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Expert Review of Clinical Immunology Oct 2018Numerous studies have clearly demonstrated that there is an altered cancer risk profile in patients with systemic lupus erythematous (SLE) versus the general population.... (Review)
Review
INTRODUCTION
Numerous studies have clearly demonstrated that there is an altered cancer risk profile in patients with systemic lupus erythematous (SLE) versus the general population. This includes a higher risk of certain cancers (e.g. hematologic, lung) and a decreased risk of others (e.g. breast cancer). Several determinants could be behind this altered risk; these include immunosuppressant drugs, viral exposures, genetic factors, and other variables. Area covered: We review what is known regarding specific risk profiles and risk factors for some key cancers in SLE, including hematologic malignancies and lung cancers. In light of this, we examine current guidelines and practices regarding cancer screening, and propose ways that patients and physicians might help manage cancer risk in SLE. Expert commentary: Despite significant progress over the past decade, not many risk factors have been precisely identified. A better understanding of the elements that drive malignancy risk in systemic autoimmune rheumatic diseases may permit the further development of guidelines (regarding. cancer screening) for SLE patients.
ABBREVIATIONS
AbTG: Anti-thyroglobulin antibodies; AbTPO: Anti-peroxydase antibodies; AML: Acute myeloid leukemia; APRIL: A proliferating-inducing ligand; BAFF: B-cell activating factor; CAPA: Canadian Arthritis Patient Alliance; CI: Confidence interval; CIN: Cervical intraepithelial neoplasia; CT: Computed tomography; DLBCL: Diffuse large B cell lymphoma; dsDNA: Double-stranded DNA; EBV: Epstein-Barr virus; EULAR European League Against Rheumatism; IBD: Inflammatory bowel disease; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; HR: Hazard ratio; HSIL: High-grade cervical squamous intraepithelial lesions; HSV: Herpes simplex virus; HL: Hodgkin lymphoma; HPV: Human papillomavirus; MALT: Mucosa-associated lymphoid tissue; MDS: Myelodysplastic syndrome; MESNA: 2-mercaptoethane sodium sulfonate; NHL: Non-Hodgkin lymphoma; OR: Odds ratio; Pap: Papanicolaou; RA: Rheumatoid arthritis; SLE: Systemic Lupus erythematous; SLICC: Systemic International Collaborating Clinics; SNPs: Single-nucleotide polymorphisms; SOGC: Society of Obstetricians and Gynaecologists of Canada.
Topics: Humans; Lupus Erythematosus, Systemic; Neoplasms; Risk Factors
PubMed: 30183456
DOI: 10.1080/1744666X.2018.1519394 -
International Journal of Clinical... Oct 2023Cisplatin should be administered with diuretics and Magnesium supplementation under adequate hydration to avoid renal impairment. Patients should be evaluated for eGFR...
Chapter 3: Management of kidney injury caused by cancer drug therapy, from clinical practice guidelines for the management of kidney injury during anticancer drug therapy 2022.
Cisplatin should be administered with diuretics and Magnesium supplementation under adequate hydration to avoid renal impairment. Patients should be evaluated for eGFR (estimated glomerular filtration rate) during the treatment with pemetrexed, as kidney injury has been reported. Pemetrexed should be administered with caution in patients with a CCr (creatinine clearance) < 45 mL/min. Mesna is used to prevent hemorrhagic cystitis in patients receiving ifosfamide. Febuxostat is effective in avoiding hyperuricemia induced by TLS (tumor lysis syndrome). Preventative rasburicase is recommended in high-risk cases of TLS. Thrombotic microangiopathy could be triggered by anticancer drugs and there is no evidence of efficacy of plasma exchange therapy. When proteinuria occurs during treatment with anti-angiogenic agents or multi-kinase inhibitors, dose reductions or interruptions based on grading should be considered. Grade 3 proteinuria and renal dysfunction require urgent intervention, including drug interruption or withdrawal, and referral to a nephrologist should be considered. The first-line drugs used for blood pressure elevation due to anti-angiogenic agents are ACE (angiotensin-converting enzyme) inhibitors and ARBs (angiotensin receptor blockers). The protein binding of drugs and their pharmacokinetics are considerably altered in patients with hypoalbuminemia. The clearance of rituximab is increased in patients with proteinuria, and the correlation with urinary IgG suggests similar pharmacokinetic changes when using other antibody drugs. AIN (acute interstitial nephritis) is the most common cause of ICI (immune checkpoint inhibitor)-related kidney injury that is often treated with steroids. The need for renal biopsy in patients with kidney injury that occurs during treatment with ICI remains controversial.
PubMed: 37453935
DOI: 10.1007/s10147-023-02382-2 -
Analytical and Bioanalytical Chemistry Nov 2023In optical biosensing, analyte-independent factors such as autofluorescence interference and excitation source fluctuation decrease the sensitivity and accuracy. Herein,...
In optical biosensing, analyte-independent factors such as autofluorescence interference and excitation source fluctuation decrease the sensitivity and accuracy. Herein, we reported a bimodal persistent luminescence strategy to design dual-emissive persistent luminescence nanoparticles (PLNPs) with built-in self-calibration to preclude interference from analyte-independent factors in biosensing. As a proof of concept, ZnGaO:Cr PLNPs with emissions at both 490 nm and 695 nm were designed. The I/I ratio of ZnGaO:Cr was readily adjusted by simply changing the doping concentration of Cr. The ZnGaO:Cr PLNPs were employed for the ratiometric detection of urinary mesna. A good linear relationship between the I/I ratio of ZnGaO:Cr-based nanoprobe and the concentration of mesna was obtained in the range of 0-40 μM. The limit of detection was about 0.40 μM. Results showed that autofluorescence interference from urine was totally eliminated by collecting the persistent luminescence signal of ZnGaO:Cr after excitation ceased. Moreover, the built-in self-calibration feature of the ratiometric ZnGaO:Cr PLNPs efficiently suppressed the interference from fluctuations in instrumental parameters during urinary mesna detection. The recovery rates of mesna in the spiked urine samples are in the range of 99.1~109.0%, showing the reliability of the ratiometric ZnGaO:Cr PLNPs in urinary mesna detection. ZnGaO:Cr can further be expanded to the detection of other analytes in complex matrices. This study may open new opportunities for the design of dual-emissive PLNPs with tunable ratios of emission intensity, and it can further promote the applications of optical biosensing in disease diagnosis, food safety, and environmental monitoring.
PubMed: 37733257
DOI: 10.1007/s00216-023-04949-4 -
Viruses Aug 2022Flavivirus infections, such as those caused by dengue and West Nile viruses, emerge as new challenges for the global healthcare sector. It has been found that these two...
Flavivirus infections, such as those caused by dengue and West Nile viruses, emerge as new challenges for the global healthcare sector. It has been found that these two viruses encode ion channels collectively termed viroporins. Therefore, drug molecules that block such ion-channel activity can serve as potential antiviral agents and may play a primary role in therapeutic purposes. We screened 2839 FDA-approved drugs and compounds in advanced experimental phases using three bacteria-based channel assays to identify such ion channel blockers. We primarily followed a negative genetic screen in which the channel is harmful to the bacteria due to excessive membrane permeabilization that can be relieved by a blocker. Subsequently, we cross-checked the outcome with a positive genetic screen and a pH-dependent assay. The following drugs exhibited potential blocker activities: plerixafor, streptomycin, tranexamic acid, CI-1040, glecaprevir, kasugamycin, and mesna were effective against dengue virus DP1. In contrast, idasanutlin, benzbromarone, 5-azacytidine, and plerixafor were effective against West Nile Virus MgM. These drugs can serve as future antiviral therapeutic agents following subsequent in vitro and in vivo efficacy studies.
Topics: Antiviral Agents; Dengue; Hematopoietic Stem Cell Mobilization; Heterocyclic Compounds; Humans; Viroporin Proteins; West Nile Fever; West Nile virus
PubMed: 36016372
DOI: 10.3390/v14081750 -
Urology Feb 2017Cyclophosphamide and ifosfamide are widely used drugs for malignancies and rheumatologic conditions. One of the most significant adverse reactions to these drugs is... (Review)
Review
Cyclophosphamide and ifosfamide are widely used drugs for malignancies and rheumatologic conditions. One of the most significant adverse reactions to these drugs is hemorrhagic cystitis. Mesna is the most widely used uroprotective agent that acts to neutralize the caustic metabolite, acrolein, responsible for induction of hemorrhagic cystitis. However, mesna is not a perfect alternative, and studies since its discovery have investigated the use of alternative drugs and adjuncts to increase mesna's efficacy. This review details some of the recent work into novel uroprotective agents for drug-induced hemorrhagic cystitis.
Topics: Antineoplastic Agents, Alkylating; Cyclophosphamide; Cystitis; Hemorrhage; Humans; Ifosfamide; Mesna; Protective Agents
PubMed: 27566144
DOI: 10.1016/j.urology.2016.07.030 -
JAMA Ophthalmology Jul 2018Multi-institutional collaborative studies that include large patient populations for the management of retinoblastoma with histopathological risk factors could provide...
IMPORTANCE
Multi-institutional collaborative studies that include large patient populations for the management of retinoblastoma with histopathological risk factors could provide important information for patient management.
OBJECTIVE
To evaluate the implementation of a strategy for the management of nonmetastatic unilateral retinoblastoma in children based on standardized diagnostic and treatment criteria.
DESIGN, SETTING, AND PARTICIPANTS
This single-arm prospective study applied a strategy based on a single-center experience. The setting was a multicenter study in Latin America (Grupo de America Latina de Oncologia Pediatrica [GALOP]). Participants were children with nonmetastatic unilateral retinoblastoma (staged with the International Retinoblastoma Staging System). The study opened on July 1, 2008, and closed on December 31, 2014. Follow-up was updated until June 30, 2017.
INTERVENTIONS
Stage 0 patients (without enucleation) were given conservative therapy without a protocol. Stage I patients (with enucleation and no residual tumor) were divided into a high-risk group (retrolaminar invasion and/or scleral invasion) and a low-risk group (all remaining patients). High-risk children received adjuvant chemotherapy with 4 alternating cycles of regimen 1 (cyclophosphamide [65 mg/kg/d] [plus sodium-2-mercaptoethane sulfonate], idarubicin hydrochloride [10 mg/m2/d], and vincristine sulfate [0.05 mg/kg/d]) and 4 cycles of regimen 2 (carboplatin [500 mg/m2/d, days 1 and 2] and etoposide [100 mg/m2/d, days 1-3]). Low-risk children did not receive adjuvant therapy. Children with buphthalmia received neoadjuvant and adjuvant chemotherapy for a total of 8 cycles.
MAIN OUTCOMES AND MEASURES
Probability of event-free survival (extraocular relapse and death from any cause were considered events).
RESULTS
Among 187 children registered in the study, 175 were evaluable (92 [52.5%] female; median age, 22 months; age range, 3-100 months). Forty-two were stage 0 children, 84 were stage I low-risk children, and 42 were stage I high-risk children; there were 7 children in the buphthalmia group. With a median follow-up of 46 months, the 3-year probability of event-free survival was 0.97 (95% CI, 0.94-0.99), and the probability of overall survival was 0.98 (95% CI, 0.94-1.00). Stage 0 patients had no events, stage I low-risk patients had 1 event (orbital relapse treated with second-line therapy), stage I high-risk patients had 2 events (1 central nervous system relapse and 1 death from sepsis), and the buphthalmia group had 1 event (orbital relapse, followed by central nervous relapse and death).
CONCLUSIONS AND RELEVANCE
Adjuvant therapy may be effective for high-risk unilateral retinoblastoma but is toxic, and neoadjuvant chemotherapy for buphthalmus appears feasible.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Child; Child, Preschool; Cyclophosphamide; Disease-Free Survival; Etoposide; Eye Enucleation; Female; Humans; Hydrophthalmos; Idarubicin; Infant; Male; Mesna; Neoplasm Metastasis; Neoplasm Staging; Prospective Studies; Retinal Neoplasms; Retinoblastoma; Survival Rate; Vincristine
PubMed: 29799944
DOI: 10.1001/jamaophthalmol.2018.1501 -
Cureus Apr 2023Primary mesenteric liposarcoma is a rare soft tissue malignant neoplasm. The authors present a case of a 42-year-old male with pain in the abdomen and abdominal mass...
Primary mesenteric liposarcoma is a rare soft tissue malignant neoplasm. The authors present a case of a 42-year-old male with pain in the abdomen and abdominal mass which showed a desmoid tumor on biopsy and CT shows a mesenteric mass present. The patient underwent exploratory laparotomy and a large tumor was excised. The specimen was sent for histopathology and showed dedifferentiated liposarcoma of the mesentery. Immunohistochemistry showed the tumor cells are diffusely positive for mouse double minute 2 (MDM2), p16, and show patchy positivity for the cluster of differentiation (CD) 34. The cells are negative for smooth muscle actin (SMA), desmin, S100, and ckit. After the surgery, the patient recovered well and was given adjuvant chemotherapy with doxorubicin, ifosfamide, and mesna. The patient has no signs or symptoms of recurrence to date. In this case, the combination of surgery and chemotherapy has shown to have a good clinical outcome.
PubMed: 37261141
DOI: 10.7759/cureus.38329 -
Diabetes, Obesity & Metabolism Nov 2023To investigate whether mesna-sodium-2-mercaptoethane sulfonate) can reduce diet-induced fat gain in mice, and to assess the safety of single ascending mesna doses in...
AIM
To investigate whether mesna-sodium-2-mercaptoethane sulfonate) can reduce diet-induced fat gain in mice, and to assess the safety of single ascending mesna doses in humans to find the dose associated with lowering of plasma tCys by at least 30%.
METHODS
C3H/HeH mice were shifted to a high-fat diet ± mesna in drinking water; body composition was measured at weeks 0, 2 and 4. In an open, phase I, single ascending dose study, oral mesna (400, 800, 1200, 1600 mg) was administered to 17 men with overweight or obesity. Mesna and tCys concentrations were measured repeatedly for a duration of 48 hours postdosing in plasma, as well as in 24-hour urine.
RESULTS
Compared with controls, mesna-treated mice had lower tCys and lower estimated mean fat mass gain from baseline (week 2: 4.54 ± 0.40 vs. 6.52 ± 0.36 g; week 4: 6.95 ± 0.35 vs. 8.19 ± 0.34 g; P = .002), but similar lean mass gain. In men with overweight, mesna doses of 400-1600 mg showed dose linearity and were well tolerated. Mesna doses of 800 mg or higher decreased plasma tCys by 30% or more at nadir (4h post-dosing). With increasing mesna dose, tCys AUC decreased (P < .001), and urine tCys excretion increased (P = .004).
CONCLUSIONS
Mesna reduces diet-induced fat gain in mice. In men with overweight, single oral doses of mesna (800-1600 mg) were well tolerated and lowered plasma tCys efficiently. The effect of sustained tCys-lowering by repeated mesna administration on weight loss in humans deserves investigation.
Topics: Humans; Male; Cysteine; Mesna; Mice, Inbred C3H; Obesity; Overweight; Animals; Mice; Clinical Trials, Phase I as Topic
PubMed: 37435697
DOI: 10.1111/dom.15210 -
The Journal of Laryngology and Otology Mar 2017Mesna (i.e. sodium 2-mercaptoethanesulfonate; C2H5NaO3S2) has been used in otological surgery such as cholesteatoma dissection and tympanic membrane lateralisation in...
OBJECTIVE
Mesna (i.e. sodium 2-mercaptoethanesulfonate; C2H5NaO3S2) has been used in otological surgery such as cholesteatoma dissection and tympanic membrane lateralisation in atelectatic ears. However, this study aimed to investigate its effect on cholesteatoma formation.
METHODS
A total of 20 Wistar rats were divided into two groups of 10 animals. The right and left ears of control animals were treated with saline (saline control group; n = 10 ears) and propylene glycol plus saline (propylene glycol control group; n = 10 ears), respectively. In the mesna group, both ears were treated with propylene glycol plus mesna (n = 20 ears). On days 1, 8 and 15, the saline control group had intratympanic injections of 0.2 ml saline and the propylene glycol control and mesna groups had intratympanic injections of 0.2 ml 100 per cent propylene glycol. On day 22, the propylene glycol control group had a single intratympanic injection of 0.2 ml saline and the mesna group had a single intratympanic injection of 10 per cent mesna. Animals were killed 12 weeks after the last injection and the temporal bones were sent for histopathological evaluation.
RESULTS
The cholesteatoma formation rate was 88 per cent in the propylene glycol control group, but was significantly lower in the mesna group (p = 0.01). There were no significant differences in granulation tissue formation (p = 0.498), cyst formation in the bulla (p = 0.381), fibrosis (p = 0.072) and epithelial hyperplasia (p = 0.081) among experimental groups.
CONCLUSION
Intratympanic propylene glycol administration is an effective method of promoting experimental cholesteatoma formation. Administration of a single dose of intratympanic mesna inhibited cholesteatoma formation in an animal model.
Topics: Animals; Cholesteatoma, Middle Ear; Fibrosis; Granulation Tissue; Hyperplasia; Injection, Intratympanic; Male; Mesna; Propylene Glycol; Protective Agents; Rats; Rats, Wistar; Solvents; Temporal Bone; Treatment Outcome
PubMed: 27995828
DOI: 10.1017/S002221511600983X -
Communications Biology Oct 2022Methanogens and anaerobic methane-oxidizing archaea (ANME) are important players in the global carbon cycle. Methyl-coenzyme M reductase (MCR) is a key enzyme in methane...
Methanogens and anaerobic methane-oxidizing archaea (ANME) are important players in the global carbon cycle. Methyl-coenzyme M reductase (MCR) is a key enzyme in methane metabolism, catalyzing the last step in methanogenesis and the first step in anaerobic methane oxidation. Divergent mcr and mcr-like genes have recently been identified in uncultured archaeal lineages. However, the assembly and biochemistry of MCRs from uncultured archaea remain largely unknown. Here we present an approach to study MCRs from uncultured archaea by heterologous expression in a methanogen, Methanococcus maripaludis. Promoter, operon structure, and temperature were important determinants for MCR production. Both recombinant methanococcal and ANME-2 MCR assembled with the host MCR forming hybrid complexes, whereas tested ANME-1 MCR and ethyl-coenzyme M reductase only formed homogenous complexes. Together with structural modeling, this suggests that ANME-2 and methanogen MCRs are structurally similar and their reaction directions are likely regulated by thermodynamics rather than intrinsic structural differences.
Topics: Archaea; Mesna; Oxidoreductases; Methane
PubMed: 36266535
DOI: 10.1038/s42003-022-04057-6