Search Results (13)

Opioids are a challenging class of drugs due to their dual role. They alleviate pain, but also pose a risk of dependency, or trigger constipation, particularly in cancer patients, who require the more potent painkillers in more advanced stages of the disease, closely linked to pain resulting from general inflammation, bone metastases, and primary or secondary tumour outgrowth-related nerve damage. Clinicians’ vigilance considering treatment with opioids is necessary, bearing in mind extensive data accumulated over decades that have reported the contribution of opioids to immunosuppression, tumour progression, or impaired tissue regeneration, either following opioid use during surgical tumour resection and post-surgical pain treatment, or as a result of other diseases like diabetes, where chronic wounds healing constitutes a challenge. During last few years, an increasing trend for seeking relationships between opioids and epithelial–mesenchymal transition (EMT) in cancer research can be observed. Transiently lasting EMT is desirable during wound healing, but in cancer, or vital organ fibrogenesis, EMT appears to be an obstacle to overcome, forcing to adjust treatment strategies that would reduce the risk for worsening of the disease outcome and patient prognosis. The same opioid may demonstrate promoting or inhibitory effect on EMT, dependently on various conditions in particular clinical cases. We have summarized current findings on this issue to uncover some rules that govern opioid-mediated EMT induction or repression; however, many aspects still remain to be elucidated. Full article

Medication-related osteonecrosis of the jaw (MRONJ) is a drug complication that can occur in patients taking antiresorptive or antiangiogenic drugs. Although it is a well-documented disease, there is no widely accepted treatment. However, several therapeutic approaches have been proposed. The surgical approach in many advanced cases appears inevitable; however, the results are not yet defined and predictable. This study aimed to propose a combined surgical approach with a piezoelectric device and laser (Er:YAG for bone ablation and Nd:YAG laser for photobiomodulation) in a young patient with breast cancer and bone metastasis under denosumab treatment, affected by spontaneous stage 3 MRONJ with maxillary sinus involvement. The patient under study reported no post-operative discomfort, with painkiller intake limited to the day after surgery. Total mucosal healing was observed without recurrences for more than 4 years after surgery. According to the results of our preliminary study, a combined surgical approach using a piezoelectric device and laser therapy is effective in managing patients affected by MRONJ, leveraging the clinical and biological advantages of these different techniques. Full article

(1) Background: The goal of this study is to evaluate psychological tolerance and health-related quality of life (QOL) in head and neck (HN) cancer patients treated with definitive accelerated radiotherapy (DART). (2) Methods: 76 recurrence-free patients eligible for the study, who were treated with DART in the CAIR-2 phase III clinical study (median of follow-up = 47 months), completed EORTC QLQ-C30 with the H&N35 module, Hospital Anxiety and Depression Scale (HADS) and Visual–Analog Scales (VAS) of pain in HN and the neck/arm areas. (3) Results: The most dominant symptoms measured with QLQ-C30 were as follows: fatigue (44/100), sleeplessness (39/100), financial problems (38/100) and pain (32/100). Within the H&N35, the highest scores were reported on the subscales of sticky saliva (60/100), mouth dryness (65/100) and increased intake of painkillers (50/100). Pain (VAS) was reported by 87% (HN area) and 78% (shoulder area) of the patients, with a mean score of 3/10. One-third of the patients reported depressive moods (HADS ≥ 15 points) with an average score of 12.5/42 p. The depressed group, who smoked more as compared to the non-depressed group before DART (96% vs. 78%) and required steroids treatment (85% vs. 58%) during DART, also scored significantly worse on 23 of the 35 subscales of QLQ-C30 and H&N35 and experienced more intense pain (VAS). Women and less-advanced patients scored better in several aspects of quality of life. (4) Conclusions: Patients treated with DART struggle with low quality of life and persistent treatment-related symptoms including constant pain. HNC survivors, especially those who are depressed, may require additional psychosocial, rehabilitation and medical intervention programmes. Full article

Background: Pharmacogenetics (PGx) aims to determine genetic signatures that can be used in clinical settings to individualize treatment for each patient, including anti-cancer drugs, anti-psychotics, and painkillers. Taken together, a better understanding of the impacts of genetic variants on the corresponding protein function or expression permits the prediction of the pharmacological response: responders, non-responders, and those with adverse drug reactions (ADRs). Objective: This work provides a comparison between innovative long-read sequencing (LRS) and short-read sequencing (SRS) techniques. Methods and Materials: The gene panel captured using PacBio HiFi^® sequencing was tested on thirteen clinical samples on GENTYANE’s platform. SRS, using a comprehensive pharmacogenetics panel, was performed in routine settings at the Civil Hospitals of Lyon. We focused on complex regions analysis, including copy number variations (CNVs), structural variants, repeated regions, and phasing-haplotyping for three key pharmacogenes: CYP2D6, UGT1A1, and NAT2. Results: Variants and the corresponding expected star (*) alleles were reported. Although only 38.4% concordance was found for haplotype determination and 61.5% for diplotype, this did not affect the metabolism scoring. A better accuracy of LRS was obtained for the detection of the CYP2D6*5 haplotype in the presence of the duplicated wild-type CYP2D6*2 form. A total concordance was performed for UGT1A1 TA repeat detection. Direct phasing using the LRS approach allowed us to correct certain NAT2 profiles. Conclusions: Combining an optimized variant-calling pipeline and with direct phasing analysis, LRS is a robust technique for PGx analysis that can minimize the risk of mis-haplotyping. Full article

Therapeutic endoscopy permits many and various treatments for cancer palliation in patients with bilio-pancreatic cancers, enabling different options, supporting patients during their route to oncologic treatments, and trying to improve their quality of life. Therefore, both endoscopic and endoscopic ultrasound (EUS)-guided techniques are performed in this scenario. We performed a literature review focusing on the role of endoscopy in the palliation of those advanced pancreatic and biliary cancers developing malignant biliary obstruction (MBO), gastric outlet obstruction (GOO), and pain unresponsive to medical therapies. Therefore, we explored and focused on the clinical outcomes of endoscopic procedures in this scenario. In fact, the endoscopic treatment is based on achieving biliary drainage in the case of MBO through endoscopic retrograde cholangiopancreatography (ERCP) or EUS-guided biliary drainage (EUS-BD), while GOO is endoscopically treated through the deployment of an enteral stent or the creation of EUS-guided gastro-entero-anastomosis (EUS-GEA). Furthermore, untreatable chronic abdominal pain is a major issue in patients unresponsive to high doses of painkillers, so EUS-guided celiac plexus neurolysis (CPN) or celiac ganglia neurolysis (CGN) helps to reduce dosage and have better pain control. Therefore, therapeutic endoscopy in the palliative setting is an effective and safe approach for managing most of the clinical manifestations of advanced biliopancreatic tumors. Full article

Chronic pain is now included in the designation of chronic diseases, such as cancer, diabetes, and cardiovascular disease, which can impair quality of life and are major causes of death and disability worldwide. Pain can be treated using cannabinoids such as ${\Delta }^9$-tetrahydrocannabinol (${\Delta }^9$-THC) and cannabidiol (CBD) due to their wide range of therapeutic benefits, particularly as sedatives, analgesics, neuroprotective agents, or anti-cancer medicines. While little is known about the pharmacokinetics of these compounds, there is increasing interest in the scientific understanding of the benefits and clinical applications of cannabinoids. In this review, we study the use of nanomaterial-based electrochemical sensing for detecting ${\Delta }^9$-THC and CBD. We investigate how nanomaterials can be functionalized to obtain highly sensitive and selective electrochemical sensors for detecting ${\Delta }^9$-THC and CBD. Additionally, we discuss the impacts of sensor pretreatment at fixed potentials and physiochemical parameters of the sensing medium, such as pH, on the electrochemical performance of ${\Delta }^9$-THC and CBD sensors. We believe this review will serve as a guideline for developing ${\Delta }^9$-THC and CBD electrochemical sensors for point-of-care applications. Full article

Opioids are widely used in cancer and non-cancer pain management. However, many transporters at the blood–brain barrier (BBB), such as P-glycoprotein (P-gp, ABCB1/MDR1), may impair their delivery to the brain, thus leading to opioid tolerance. Nonetheless, opioids may regulate P-gp expression, thus altering the transport of other compounds, namely chemotherapeutic agents, resulting in pharmacoresistance. Other kinds of painkillers (e.g., acetaminophen, dexamethasone) and adjuvant drugs used for neuropathic pain may act as P-gp substrates and modulate its expression, thus making pain management challenging. Inflammatory conditions are also believed to upregulate P-gp. The role of P-gp in drug–drug interactions is currently under investigation, since many P-gp substrates may also act as substrates for the cytochrome P450 enzymes, which metabolize a wide range of xenobiotics and endobiotics. Genetic variability of the ABCB1/MDR1 gene may be accountable for inter-individual variation in opioid-induced analgesia. P-gp also plays a role in the management of opioid-induced adverse effects, such as constipation. Peripherally acting mu-opioid receptors antagonists (PAMORAs), such as naloxegol and naldemedine, are substrates of P-gp, which prevent their penetration in the central nervous system. In our review, we explore the interactions between P-gp and opioidergic drugs, with their implications in clinical practice. Full article

Opioids are widely used as therapeutic agents against moderate to severe acute and chronic pain. Still, these classes of analgesic drugs have many potential limitations as they induce analgesic tolerance, addiction and numerous behavioural adverse effects that often result in patient non-compliance. As opium and opioids have been traditionally used as painkillers, the exact mechanisms of their adverse reactions over repeated use are multifactorial and not fully understood. Older adults suffer from cancer and non-cancer chronic pain more than younger adults, due to the physiological changes related to ageing and their reduced metabolic capabilities and thus show an increased number of adverse reactions to opioid drugs. All clinically used opioids are μ-opioid receptor agonists, and the major adverse effects are directly or potentially connected to this receptor. Multifunctional opioid ligands or peripherally restricted opioids may elicit fewer adverse effects, as shown in preclinical studies, but these results need reproducibility from further extensive clinical trials. The current review aims to overview various mechanisms involved in the adverse effects induced by opioids, to provide a better understanding of the underlying pathophysiology and, ultimately, to help develop an effective therapeutic strategy to better manage pain. Full article

Endometriosis is defined as endometrial-like tissue outside the uterine cavity. It is a chronic inflammatory estrogen-dependent disease causing pain and infertility in about 10% of women of reproductive age. Treatment nowadays consists of medical and surgical therapies. Medical treatments are based on painkillers and hormonal treatments. To date, none of the medical treatments have been able to cure the disease and symptoms recur as soon as the medication is stopped. The development of new biomedical targets, aiming at the cellular and molecular mechanisms responsible for endometriosis, is needed. This article summarizes the most recent medications under investigation in endometriosis treatment with an emphasis on non-coding RNAs that are emerging as key players in several human diseases, including cancer and endometriosis. Full article

Background: Primary or recurrent head and neck cancer of skin or mucosa represents a challenge for clinicians and could be debilitating for the patient. Electrochemotherapy (ECT) emerged as a local ablative procedure for cutaneous and mucosal head and neck tumors. The aim of this observational study was the evaluation of quality of life (QoL) after ECT in patients without other surgical or radiation options as curative treatment. Materials and methods: The procedure was performed according the ESOPE (European Standard Operating procedure of Electrochemotherapy) protocol. Twenty-seven patients were evaluated before ECT (T0) and 1 (T1), 3 (T2), and 6 (T3) months after the procedure. QoL was assessed by means of the EORTC QLQ-C30 and EORTC QLQ-H&N35 questionnaires. Results: The objective tumor response rate was 48% (11% CR, 37% PR). Bleeding control was achieved in 7/7 patients who experienced bleeding prior to ECT. QoL improvement was observed after the procedure. In particular, global health status and social functioning were higher after ECT (p 0.026 and 0.043), while pain, pain-killers use and appetite loss decreased (p 0.045, 0.025 and 0.002). Conclusion: ECT represents a safe and effective treatment for skin and mucosal head and neck tumors without other curative options. It ensures a good pain and bleeding control without worsening of QoL. Full article

Several studies have compared laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) in patients with periampullary carcinoma; however, only a few studies have made such a comparison on patients with ampulla of Vater cancer (AVC). We compared the perioperative and oncologic outcomes between LPD and OPD in patients with AVC using propensity-score-matched analysis. A total of 359 patients underwent PD due to AVC during the study period (76 LPD, 283 OPD). After propensity score matching, the LPD group showed significantly longer operation time than did the OPD group (400.2 vs. 344.6 min, p < 0.001). Nevertheless, the LPD group had fewer painkiller administrations (8.3 vs. 11.1, p < 0.049), fewer Grade II or more severe postoperative complications (15.9% vs. 34.8%, p = 0.012), and shorter postoperative hospital stays (13.7 vs. 17.3 days, p = 0.048), compared with the OPD group. There was no significant difference in recurrence-free outcomes and overall survival between the two groups (p = 0.754 and 0.768, respectively). Compared with OPD, LPD for AVC had comparative oncologic outcomes with less pain, less postoperative morbidity, and shorter hospital stays. LPD may serve as a promising alternative to OPD in patients with AVC. Full article

Natural products, especially secondary metabolites produced by plants under stressed conditions, are shown to have different pharmacological impacts from one to another. Aeluropus lagopoides is one of the common halophyte plants that survive under stressed conditions, and has been used for healing wounds and as a painkiller. The bioactivity and the chemical composition of this plant have been poorly investigated. Consequently, the chemical components of A. lagopoides leaves were extracted using hexane (nonpolar), ethyl acetate (semi-polar), and n-butanol (polar) to extract the most extensive variety of metabolites. The cytotoxicity and anticancer impact of extracted secondary metabolites were evaluated against breast (MCF-7), colon (HCT-116), and liver (HepG2) cancer cell lines using a SulphoRhodamine-B (SRB) test. Their mechanisms of action were verified by observing the appearance of apoptotic bodies using the fluorescent microscope, while their antiproliferative impacts were evaluated using a flow cytometer. Results revealed that secondary metabolites extracted using hexane and ethyl acetate had the highest cytotoxicity and thus the greatest anticancer activity effect on HepG2 with IC₅₀ (24.29 ± 0.85 and 11.22 ± 0.679 µg/mL, respectively). On the other hand, flow cytometer results showed that secondary metabolites could inhibit the cell cycle in the G0/G1 phase. To ascertain the chemical composition–function relationship, the extracts were analyzed using LC-MS/MS. Accordingly, A. lagopoides hexane and ethyl acetate extracts may contain agents with anticancer potential. Full article

Pain is inadequately relieved by escalating doses of a strong opioid analgesic such as morphine in up to 25% of patients with cancer-related severe pain complicated by a neuropathic (nerve damage) component. Hence, there is an unmet medical need for research on novel painkiller strategies. In the present work, we used supercritical fluid polymer encapsulation to develop sustained-release poly(lactic-co-glycolic acid) (PLGA) biodegradable microparticles containing the analgesic adjuvant drug ketamine, for injection by the intrathecal route. Using this approach with a range of PLGA co-polymers, drug loading was in the range 10–60%, with encapsulation efficiency (EE) of 60–100%. Particles were mainly in the size range 20–45 µm and were produced in the absence of organic solvents and surfactants/emulsifiers. Investigation of the ketamine release profiles from these PLGA-based microparticles in vitro showed that release took place over varying periods in the range 0.5–4.0 weeks. Of the polymers assessed, the ester end-capped PLGA5050DLG-1.5E gave the best-controlled release profile with drug loading at 10%. Full article