scholarly journals Updates on Molecular and Biochemical Development and Progression of Prostate Cancer

2021 ◽  
Vol 10 (21) ◽  
pp. 5127
Author(s):  
Omar Fahmy ◽  
Nabil A. Alhakamy ◽  
Waleed Y. Rizg ◽  
Alaa Bagalagel ◽  
Abdulmohsin J. Alamoudi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Targeted Therapy ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Treatment Modalities ◽  
Future Research ◽  
Natural Behaviour ◽  
Biomarker Analysis ◽  
New Treatment ◽  
Antiandrogen Therapy

Prostate cancer (PCa) represents the most commonly non-cutaneous diagnosed cancer in men worldwide and occupies a very wide area of preclinical and clinical research. Targeted therapy for any cancer depends on the understanding of the molecular bases and natural behaviour of the diseases. Despite the well-known effect of androgen deprivation on PCa, many patients develop resistance either for antiandrogen therapy or other new treatment modalities such as checkpoint inhibitors and chemotherapy. Comprehensive understanding of the development of PCa as well as of the mechanisms underlying its progression is mandatory to maximise the benefit of the current approved medications or to guide the future research for targeted therapy of PCa. The aim of this review was to provide updates on the most recent mechanisms regarding the development and the progression of PCa. According to the current understanding, future treatment strategies should include more predictive genetic and biomarker analysis to assign different patients to the expected most appropriate and effective treatment.

The Current Role of Immunotherapy in mCRPC: A Systematic Review

2021 ◽  
Vol 8 (7) ◽  
Author(s):  
Dalibey H ◽  
◽  
Hansen TF ◽  
Zedan AH ◽  
◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Specific Antigen ◽  
Treatment Modalities ◽  
Significant Difference

Background: The development of immunotherapy has shown promising results in several malignant diseases, including prostate cancer, calling for a systematic review of the current literature. This review aims to evaluate the present data and prospects of immune checkpoint inhibitors in metastatic Castration Resistant Prostate Cancer (mCRPC). Methods: Articles were identified via a systematic search of the electronic database Pubmed, in accordance with the PICO process and following the PRISMA guidelines. Articles in English studying immune checkpoint inhibitors in patients with mCRPC published between March 2010 and March 2020 were eligible for inclusion. Endpoints of interest were Overall Survival (OS), Progression-Free Survival (PFS), clinical Overall Response Rate (ORR), and Prostate-Specific Antigen (PSA) response rate. Results: Ten articles were identified as eligible for inclusion. The studies primarily explored the use of Ipilimumab, a CTLA-4 inhibitor, and Pembrolizumab, a PD-1 inhibitor. These drugs were both used either as monotherapy or in combination with other treatment modalities. The largest trial included in the review demonstrated no significant difference in overall survival between the intervention and placebo. However, two studies presented promising data combing immunotherapy and immune vaccines. Grade 3 and 4 adverse events ranging from 10.1% to 82.3%, whit diarrhea, rash, and fatigue were the most frequently reported. Forty relevant ongoing trials were identified exploring immunotherapy with or without a parallel treatment modality. Conclusion: Overall, the current data shows that the effect of immune checkpoint inhibitors as monotherapy may have limited impact on mCRPC, and the results from ongoing combinational trials are eagerly awaited.

scholarly journals Development of new 5-chromenyl-2,4-thiazolidinediones as antimicrobial agents

2015 ◽  
Vol 89 (1) ◽  
pp. 122-127 ◽  
Author(s):  
Cristina Mariana Nastasă ◽  
Mihaela Duma ◽  
Adrian Pîrnău ◽  
Laurian Vlase ◽  
Brîndușa Tiperciuc ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Treatment Strategies ◽  
Inhibition Zone ◽  
Diffusion Method ◽  
Future Research ◽  
Physico Chemical ◽  
New Chemical Entities ◽  
New Treatment ◽  
Antibacterial And Antifungal ◽  
New Compounds

Background and aims. In the context of the increasing phenomenon of microbial resistance to usual drugs, the development of new treatment strategies and new therapeutic protocols is a constant need. Thiazolidinedione and chromone represent two important scaffolds in medicinal chemistry due to their large pharmacological applicability.Methods. We synthesized a new 5-(chromene-3-yl)methylene-2,4-thiazolidinedione starting from 6,8-dichloro-4-oxo-4H-chromene-3-carbaldehyde. Then, by treating with different α-bromoalkylarylketones, we obtained N-substituted derivatives. All new compounds were investigated for their antimicrobial potential, using the diffusion method, against Listeria monocytogenes ATCC 13932, Staphylococcus aureus ATCC 49444, Escherichia coli ATCC 25922, Salmonella typhimurium ATCC 14028 and Candida albicans ATCC 10231. Three concentrations, 10 mg/ml, 5 mg/ml and 1 mg/ml of compounds were used. The results were evaluated by the measurement of the inhibition zone diameters and compared to those of gentamicin and fluconazole respectively, as reference drugs.Results. All new synthesized compounds were characterized using physico-chemical and spectrometric methods. They displayed modest to good antimicrobial activity. New molecules 8, 9 and 10 may represent promising candidates, showing zone inhibition diameters superior to those of reference drugs.Conclusions. This work presents chemical synthesis, characterization and investigation of the antibacterial and antifungal potential of 5-(chromene-3-yl)methylene-2,4-thiazolidinedione derivatives, which may be worthy of future research for designing new chemical entities.

Treatment Innovations of Opiate Dependence Treatment

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
W. van den Brink
Keyword(s):  
Partial Agonist ◽  
Treatment Strategies ◽  
Oral Morphine ◽  
Treatment Compliance ◽  
Psychosocial Interventions ◽  
Opiate Dependence ◽  
Treatment Modalities ◽  
List Type ◽  
Number Of Patients ◽  
New Treatment

Opiate dependence is a serious psychiatric disorder with substantial suffering for the patient, his environment and society as a whole. Currently available treatments include abstinence oriented treatment with naltrexone and substitutian treatments with methadone and buprenorphine. However, treatment compliance with naltrexone is very low resulting in low effectiveness. In addition, existing substituation treatments only show moderate effectiveness resulting in a large number of patients showing continued drug use and serious psychological, somatic and functional impairment.New treatment strategies involve:a.the development of long acting opiate antagonists (naltrexone) and partial agonist (buprenorphine) to improve treatment compliance and treatment retention,b.new substitution options such as slow release oral morphine (SROM), oral diacetylmorphine (heroin) and inhalable and injectable diacetyl morphine (heroin assisted treatment: HAT).Recently, a new approach using neurosurgical and neuromodulatory techniques has been advocated to help treatment refractory opiate dependent patients. Finally, certain combinations of farmacotherapy and psychosocial interventions have shown promise for future improvements.This presentation reviews the evidence of existing treatments for opiate dependence and explores the new treatment options for patients not fully responsive to the existing treatment modalities.

scholarly journals Multimodal Treatment in Glioblastomas

2021 ◽  
Author(s):  
Ercan Çetin ◽  
Serdar Kabataş
Keyword(s):  
Overall Survival ◽  
Multimodal Treatment ◽  
Poor Prognosis ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Modalities ◽  
Tumor Vaccines ◽  
Tumor Treating Fields ◽  
The Poor ◽  
New Treatment

Glioblastomas are the most common primary brain tumors. Despite aggressive resection, radiotherapy and concomitant chemotheraphy overall survival is 14-16 months, and 5 year survivial rate is only 2%. The poor prognosis required development of new treatment modalities. Tumor Treating Fields, molecularly targetted drugs, antiangiogenic molecules, immune checkpoint inhibitors, tumor vaccines, Chimeric Antigen Receptor-T cell, viral theraphy and oncolytic viruse and mesenchymal stem cell vectors are some of the modalities that are currently being developed.

scholarly journals The castration level of testosterone and hormonal resistance of prostate cancer in androgen deprivation therapy

2020 ◽  
pp. 100-108
Author(s):  
I. G. Rusakov ◽  
A. A. Gritskevich ◽  
T. P. Baitman ◽  
S. V. Mishugin
Keyword(s):  
Prostate Cancer ◽  
Disease Progression ◽  
Androgen Deprivation Therapy ◽  
Specific Antigen ◽  
Treatment Strategies ◽  
Significant Risk ◽  
Androgen Deprivation ◽  
Early Detection Of Disease ◽  
Biomarker Analysis ◽  
The Impact

This review is dedicated to the impact of modern achievements on the definition and diagnostics of castration-resistant prostate cancer (PCa) (CRPC), prognostic factors for its progression, and treatment strategies.It was proven with new sensitive methods of diagnostics that surgical castration (CS) decreases serum testosterone (T) levels to < 20 ng/dL, while achieving T < 20 ng/dL improves outcomes and delays the development of CRPC. Regular assessment of the T level makes it possible to understand whether this androgen is adequately suppressed in the setting of potential progression of CRPC, given that late dosing may lead to an increase in T level. Improved imaging techniques and biomarker analysis enable early detection of disease progression. Prognostically significant risk factors for CRPC progression include Gleason score, the extent of metastatic spread, hereditary characteristics such as gene mutations affecting androgen receptor (AR) amplification or DNA repair deficiency mutations, prostate-specific antigen (PSA) kinetics, and biomarker levels. Today, treatment options for CRPC have gone beyond androgen deprivation therapy (ADT) to include therapy that blocks T-synthesis and/or suppresses its activity through various mechanisms. Future directions include therapies using new biological targets, drug combinations and personalized therapies. It is necessary to assess the possible reasons for the difference in the pharmacodynamics and pharmacokinetics of androgendeprivation drugs, to study the features of the processes of destruction of drugs under the action of endogenous enzymes and resorption in the subcutaneous or muscle depot, which may cause the resistance to therapy.The aim of improved treatment and diagnostic options for PCa is to delay its progression to CRPC and to prolong patient survival. Rethinking of the castration concept and advances in understanding the biology of disease progression make it necessary to revise diagnostic and treatment strategies. ADT is a fundamental vector of treatment, and it should be continued even if some new ways of treatment for CRPC are introduced.

scholarly journals Radiotherapy and inhibition of the EGF family as treatment strategies for prostate cancer: combining theragnostics with theragates

2011 ◽  
Vol 5 (2) ◽  
pp. 119 ◽  
Author(s):  
Wolfgang Lilleby ◽  
Flavio Solca ◽  
Kathrine Røe
Keyword(s):  
Prostate Cancer ◽  
Signal Transduction ◽  
Solid Tumors ◽  
Kinase Inhibitors ◽  
Nuclear Translocation ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Signal Transduction Pathway ◽  
Protein Kinase Inhibitors ◽  
Treatment Modalities

Prostate cancer is one of the most common solid tumors affecting men. Localized stages can be cured, however, once disseminated to distant organs the median survival drops below 12 months. The challenge for the future consists of unifying gained insights of cellular signal dysfunctioning (‘‘theragates’’) with the knowledge of disease detection (‘‘theragnostics’’) in personalized therapy. In solid malignancies, multiple signal transduction molecules are often deregulated simultaneously, within the same tumor. A multi-targeted approach may possibly improve efficacy, but will also increase toxicity, thus, potentially limiting the use of various combinations. On the other hand, well-established treatment modalities in prostate cancer, such as radiotherapy with its known efficacy and limited toxicity, may be an attractive combination partner for protein kinase inhibitors. Deregulation of the epidermal growth factor receptor (EGFR) signal transduction pathway is observed in a variety of solid tumors, including prostate cancer. Furthermore, one important DNA repair mechanism is dependent on EGFR nuclear translocation, thus, providing a rationale for combining radiotherapy with EGFR inhibitors. This article reviews current knowledge regarding this combination paradigm, revealing an intriguing therapy option to be explored for patients with advanced prostate cancer.

scholarly journals MEIS-mediated suppression of human prostate cancer growth and metastasis through HOXB13-dependent regulation of proteoglycans

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Calvin VanOpstall ◽  
Srikanth Perike ◽  
Hannah Brechka ◽  
Marc Gillard ◽  
Sophia Lamperis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Treatment Strategies ◽  
Human Prostate ◽  
Protein Activity ◽  
Prostate Epithelial Cells ◽  
New Treatment ◽  
Hox Protein

The molecular roles of HOX transcriptional activity in human prostate epithelial cells remain unclear, impeding the implementation of new treatment strategies for cancer prevention and therapy. MEIS proteins are transcription factors that bind and direct HOX protein activity. MEIS proteins are putative tumor suppressors that are frequently silenced in aggressive forms of prostate cancer. Here we show that MEIS1 expression is sufficient to decrease proliferation and metastasis of prostate cancer cells in vitro and in vivo murine xenograft models. HOXB13 deletion demonstrates that the tumor-suppressive activity of MEIS1 is dependent on HOXB13. Integration of ChIP-seq and RNA-seq data revealed direct and HOXB13-dependent regulation of proteoglycans including decorin (DCN) as a mechanism of MEIS1-driven tumor suppression. These results define and underscore the importance of MEIS1-HOXB13 transcriptional regulation in suppressing prostate cancer progression and provide a mechanistic framework for the investigation of HOXB13 mutants and oncogenic cofactors when MEIS1/2 are silenced.

scholarly journals The Position of Inhaled Chemotherapy in the Care of Patients with Lung Tumors: Clinical Feasibility and Indications According to Recent Pharmaceutical Progresses

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 329 ◽  
Author(s):  
Rémi Rosière ◽  
Thierry Berghmans ◽  
Paul De Vuyst ◽  
Karim Amighi ◽  
Nathalie Wauthoz
Keyword(s):  
Checkpoint Inhibitors ◽  
Dry Powder Inhaler ◽  
Lung Tumors ◽  
Cytotoxic Chemotherapy ◽  
Treatment Modalities ◽  
Drug Doses ◽  
Controlled Release Formulations ◽  
New Treatment ◽  
Distribution In The Organism ◽  
Causes Of Failure

Despite new treatment modalities, including targeted therapies and checkpoint inhibitors, cytotoxic chemotherapy remains central in the care of patients with lung tumors. Use of the pulmonary route to deliver chemotherapy has been proved to be feasible and safe in phase I, Ib/IIa and II trials for lung tumors, with the administration of drug doses to the lungs without prior distribution in the organism. The severe systemic toxicities commonly observed with conventional systemic chemotherapy are consequently reduced. However, development has failed in phase II at best. This review first focuses on the causes of failure of inhaled chemotherapy. It then presents new promising technologies able to take up the current challenges. These technologies include the use of a dry powder inhaler or a smart nebulizer with advanced drug formulations such as controlled-release formulations and nanomedicine. Finally, the potential position of inhaled chemotherapy in patient care is discussed and some indications are proposed based on the literature.

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