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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 -
Biochimica Et Biophysica Acta.... Dec 2022Perineural invasion (PNI) driven by the tumor microenvironment (TME) has emerged as a key pattern of metastasis of prostate cancer (PCa), while its underlying mechanism...
Perineural invasion (PNI) driven by the tumor microenvironment (TME) has emerged as a key pattern of metastasis of prostate cancer (PCa), while its underlying mechanism is still elusive. Here, we identified increased CAFs and YAP1 expression levels in patients with metastatic PCa. In the cultured PCa cell line LNCaP, co-culture with cancer-associated fibroblasts (CAFs) could upregulate YAP1 protein expression. Either ectopic overexpression of YAP1 or co-culture with CAFs could promote the infiltration of LNCaPs towards dorsal root ganglia (DRG). This effect could be blocked using an YAP1 inhibitor. In vivo, overexpression of YAP1 could increase PNI in a mouse model of sciatic nerve tumor invasion. Mechanistically, TEAD1 binds to the NGF promotor and YAP1/TEAD1 activates its transcription and consequently increases NGF secretion. In turn, PCa cells treated with CM from CAFs or stable YAP1 overexpression can stimulate DRG to secrete CCL2. The epithelial-to-mesenchymal transition (EMT) of PCa cells is thus activated via CCL2/CCR2. Overall, our data demonstrate that CAFs can activate YAP1/TEAD1 signaling and increase the secretion of NGF, therefore promoting PCa PNI. In addition, EMT induced by PNI suggests a feedback loop is present between neurons and PCa cells.
Topics: Animals; Cancer-Associated Fibroblasts; Cell Line, Tumor; DNA-Binding Proteins; Epithelial-Mesenchymal Transition; Humans; Male; Mice; Nerve Growth Factor; Nuclear Proteins; Prostatic Neoplasms; TEA Domain Transcription Factors; Tumor Microenvironment; YAP-Signaling Proteins
PubMed: 36100154
DOI: 10.1016/j.bbadis.2022.166540 -
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 -
Nutrients Apr 2022Since Otto Warburg's first report on the increased uptake of glucose and lactate release by cancer cells, dysregulated metabolism has been acknowledged as a hallmark of... (Review)
Review
Since Otto Warburg's first report on the increased uptake of glucose and lactate release by cancer cells, dysregulated metabolism has been acknowledged as a hallmark of cancer that promotes proliferation and metastasis. Over the last century, studies have shown that cancer metabolism is complex, and by-products of glucose and glutamine catabolism induce a cascade of both pro- and antitumorigenic processes. Some vitamins, which have traditionally been praised for preventing and inhibiting the proliferation of cancer cells, have also been proven to cause cancer progression in a dose-dependent manner. Importantly, recent findings have shown that the nervous system is a key player in tumor growth and metastasis via perineural invasion and tumor innervation. However, the link between cancer-nerve crosstalk and tumor metabolism remains unclear. Here, we discuss the roles of relatively underappreciated metabolites in cancer-nerve crosstalk, including lactate, vitamins, and amino acids, and propose the investigation of nutrients in cancer-nerve crosstalk based on their tumorigenicity and neuroregulatory capabilities. Continued research into the metabolic regulation of cancer-nerve crosstalk will provide a more comprehensive understanding of tumor mechanisms and may lead to the identification of potential targets for future cancer therapies.
Topics: Cell Proliferation; Glucose; Humans; Lactates; Neoplasms; Vitamins
PubMed: 35565690
DOI: 10.3390/nu14091722 -
The British Journal of Radiology Dec 2021Perineural spread (PNS) is an important potential complication of head and neck malignancy, as it is associated with decreased survival and a higher risk of local... (Review)
Review
Perineural spread (PNS) is an important potential complication of head and neck malignancy, as it is associated with decreased survival and a higher risk of local recurrence and metastasis. There are many review articles focused on the imaging findings of PNS. However, a false-positive diagnosis of PNS can be just as harmful to the patient as an overlooked case. In this manuscript, we delineate and classify various imaging mimics of PNS. Mimics can be divided into the following categories: normal variants (including vascular structures and failed fat suppression), infections, inflammatory disease (including granulomatous disease and demyelination), neoplasms, and post-traumatic/surgical changes. Knowledge of potential mimics of PNS will prevent false-positive imaging interpretation, and enable appropriate oncologic management.
Topics: Diagnosis, Differential; Head and Neck Neoplasms; Humans; Magnetic Resonance Imaging; Neoplasm Invasiveness; Peripheral Nerves; Peripheral Nervous System Diseases; Tomography, X-Ray Computed
PubMed: 34491810
DOI: 10.1259/bjr.20210099 -
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 -
Aesthetic Surgery Journal. Open Forum 2023Treating facial aging with CO lasering or microneedling are cornerstones of facial rejuvenation. Skin rejuvenation utilizing thermal and mechanical treatments have...
BACKGROUND
Treating facial aging with CO lasering or microneedling are cornerstones of facial rejuvenation. Skin rejuvenation utilizing thermal and mechanical treatments have historically been considered too injurious to be combined at a single setting. Autologous nanofat has been shown to deliver wound healing properties. We investigated the safety and efficacy of co-terminus CO lasering and microneedling to resolve fine lines and rhytids in facial skin with addition of autologous nanofat to aid in recovery.
OBJECTIVES
Combination treatments may result in better results with faster recovery. We investigated the safety and efficacy of co-terminus CO lasering and microneedling to resolve fine lines and rhytids in facial skin with addition of autologous nanofat to aid in recovery.
METHODS
Twenty-three patients underwent facial treatment with CO lasering followed by microneedling and application of autologous nanofat (LaMiNa). One volunteer patient had tissue biopsies of treatment areas to demonstrate histologic tissue level changes.
RESULTS
All patients verbally reported no pain (Numerical Rating System 0-10) following procedure and had rapid recovery within an average of 5 days. Pathology results demonstrated that CO and microneedling had persistent epidermal disruption and perineural inflammation at 4 days, while the introduction of autologous nanofat at the time of CO and microneedling resulted in full recovery of epidermis and resolution of perineural inflammation.
CONCLUSIONS
Triple therapy (LaMiNa) with thermal CO remodeling and mechanical microneedling penetration have accelerated and pain-free recovery with the addition of autologous nanofat. Histologic analysis reveals that epidermal recovery is accelerated and perineural inflammation is reduced with the addition of autologous nanofat following skin remodeling from combined CO and microneedling.
PubMed: 37089168
DOI: 10.1093/asjof/ojad028 -
Surgical Neurology International 2020Perineural invasion (PNI) and spread are one of the grimmest prognostic factors associated with primary skin and head-and-neck cancers, yet remain an often confused, and... (Review)
Review
BACKGROUND
Perineural invasion (PNI) and spread are one of the grimmest prognostic factors associated with primary skin and head-and-neck cancers, yet remain an often confused, and underreported, phenomenon. Adding complexity to reaching a diagnosis and treating perineural spread (PNS) is the finding that patients may have no known primary tumor, history of skin cancer, and/or incidental PNI in the primary tumor. These delays in diagnosis and treatment are further compounded by an already slow disease process and often require multidisciplinary care with combinations of stereotactic radiosurgery, surgical resection, and novel treatments such as checkpoint inhibitors.
METHODS
Six patients with metastatic cancer to the cranial nerves who underwent Gamma Knife radiosurgery (GKRS) treatment were chosen for retrospective analysis. This information included age, gender, any past surgeries (both stereotactic and regular surgery), dose of radiation and volume of the tumor treated in the GKRS, date of PNS, comorbidities, the patient follow-up, and pre- and post-GKRS imaging. The goal of the follow-up with radiographing imaging was to assess the efficacy of GKSS.
RESULTS
The clinical course of six patients with PNS is presented. Patients followed variable courses with mixed outcomes: two patients remain living, one was lost to follow-up, and three expired with a median survival of 12 months from date of diagnosis. Patients at our institution are ideally followed for life.
CONCLUSION
Given the morbidity and mortality of PNS of cancer, time is limited, and further understanding is required to improve outcomes. Here, we provide a case series of patients with PNS treated with stereotactic radiosurgery, discuss their clinical courses, and review the known literature.
PubMed: 32874709
DOI: 10.25259/SNI_146_2020 -
Cancer Jul 2021Orbital exenteration (OE) is an ablative procedure used in the management of malignancies of the orbit of either primary or secondary origin. Publications evaluating...
BACKGROUND
Orbital exenteration (OE) is an ablative procedure used in the management of malignancies of the orbit of either primary or secondary origin. Publications evaluating this procedure have suffered from small patient numbers, heterogeneity of pathologies, and poor patient follow-up. The purpose of this study was to assess patient outcomes in a large cohort of patients undergoing OE at a tertiary cancer center.
METHODS
A retrospective review was conducted of 180 consecutive patients who underwent OE at the authors' institution. Overall survival (OS) was the primary end point measured in the study. Time to locoregional recurrence (progression-free survival [PFS]) and disease-free survival were secondary end points.
RESULTS
Between the years 1993 and 2011, 180 consecutive patients received OE for craniofacial malignancy at the authors' institution. The median follow-up for the cohort was 9.7 years (116 months). The median OS was 73 months, and the median PFS was 96 months. The presence of perineural invasion was associated with shorter OS (P = .01) and PFS (P < .01). Magnetic resonance imaging was predictive of perineural invasion (P < .01). Positive margins were associated with shorter PFS than negative margins (P < .01) but with no change in OS (P = .15). The overall complication rate was 15%. The major complication rate (Clavien-Dindo 3b or greater) was 2.8% (n = 5), and there was 1 death observed (0.6%).
CONCLUSIONS
Used judiciously in the setting of a multidisciplinary management plan, OE for tumor control is a safe therapy.
LAY SUMMARY
Between the years 1993 and 2011, 180 consecutive patients received orbital exenteration for craniofacial malignancy at the MD Anderson Cancer Center. The median follow-up for the cohort was 9.7 years. The presence of perineural invasion was associated with shorter overall survival (P = .01) and progression-free survival (P < .01). Magnetic resonance imaging was predictive of perineural invasion (P < .01). Positive margins were associated with shorter progression-free survival than negative margins (P < .01). The overall complication rate was 15%. The major complication rate (Clavien-Dindo 3b or greater) was 2.8% (n = 5).
Topics: Cohort Studies; Disease-Free Survival; Humans; Orbit Evisceration; Progression-Free Survival; Retrospective Studies
PubMed: 33799313
DOI: 10.1002/cncr.33526 -
American Journal of Stem Cells 2021Most epithelium tissues continuously undergo self-renewal through proliferation and differentiation of epithelial stem cells (known as homeostasis), within a specialized... (Review)
Review
Most epithelium tissues continuously undergo self-renewal through proliferation and differentiation of epithelial stem cells (known as homeostasis), within a specialized stem cell niche. In highly innervated epithelium, peripheral nerves compose perineural niche and support stem cell homeostasis by releasing a variety of neurotransmitters, hormones, and growth factors and supplying trophic factors to the stem cells. Emerging evidence has shown that both sensory and motor nerves can regulate the fate of epithelial stem cells, thus influencing epithelium homeostasis. Understanding the mechanism of crosstalk between epithelial stem cells and neurons will reveal the important role of the perineural niche in physiological and pathological conditions. Herein, we review recent discoveries of the perineural niche in epithelium mainly in tissue homeostasis, with a limited touch in wound repair and pathogenesis.
PubMed: 34849302
DOI: No ID Found