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Ovarian cancer is the primary cause of death from cancer in female patients. The existing treatments for ovarian cancer are restricted and ineffective in achieving a cure for the disease. To address this issue, we provide a novel approach to treating ovarian cancer by utilizing a liposomal carrier that effectively delivers the chemotherapeutic drugs carmustine (BCNU) and cabazitaxel (CTX). Initially, the combined impact of BCNU and CTX was confirmed, revealing that this impact reaches its maximum at a ratio of 1:2 mol/mol (BCNU/CTX). After that, the BC-Lipo co-delivery system was developed, which has a high capability for loading drugs (97.48% ± 1.14 for BCNU, 86.29% ± 3.03 for CTX). This system also has a sustained release profile and a beneficial long-circulating feature. The accumulation of BC-Lipo in tumors was dramatically enhanced compared to the accumulation of the free drug. Furthermore, BC-Lipo demonstrated similar levels of cytotoxicity to free BCNU and CTX (BCNU/CTX) when tested on HeyA8 cells in an in vitro model. Biochemical staining methods investigated the cancer cell's morphological examination. The apoptosis was confirmed by FITC-Annexin-V/PI staining by flow cytometry analysis. In addition, the investigation of fluorescence and protein markers examined the apoptosis mechanistic pathway, and the results indicated that BC-Lipo induced apoptosis due to mitochondrial membrane potential variation. This proof-of-concept study has established the probability of these BCNU-CTX combined treatments as active drug delivery nanocarriers for poorly soluble BCNU and CTX. [ABSTRACT FROM AUTHOR]

Background: Peripheral T‐cell lymphomas (PTCL) frequently result in relapsed or refractory diseases. Upfront autologous hematopoietic stem cell transplantation (ASCT) using the BEAM (carmustine, etoposide, cytarabine, and melphalan) regimen is recommended. However, relapses are common in PTCL, highlighting a critical need for improved survival outcomes in these patients. Objective: Anthracycline drugs are essential in treating PTCL. We compared the efficacy and tolerability of a high‐dose mitoxantrone‐based conditioning regimen [mitoxantrone, cyclophosphamide, and etoposide (MCE)] to the BEAM regimen in upfront ASCT for newly diagnosed PTCL patients who achieved complete or partial remission after induction therapy. Study Design: A retrospective study was conducted to analyze the treatment response, progression‐free survival (PFS), overall survival (OS), hematologic engraftment time, and adverse events of 64 patients between two regimens, who achieved complete or partial remission after induction chemotherapy. Twenty‐eight patients received the MCE regimen, while 36 patients were treated with the BEAM regimen. Results: There were no significant differences in clinical characteristics or the incidence of adverse events between the two groups. However, the median OS significantly favored the MCE group at 102.4 (95% CI, 87.0–117.8) months compared to 62.6 (95% CI, 50.8–74.5) months in the BEAM group (p = 0.023). Similarly, the median PFS was longer in the MCE group at 87.8 (95% CI, 65.8–109.8) months versus 42.5 (95% CI, 30.0–55.0) months in the BEAM group (p = 0.031). Conclusion: ASCT with the mitoxantrone‐based conditioning regimen is tolerable and appears to significantly improve the prognosis of PTCL patients, offering a promising alternative to the current standard of care. [ABSTRACT FROM AUTHOR]

Simple Summary: Intracavitary chemotherapy by Carmustine wafer implantation represents a therapeutic option for the management of high-grade gliomas both at diagnosis and at progression. However, this strategy is very controversial as it can lead to potential complications and previous studies have raised doubts regarding its efficacy in terms of oncological outcomes. Moreover, the results associated with Carmustine wafer implantation have been more frequently studied at diagnosis than at progression. Therefore, the aim of the present study was to precisely identify the predictors of complications and onco-functional outcomes in a series of 53 patients with a high-grade glioma surgically managed at progression with implantation of Carmustine wafers. These analyses will help to better identify and select the patients who are the best candidates to receive Carmustine wafers at progression and to guide intraoperative and postoperative management. Background/Objectives: The aim was to determine the complication rate and the predictors of complications and survival in high-grade glioma surgically managed at progression with implantation of Carmustine wafers. Methods: A retrospective series of 53 consecutive patients operated on between 2017 and 2022 was built. Results: The median age was 55 ± 10.9 years. The rates of global and infectious complications were 35.8% and 18.9%, respectively. In multivariate analysis, patients with a preoperative neurological deficit were more prone to develop a postoperative complication (HR = 5.35 95% CI 1.49–19.26, p = 0.01). No predictor of infectious complication was identified. In the grade 4 glioma subgroup (n = 44), progression-free and overall survival (calculated starting from the reresection) reached 3.95 months, 95% CI 2.92–5.21 and 11.51 months, 95% CI 9.11–17.18, respectively. Preoperative KPS > 80% (HR = 0.97 95% CI 0.93–0.99, p = 0.04), Gross Total Resection (HR = 0.38 95% CI 0.18–0.80, p = 0.01), and 3-month postoperative KPS > 80% (HR = 0.35 95% CI 0.17–0.72, p = 0.004) were predictors of prolonged overall survival. Conclusions: Surgical resection is a relevant option in high-grade gliomas at progression, especially in patients with a preoperative KPS > 80%, without preoperative neurological deficit, and amenable to complete resection. In patients elected for surgery, Carmustine wafer implantation is associated with a high rate of complications. It is consequently critical to closely monitor the patients for whom this option is chosen. [ABSTRACT FROM AUTHOR]

PURPOSE: High-dose methotrexate (HD-MTX) is the backbone of curative therapy for CNS lymphoma. Because of toxicity, MTX is administered in the inpatient setting along with hyperhydration and monitoring until MTX clearance is documented (3-5 days). Frequent hospitalizations result in patient time away from work, home, and exposure to potential iatrogenic/nosocomial complications. Here, we aim to demonstrate feasibility of HD-MTX administration in the outpatient setting with low-dose glucarpidase facilitating clearance. METHODS: This is a prospective nonrandomized study of outpatient HD-MTX followed by glucarpidase 2000u (ClinicalTrials.gov identifier: NCT03684980). Eligible patients had CNS lymphoma, creatinine <1.3 mg/dL, and previously tolerated HD-MTX. Patients were enrolled between May 2020 December 2021 for one HD-MTX treatment. Patients could re-enroll for subsequent doses of HD-MTX as eligibility and slots permitted. MTX 3.5 g/m2 was administered once over 2 hours, preceded by standard hydration and followed by an additional 2 hours of dextrose 5% in water with NaHCO3 75 mEq at 150 cc/h. Glucarpidase 2000u was administered once in the clinic 24 hours later. The primary end point was MTX level 48 hours after HD-MTX. RESULTS: Twenty doses of outpatient HD-MTX with glucarpidase were administered to seven patients. After 20 of 20 (100%) treatments, serum MTX levels were reduced to <100 nmol/L. Treatments were well-tolerated, and no admissions were required. One patient received additional outpatient hydration for elevated creatinine. Development of antiglucarpidase antibody was rare and did not affect treatment. CONCLUSION: Outpatient HD-MTX with glucarpidase is safe and well-tolerated and has the potential to alter standard treatment for CNS lymphoma. CNS lymphoma patients received glucarpidase to avoid hospitalization for MTX therapy. [ABSTRACT FROM AUTHOR]

The goal of the present study was to prepare an in situ carmustine gel to evaluate the viability of brain targeting via nasal administration. Initial formulations (CG1–CG5) were made, and their varied medicinal properties were assessed. Polymers that were employed as mucoadhesive with thermoreversible materials were carbopol 934 and poloxamer 407 respectively. The gel formulations were made using a cold process. Using a visual technique, the phase transition temperature was determined. The in vitro release, ex vivo carmustine permeability via goat nasal mucosal membrane, pH, mucoadhesive strength, and in vivo pharmacokinetic studies of the gels were assessed. The purpose of the histological analysis of the nasal mucosal membrane was to look for signs of harmful effects caused by carmustine permeability. It was discovered that the 18.00 percentage w/v poloxamer mixture was exhibiting a phase change at physiological temperatures (34.00 to 35.00 °C). The gelling temperature was found to drop when the carbopol 934 proportion was raised as of 0.1– 0.5 percentage weight/volume. The mucoadhesive strength of every preparation was more than 3500 dynes/cm2. A study on carmustine permeation has shown that employing carbopol 934 at concentrations higher than 0.3% w/v can accelerate the rate of carmustine permeation. No indication of injury has been found in the histological investigation of the nasal mucosa following the carmustine permeation trial. Compared to commercial intravenous (IV) injections of carmustine, in vivo pharmacokinetic analysis of carmustine in situ gel revealed increased Cmax, AUC0→t, and AUC0→∞ and lower Tmax (1 h) data in the brain. Hence, in situ thermoreversible mucoadhesive intranasal gel of carmustine might be an impactful therapy in the management of glioblastoma (GBM). [ABSTRACT FROM AUTHOR]

In terms of primary brain tumors, glioblastoma is one of the most aggressive and common brain tumors. The high resistance of glioblastoma to chemotherapy has made it vital to find alternative treatments and biological mechanisms to reduce the survival of cancer cells. Given that, the objective of the present research was to explore the potential of let-7a-3p when used in combination with carmustine in human glioblastoma cancer cells. Based on previous studies, the expression of let-7a is downregulated in the U87MG cell line. Let-7a-3p transfected into U87MG glioblastoma cells. Cell viability of the cells was assessed by MTT assay. The apoptotic induction in U87MG cancerous cells was determined through the utilization of DAPI and Annexin V/PI staining techniques. Moreover, the induction of autophagy and cell cycle arrest was evaluated by flow cytometry. Furthermore, cell migration was evaluated by the wound healing assay while colony formation assay was conducted to evaluate colony formation. Also, the expression of the relevant genes was evaluated using qRT-PCR. Transfection of let-7a-3p mimic in U87MG cells increased the expression of the miRNA and also increased the sensitivity of U87MG cells to carmustine. Let-7a-3p and carmustine induced sub-G1 and S phase cell cycle arrest, respectively. Combination treatment of let-7a-3p and carmustine synergistically increased arrested cells and induced apoptosis through regulating involved genes including P53, caspase-3, Bcl-2, and Bax. Combined treatment with let-7a-3p and carmustine also induced autophagy and increased the expression of the ATG5 and Beclin 1 (ATG6). Furthermore, let-7a-3p combined with carmustine inhibited cell migration via decreasing the expression of MMP-2. Moreover, the combination therapy decreased the ability of U87MG to form colonies through downregulating CD-44. In conclusion, our work suggests that combining let-7a-3p replacement therapy with carmustine treatment could be considered a promising strategy in treatment and can increase efficiency of glioblastoma chemotherapy. Summary of conducted assays in this research. After selection of let-7a-3p, this miRNA transfected into U87MG cells via electroporation. Optimum dose and time of the miRNA were evaluated by the qRT-PCR. In order to find IC50 of the carmustine, U87MG cells were treated with different doses of this chemotherapy drug and MTT assay conducted. Then cells were transfected with optimum doses of let-7a-3p and treated with IC50 of carmustine. In order to assess the combined effect of these two methods, apoptosis induction, cell cycle arrest, autophagy induction, cell migration, colony formation, and expression of the involved genes were evaluated. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Peripheral T‐cell lymphomas (PTCL) frequently result in relapsed or refractory diseases. Upfront autologous hematopoietic stem cell transplantation (ASCT) using the BEAM (carmustine, etoposide, cytarabine, and melphalan) regimen is recommended. However, relapses are common in PTCL, highlighting a critical need for improved survival outcomes in these patients. Objective Anthracycline drugs are essential in treating PTCL. We compared the efficacy and tolerability of a high‐dose mitoxantrone‐based conditioning regimen [mitoxantrone, cyclophosphamide, and etoposide (MCE)] to the BEAM regimen in upfront ASCT for newly diagnosed PTCL patients who achieved complete or partial remission after induction therapy. Study Design A retrospective study was conducted to analyze the treatment response, progression‐free survival (PFS), overall survival (OS), hematologic engraftment time, and adverse events of 64 patients between two regimens, who achieved complete or partial remission after induction chemotherapy. Twenty‐eight patients received the MCE regimen, while 36 patients were treated with the BEAM regimen. Results There were no significant differences in clinical characteristics or the incidence of adverse events between the two groups. However, the median OS significantly favored the MCE group at 102.4 (95% CI, 87.0–117.8) months compared to 62.6 (95% CI, 50.8–74.5) months in the BEAM group (p = 0.023). Similarly, the median PFS was longer in the MCE group at 87.8 (95% CI, 65.8–109.8) months versus 42.5 (95% CI, 30.0–55.0) months in the BEAM group (p = 0.031). Conclusion ASCT with the mitoxantrone‐based conditioning regimen is tolerable and appears to significantly improve the prognosis of PTCL patients, offering a promising alternative to the current standard of care.

For missions beyond low Earth orbit to the moon or Mars, space explorers will encounter a complex radiation field composed of various ion species with a broad range of energies. Such missions pose significant radiation protection challenges that need to be solved in order to minimize exposures and associated health risks. An innovative galactic cosmic ray simulator (GCRsim) was recently developed at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL). The GCRsim technology is intended to represent major components of the space radiation environment in a ground analog laboratory setting where it can be used to improve understanding of biological risks and serve as a testbed for countermeasure development and validation. The current GCRsim consists of 33 energetic ion beams that collectively simulate the primary and secondary GCR field encountered by humans in space over the broad range of particle types, energies, and linear energy transfer (LET) of interest to health effects. A virtual workshop was held in December 2020 to assess the status of the NASA baseline GCRsim. Workshop attendees examined various aspects of simulator design, with a particular emphasis on beam selection strategies. Experimental results, modeling approaches, areas of consensus, and questions of concern were also discussed in detail. This report includes a summary of the GCRsim workshop and a description of the current status of the GCRsim. This information is important for future advancements and applications in space radiobiology.

Drug delivery systems (DDSs) are used to transport drugs which are characterized by some pharmaceutical problems to the specific target site, enhancing therapeutic efficacy and reducing off-target accumulation in the body. In this work, one of the recently synthesized molecules, 1,10-N,N'-bis-(β-ᴅ-ureidocellobiosyl)-4,7,13,16-tetraoxa-1,10-diazacyclooctadecane (TN), was tested as a potential drug carrier towards the anticancer drug carmustine. For this purpose, different techniques were used, from synthesis and calculations to cytotoxicity assessment. Our results showed that TN is characterized by a very compact geometry, which significantly impacts its complexation properties. Although it forms a very stable complex with carmustine, it adopts a non-inclusion geometry, as verified by both experimental and theoretical NMR analyses. The cytotoxicity study performed for all analyzed molecules (TN; carmustine; TN:carmustine complex) towards normal and cancer (breast and colon) cells revealed that TN is not toxic and that the formation of complexes with carmustine reduces the toxicity of carmustine to normal cells. [ABSTRACT FROM AUTHOR]

Peripheral T-cell lymphomas are rare heterogeneous haematological malignancies that may also involve peripheral nerves in a very small subset of cases. We report a patient with a diagnostically challenging cutaneous T-cell lymphoma and multifocal mononeuropathies in whom a targeted nerve biopsy identified lymphomatous infiltration of nerves and expedited combination treatment with chemotherapy and an autologous stem cell transplant. She showed an excellent response with a complete metabolic response on positron emission tomography imaging and significant clinical improvement, maintained 5 years post-treatment. [ABSTRACT FROM AUTHOR]

The delivery of chemotherapeutics through the blood-brain barrier remains a challenge for glioblastoma therapeutics. The overdosage of these agents also causes severe side effects among patients. Hence, there has been an urge to find alternative techniques to deliver these agents to the targeted site with limited dosage having a maximum outcome. However, when these drugs incorporated into liposomes are directed toward the tumor site, there is a higher possibility of the drugs crossing the barrier and rendering their mode of action. In our study, we aimed at formulating pH-responsive nanoliposomes loaded with carmustine that possesses selective toxicity on U87MG cells owing to the acidic pH and also evaluated their efficacy in seizing endothelial sprouting. [ABSTRACT FROM AUTHOR]