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Cancers Oct 2022Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive primary malignancy of the pancreas, with a dismal prognosis and limited treatment options. It possesses a... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive primary malignancy of the pancreas, with a dismal prognosis and limited treatment options. It possesses a unique tumor microenvironment (TME), generating dense stroma with complex elements cross-talking with each other to promote tumor growth and progression. Diversified neural components makes for not having a full understanding of their influence on its aggressive behavior. The aim of the study was to summarize and integrate the role of nerves in the pancreatic tumor microenvironment. The role of autonomic nerve fibers on PDAC development has been recently studied, which resulted in considering the targeting of sympathetic and parasympathetic pathways as a novel treatment opportunity. Perineural invasion (PNI) is commonly found in PDAC. As the severity of the PNI correlates with a poorer prognosis, new quantification of this phenomenon, distinguishing between perineural and endoneural invasion, could feature in routine pathological examination. The concepts of cancer-related neurogenesis and axonogenesis in PDAC are understudied; so, further research in this field may be warranted. A better understanding of the interdependence between the neural component and cancer cells in the PDAC microenvironment could bring new nerve-oriented treatment options into clinical practice and improve outcomes in patients with pancreatic cancer. In this review, we aim to summarize and integrate the current state of knowledge and future challenges concerning nerve-cancer interactions in PDAC.
PubMed: 36358664
DOI: 10.3390/cancers14215246 -
Oral Oncology Jan 2015Perineural growth is a unique route of tumor metastasis that is associated with poor prognosis in several solid malignancies. It is diagnosed by the presence of tumor... (Review)
Review
Perineural growth is a unique route of tumor metastasis that is associated with poor prognosis in several solid malignancies. It is diagnosed by the presence of tumor cells inside the neural space seen on histological or imaging evaluations. Little is known about molecular mechanisms involved in the growth and spread of tumor cells in neural spaces. The poor prognosis associated with perineural growth and lack of targeted approaches necessitates the study of molecular factors involved in communication between tumor and neural cells. Perineural growth rates, shown to be as high as 63% in head and neck squamous cell carcinoma (HNSCC), correlate with increased local recurrence and decreased disease-free survival. Here we describe the literature on perineural growth in HNSCC. In addition, we discuss factors implicated in perineural growth of cancer. These factors include brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 and -4, glial cell-line derived neurotrophic factor (GDNF), the neural cell adhesion molecule (NCAM), substance P (SP), and chemokines. We also explore the literature on membrane receptors, including the Trk family and the low-affinity nerve growth factor receptor. This review highlights areas for further study of the mechanisms of perineural invasion which may facilitate the identification of therapeutic targets in HNSCC.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Neoplasm Metastasis
PubMed: 25456006
DOI: 10.1016/j.oraloncology.2014.10.004 -
Anaesthesia Jul 2021Both perineural and intravenous dexamethasone and dexmedetomidine are used as local anaesthetic adjuncts to enhance peripheral nerve block characteristics. However, the... (Meta-Analysis)
Meta-Analysis
Both perineural and intravenous dexamethasone and dexmedetomidine are used as local anaesthetic adjuncts to enhance peripheral nerve block characteristics. However, the effects of dexamethasone and dexmedetomidine based on their administration routes have not been directly compared, and the relative extent to which each adjunct prolongs sensory blockade remains unclear. This network meta-analysis sought to compare and rank the effects of perineural and intravenous dexamethasone and dexmedetomidine as supraclavicular block adjuncts. We sought randomised trials investigating the effects of adding perineural and intravenous dexamethasone or dexmedetomidine to long-acting local anaesthetics on supraclavicular block characteristics, including time to block onset and durations of sensory, motor and analgesic blockade. Data were compared and ranked according to relative effectiveness for each outcome. Our primary outcome was sensory block duration, with a 2-h difference considered clinically important. We performed a frequentist analysis, using the GRADE framework to appraise evidence. One-hundred trials (5728 patients) were included. Expressed as mean (95%CI), the control group (local anaesthetic alone) had a duration of sensory block of 401 (366-435) min, motor block duration of 369 (330-408) min and analgesic duration of 435 (386-483) min. Compared with control, sensory block was prolonged most by intravenous dexamethasone [mean difference (95%CI) 477 (160-795) min], followed by perineural dexamethasone [411 (343-480) min] and perineural dexmedetomidine [284 (235-333) min]. Motor block was prolonged most by perineural dexamethasone [mean difference (95%CI) 294 (236-352) min], followed by intravenous dexamethasone [289 (129-448)min] and perineural dexmedetomidine [258 (212-304)min]. Analgesic duration was prolonged most by perineural dexamethasone [mean difference (95%CI) 518 (448-589) min], followed by intravenous dexamethasone [478 (277-679) min] and perineural dexmedetomidine [318 (266-371) min]. Intravenous dexmedetomidine did not prolong sensory, motor or analgesic block durations. No major network inconsistencies were found. The quality of evidence for intravenous dexamethasone, perineural dexamethasone and perineural dexmedetomidine for prolongation of supraclavicular sensory block duration was 'low', 'very low' and 'low', respectively. Regardless of route, dexamethasone as an adjunct prolonged the durations of sensory and analgesic blockade to a greater extent than dexmedetomidine. Differences in block characteristics between perineural and intravenous dexamethasone were not clinically important. Intravenous dexmedetomidine did not affect block characteristics.
Topics: Adjuvants, Anesthesia; Administration, Intravenous; Anesthetics, Local; Brachial Plexus Block; Dexamethasone; Dexmedetomidine; Humans; Network Meta-Analysis
PubMed: 33118163
DOI: 10.1111/anae.15288 -
Frontiers in Cell and Developmental... 2020Studies have reported the vital role of nerves in tumorigenesis and cancer progression. Nerves infiltrate the tumor microenvironment thereby enhancing cancer growth and... (Review)
Review
Studies have reported the vital role of nerves in tumorigenesis and cancer progression. Nerves infiltrate the tumor microenvironment thereby enhancing cancer growth and metastasis. Perineural invasion, a process by which cancer cells invade the surrounding nerves, provides an alternative route for metastasis and generation of tumor-related pain. Moreover, central and sympathetic nervous system dysfunctions and psychological stress-induced hormone network disorders may influence the malignant progression of cancer through multiple mechanisms. This reciprocal interaction between nerves and cancer cells provides novel insights into the cellular and molecular bases of tumorigenesis. In addition, they point to the potential utility of anti-neurogenic therapies. This review describes the evolving cross-talk between nerves and cancer cells, thus uncovers potential therapeutic targets for cancer.
PubMed: 33392191
DOI: 10.3389/fcell.2020.601738 -
Current Health Sciences Journal 2021Squamous cell carcinomas (SCC) represent 20% of all nonmelanoma skin cancers, most tumors responding favorably to the conventional therapy. Incisional or excisional...
Squamous cell carcinomas (SCC) represent 20% of all nonmelanoma skin cancers, most tumors responding favorably to the conventional therapy. Incisional or excisional biopsy is essential for diagnosis and prognosis evaluation. The study included 103 cases of SCC, following the assessment of some clinical and histopathological aggressivity factors, which were digitally stored and statistically analyzed using comparison tests. The tumor grade was significantly associated with the histological variant, the maximum tumor size, the perineural and lymphovascular invasion, the depth of the invasion and the status of resection limits. The pT category was significantly associated with the location and maximum tumor size, perineural invasion, depth of invasion and status of resection limits. It was observed a significant association of tumor grade and pT category. The evaluation of the clinical and histological characteristics of SCC is an important step in obtaining relevant prognostic information and applying appropriate therapy.
PubMed: 34211749
DOI: 10.12865/CHSJ.47.01.10 -
Pharmacology & Therapeutics Aug 2019Pancreatic ductal adenocarcinoma (PDA) is a dismal malignant disease with the lowest stage-combined overall survival rate compared to any other cancer type. PDA has a... (Review)
Review
Pancreatic ductal adenocarcinoma (PDA) is a dismal malignant disease with the lowest stage-combined overall survival rate compared to any other cancer type. PDA has a unique tumor microenvironment (TME) comprised of a dense desmoplastic reaction comprising over two-thirds of the total tumor volume. The TME is comprised of cellular and acellular components that all orchestrate different signaling mechanisms together to promote tumorigenesis and disease progression. Particularly, the neural portion of the TME has recently been appreciated in PDA progression. Neural remodeling and perineural invasion (PNI), the neoplastic invasion of tumor cells into nerves, are common adverse histological characteristics of PDA associated with a worsened prognosis and increased cancer aggressiveness. The TME undergoes dramatic neural hypertrophy and increased neural density that is associated with many signaling pathways to promote cell invasion. PNI is also considered one of the main routes for cancer recurrence and metastasis after surgical resection, which remains the only current cure for PDA. Recent studies have shown multiple cell types in the TME signal through autocrine and paracrine mechanisms to enhance perineural invasion, pancreatic neural remodeling and disease progression in PDA. This review summarizes the current findings of the signaling mechanisms and cellular and molecular players involved in neural signaling in the TME of PDA.
Topics: Animals; Fibroblasts; Humans; Neurons; Pancreas; Pancreatic Neoplasms; Signal Transduction; Tumor Microenvironment
PubMed: 31047906
DOI: 10.1016/j.pharmthera.2019.04.010 -
Cancers Sep 2021Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with the highest incidence of perineural invasion (PNI), which often indicates a poor prognosis. Aggressive... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with the highest incidence of perineural invasion (PNI), which often indicates a poor prognosis. Aggressive tumor cells invade nerves, causing neurogenic inflammation; the tumor microenvironment also induces nerves to undergo a series of structural and functional reprogramming. In turn, neurons and the surrounding glial cells promote the development of pancreatic cancer through autocrine and/or paracrine signaling. In addition, hyperalgesia in PDAC patients implies alterations of pain transmission in the peripheral and central nervous systems. Currently, the studies on this topic are relatively limited. This review will elaborate on the mechanisms of tumor-neural interactions and its possible relationship with pain from several aspects that have been focused on in recent years.
PubMed: 34572820
DOI: 10.3390/cancers13184594 -
Nigerian Journal of Clinical Practice Jul 2022This experimental study was designed to test the hypothesis that ondansetron, a selective 5-HT3 receptor antagonist, would decrease the duration of motor, sensory, and...
BACKGROUND AND AIMS
This experimental study was designed to test the hypothesis that ondansetron, a selective 5-HT3 receptor antagonist, would decrease the duration of motor, sensory, and proprioception blockade in a dose-dependent fashion in a bupivacaine-induced sciatic nerve blockade.
MATERIALS AND METHODS
Forty-nine male Wistar Albino rats who underwent unilateral sciatic nerve block were divided into seven groups with an equal number in each group. Group B: only perineural block (PB), Group BO200: PB and perineural 200 μg ondansetron, Group BO400: PB and perineural 400 μg ondansetron, Group BO800: PB and perineural 800 μg ondansetron, Group BO800IP: PB and intraperitoneal 800 μg ondansetron, Group O800: only perineural 800 μg ondansetron, Group S: sham-operated. The rats' motor, sensory, and proprioception functions were evaluated by a blinded investigator every 10 min until they returned to normal function. The recovery times of the motor, sensory, and proprioception functions were recorded and compared. All sciatic nerves were removed and examined by electron microscopy for neurotoxic signs.
RESULTS
In which sciatic nerve block was formed with bupivacaine, the duration of the motor, sensory, and proprioception functions blockade was decreased, and the duration to return to normal functions was significantly shortened at Group BO800 (p < 0.05). According to electron microscopy results, perineural 200 μg, 400 μg, and 800 μg ondansetron were not neurotoxic.
CONCLUSION
This is the first study showing that perineural ondansetron administration (800 μg dose) reverses the effect of the local anesthetics and shortens the duration of the motor, sensory, and proprioception functions blockade.
Topics: Animals; Bupivacaine; Male; Nerve Block; Ondansetron; Rats; Rats, Wistar; Sciatic Nerve
PubMed: 35859477
DOI: 10.4103/njcp.njcp_1804_21 -
Pharmaceutics Nov 2019One of the most challenging aspects of treating disorders of the central nervous system (CNS) is the efficient delivery of drugs to their targets within the brain. Only... (Review)
Review
One of the most challenging aspects of treating disorders of the central nervous system (CNS) is the efficient delivery of drugs to their targets within the brain. Only a small fraction of drugs is able to cross the blood-brain barrier (BBB) under physiological conditions, and this observation has prompted investigation into the routes of administration that may potentially bypass the BBB and deliver drugs directly to the CNS. One such route is the intranasal (IN) route. Increasing evidence has suggested that intranasally-administered drugs are able to bypass the BBB and access the brain through anatomical pathways connecting the nasal cavity to the CNS. Though the exact mechanisms regulating the delivery of therapeutics following IN administration are not fully understood, current evidence suggests that the perineural and perivascular spaces of the olfactory and trigeminal nerves are involved in brain delivery and cerebral perivascular spaces are involved in widespread brain distribution. Here, we review evidence for these delivery and distribution pathways, and we address questions that should be resolved in order to optimize the IN route of administration as a viable strategy to treat CNS disease states.
PubMed: 31726721
DOI: 10.3390/pharmaceutics11110598 -
Journal of Neurological Surgery. Part... Apr 2016Head and neck malignancies have the propensity to invade nerves. Perineural tumor invasion is common, with some series reporting rates of 30 to 100%. Squamous cell... (Review)
Review
Head and neck malignancies have the propensity to invade nerves. Perineural tumor invasion is common, with some series reporting rates of 30 to 100%. Squamous cell carcinoma and adenoid cystic carcinoma are the most commonly involved tumors. The most commonly involved nerves are the trigeminal (cranial nerve [CN] V) and facial (CN VII) and their branches. Neural spread away from a tumor is encountered less often and usually causes specific symptoms such as pain, muscle weakness, and atrophy, depending on the involved nerves. While clinical symptoms and physical examination may suggest the presence of neural invasion, specific imaging modalities such as fat-suppressed T1-weighted magnetic resonance images, should be utilized to identify perineural tumor spread in its early phases. Perineural tumor spread should be considered and addressed in the treatment planning of patients with head and neck or skull base cancers as it can influence the extent of surgery, and the dosage and fields of radiation therapy. In the current review, we discuss the clinical course of perineural tumor spread and its therapeutic implications.
PubMed: 27123384
DOI: 10.1055/s-0036-1571834