.4%, between 2000 and 2009 88.4%, and between 2010 and 2014 87.1%). Relapse-free survival did not change significantly. Conclusions: During the study period treatment outcomes improved. For relapsed/refractory Hodgkin lymphoma patients novel treatment options may offer better chance for cure. Orv. Hetil., 2015, 156(45), 1824–1833.

scholarly journals 4E Interacting Protein as a Potential Novel Drug Target for Nucleoside Analogues in Trypanosoma Brucei

2021 ◽  
Vol 9 (4) ◽  
pp. 826
Author(s):  
Dorien Mabille ◽  
Camila Cardoso Santos ◽  
Rik Hendrickx ◽  
Mathieu Claes ◽  
Peter Takac ◽  
...  
Keyword(s):  
Mode Of Action ◽  
Drug Target ◽  
Drug Targets ◽  
De Novo ◽  
Treatment Options ◽  
Adenosine Kinase ◽  
Nucleoside Analogues ◽  
Purine Salvage ◽  
Interacting Protein ◽  
Novel Drug

Human African trypanosomiasis is a neglected parasitic disease for which the current treatment options are quite limited. Trypanosomes are not able to synthesize purines de novo and thus solely depend on purine salvage from the host environment. This characteristic makes players of the purine salvage pathway putative drug targets. The activity of known nucleoside analogues such as tubercidin and cordycepin led to the development of a series of C7-substituted nucleoside analogues. Here, we use RNA interference (RNAi) libraries to gain insight into the mode-of-action of these novel nucleoside analogues. Whole-genome RNAi screening revealed the involvement of adenosine kinase and 4E interacting protein into the mode-of-action of certain antitrypanosomal nucleoside analogues. Using RNAi lines and gene-deficient parasites, 4E interacting protein was found to be essential for parasite growth and infectivity in the vertebrate host. The essential nature of this gene product and involvement in the activity of certain nucleoside analogues indicates that it represents a potential novel drug target.

scholarly journals Role of Enzymes in Causing Neurological Disorders

2021 ◽  
Vol 12 (1) ◽  
pp. 466-476
Author(s):  
Vysakh Visweswaran ◽  
Roshni PR
Keyword(s):  
Neurological Disorders ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Treatment Options ◽  
Direct Result ◽  
Permanent Disability ◽  
Genetic Abnormalities ◽  
Underlying Pathology

Diseases of the nervous system are always associated with poor prognosis and limited treatment options. The fragile nature of the neurons and their inability to replicate means that neurological disorders are associated with a permanent disability. Pharmacotherapy of neurological diseases requires understanding the molecular mechanisms involved in the disease pathology. In most of the cases a faulty cellular biochemical pathway is involved, resulting from a defective enzyme. This article focusses on role of enzymes in various neurological disorders. To review pertinent literature and summarise the role of enzymes in the underlying pathology of various neurological disorders. A comprehensive literature search was conducted using PubMed, SCOPUS, J-GATE and Google Scholar and relevant papers were collected using the keywords enzymes, Alzheimer's disease, redox, thiamine, depression, neurotransmitters, epileptogenesis. The literature review highlighted the role of enzymes in major neurological disorders and their potential to be used as drug targets and biomarkers. Identifying defective enzymes gives us new molecular targets to focus on for developing more effective pharmacotherapeutic options. They can be also considered as potential biomarkers. An abnormal enzyme is most often a direct result of an underlying genetic abnormality. Identifying and screening for these genetic abnormalities can be used in early identification and prevention of disease in individuals who have a genetic predisposition. The modern advances in genetic engineering shows a lot of promise in correcting these abnormalities and development of revolutionary cures although ethical concerns remain. 

scholarly journals Vulpinic Acid as a Natural Compound Inhibits the Proliferation of Metastatic Prostate Cancer Cell by Inducing Apoptosis

2021 ◽  
Author(s):  
Demet Cansaran Duman ◽  
Gamze Guney Eskiler ◽  
Betül Çolak ◽  
Elif Sozen Kucukkara
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Annexin V ◽  
Current Treatment ◽  
Pcr Analysis ◽  
G1 Arrest ◽  
Advanced Analysis ◽  
Induced Apoptosis

Abstract Lichen secondary metabolites have drawn considerable attention in recent years due to limitations of current treatment options. Vulpinic acid (VA) obtained from Letharia vulpina lichen species exerts a remarkable cytotoxic effect on different cancer types. However, the therapeutic efficacy of VA in metastatic prostate cancer (mPC) cells has not been investigated. In the present study, we aimed to identify VA-mediated cytotoxicity in PC-3 mPC cells compared with control cells. After identification of the cytotoxic concentrations of VA, VA induced apoptosis was analyzed by Annexin V, cell cycle, acridine orange and propidium iodide staining and RT-PCR analysis. Our findings showed that VA significantly decreased the viability of PC-3 cells (p < 0.01) and caused a considerable early apoptotic effect through G0/G1 arrest, nuclear bleebing and the activation of particularly initiator caspases. Therefore, VA may be a potential treatment option for mPC patients. However, the underlying molecular mechanisms of VA-induced apoptosis with advanced analysis should be further performed.

Protein Glycation: An Old Villain is Shedding Secrets

2019 ◽  
Vol 22 (6) ◽  
pp. 362-369
Author(s):  
Gerald H. Lushington ◽  
Anthony C. Barnes
Keyword(s):  
Drug Targets ◽  
Current Knowledge ◽  
Treatment Options ◽  
Protein Glycation ◽  
Target Area ◽  
Disease Etiology ◽  
Glycated Proteins ◽  
Parkinson’S Diseases ◽  
Challenges And Opportunities ◽  
Novel Drug

: The glycation of proteins is non-physiological post-translational incorporation of carbohydrates onto the free amines or guanidines of proteins and some lipids. Although the existence of glycated proteins has been known for forty years, a full understanding of their pathogenic nature has been slow in accruing. In recent years, however, glycation has gained widespread acceptance as a contributing factor in numerous metabolic, autoimmune, and neurological disorders, tying together several confounding aspects of disease etiology. From diabetes, arthritis, and lupus, to multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer’s, and Parkinson’s diseases, an emerging glycation/inflammation paradigm now offers significant new insight into a physiologically important toxicological phenomenon. It exposes novel drug targets and treatment options, and may even lay foundations for long-awaited breakthroughs. : This ‘current frontier’ article briefly profiles current knowledge regarding the underlying causes of glycation, the structural biology implications of such modifications, and their pathological consequences. Although several emerging therapeutic strategies for addressing glycation pathologies are introduced, the primary purpose of this mini-review is to raise awareness of the challenges and opportunities inherent in this emerging new medicinal target area.

scholarly journals ERS International Congress, Madrid, 2019: highlights from the Basic and Translational Science Assembly

2020 ◽  
Vol 6 (1) ◽  
pp. 00350-2019
Author(s):  
Niki D. Ubags ◽  
Jonathan Baker ◽  
Agnes Boots ◽  
Rita Costa ◽  
Natalia El-Merhie ◽  
...  
Keyword(s):  
Lung Disease ◽  
Molecular Mechanisms ◽  
Respiratory Infections ◽  
Function Analysis ◽  
Treatment Options ◽  
Cell Types ◽  
International Congress ◽  
European Respiratory Society ◽  
Lung Health

In this review, the Basic and Translational Sciences Assembly of the European Respiratory Society (ERS) provides an overview of the 2019 ERS International Congress highlights. In particular, we discuss how the novel and very promising technology of single cell sequencing has led to the development of a comprehensive map of the human lung, the lung cell atlas, including the discovery of novel cell types and new insights into cellular trajectories in lung health and disease. Further, we summarise recent insights in the field of respiratory infections, which can aid in a better understanding of the molecular mechanisms underlying these infections in order to develop novel vaccines and improved treatment options. Novel concepts delineating the early origins of lung disease are focused on the effects of pre- and post-natal exposures on neonatal lung development and long-term lung health. Moreover, we discuss how these early life exposures can affect the lung microbiome and respiratory infections. In addition, the importance of metabolomics and mitochondrial function analysis to subphenotype chronic lung disease patients according to their metabolic program is described. Finally, basic and translational respiratory science is rapidly moving forward and this will be beneficial for an advanced molecular understanding of the mechanisms underlying a variety of lung diseases. In the long-term this will aid in the development of novel therapeutic targeting strategies in the field of respiratory medicine.

scholarly journals How I treat relapsed acute lymphoblastic leukemia in the pediatric population

Blood ◽  
2020 ◽  
Vol 136 (16) ◽  
pp. 1803-1812 ◽  
Author(s):  
Stephen P. Hunger ◽  
Elizabeth A. Raetz
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Pediatric Population ◽  
Lymphoblastic Leukemia ◽  
Treatment Options ◽  
Survival Rates ◽  
Treatment Decision ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
The Past

Abstract Relapsed acute lymphoblastic leukemia (ALL) has remained challenging to treat in children, with survival rates lagging well behind those observed at initial diagnosis. Although there have been some improvements in outcomes over the past few decades, only ∼50% of children with first relapse of ALL survive long term, and outcomes are much worse with second or later relapses. Recurrences that occur within 3 years of diagnosis and any T-ALL relapses are particularly difficult to salvage. Until recently, treatment options were limited to intensive cytotoxic chemotherapy with or without site-directed radiotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). In the past decade, several promising immunotherapeutics have been developed, changing the treatment landscape for children with relapsed ALL. Current research in this field is focusing on how to best incorporate immunotherapeutics into salvage regimens and investigate long-term survival and side effects, and when these might replace HSCT. As more knowledge is gained about the biology of relapse through comprehensive genomic profiling, incorporation of molecularly targeted therapies is another area of active investigation. These advances in treatment offer real promise for less toxic and more effective therapy for children with relapsed ALL, and we present several cases highlighting contemporary treatment decision-making.

scholarly journals Genetic Analysis of Azole Resistance by Transposon Mutagenesis in Saccharomyces cerevisiae

1999 ◽  
Vol 43 (11) ◽  
pp. 2731-2735 ◽  
Author(s):  
D. P. Kontoyiannis
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Screening Tool ◽  
Transposon Mutagenesis ◽  
Antifungal Drugs ◽  
Azole Resistance ◽  
Recessive Mutations ◽  
Novel Drug ◽  
Novel Drug Targets

ABSTRACT The increasing resistance of Candida species to fluconazole is cause for concern. To determine the molecular mechanisms involved in resistance to fluconazole, I used a scheme of transposon mutagenesis in Saccharomyces cerevisiae, a genetically tractable yeast that is closely related to Candida albicans. This technique, which permits the generation and analysis of multiple random Tn3::LEU2::lacZfusions, can be used as a disruption mutagen (N. B. Burns et al., Genes Dev. 8:1087–1105, 1994). By using the Tn3::LEU2::lacZlibrary as a disruption mutagen, I found recessive mutations in genes that were previously found to be involved in azole resistance, e.g.,PDR5 and CPR1, and in genes previously found to be involved in azole sensitivity, e.g., ERG3. This approach also enabled me to identify recessive mutations in three genes not previously known to be involved in azole sensitivity. Two of the genes,ADA3 and SPT7, are general transcriptional regulators; the third, YMR034c, is a putative sterol transporter. Finally, by screening the Tn3::LEU2::lacZlibrary for lacZ fusions induced by a low concentration of fluconazole, I identified genes known to be induced by azoles as well as a variety of other genes not previously known to be induced by the drug. In conclusion, transposon mutagenesis is a promising screening tool for use in identifying novel drug targets and in uncovering the mechanisms involved in the response of S. cerevisiae to antifungal drugs.

Role of the urologist in whether locoregional prostate cancer patients consult with a radiation oncologist.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16029-e16029
Author(s):  
Ruben G. W. Quek ◽  
Kevin C. Ward ◽  
Viraj A. Master ◽  
Chun Chieh Lin ◽  
Katherine S. Virgo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Clinical Judgment ◽  
Treatment Options ◽  
Critical Role ◽  
Medical Schools ◽  
Initial Therapy ◽  
Radiation Oncologist ◽  
Multilevel Regression ◽  
Institutional Settings

e16029 Background: Multiple treatment options exist for prostate cancer patients, and therapeutic recommendations may differ depending on characteristics of the specialist consulted. The clinical judgment of specialists can play a critical role in the initial treatment choice, especially in cases where there is no professional consensus regarding the optimal treatment strategy. We examined the association between prostate cancer patients’ urologists’ practice affiliation with medical schools on the likelihood the patient would consult a radiation oncologist. Methods: Using the Surveillance, Epidemiology and End Results – Medicare linked database and the American Medical Association Physician Masterfile, we conducted a retrospective cohort study of 39,915 patients aged 66 years or older who were diagnosed between 2004 - 2007 with locoregional prostate cancer, and the 2,404 urologists who performed the diagnostic biopsies. Multilevel regression analysis was used to evaluate the influence of patients’ urologists’ practice affiliations with medical schools on the patients’ consultation with a radiation oncologist within 9 months of diagnosis. Results: Overall, 25,110 (62.9%) patients consulted with a radiation oncologist. After adjusting for patient, tumor and urologist characteristics, patients who saw urologists practicing within non-institutional settings were significantly more likely to consult with a radiation oncologist (odds ratio [OR], 1.19; 95% confidence interval [95% CI], 1.05-1.34, p = 0.006) when compared to those who saw urologists practicing within settings with a major medical school affiliation. In addition, patients who saw urologists ≥ 58 years old were significantly more likely to consult with a radiation oncologist (OR, 1.71; 95% CI, 1.16-2.50, p = 0.006) when compared to those who saw urologists < 43 years old. Conclusions: Locoregional prostate cancer patients who received their diagnostic biopsy by urologists practicing in non-institutional settings and those who saw older urologists were significantly more likely to eventually consult with a radiation oncologist. This may have implications on which patient eventually receives radiation as initial therapy.

A phase III protocol of androgen suppression (AS) and 3DCRT/IMRT versus AS and 3DCRT/IMRT followed by chemotherapy (CT) with docetaxel and prednisone for localized, high-risk prostate cancer (RTOG 0521).

2015 ◽  
Vol 33 (18_suppl) ◽  
pp. LBA5002-LBA5002 ◽  
Author(s):  
Howard M. Sandler ◽  
Chen Hu ◽  
Seth A. Rosenthal ◽  
Oliver Sartor ◽  
Leonard G. Gomella ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Type I ◽  
Current Standard ◽  
T Stage

LBA5002 Background: High-risk, localized prostate cancer (PCa) patients have a relatively poor prognosis. We hypothesized that the addition of adjuvant docetaxel and prednisone to long-term (24 month) AS and radiation therapy (RT) would improve overall survival (OS). Methods: RTOG 0521 opened December 2005 and closed August 2009 with targeted accrual of 600 cases. It was designed to detect improvement in 4-year OS from 86% to 93% with a 51% hazard reduction (HR = 0.49). Under a 0.05 1-sided type I error and 90% power, at least 78 deaths were required to analyze the OS endpoint. Patients had 1) Gleason (Gl) 7-8, any T-stage, and PSA > 20, or 2) Gl 8, ≥ T2, any PSA, or 3) Gl 9-10, any T-stage, any PSA. All had PSA ≤ 150. RT dose was 75.6 Gy. CT consisted of 6, 21-day cycles of docetaxel + prednisone starting 28 days after RT. Results: Of 612 enrolled, 50 were excluded for eligibility issues, leaving 562 evaluable. Median age = 66, median PSA = 15.1, 53% had Gl 9-10, 27% had cT3-4. Median follow-up = 5.5 yrs. 4-yr OS rates were 89% [95% CI: 84-92%] for the AS+RT arm and 93% [95% CI: 90-96%] for the AS+RT+CT arm (1-sided p = 0.03, HR = 0.68 [95% CI: 0.44, 1.03]). There were 52 centrally-reviewed deaths in the AS+RT arm and 36 in the AS+RT+CT arm, with fewer deaths both due to PCa/treatment (20 vs 16) and due to other causes/unknown (32 vs 20) in the AS+RT+CT arm. 5-yr disease-free survival rates were 66% for AS+RT and 73% for AS+RT+CT (2-sided p = 0.05, HR = 0.76 [95% CI: 0.57, 1.00]). There was 1, Gr 5 unlikely-related adverse event (AE) in the AS+RT arm and 2, Gr 5 possibly/probably-related AEs with AS+RT+CT. Conclusions: For high-risk, localized PCa, adjuvant CT improved the OS from 89% to 93% at 4 years. Toxicity was acceptable. This trial was designed with a short OS assessment period and additional follow-up is warranted to determine the long-term benefit of CT to the current standard of care of long-term AS+RT. This project was supported by grants U10CA21661, U10CA180868, U10CA180822, from the National Cancer Institute and Sanofi with additional support from AstraZeneca for Australian site participation. Clinical trial information: NCT00288080.

Sign in / Sign up

Export Citation Format

Share Document