scholarly journals Enhancing doxorubicin anticancer activity with a novel polymeric platform photoreleasing nitric oxide

2020 ◽  
Vol 8 (5) ◽  
pp. 1329-1344 ◽  
Author(s):  
Federica Sodano ◽  
Robert J. Cavanagh ◽  
Amanda K. Pearce ◽  
Loretta Lazzarato ◽  
Barbara Rolando ◽  
...  

Combination of Doxorubicin with light-regulated NO release achieved through formulation strategy of tailored polymeric conjugate nanoparticles may open new treatment modalities to improve cancer therapies.

RSC Advances ◽  
2015 ◽  
Vol 5 (3) ◽  
pp. 2137-2146
Author(s):  
Amrita Sarkar ◽  
Subhendu Karmakar ◽  
Sudipta Bhattacharyya ◽  
Kallol Purkait ◽  
Arindam Mukherjee

Our work shows that NO release is a feasible pathway of action for aromatic and heterocyclic N-(2-chloroethyl)-N-nitrosoureas and faster NO release may not lead to higher cytotoxicity.


Children ◽  
2021 ◽  
Vol 8 (12) ◽  
pp. 1200
Author(s):  
Hugo R. Martinez ◽  
Gary S. Beasley ◽  
Jason F. Goldberg ◽  
Mohammed Absi ◽  
Kaitlin A. Ryan ◽  
...  

Survival for pediatric patients diagnosed with cancer has improved significantly. This achievement has been made possible due to new treatment modalities and the incorporation of a systematic multidisciplinary approach for supportive care. Understanding the distinctive cardiovascular characteristics of children undergoing cancer therapies has set the underpinnings to provide comprehensive care before, during, and after the management of cancer. Nonetheless, we acknowledge the challenge to understand the rapid expansion of oncology disciplines. The limited guidelines in pediatric cardio-oncology have motivated us to develop risk-stratification systems to institute surveillance and therapeutic support for this patient population. Here, we describe a collaborative approach to provide wide-ranging cardiovascular care to children and young adults with oncology diseases. Promoting collaboration in pediatric cardio-oncology medicine will ultimately provide excellent quality of care for future generations of patients.


VASA ◽  
2012 ◽  
Vol 41 (3) ◽  
pp. 163-176 ◽  
Author(s):  
Weidenhagen ◽  
Bombien ◽  
Meimarakis ◽  
Geisler ◽  
A. Koeppel

Open surgical repair of lesions of the descending thoracic aorta, such as aneurysm, dissection and traumatic rupture, has been the “state-of-the-art” treatment for many decades. However, in specialized cardiovascular centers, thoracic endovascular aortic repair and hybrid aortic procedures have been implemented as novel treatment options. The current clinical results show that these procedures can be performed with low morbidity and mortality rates. However, due to a lack of randomized trials, the level of reliability of these new treatment modalities remains a matter of discussion. Clinical decision-making is generally based on the experience of the vascular center as well as on individual factors, such as life expectancy, comorbidity, aneurysm aetiology, aortic diameter and morphology. This article will review and discuss recent publications of open surgical, hybrid thoracic aortic (in case of aortic arch involvement) and endovascular repair in complex pathologies of the descending thoracic aorta.


2020 ◽  
Vol 16 (35) ◽  
pp. 2997-3013
Author(s):  
Kentaro Kogushi ◽  
Michael LoPresti ◽  
Shunya Ikeda

Background: Synovial sarcoma (SS) is a rare, aggressive soft tissue sarcoma with a poor prognosis after metastasis. The objective of this study was to conduct a systematic review of the clinical evidence for therapeutic options for adults with metastatic or advanced SS. Materials & methods: Relevant databases were searched with predefined keywords. Results: Thirty-nine publications reported clinical data for systemic treatment and other interventions. Data on survival outcomes varied but were generally poor (progression-free survival: 1.0–7.7 months; overall survival: 6.7–29.2 months) for adults with metastatic and advanced SS. A high frequency of neutropenia with systemic treatment and low quality of life post-progression were reported. Conclusion: Reported evidence suggests poor outcomes in adults with metastatic and advanced SS and the need for the development of new treatment modalities.


Toxins ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 157 ◽  
Author(s):  
Adriana Tomoko Nishiya ◽  
Marcia Kazumi Nagamine ◽  
Ivone Izabel Mackowiak da Fonseca ◽  
Andrea Caringi Miraldo ◽  
Nayra Villar Scattone ◽  
...  

Canine oral mucosal melanomas (OMM) are the most common oral malignancy in dogs and few treatments are available. Thus, new treatment modalities are needed for this disease. Bacillus anthracis (anthrax) toxin has been reengineered to target tumor cells that express urokinase plasminogen activator (uPA) and metalloproteinases (MMP-2), and has shown antineoplastic effects both, in vitro and in vivo. This study aimed to evaluate the effects of a reengineered anthrax toxin on canine OMM. Five dogs bearing OMM without lung metastasis were included in the clinical study. Tumor tissue was analyzed by immunohistochemistry for expression of uPA, uPA receptor, MMP-2, MT1-MMP and TIMP-2. Animals received either three or six intratumoral injections of the reengineered anthrax toxin prior to surgical tumor excision. OMM samples from the five dogs were positive for all antibodies. After intratumoral treatment, all dogs showed stable disease according to the canine Response Evaluation Criteria in Solid Tumors (cRECIST), and tumors had decreased bleeding. Histopathology has shown necrosis of tumor cells and blood vessel walls after treatment. No significant systemic side effects were noted. In conclusion, the reengineered anthrax toxin exerted inhibitory effects when administered intratumorally, and systemic administration of this toxin is a promising therapy for canine OMM.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Sebastian Kühn ◽  
Joanna Freyse ◽  
Passant Atallah ◽  
Jörg Rademann ◽  
Uwe Freudenberg ◽  
...  

Abstract The delivery of chemotactic signaling molecules via customized biomaterials can effectively guide the migration of cells to improve the regeneration of damaged or diseased tissues. Here, we present a novel biohybrid hydrogel system containing two different sulfated glycosaminoglycans (sGAG)/sGAG derivatives, namely either a mixture of short heparin polymers (Hep-Mal) or structurally defined nona-sulfated tetrahyaluronans (9s-HA4-SH), to precisely control the release of charged signaling molecules. The polymer networks are described in terms of their negative charge, i.e. the anionic sulfate groups on the saccharides, using two parameters, the integral density of negative charge and the local charge distribution (clustering) within the network. The modulation of both parameters was shown to govern the release characteristics of the chemotactic signaling molecule SDF-1 and allows for seamless transitions between burst and sustained release conditions as well as the precise control over the total amount of delivered protein. The obtained hydrogels with well-adjusted release profiles effectively promote MSC migration in vitro and emerge as promising candidates for new treatment modalities in the context of bone repair and wound healing.


Author(s):  
Aida Nourbakhsh ◽  
Brett M. Colbert ◽  
Eric Nisenbaum ◽  
Aziz El-Amraoui ◽  
Derek M. Dykxhoorn ◽  
...  

AbstractProgressive non-syndromic sensorineural hearing loss (PNSHL) is the most common cause of sensory impairment, affecting more than a third of individuals over the age of 65. PNSHL includes noise-induced hearing loss (NIHL) and inherited forms of deafness, among which is delayed-onset autosomal dominant hearing loss (AD PNSHL). PNSHL is a prime candidate for genetic therapies due to the fact that PNSHL has been studied extensively, and there is a potentially wide window between identification of the disorder and the onset of hearing loss. Several gene therapy strategies exist that show potential for targeting PNSHL, including viral and non-viral approaches, and gene editing versus gene-modulating approaches. To fully explore the potential of these therapy strategies, a faithful in vitro model of the human inner ear is needed. Such models may come from induced pluripotent stem cells (iPSCs). The development of new treatment modalities by combining iPSC modeling with novel and innovative gene therapy approaches will pave the way for future applications leading to improved quality of life for many affected individuals and their families.


1994 ◽  
Vol 267 (1) ◽  
pp. F190-F195 ◽  
Author(s):  
H. Tsukahara ◽  
Y. Krivenko ◽  
L. C. Moore ◽  
M. S. Goligorsky

It has been hypothesized that fluctuations of the ionic composition in the interstitium of juxtaglomerular apparatus (JGA) modulate the function of extraglomerular mesangial cells (MC), thereby participating in tubuloglomerular feedback (TGF) signal transmission. We examined the effects of isosmotic reductions in ambient sodium concentration ([Na+]) and [Cl-] on cytosolic calcium concentration ([Ca2+]i) in cultured rat MC. Rapid reduction of [Na+] or [Cl-] in the bath induced a concentration-dependent rise in [Ca2+]i. MC are much more sensitive to decreases in ambient [Cl-] than to [Na+]; a decrease in [Cl-] as small as 14 mM was sufficient to elicit a detectable [Ca2]i response. These observations suggest that MC can be readily stimulated by modest perturbations of extracellular [Cl-]. Next, we examined whether activation of MC by lowered ambient [Cl-] influences cellular nitric oxide (NO) production. Using an amperometric NO sensor, we found that a 13 mM decrease in ambient [Cl-] caused a rapid, Ca2+/calmodulin-dependent rise in NO release from MC. This response was not inhibitable by dexamethasone, indicating the involvement of the constitutive rather than the inducible type of NO synthase in MC. In addition, the NO release was blunted by indomethacin pretreatment, suggesting that a metabolite(s) of cyclooxygenase regulates the activation of NO synthase in MC. Our findings that small perturbations in external [Cl-] stimulate MC to release NO, a highly diffusible and rapidly acting vasodilator, provide a possible mechanism to explain the transmission of the signal for the TGF response within the JGA.


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