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Anticancer Research Jul 2024There is limited evidence regarding the systemic treatment of retroperitoneal soft-tissue sarcoma, and the current Japanese guidelines fail to make definitive...
BACKGROUND/AIM
There is limited evidence regarding the systemic treatment of retroperitoneal soft-tissue sarcoma, and the current Japanese guidelines fail to make definitive suggestions. Here, we report our experience with combination chemotherapy of mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) in this population.
PATIENTS AND METHODS
We retrospectively reviewed the records of eight patients (three male and five female) who received MAID for pathologically diagnosed metastatic unresectable retroperitoneal sarcoma (either leiomyosarcoma or pleomorphic sarcoma) between October 2019 and January 2022. Treatment efficacy, tolerability (need for dose reduction), and safety profiles were evaluated and summarized.
RESULTS
At initiation, the median age was 56.0 years, and the body mass index was 20.0 kg/cm Six patients had Eastern Cooperative Oncology Group performance status scores of 0. The net clinical benefit was a partial response in three (37.5%) patients, stable disease in four (50.0%), and progressive disease in one (12.5%). During the median 90.8 weeks of follow-up, disease in five patients progressed, resulting in a median progression-free survival of 48.4 weeks, and five deaths occurred, resulting in an overall survival of 95.1 weeks. Commonly observed adverse events were neutropenia (eight patients), anemia (eight patients), and decreased platelet count (seven patients), which led to dose reduction (60-80%) in six patients.
CONCLUSION
MAID combination therapy may be an acceptable option for advanced retroperitoneal sarcoma; however, its benefits must be carefully assessed owing to its not insignificant toxicity.
Topics: Humans; Male; Female; Middle Aged; Ifosfamide; Doxorubicin; Antineoplastic Combined Chemotherapy Protocols; Retroperitoneal Neoplasms; Sarcoma; Mesna; Aged; Dacarbazine; Retrospective Studies; Adult
PubMed: 38925814
DOI: 10.21873/anticanres.17137 -
ACS Omega Feb 2024This study aimed at designing an S-protected thiolated β-cyclodextrin (β-CD) exhibiting enhanced mucoadhesive properties. The native β-CD was thiolated with...
This study aimed at designing an S-protected thiolated β-cyclodextrin (β-CD) exhibiting enhanced mucoadhesive properties. The native β-CD was thiolated with phosphorus pentasulfide resulting in a thiolated β-CD (β-CD-SH) and subsequently S-protected with 2-mercaptoethanesulfonate (MESNA) to form β-CD-SS-MESNA. The structure of the novel excipient was confirmed by H NMR and Fourier-transform infrared spectroscopy. The sulfhydryl content of β-CD-SH, determined by Ellman's test, was 2281.00 ± 147 μmol/g, and it was decreased to 45.93 ± 19.40 μmol/g by S-protection. Due to thiolation and S-protection, the viscosity of the mixture of mucus with β-CD-SH and β-CD-SS-MESNA increased 1.8 and 4.1-fold, compared to native β-CD, respectively. The unprotected β-CD-SH diffused to a lesser extent into the mucus than native β-CD, while S-protected β-CD-SS-MESNA showed the highest mucodiffusion among the applied CDs. A 1.5- and 3.0-fold higher cellular uptake of β-CD-SH and β-CD-SS-MESNA, compared to the native one, was established on Caco-2 cell line by flow cytometry, respectively, causing slightly decreased cell viability. On account of the enhanced mucoadhesion, this higher cellular uptake does not affect the application potential of β-CD-SS-MESNA as an oral drug delivery system since the carrier remains in the mucus and does not reach the underlying epithelial layer. According to these results, the S-protection of β-CD-SH with MESNA promotes improved mucodiffusion, strong mucoadhesion, and prolonged mucosal residence time.
PubMed: 38343993
DOI: 10.1021/acsomega.3c08836 -
Journal of Osteopathic Medicine Mar 2024An important diagnostic tool, ultrasound (US) has been incorporated into the curriculum of medical schools for more than 20 years. In the last decade, the interest in...
CONTEXT
An important diagnostic tool, ultrasound (US) has been incorporated into the curriculum of medical schools for more than 20 years. In the last decade, the interest in US educational research has experienced exponential growth but mostly from Medical Doctor (MD)-granted schools. The extent to which US is embedded in the curricula of the colleges of osteopathic medicine (COM) still requires a comprehensive evaluation.
OBJECTIVES
This survey is designed to evaluate the current status of US teaching in COMs with an emphasis on the inclusion of the US in osteopathic manipulative medicine (OMM) training.
METHODS
An anonymous, voluntary, 22-question online survey was created and administered to all COMs to collect data about the current state of US teaching. A descriptive analysis was performed to describe and summarize the final data. Fisher's exact test was utilized for the comparison of study variables.
RESULTS
We received responses from 36 of the 43 (83.7 %) COMs invited to participate in the survey, all of which had US training within their curriculum, most commonly integrated into the year 1 curriculum (86.1 %). Focused US training is incorporated into 83.3 % of these schools (30 of 36). Focused US training is covered in 83.3 % of schools (30 of 36). US is mostly taught in the anatomy course (38.8 %). US is incorporated in the OMM course in 12 of 36 schools (33.3 %). The majority of respondents feel that US training will make osteopathic students more competitive in the job market (88.9 %) and want more US in their curriculum (86.1 %). The idea that US is useful for a better understanding of the key OMM concepts is believed by 62.9 % of respondents. The major obstacle to the implementation of US in the curriculum is having appropriately trained faculty (86.1 %). The majority of the respondents did not feel that an adequate budget is a handicap to implementing US in the curriculum.
CONCLUSIONS
US is included within the curriculum of all respondents to our survey, a third of whom included US within their OMM curriculum. US is treated as a useful and important skill for future osteopathic physicians. The majority of COMs desire more US training in the curriculum. The main barrier to implementing US in the curriculum is the lack of appropriately trained faculty.
Topics: Humans; Schools, Medical; Curriculum; Emotions; Manipulation, Osteopathic; Mesna
PubMed: 38053432
DOI: 10.1515/jom-2023-0027 -
Biology May 2022Hemorrhagic cystitis is the main adverse effect associated with the clinical use of oxazaphosphorine, resulting in increased oxidative stress and proinflammatory...
Hemorrhagic cystitis is the main adverse effect associated with the clinical use of oxazaphosphorine, resulting in increased oxidative stress and proinflammatory cytokines, which culminate in injury of the bladder tissue. The aim of this study was to evaluate the protective effect of isopropyl gallate (IPG) against ifosfamide (IFOS)-induced hemorrhagic cystitis in mice. The induction of the hemorrhagic cystitis model was carried out using a single dose of IFOS (400 mg/kg, i.p.) four hours after oral pretreatment with IPG (6.25, 12.5, 25, and 50 mg/kg) or saline (vehicle). Mesna (positive control; 80 mg/kg, i.p.) was administered four hours before and eight hours after induction of cystitis. In the present study, IPG 25 mg/kg significantly decreased edema and hemorrhage, with a reduction of the bladder wet weight (36.86%), hemoglobin content (54.55%), and peritoneal vascular permeability (42.94%) in urinary bladders of mice. Interestingly, IPG increased SOD activity (89.27%) and reduced MDA levels (35.53%), as well as displayed anti-inflammatory activity by decreasing TNF-α (88.77%), IL-1β (62.87%), and C-reactive protein (56.41%) levels. Our findings demonstrate that IPG has a substantial protective role against IFOS-induced hemorrhagic cystitis in mice by enhancing antioxidant activity and proinflammatory mechanisms. Thus, IPG represents a promising co-adjuvant agent in oxazaphosphorine-based chemotherapy treatments.
PubMed: 35625456
DOI: 10.3390/biology11050728 -
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 -
The Journal of Surgical Research Jul 2020Adhesion formation is a common complication of abdominal surgeries. Mesna is a drug with fibrinolytic properties which has been used in surgical field to facilitate...
BACKGROUND
Adhesion formation is a common complication of abdominal surgeries. Mesna is a drug with fibrinolytic properties which has been used in surgical field to facilitate tissue dissection. The aim of this experimental animal study was to investigate the effect of mesna on prevention of intra-abdominal adhesion in rats.
MATERIALS AND METHODS
Twenty-eight Wistar albino rats were used in the study. To create abdominal adhesion, cecum was abraded in all rats. No additional surgical procedure was performed other than adhesion in group 1 (only adhesion). In the other groups, rats were treated topically by administering 0.9% saline (group 2), 40 mg/kg mesna (group 3), and 400 mg/kg mesna (group 4). All rats were sacrificed on postoperative 21st day. Histopathological and macroscopic evaluations of adhesion formation were performed.
RESULTS
Quantity of adhesion scores (P = 0.022), severity of adhesion scores (P = 0.041), total adhesion scores (P = 0.023), and histopathological adhesion grading scores (P < 0.001) were reduced by 400 mg/kg mesna.
CONCLUSIONS
This is the first study for mesna on prevention of abdominal adhesion formation in rats. We concluded that dose-dependent reduction of adhesion was achieved by mesna. With future studies, topical administration of mesna during open abdominal surgeries may be used to prevent adhesion formation.
Topics: Abdomen; Animals; Drug Evaluation, Preclinical; Mesna; Protective Agents; Rats, Wistar; Tissue Adhesions
PubMed: 32145558
DOI: 10.1016/j.jss.2020.01.027 -
Analytical Chemistry May 2022Mesna is an important regional antidote for protecting the urinary system of chemotherapy patients, which requires monitoring its level in real time to ensure the...
Mesna is an important regional antidote for protecting the urinary system of chemotherapy patients, which requires monitoring its level in real time to ensure the curative effect. The fluorescence method is a powerful tool in real-time detection with the advantages of fast response and visualization. However, the background interference limits its application in biological sensing. Here, we developed a portable sensing platform using an upconversion-based nanosensor for visual quantitative monitoring of mesna in real-time/on-site conditions. The nanosensor was constructed by upconversion nanoparticles (UCNPs) and ethyl violet (EV), in which the UCNPs emitted red and green light, while EV quenched the green light due to the inner filter effect (IFE). The reaction of mesna with EV caused its fading and broke the IFE process, leading to the recovery of green light. By the fluorescence and colorimetric chromaticity variations, the nanosensor achieved a dual-readout detection for mesna with low limits of detection (LODs) of 26 and 48 nM, respectively. Furthermore, a highly compatible sensing platform was fabricated for facile determination of mesna with an LOD of 56 nM, realizing visual quantitative monitoring of the mesna level to ensure the curative effect and providing a new strategy for point-of-care testing of drugs in clinical settings.
Topics: Colorimetry; Excipients; Humans; Limit of Detection; Mesna; Nanoparticles
PubMed: 35587268
DOI: 10.1021/acs.analchem.2c00380 -
Clinical Rheumatology Jan 2021Standard regimens for scleroderma interstitial lung diseases (SSc-ILDs) are pulse intravenous (IV) and oral daily cyclophosphamide (CYC). However, IV CYC has limited...
INTRODUCTION
Standard regimens for scleroderma interstitial lung diseases (SSc-ILDs) are pulse intravenous (IV) and oral daily cyclophosphamide (CYC). However, IV CYC has limited access to diffuse cutaneous SSc, and oral daily CYC is associated with febrile neutropenia and hemorrhagic cystitis. Pulse oral CYC regimen has never been studied.
OBJECTIVE
To determine the effectiveness of pulse oral CYC therapy in SSc-ILDs, predictors of effectiveness, and side-effects.
METHODS
A historical cohort study enrolled SSc-ILDs from the SSc database registry at Srinagarind Hospital, Thailand from 1 January 2012 to 1 October 2018. All patients received monthly oral dosages of CYC 600-750 mg/m, Mesna, and daily prednisolone of 10 mg for 2 years. Changes of FVC, chest radiography, HRCT, 6MWT, and side effects were recorded for the baseline and at the end of the treatment. Response to treatment was defined by (a) stable FVC or a decline ≤ 10% of predicted, (b) unchanged or improved radiographic findings, or (c) a decline 6MWT of ≤ 30 m compared with the baseline.
RESULTS
A total of 76 patients with female 52 patients (68.4%) and with a median age of 54.2 years (IQR 46.6-59.6). The majority was dcSSc subset (59 patients; 78.6%). Fifty-four patients (71%) were defined as responsive to therapy. The mean FVC improvement was 1 ml (SD 9.5). The only factor associated with treatment response was limited cutaneous SSc (OR 7.69, 95% CI (1.01, 339.68), p = 0.029). Hemorrhagic cystitis was found in 1 patient.
CONCLUSIONS
Nearly three-quarters of SSc-ILDs patients had a good response to the pulse oral CYC therapy for 2 years with a few serious side effects. Pulse oral CYC therapy had been effective for SSc-ILDs in case of difficult IV access. Key Point • Pulse oral cyclophosphamide has been used for scleroderma lung disease. It has shown efficacy and safety in scleroderma patients. In patients who have difficulty with intravenous access, pulse oral cyclophosphamide can be an alternative regimen.
Topics: Cohort Studies; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Middle Aged; Respiratory Function Tests; Scleroderma, Systemic; Thailand; Treatment Outcome
PubMed: 32519048
DOI: 10.1007/s10067-020-05217-x -
Proceedings of the National Academy of... Sep 2022Mercaptoethane sulfonate or coenzyme M (CoM) is the smallest known organic cofactor and is most commonly associated with the methane-forming step in all methanogenic...
Mercaptoethane sulfonate or coenzyme M (CoM) is the smallest known organic cofactor and is most commonly associated with the methane-forming step in all methanogenic archaea but is also associated with the anaerobic oxidation of methane to CO in anaerobic methanotrophic archaea and the oxidation of short-chain alkanes in species. It has also been found in a small number of bacteria capable of the metabolism of small organics. Although many of the steps for CoM biosynthesis in methanogenic archaea have been elucidated, a complete pathway for the biosynthesis of CoM in archaea or bacteria has not been reported. Here, we present the complete CoM biosynthesis pathway in bacteria, revealing distinct chemical steps relative to CoM biosynthesis in methanogenic archaea. The existence of different pathways represents a profound instance of convergent evolution. The five-step pathway involves the addition of sulfite, the elimination of phosphate, decarboxylation, thiolation, and the reduction to affect the sequential conversion of phosphoenolpyruvate to CoM. The salient features of the pathway demonstrate reactivities for members of large aspartase/fumarase and pyridoxal 5'-phosphate-dependent enzyme families.
Topics: Anaerobiosis; Archaea; Bacteria; Coenzymes; Euryarchaeota; Mesna; Methane; Oxidation-Reduction; Phosphates
PubMed: 36037354
DOI: 10.1073/pnas.2207190119 -
Transplantation and Cellular Therapy Jul 2022Post-transplantation cyclophosphamide (PTCy) has improved hematopoietic stem cell transplantation outcomes for patients with major HLA disparities. Although PTCy in... (Review)
Review
A Clinical Review of the Different Strategies to Minimize Hemorrhagic Cystitis Associated with the Use of Post-Transplantation Cyclophosphamide in an Allogeneic Transplant.
Post-transplantation cyclophosphamide (PTCy) has improved hematopoietic stem cell transplantation outcomes for patients with major HLA disparities. Although PTCy in combination with calcineurin inhibitors is a successful graft-versus-host disease regimen, giving high doses of cyclophosphamide may cause hemorrhagic cystitis (HC). The strategies used to prevent HC are adapted from published data in the pre-transplantation conditioning setting. However, there is no consensus on what the optimal strategy is to prevent PTCy-associated HC. This review provides a summary of the different preventative strategies used in this setting. Based on the results published in current literature, hyperhydration is an effective preventative strategy, but it may cause fluid overload and other complications. Additionally, mesna at least 100% of the PTCy dose should be administered as a continuous infusion or frequent intermittent bolus infusion. More comparative studies between these strategies are needed to provide a definitive solution for preventing HC associated with PTCy.
Topics: Cyclophosphamide; Cystitis; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hemorrhage; Humans; Transplantation, Homologous
PubMed: 35580733
DOI: 10.1016/j.jtct.2022.05.012