The oxygen effect and therapeutic approaches to tumour hypoxia

The magnitude of the host immune response can be regulated by either stimulatory or inhibitory immune checkpoint molecules. Receptor-ligand binding between inhibitory molecules is often exploited by tumours to suppress anti-tumour immune responses. Immune checkpoint inhibitors that block these inhibitory interactions can relieve T-cells from negative regulation, and have yielded remarkable activity in the clinic. Despite this success, clinical data reveal that durable responses are limited to a minority of patients and malignancies, indicating the presence of underlying resistance mechanisms. Accumulating evidence suggests that tumour hypoxia, a pervasive feature of many solid cancers, is a critical phenomenon involved in suppressing the anti-tumour immune response generated by checkpoint inhibitors. In this review, we discuss the mechanisms associated with hypoxia-mediate immunosuppression and focus on modulating tumour hypoxia as an approach to improve immunotherapy responsiveness.

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Nanotheranostic agents for neurodegenerative diseases

Emerging Topics in Life Sciences ◽

10.1042/etls20190141 ◽

2020 ◽

Vol 4 (6) ◽

pp. 645-675

Author(s):

Parasuraman Padmanabhan ◽

Mathangi Palanivel ◽

Ajay Kumar ◽

Domokos Máthé ◽

George K. Radda ◽

...

Keyword(s):

Drug Delivery ◽

Neurodegenerative Diseases ◽

Cell Types ◽

Specific Cell ◽

Ageing Population ◽

Target Tissue ◽

Therapeutic Approaches ◽

Surface Receptors ◽

Theranostic Agents ◽

Preclinical Animal Models

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.

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Lessons From the Neural Bases of Speech and Voice

Perspectives on Speech Science and Orofacial Disorders ◽

10.1044/ssod21.1.5 ◽

2011 ◽

Vol 21 (1) ◽

pp. 5-14

Author(s):

Christy L. Ludlow

Keyword(s):

Brain Networks ◽

Neural Substrates ◽

Voice Behavior ◽

Therapeutic Approaches ◽

Neural Bases ◽

Sound Foundation ◽

The Brain ◽

Normal Speech

The premise of this article is that increased understanding of the brain bases for normal speech and voice behavior will provide a sound foundation for developing therapeutic approaches to establish or re-establish these functions. The neural substrates involved in speech/voice behaviors, the types of muscle patterning for speech and voice, the brain networks involved and their regulation, and how they can be externally modulated for improving function will be addressed.

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Physiologic Studies Provide New Perspectives on Early Speech Development

Perspectives on Speech Science and Orofacial Disorders ◽

10.1044/ssod20.2.29 ◽

2010 ◽

Vol 20 (2) ◽

pp. 29-36

Author(s):

Erin M. Wilson ◽

Ignatius S. B. Nip

Keyword(s):

Motor Control ◽

Motor Development ◽

Motion Tracking ◽

Speech Development ◽

Speech Motor Control ◽

Therapeutic Approaches ◽

Facial Motion ◽

Disordered Speech ◽

Speech Motor ◽

Physiologic Data

Abstract Although certain speech development milestones are readily observable, the developmental course of speech motor control is largely unknown. However, recent advances in facial motion tracking systems have been used to investigate articulator movements in children and the findings from these studies are being used to further our understanding of the physiologic basis of typical and disordered speech development. Physiologic work has revealed that the emergence of speech is highly dependent on the lack of flexibility in the early oromotor system. It also has been determined that the progression of speech motor development is non-linear, a finding that has motivated researchers to investigate how variables such as oromotor control, cognition, and linguistic factors affect speech development in the form of catalysts and constraints. Physiologic data are also being used to determine if non-speech oromotor behaviors play a role in the development of speech. This improved understanding of the physiology underlying speech, as well as the factors influencing its progression, helps inform our understanding of speech motor control in children with disordered speech and provide a framework for theory-driven therapeutic approaches to treatment.

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Popliteal entrapment syndrome and age

VASA ◽

10.1024/0301-1526/a000201 ◽

2012 ◽

Vol 41 (4) ◽

pp. 262-268 ◽

Cited By ~ 3

Author(s):

Schweizer ◽

Hügli ◽

Koella ◽

Jeanneret

Keyword(s):

Risk Factors ◽

Leg Pain ◽

Walking Distance ◽

Therapeutic Approaches ◽

Long Distance ◽

Entrapment Syndrome ◽

Long Distance Running ◽

Popliteal Entrapment ◽

Popliteal Entrapment Syndrome ◽

Atherosclerotic Risk Factors

On the occasion of diagnosing a popliteal entrapment syndrome in a 59-year old man with no cardiovascular risk factors, who developed acute ischemic leg pain during long distance running, we give an overview on this entity with emphasis on patientsage. The different types of the popliteal artery compression syndrome are summarized. The diagnostic and therapeutic approaches are discussed. The most important clinical sign of a popliteal entrapment syndrome is the lack of atherosclerotic risk factors in patients with limited walking distance. Not only in young athletes but also in patients more than 50 years old the popliteal entrapment syndrome has to be taken into account.

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Endoscopic mucosal resection for recurrent gastric antral vascular ectasia

VASA ◽

10.1024/0301-1526.37.3.289 ◽

2008 ◽

Vol 37 (3) ◽

pp. 289-292 ◽

Cited By ~ 5

Author(s):

Katsinelos ◽

Chatzimavroudis ◽

Katsinelos ◽

Panagiotopoulou ◽

Kotakidou ◽

...

Keyword(s):

Endoscopic Mucosal Resection ◽

Argon Plasma Coagulation ◽

Argon Plasma ◽

Deficiency Anemia ◽

Gastric Antral Vascular Ectasia ◽

Therapeutic Approaches ◽

Plasma Coagulation ◽

Vascular Ectasia ◽

Mucosal Resection ◽

First Case

Gastric antral vascular ectasia (GAVE) is an overt or occult source of gastrointestinal bleeding. Despite several therapeutic approaches have been successfully tested for preventing chronic bleeding, some patients present recurrence of GAVE lesions. To the best of our knowledge, we report the first case, of a 86-year-old woman who presented severe iron-deficiency anemia due to GAVE and showed recurrence of GAVE lesion despite the intensive argon plasma coagulation treatment. We performed endoscopic mucosal resection of bleeding GAVE with resolution of anemia.

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