-
Endokrynologia Polska 2023Radioactive iodine therapy (RIT) is an effective, safe, and cheap method in benign and malignant thyroid diseases. There is still an unresolved question of whether RIT...
Radioactive iodine therapy (RIT) is an effective, safe, and cheap method in benign and malignant thyroid diseases. There is still an unresolved question of whether RIT treatment also plays a role in the treatment of, for example, breast cancer, lung cancer, or glioblastoma multiforme (GBM). These studies are currently being carried out in rats in combination with genes, but it may be an interesting challenge to assess "pure" RIT alone, thanks to the expression of sodium iodide symporter (NIS), is effective in other organ nodules, both benign and malignant. Cloning of the NIS in 1996 provided an opportunity to use NIS as a powerful theranostic transgene. In addition, NIS is a sensitive reporter gene that can be monitored by high-resolution PET imaging using the radiolabels [¹²⁴I]sodium iodide ([¹²⁴I]NaI) or [18F] tetrafluoroborate ([¹⁸F]TFB). Based on published positron emission tomography (PET) results, [¹²⁴I]sodium iodide and internally synthesized [18F]TFB were compared in an orthotopic animal model of NIS-expressing glioblastoma. The results showed improved image quality using [¹⁸F]TFB. Based on these results, we will be able to extend the NIS gene therapy approach using non-viral gene delivery vehicles to target orthotopic tumour models with low-volume disease such as GBM. Is it possible to treat RIT alone without using the NIS gene in GBM? After all, the NIS symporter was detected not only in the thyroid gland, but also in different tumours. The administration of RIT is completely harmless; the only complication is hypothyroidism. Indeed, recently it has been shown that, for example, in the case of thyroid cancer, the maximum RIT is 37000 MBq (1000 mCi). When beneficial effects of therapy in GBM are not possible (e.g. neurosurgery, modulated electro-hyperthermia, chemotherapy, immunotherapy, cancer vaccines, or oncolytic viruses), could RIT provide a "revolution" using NIS?
Topics: Rats; Animals; Thyroid Neoplasms; Iodine Radioisotopes; Glioblastoma; Sodium Iodide; Lung Neoplasms; Antiviral Agents
PubMed: 38159203
DOI: 10.5603/ep.95505 -
Materials Today. Bio Dec 2023Aggressive benign, malignant and metastatic bone tumors can greatly decrease the quality of patients' lives and even lead to substantial mortality. Several clinical... (Review)
Review
Aggressive benign, malignant and metastatic bone tumors can greatly decrease the quality of patients' lives and even lead to substantial mortality. Several clinical therapeutic strategies have been developed to treat bone tumors, including preoperative chemotherapy, surgical resection of the tumor tissue, and subsequent systemic chemo- or radiotherapy. However, those strategies are associated with inevitable drawbacks, such as severe side effects, substantial local tumor recurrence, and difficult-to-treat bone defects after tumor resection. To overcome these shortcomings and achieve satisfactory clinical outcomes, advanced bifunctional biomaterials which simultaneously promote bone regeneration and combat bone tumor growth are increasingly advocated. These bifunctional bone substitute materials fill bone defects following bone tumor resection and subsequently exert local anticancer effects. Here we describe various types of the most prevalent bone tumors and provide an overview of common treatment options. Subsequently, we review current progress regarding the development of bifunctional bone substitute materials combining osteogenic and anticancer efficacy. To this end, we categorize these biomaterials based on their anticancer mechanism deriving from i) intrinsic biomaterial properties, ii) local drug release of anticancer agents, and iii) oxidative stress-inducing and iv) hyperthermia-inducing biomaterials. Consequently, this review offers researchers, surgeons and oncologists an up-to-date overview of our current knowledge on bone tumors, their treatment options, and design of advanced bifunctional biomaterials with strong potential for clinical application in oncological orthopedics.
PubMed: 38149015
DOI: 10.1016/j.mtbio.2023.100889 -
Urology Case Reports Jan 2024Upper tract urothelial carcinoma (UTUC) is a relatively rare malignant neoplasm of the urinary system. Due to its highly aggressiveness, the tumor has already undergone...
Upper tract urothelial carcinoma (UTUC) is a relatively rare malignant neoplasm of the urinary system. Due to its highly aggressiveness, the tumor has already undergone invasive growth when most UTUC patients are diagnosed. In addition, the most common cause of fever in cancer patients is infection, and cancer patients with neoplastic fever are relatively rare. We reported a 58-year-old man with invasive high-grade UTUC accompanied by hyperthermia.
PubMed: 38148853
DOI: 10.1016/j.eucr.2023.102634 -
Biomolecules Nov 2023Calsequestrin (CASQ) is a key intra-sarcoplasmic reticulum Ca-handling protein that plays a pivotal role in the contraction of cardiac and skeletal muscles. Its... (Review)
Review
Calsequestrin (CASQ) is a key intra-sarcoplasmic reticulum Ca-handling protein that plays a pivotal role in the contraction of cardiac and skeletal muscles. Its Ca-dependent polymerization dynamics shape the translation of electric excitation signals to the Ca-induced contraction of the actin-myosin architecture. Mutations in CASQ are linked to life-threatening pathological conditions, including tubular aggregate myopathy, malignant hyperthermia, and Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). The variability in the penetrance of these phenotypes and the lack of a clear understanding of the disease mechanisms associated with CASQ mutations pose a major challenge to the development of effective therapeutic strategies. In vitro studies have mainly focused on the polymerization and Ca-buffering properties of CASQ but have provided little insight into the complex interplay of structural and functional changes that underlie disease. In this review, the biochemical and structural natures of CASQ are explored in-depth, while emphasizing their direct and indirect consequences for muscle Ca physiology. We propose a novel functional classification of CASQ pathological missense mutations based on the structural stability of the monomer, dimer, or linear polymer conformation. We also highlight emerging similarities between polymeric CASQ and polyelectrolyte systems, emphasizing the potential for the use of this paradigm to guide further research.
Topics: Humans; Calsequestrin; Heart; Tachycardia, Ventricular; Sarcoplasmic Reticulum; Mutation, Missense; Calcium
PubMed: 38136565
DOI: 10.3390/biom13121693 -
Children (Basel, Switzerland) Dec 2023Multiple endocrine neoplasia 2B (MEN2B) is a rare syndrome with prevalence estimated at approximately 0.2 per 100,000; it is caused by mutation of the RET...
Multiple endocrine neoplasia 2B (MEN2B) is a rare syndrome with prevalence estimated at approximately 0.2 per 100,000; it is caused by mutation of the RET proto-oncogene. MEN2B is characterized by early-onset medullary thyroid carcinoma (MTC), ganglioneuromatosis of the aerodigestive tract, marfanoid habitus, ophthalmologic abnormalities, and pheochromocytoma in adulthood. Mutations in the RyR1 gene manifest clinically in congenital myopathies and/or malignant hyperthermia susceptibility. We present a case of a 4-year-old boy with an accidentally detected RET and RyR1 mutations in the course of diagnostic approach of short stature and delayed motor development. Due to a poor and blurred clinical picture of MEN2B syndrome, accompanied by RyR1 mutation symptoms, the diagnostic path was extended. Our patient had no family history of MTC. In the imaging studies of the thyroid gland, no abnormalities were found, whereas the serum level of calcitonin was elevated to 34 pg/mL (N < 5.0). The patient qualified for total thyroidectomy, and the histopathological examination confirmed the diagnosis of MTC. The postoperative serum calcitonin level dropped to normal ranges. This case shows how new genetic diagnostic procedures could be crucial in accidentally diagnosing rare endocrine disease with atypical symptoms, giving an opportunity for relatively early intervention.
PubMed: 38136118
DOI: 10.3390/children10121916 -
Multiple Sclerosis (Houndmills,... Feb 2024Monoamine oxidase (MAO) inhibitors can interact with selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs). There is...
BACKGROUND
Monoamine oxidase (MAO) inhibitors can interact with selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs). There is clinical interest surrounding use of ozanimod with SSRIs/SNRIs because the major metabolites of ozanimod are weak inhibitors of MAO-B in vitro.
OBJECTIVE
To evaluate the incidence of treatment-emergent adverse events (TEAEs) potentially related to serotonin accumulation (SA) during concomitant ozanimod and SSRI/SNRI use by performing analyses of data from an open-label, oral ozanimod 0.92 mg trial (DAYBREAK; NCT02576717).
METHODS
SA narrow (serotonin syndrome, neuroleptic malignant syndrome, and hyperthermia malignant) and broad (terms potentially associated with SA) MedDRA v24.0 searches were performed using TEAE data from participants with relapsing multiple sclerosis who entered DAYBREAK from phase 3 studies (cutoff February 1, 2022). Incidences of TEAEs matching terms from each search were stratified by SSRI/SNRI use.
RESULTS
Of 2257 DAYBREAK participants, 274 (12.1%) used an SSRI/SNRI. No participants had TEAEs matching the SA narrow search terms. There was no significant difference in the percentage of participants with ⩾1 TEAE matching the SA broad search for those on versus off SSRIs/SNRIs (on: 12.4%, = 34/274; off: 15.6%, = 310/1982, nominal = 0.1630).
CONCLUSION
MedDRA searches showed no increase in TEAEs potentially associated with SA with concomitant SSRI/SNRI and ozanimod use.
Topics: Humans; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Serotonin; Multiple Sclerosis; Antidepressive Agents; Indans; Oxadiazoles
PubMed: 38130041
DOI: 10.1177/13524585231216854 -
The American Journal of Case Reports Dec 2023BACKGROUND The anesthetic management of patients with Charcot-Marie-Tooth disease (CMT) requires special deliberation. Previous literature has suggested that patients...
BACKGROUND The anesthetic management of patients with Charcot-Marie-Tooth disease (CMT) requires special deliberation. Previous literature has suggested that patients with CMT may have increased sensitivity to non-depolarizing neuromuscular blocking agents, and hyperkalemia associated with the administration of succinylcholine has been reported. The potential risk of malignant hyperthermia and underlying cardiopulmonary abnormalities, such as pre-existing arrhythmias, cardiomyopathy, or respiratory muscle weakness, must also be considered in patients with CMT. CASE REPORT We describe a case of a patient with a history of CMT and multivessel coronary artery disease who underwent coronary artery bypass grafting (CABG). Careful consideration was given to the anesthetic plan, which consisted of thorough pre- and perioperative evaluation of cardiac function, total intravenous anesthesia with propofol and remifentanil infusions, the use of a non-depolarizing neuromuscular blocking agent, and utilization of a malignant hyperthermia protocol with avoidance of volatile anesthetics to decrease the possible risk of malignant hyperthermia. Following a 3-vessel CABG, no anesthetic or surgical complications were noted and the patient was discharged on postoperative day 6 after an uneventful hospital course. CONCLUSIONS Exacerbation of underlying cardiac and pulmonary abnormalities associated with the pathophysiology of CMT, as well as patient response to neuromuscular blocking and volatile agents, should be of concern for the anesthesiologist when anesthetizing a patient with CMT. Therefore, CMT patients undergoing surgery require special consideration of their anesthetic management plan in order to ensure patient safety and optimize perioperative outcomes.
Topics: Humans; Coronary Artery Disease; Charcot-Marie-Tooth Disease; Malignant Hyperthermia; Anesthetics; Coronary Artery Bypass
PubMed: 38117749
DOI: 10.12659/AJCR.940284 -
Scientific Reports Dec 2023Malignant neoplasms are one of the main causes of death, especially in children, on a global scale, despite strenuous efforts made at advancing both diagnostic and...
Malignant neoplasms are one of the main causes of death, especially in children, on a global scale, despite strenuous efforts made at advancing both diagnostic and therapeutic modalities. In this regard, a new nanocarrier Vincristine (VCR)-loaded Pluronic f127 polymer-coated magnetic nanoparticles conjugated with folic acid and transferrin (PMNP-VCR-FA-TF) were synthesized and characterized by various methods. The cytotoxicity of these nanoparticles was evaluated in vitro and ex vivo conditions. The in vitro anti-tumor effect of the nanoparticles was evaluated by colony formation assay (CFA) and reactive oxygen species (ROS) in Y79 cell line. The results showed that nanoparticles with two ligands conferred greater toxicity toward Y79 cancer cells than ARPE19 normal cells. Under an alternating magnetic field (AMF), these nanoparticles demonstrated a high specific absorption rate. The CFA and ROS results indicated that the AMF in combination with PMNP-VCR-FA-TF conferred the highest cytotoxicity toward Y79 cells compared with other groups (P < 0.05). PMNP-VCR-FA-TF could play an important role in converting externally applied radiofrequency energy into heat in cancer cells. The present study confirmed that dual targeting chemo-hyperthermia using PMNP-VCR-FA-TF was significantly more effective than hyperthermia or chemotherapy alone, providing a promising platform for precision drug delivery as an essential component in the chemotherapy of retinoblastoma.
Topics: Child; Humans; Retinoblastoma; Reactive Oxygen Species; Folic Acid; Transferrin; Magnetite Nanoparticles; Hyperthermia, Induced; Vincristine; Retinal Neoplasms; Nanoparticles; Cell Line, Tumor
PubMed: 38102193
DOI: 10.1038/s41598-023-49171-5 -
The American Journal of Case Reports Dec 2023BACKGROUND Malignant mesotheliomas are rare, yet highly malignant tumors. Mesotheliomas are tumors that develop from mesothelial surfaces, with the pleura being the most...
A 51-Year-Old Woman with Advanced Peritoneal Mesothelioma and Stage 3b Chronic Kidney Disease Treated with Cytoreductive Surgery and Bidirectional Intraperitoneal Cisplatin and Ifosfamide Chemotherapy: A Case Report.
BACKGROUND Malignant mesotheliomas are rare, yet highly malignant tumors. Mesotheliomas are tumors that develop from mesothelial surfaces, with the pleura being the most common, followed by the peritoneum. The diagnosis of malignant peritoneal mesothelioma (MPM) is usually established when the disease is advanced, owing to the nonspecific clinical appearance and abdominal symptoms. Initially, MPM was treated with palliative systemic chemotherapy, with or without palliative surgery. However, cytoreductive surgery (CRS) combined with bidirectional intraoperative chemotherapy (BDIC) has recently emerged as a treatment option for MPM. BDIC creates a bidirectional chemotherapy gradient in the peritoneal tumor cells through the simultaneous use of intraperitoneal and intravenous chemotherapy. CRS, combined with BDIC (CRS-BDIC), allows the complete elimination of residual tiny tumor cells after complete removal of the visible tumor nodules. CASE REPORT Herein, we present a case of a 51-year-old woman with MPM and chronic kidney disease (CKD) stage 3b. Her treatment consisted of neoadjuvant chemotherapy and immunotherapy, followed by CRS-BDIC using intraperitoneal cisplatin and doxorubicin, and intravenous ifosfamide. The surgery was successful, with no immediate complications or decline in the patient's kidney function. On follow up 2 months later, the patient denies suffering any chemotherapy-related adverse effects, and her kidney profile remains stable. CONCLUSIONS In conclusion, nephrotoxicity, a known adverse effect of cisplatin and ifosfamide, might not be a contraindication for the use of these potentially nephrotoxic drugs in CRS-BDIC in patients with renal impairment.
Topics: Female; Humans; Middle Aged; Mesothelioma, Malignant; Cisplatin; Peritoneal Neoplasms; Ifosfamide; Cytoreduction Surgical Procedures; Combined Modality Therapy; Hyperthermia, Induced; Mesothelioma; Antineoplastic Combined Chemotherapy Protocols; Renal Insufficiency; Renal Insufficiency, Chronic
PubMed: 38093612
DOI: 10.12659/AJCR.941726 -
Anaesthesiology Intensive Therapy 2023
Topics: Humans; Droperidol; Metoclopramide; Neuroleptic Malignant Syndrome; Antiemetics; Postoperative Complications; Rhabdomyolysis; Double-Blind Method
PubMed: 38084576
DOI: 10.5114/ait.2023.132910