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Evidence-based Complementary and... 2022Patients treated with cyclophosphamide (CP) usually suffer from severe hemorrhagic cystitis (HC). Our previous study exhibited that mesna + celery cotherapy...
Patients treated with cyclophosphamide (CP) usually suffer from severe hemorrhagic cystitis (HC). Our previous study exhibited that mesna + celery cotherapy partially ameliorated HC. Therefore, there is a substantial need to seek alternative regimens to get complete protection against CP-induced HC. The current study investigated the effects of mesna + celery seed oil (MCSO) or mesna + manuka honey (MMH) cotherapy against CP-induced HC in adult male rabbits. The forty rabbits were divided into four equal groups and treated for three weeks. The control group (G1) received distilled water and the second group (G2) received CP (50 mg/kg/week). The third group (G3) received CP + MCSO (CPMCSO regimen), and the fourth group (G4) received CP + MMH (CPMMH regimen). The urinary bladder (UB) specimens were processed to evaluate UB changes through histopathological, immunohistochemical, ultrastructural, and biochemical investigations. In G2, CP provoked HC features (urothelial necrosis, ulceration, and sloughing), UB fibrosis, and TNF- immunoexpression. Besides, CP reduced the activity of antioxidant enzymes (GPx1, SOD3, and CAT) and elevated the serum levels of NF-B, TNF-, IL-1B, and IL-6 cytokines in G2 rabbits. In contrast, the CPMMH regimen caused significant increments of UB protection against HC in G4 rabbits compared to the partial protection by the CPMCSO regimen in G3. Therefore, our study indicated for the first time that the novel CPMMH regimen resulted in complete UB protection against CP-induced HC via combined antioxidant, anti-inflammatory, and antifibrotic properties.
PubMed: 35341158
DOI: 10.1155/2022/2863023 -
Journal of the Advanced Practitioner in... Nov 2021Retroperitoneal liposarcomas (RLPS) are rare tumors that have variable clinical behavior and complex treatment strategies based on presentation, histopathology, and...
Retroperitoneal liposarcomas (RLPS) are rare tumors that have variable clinical behavior and complex treatment strategies based on presentation, histopathology, and genomics. Early identification is critical, and complete surgical resection remains the primary treatment, although chemotherapy and radiation are used on individual bases. Presenting symptoms are often nonspecific; therefore, a high degree of suspicion is essential for early diagnosis. In this report, the management of a 37-year-old otherwise healthy male with a large RLPS causing right groin/testicular pain is presented. After three evaluations in the emergency department, the patient was diagnosed and received two cycles of doxorubicin/ifosfamide/mesna (AIM) neoadjuvant chemotherapy. His physical exam on presentation for second opinion demonstrated a large palpable abdominal mass and fullness around the right spermatic cord. There was no appreciable change in tumor size or distant metastases on repeat scanning. Given some obstructive symptoms, a multidisciplinary team advised neoadjuvant radiation followed by radical resection of RLPS. Final pathology demonstrated a 31-cm grade II well-differentiated (WD) liposarcoma with low-grade dedifferentiation. Scattered foci of microscopic positive WD margins were noted, and the remainder of margins were negative. Genomic evaluation showed amplification of , and . A concise literature review of common presentations, histopathology, genomics, and treatment information is discussed herein. Thorough physical exams, attention to subtle findings, appropriate medical imaging studies, and a high index of suspicion when evaluating vague symptomatology can lead to earlier diagnosis and treatment of RLPS, and ultimately better patient outcomes.
PubMed: 35295543
DOI: 10.6004/jadpro.2021.12.8.6 -
IJU Case Reports Mar 2022Prostate leiomyosarcoma is a rare, aggressive neoplasm.
INTRODUCTION
Prostate leiomyosarcoma is a rare, aggressive neoplasm.
CASE PRESENTATION
A 52-year-old man presented with worsening frequent micturition and painful urination. Rectal examination revealed a significantly enlarged prostate. Magnetic resonance imaging showed a large prostate tumor with urinary bladder and bilateral seminal vesicle invasion. A prostate biopsy revealed diffuse proliferation of pleomorphic atypical cells. Immunohistochemistry confirmed the diagnosis of prostrate leiomyosarcoma. The patient received three cycles of the mesna, doxorubicin, ifosfamide, and dacarbazine regime (mesna 6000 mg/m, doxorubicin 60 mg/m, ifosfamide 7500 mg/m, and dacarbazine 900 mg/m) at 4-week intervals. The tumor shrank by 28% and exhibited necrotic changes. He underwent total pelvic exenteration with en bloc resection of the prostate, bladder, rectum, and anus. Pathological surgical margin was negative. The patient is alive with no disease at 5 years postoperatively.
CONCLUSION
Neoadjuvant chemotherapy and surgical resection are essential to achieve a long-term survival of patients with localized prostate leiomyosarcoma.
PubMed: 35252786
DOI: 10.1002/iju5.12400 -
Pediatric Blood & Cancer May 2022To assess feasibility and safety of outpatient administration of ifosfamide and etoposide (IE) for pediatric Ewing sarcoma (EWS) patients in a resource-limited setting...
Feasibility and safety of outpatient administration of ifosfamide and etoposide for pediatric patients with Ewing sarcoma in a resource-limited setting amid the COVID-19 pandemic.
BACKGROUND
To assess feasibility and safety of outpatient administration of ifosfamide and etoposide (IE) for pediatric Ewing sarcoma (EWS) patients in a resource-limited setting amid the COVID-19 pandemic.
MATERIALS AND METHODS
Retrospective study of patients with EWS who received outpatient IE from January 2020 until January 2021 at our institution. Ifosfamide 1800 mg/m was given for 5 days with MESNA (2-mercaptoethane sulfonate sodium) infusion and additional boluses before and after 9 hours of hydration. Patients >10 years of age with the ability to drink orally at home, no pre-existing renal dysfunction or history of hematuria were included. They were monitored for hemorrhagic cystitis with a urine dipstick before, midway, and at end of infusion. A urine analysis was done 24 hours after the last dose of ifosfamide.
RESULTS
Forty-seven (100%) cycles were given as outpatient during the study period. Thirty-five (74%) cycles were given on time, two (4%) cycles were delayed due to mucositis, two (4%) due to delayed count recovery, and eight (18%) due to unavailability of outpatient appointments. The median interval between these cycles was 15 days (range 14-44 days). No episode of hemorrhagic cystitis was reported. Urine analysis was not done at 24 hours for 27 (58%) cycles, so microscopic hematuria may have been missed. This outpatient protocol saved 32% (USD 299) per cycle in cost and 282 days of hospitalization.
CONCLUSION
Outpatient administration of IE for pediatric patients with EWS is feasible, safe, and cost-effective during the COVID-19 pandemic.
Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Etoposide; Feasibility Studies; Humans; Ifosfamide; Outpatients; Pandemics; Retrospective Studies; Sarcoma, Ewing; COVID-19 Drug Treatment
PubMed: 35234343
DOI: 10.1002/pbc.29595 -
Autophagy Sep 2022Macroautophagy/autophagy is an evolutionarily conserved intracellular degradation pathway that maintains cellular homeostasis. Over the past two decades, a series of... (Review)
Review
Macroautophagy/autophagy is an evolutionarily conserved intracellular degradation pathway that maintains cellular homeostasis. Over the past two decades, a series of scientific breakthroughs have helped explain autophagy-related molecular mechanisms and physiological functions. This tremendous progress continues to depend largely on powerful research methods, specifically, various autophagy marker Atg8-PE protein-based methods for studying membrane dynamics and monitoring autophagic activity. Recently, several biochemical approaches have been successfully developed to produce the lipidated protein Atg8-PE or its mimics , including enzyme-mediated reconstitution systems, chemically defined reconstitution systems, cell-free lipidation systems and protein chemical synthesis. These approaches have contributed important insights into the mechanisms underlying Atg8-mediated membrane dynamics and protein-protein interactions, creating a new perspective in autophagy studies. In this review, we comprehensively summarize Atg8-PE protein-based biochemical approaches and recent advances to facilitate a better understanding of autophagy mechanisms. In addition, we highlight the advantages and disadvantages of various Atg8-PE protein-based approaches to provide general guidance for their use in studying autophagy. ATG: autophagy related; ATP: adenosine triphosphate; COPII: coat protein complex II; DGS-NTA: 1,2-dioleoyl--glycero-3-[(N-(5-amino-1-carboxypentyl)iminodiacetic acid)succinyl] (nickel salt); DPPE: 1,2-dipalmitoyl--glycero-3-phosphoethanolamine; DSPE: 1,2-distearoyl--glycero-3-phosphoethanolamine; ; EPL: expressed protein ligation; ERGIC: ER-Golgi intermediate compartment; GABARAP: GABA type A receptor-associated protein; GABARAPL1: GABA type A receptor associated protein like 1; GABARAPL2: GABA type A receptor associated protein like 2; GFP: green fluorescent protein; GUVs: giant unilamellar vesicles; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MBP: maltose binding protein; MEFs: mouse embryonic fibroblasts; MESNa: 2-mercaptoethanesulfonic acid sodium salt; NCL: native chemical ligation; NTA: nitrilotriacetic acid; PE: phosphatidylethanolamine; PS: phosphatidylserine; PtdIns3K: class III phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; SPPS: solid-phase peptide synthesis; TEV: tobacco etch virus; WT: wild-type.
Topics: Animals; Autophagy; Autophagy-Related Protein 8 Family; Escherichia coli; Fibroblasts; Mice; Microtubule-Associated Proteins; gamma-Aminobutyric Acid
PubMed: 35072587
DOI: 10.1080/15548627.2022.2025572 -
Journal of Chromatography. B,... Jan 2022Sodium 2-mercaptoethane sulfonate (MESNA) is a thiol-containing compound that has proven to be effective in inactivating acrolein, the toxic metabolite of some...
Sodium 2-mercaptoethane sulfonate (MESNA) is a thiol-containing compound that has proven to be effective in inactivating acrolein, the toxic metabolite of some anti-cancer drugs (e.g., cyclophosphamide and ifosphamide). Also, it scavenges free radicals which cause numerous disorders by attacking biological molecules. Current methods available to analyze MESNA in biological matrices include colorimetry and high-performance liquid chromatography (HPLC) with ultraviolet, fluorescence, or electrochemical detection. These methods have several limitations including low sensitivity, poor selectivity, a high degree of difficulty, and long analysis times. Hence, a rapid, simple, and sensitive HPLC tandem mass spectrometry (MS/MS) method was developed and validated to quantify MESNA in rat plasma following IP administration. The analysis of MESNA was accomplished via plasma protein precipitation, centrifugation, supernatant evaporation, reconstitution, and HPLC-MS/MS analysis. The method showcases an outstanding limit of detection (20 nM), excellent linearity (R = 0.999, and percent residual accuracy >90%) and a wide linear range (0.05-200 μM). The method also produced good accuracy and precision (100 ± 10% and <10% relative standard deviation, respectively). The validated method was successfully used to analyze MESNA from treated animals and will allow easier development of MESNA for therapeutic purposes.
Topics: Animals; Chromatography, High Pressure Liquid; Drug Stability; Limit of Detection; Linear Models; Male; Mesna; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Tandem Mass Spectrometry
PubMed: 34974317
DOI: 10.1016/j.jchromb.2021.123088 -
Pharmaceuticals (Basel, Switzerland) Nov 2021One of the major side effects of cyclophosphamide (CPX)-an alkylating anticancer drug that is still clinically used-is urotoxicity with hemorrhagic cystitis. The present...
One of the major side effects of cyclophosphamide (CPX)-an alkylating anticancer drug that is still clinically used-is urotoxicity with hemorrhagic cystitis. The present study was designed to evaluate the ability of carvedilol to protect rats from cyclophosphamide-induced urotoxicity. Rats were injected intraperitoneally () with CPX (200 mg/kg) and administered carvedilol (2 mg/kg) intragastrically a day before, at the day and a day after a single . injection of CPX, with or without mesna (40, 80, and 80 mg/kg 20 min before, 4 h and 8 h after CPX administration, respectively). Pretreatment with carvedilol partly prevented the CPX-induced increase in urinary bladder and kidney index, and completely protects from CPX-evoked alterations in serum potassium and creatinine level, but did not prevent histological alterations in the urinary bladder and hematuria. However, carvedilol administration resulted in significant restoration of kidney glutathione (GSH) level and a decrease in kidney interleukin 1β (IL-1β) and plasma asymmetric dimethylarginine (ADMA) concentrations. Not only did mesna improve kidney function, but it also completely reversed histological abnormalities in bladders and prevented hematuria. In most cases, no significant interaction of carvedilol with mesna was observed, although the effect of both drugs together was better than mesna given alone regarding plasma ADMA level and kidney IL-1β concentration. In conclusion, carvedilol did not counteract the injury caused in the urinary bladders but restored kidney function, presumably via its antioxidant and anti-inflammatory properties.
PubMed: 34959638
DOI: 10.3390/ph14121237 -
Orthopedic Research and Reviews 2021To the best of the authors' knowledge, this is the first published case of monophasic synovial sarcoma (SS) initially diagnosed as Ewing's sarcoma (ES), yet successfully...
To the best of the authors' knowledge, this is the first published case of monophasic synovial sarcoma (SS) initially diagnosed as Ewing's sarcoma (ES), yet successfully treated with chemotherapy in a 24-year-old patient. The initial diagnosis showed a monotonous round cell tumor and positivity for CD99, characteristic of ES; however, the cytology was negative for the classic EWSR1 rearrangement of ES. The patient was treated with the standard chemotherapy protocol of ES - COG AEWS1031 Regimen A with vincristine, doxorubicin, cyclophosphamide, and mesna - as well as with wide resection. Post-resection tissue submission showed additional morphologic features which led to a re-evaluation of the classification of the tumor as well as additional molecular studies; these revealed positivity for translocations of SS18 (18q11.1) in 100% of the nuclei, which is most characteristic of SS, thus, reclassifying the neoplasm as a SS tumor. This case underscores the importance of considering several pathologic entities in the differential diagnosis of small, round blue cell tumors, including ES, SS, and lymphoma. It also demonstrates the importance of using chromosomal identification for a more definitive diagnosis, rather than relying on histological features and markers which are found in more than one tumor classification. There is conflicting evidence of the impact of chemotherapy on survival in SS, as it is primarily treated with radiation therapy. Since SS is rare, prospective studies on the effect of chemotherapy on survival are limited in number. However, our case study demonstrates that chemotherapy is another modality that can be used in the treatment of SS neoplasms.
PubMed: 34866942
DOI: 10.2147/ORR.S332441 -
Journal of Medicinal Chemistry Dec 2021Commonly used non-antibiotic drugs have been associated with changes in gut microbiome composition, paving the way for the possibility of repurposing FDA-approved...
Commonly used non-antibiotic drugs have been associated with changes in gut microbiome composition, paving the way for the possibility of repurposing FDA-approved molecules as next-generation microbiome therapeutics. Herein, we developed and validated an high-throughput screening platform─the mini gut model─to underpin human gut microbiome response to molecular modulators. Ten FDA-approved compounds, selected based on maximum structural diversity of molecular fingerprints, were screened against the gut microbiome of five healthy subjects to characterize the ability of human-targeted drugs to modulate the human gut microbiome network. Three compounds, THIP hydrochloride, methenamine, and mesna, have shown promise as novel gut microbiome therapeutics in light of their capability of promoting health-associated features of the gut microbiome. Our findings provide a resource for future research on drug-microbiome interactions and lay the foundation for a new era of more precise gut microbiome modulation through drug repurposing, aimed at targeting specific dysbiotic events.
Topics: Drug Repositioning; Gastrointestinal Microbiome; Gene Expression Profiling; High-Throughput Screening Assays; Humans; Validation Studies as Topic
PubMed: 34846885
DOI: 10.1021/acs.jmedchem.1c01333 -
Supportive Care in Cancer : Official... Mar 2022To characterize and compare both the outcome and cost of treatment of outpatient (OP) and inpatient (IP) ifosfamide therapy.
PURPOSE
To characterize and compare both the outcome and cost of treatment of outpatient (OP) and inpatient (IP) ifosfamide therapy.
METHODS
A single-center retrospective chart review of patients 18 years and older receiving ifosfamide therapy. The primary endpoint compares and evaluates the side effect profiles of ifosfamide-treated patients in the OP/IP settings. The adverse event grading system was characterized using the CTCAE Version 5.0. The highest grade was documented per cycle. The secondary endpoint of this study compares the costs of OP/IP therapy. It was assumed that the cost of medication was equivalent for IP/OP treatments. The cost saved with OP administration was determined by the average cost of hospital stay for IP admission.
RESULTS
Ifosfamide therapy of 86 patients (57 OP, 29 IP) was reviewed. The predominant OP regimens were doxorobucin-ifosfamide-mesna (AIM) with 43.9% and ifosfamide-etoposide (IE) with 29.8%. Grade 4 anemia, thrombocytopenia, and neutropenia were most frequent in IP vs OP therapies (22.9% IP vs 4.3% OP, 21.6% IP vs 9.2% OP, and 22.8% IP vs 19.6% OP respectively). Neutropenic fever (NF) occurred in 20 OP patients which were predominantly treated with AIM or IE and led to average hospital stay of 6 days. Neurotoxicity, treated with methylene blue (MB) occurred in 4 OP patients. OP therapy saved a total of 783 hospital days, leading to a cost savings of $2,103,921.
CONCLUSIONS
Transitioning ifosfamide to the OP setting is feasible for academic and community infusion centers with the OP administration being safe, well-tolerated, and associated with decreased total cost of care. The current processes allow for safe transition of chemotherapy of chemotherapy under times of COVID.
Topics: Antineoplastic Combined Chemotherapy Protocols; COVID-19; Cost Savings; Etoposide; Humans; Ifosfamide; Retrospective Studies; SARS-CoV-2
PubMed: 34825982
DOI: 10.1007/s00520-021-06653-4