Emergence of Ad-Mediated Combination Therapy Against Cancer: What to Expect?

2018 ◽  
Vol 18 (2) ◽  
pp. 139-152 ◽  
Author(s):  
JinWoo Hong ◽  
Chae-Ok Yun

Novel treatment modalities are rapidly advancing toward clinical use as many malignant cancers still remain incurable. Adenovirus (Ad) in particular has been extensively researched as a promising alternative to conventional cancer therapy in the past decades. Although Ad has demonstrated promising therapeutic outcome and cancer specificity in preclinical models, its therapeutic efficacy in clinical trials is still insufficient due to several drawbacks such as rapid clearance of viral particles by host immune response, induction of acute inflammatory response, and hepatotoxicity. In this regard, combination of Ad with other cancer treatment modalities, such as chemotherapy, radiotherapy, or immunotherapy, can be an effective strategy to overcome the limitations of Ad. Cancerspecific and effective expression of multifunctional therapeutic genes by Ad can enhance the therapeutic profile of other treatment modalities, making it a logical candidate for combination therapy to combat malignant tumors.

Author(s):  
Deepak K. Sarpal ◽  
Anil K. Malhotra

Over the past several decades, considerable work has established our current repertoire of approaches to treatment of psychosis. This chapter provides an overview of current treatments for psychotic disorders with a focus on schizophrenia. Diagnostic considerations will be introduced, followed by discussions of first generation and second generation antipsychotic drugs, our current mainstay for treatment. Adverse effects of medications will be examined, as well as approaches to treatment refractory illness and nonpharmacologic treatment modalities. Finally, in light of recent advances in our understanding of the neurobiology of psychotic disorders, we will briefly discuss treatment-related biomarkers, and novel treatment targets under development.


2021 ◽  
Vol 53 (07) ◽  
pp. 413-424
Author(s):  
Ramazan Sari ◽  
Meric A. Altinoz ◽  
Eylem Burcu Kahraman Ozlu ◽  
Aydin Sav ◽  
Ayca Ersen Danyeli ◽  
...  

AbstractDespite most of the prolactinomas can be treated with endocrine therapy and/or surgery, a significant percentage of these tumors can be resistant to endocrine treatments and/or recur with prominent invasion into the surrounding anatomical structures. Hence, clinical, pathological, and molecular definitions of aggressive prolactinomas are important to guide for classical and novel treatment modalities. In this review, we aimed to define molecular endocrinological features of dopamine agonist-resistant and aggressive prolactinomas for designing future multimodality treatments. Besides surgery, temozolomide chemotherapy and radiotherapy, peptide receptor radionuclide therapy, estrogen pathway modulators, progesterone antagonists or agonists, mTOR/akt inhibitors, pasireotide, gefitinib/lapatinib, everolimus, and metformin are tested in preclinical models, anecdotal cases, and in small case series. Moreover, chorionic gonadotropin, gonadotropin releasing hormone, TGFβ and PRDM2 may seem like possible future targets for managing aggressive prolactinomas. Lastly, we discussed our management of a unique prolactinoma case by asking which tumors’ proliferative index (Ki67) increased from 5–6% to 26% in two subsequent surgeries performed in a 2-year period, exerted massive invasive growth, and secreted huge levels of prolactin leading up to levels of 1 605 671 ng/dl in blood.


2014 ◽  
Vol 155 (33) ◽  
pp. 1295-1300
Author(s):  
Annamária Erdei ◽  
Annamária Gazdag ◽  
Miklós Bodor ◽  
Eszter Berta ◽  
Mónika Katkó ◽  
...  

Graves’ orbitopathy is the most common extrathyroidal manifestation of Graves’ disease. Up to now, curative treatment modalities for the most severe sight-threatening cases have not been developed. Here the authors summarize the treatment protocol of Graves’ orbitopathy and review novel therapeutic options. They review the literature on this topic and present their own clinical experience. The authors point out that anti-CD20 antibody could positively influence the clinical course of Graves’ orbitopathy. Selenium is efficient in mild cases. Further prospective investigations are warranted. Orv. Hetil., 2014, 155(33), 1295–1300.


Author(s):  
Rohan Aggarwal ◽  
Monika Targhotra ◽  
Bhumika Kumar ◽  
P.K Sahoo ◽  
Meenakshi K Chauhan

In the past few years gene delivery system has gained a huge attention owing to its proved efficacy in several diseases especially in those caused by genetic and/oroncological malfunctioning. The effective gene delivery mainly depends on the carrier molecules that can ensure the safe and specific delivery of the nucleic acidmolecules. Viral vectors have been used for a longer period as the gene transfer vehicle. However, these viral vectors have potential immunological disadvantages that made them less preferred. Recently, non-viral vectors such as polyplexes have emerged as a promising alternative for viral vectors. Polyplexes are formed by conjugating a polymer with DNA and in maximum cases the cationic polymers are preferred over others. The structure and stability of the polyplexes depends on various factors. The ability of the polymer to condense the DNA mainly dictates the efficiency of the polyplex mediated transfection. In this review we are going to provide a framework for the synthesis and design of the polyplexes along with the structure and stability of the complexes pertaining to mechanism of action, characterization and therapeutic application, including polyethyleneimine mediated cytotoxicity as well as newer strategies for the generation of better polyplexes.


Author(s):  
Gabriele Stephan ◽  
Niklas Ravn-Boess ◽  
Dimitris G Placantonakis

Abstract Members of the adhesion family of G protein-coupled receptors (GPCRs) have received attention for their roles in health and disease, including cancer. Over the past decade, several members of the family have been implicated in the pathogenesis of glioblastoma. Here, we discuss the basic biology of adhesion GPCRs and review in detail specific members of the receptor family with known functions in glioblastoma. Finally, we discuss the potential use of adhesion GPCRs as novel treatment targets in neuro-oncology.


2021 ◽  
pp. 106689692098834
Author(s):  
Raquel Machado-Neves ◽  
Bernardo Teixeira ◽  
Elsa Fonseca ◽  
Pedro Valente ◽  
Joaquim Lindoro ◽  
...  

Most malignant tumors of the penis are squamous cell carcinomas (SCC), being divided in 2 groups, one human papillomavirus (HPV)-related and another non-HPV-related, with lymphoepithelioma-like carcinoma (LELC) being one of the rarest HPV-related SCC. In this article, we report a case of a 50-year-old man who presented testicular swelling and pain for the past 3 months. A penile mass was identified, and the patient was submitted to a total penectomy. The penectomy specimen showed an ulcerated lesion at the glans reaching the cavernous bodies. Microscopic examination showed undifferentiated epithelial cells with syncytial growth pattern mix with a dense lymphoplasmacytic infiltrate, consistent with LELC. The tumor cells expressed p16 and all 3 different clones of PDL1 (22C3, SP263, and SP142). The patient is alive and well with a follow-up of 3 months. To our knowledge, this is the third LELC of the penis reported in literature and the first case reported with PDL1 expression.


Author(s):  
Fabrice Gallais ◽  
Olivier Pible ◽  
Jean-Charles Gaillard ◽  
Stéphanie Debroas ◽  
Hélène Batina ◽  
...  

AbstractCOVID-19 is the most disturbing pandemic of the past hundred years. Its causative agent, the SARS-CoV-2 virus, has been the subject of an unprecedented investigation to characterize its molecular structure and intimate functioning. While markers for its detection have been proposed and several diagnostic methodologies developed, its propensity to evolve and evade diagnostic tools and the immune response is of great concern. The recent spread of new variants with increased infectivity requires even more attention. Here, we document how shotgun proteomics can be useful for rapidly monitoring the evolution of the SARS-CoV-2 virus. We evaluated the heterogeneity of purified SARS-CoV-2 virus obtained after culturing in the Vero E6 cell line. We found that cell culture induces significant changes that are translated at the protein level, such changes being detectable by tandem mass spectrometry. Production of viral particles requires careful quality control which can be easily performed by shotgun proteomics. Although considered relatively stable so far, the SARS-CoV-2 genome turns out to be prone to frequent variations. Therefore, the sequencing of SARS-CoV-2 variants from patients reporting only the consensus genome after its amplification would deserve more attention and could benefit from more in-depth analysis of low level but crystal-clear signals, as well as complementary and rapid analysis by shotgun proteomics. Graphical abstract


2019 ◽  
Vol 2019 ◽  
pp. 1-5
Author(s):  
Kanksha Peddi ◽  
Alexander L. Hsu ◽  
Tomas H. Ayala

ST-elevation myocardial infarction (STEMI) is a rare and potentially fatal complication of infective endocarditis. We report the ninth case of embolic native aortic valve infective endocarditis causing STEMI and the first case to describe consecutive embolisms leading to infarctions of separate coronary territories. Through examination of this case in the context of the previous eight similar documented cases in the past, we find that infective endocarditis of the aortic valve can and frequently affect more than a single myocardial territory and can occur consecutively. Further, current treatment modalities for embolic infective endocarditis causing acute myocardial infarction are limited and unproven. This index case illustrates the potential severity of complications and the challenges in developing standardized management for such patients.


Neurosurgery ◽  
2014 ◽  
Vol 74 (suppl_1) ◽  
pp. S92-S101 ◽  
Author(s):  
Jorge L. Eller ◽  
Travis M. Dumont ◽  
Grant C. Sorkin ◽  
Maxim Mokin ◽  
Elad I. Levy ◽  
...  

Abstract Carotid artery stenting has become a viable alternative to carotid endarterectomy in the management of carotid stenosis. Over the past 20 years, many trials have attempted to compare both treatment modalities and establish the indications for each one, depending on clinical and anatomic features presented by patients. Concurrently, carotid stenting techniques and devices have evolved and made endovascular management of carotid stenosis safe and effective. Among the most important innovations are devices for distal and proximal embolic protection and new stent designs. This paper reviews these advances in the endovascular management of carotid artery stenosis within the context of the historical background.


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