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International Journal of Molecular... Apr 2024Gonadotoxic agents could impair spermatogenesis and may lead to male infertility. The present study aimed to evaluate the effect of IL-1β on the development of...
Gonadotoxic agents could impair spermatogenesis and may lead to male infertility. The present study aimed to evaluate the effect of IL-1β on the development of spermatogenesis from cells isolated from seminiferous tubules (STs) of normal and busulfan-treated immature mice in vitro. Cells were cultured in a 3D in vitro culture system for 5 weeks. We examined the development of cells from the different stages of spermatogenesis by immunofluorescence staining or qPCR analyses. Factors of Sertoli and Leydig cells were examined by qPCR analysis. We showed that busulfan (BU) treatment significantly reduced the expression of testicular IL-1β in the treated mice compared to the control group (CT). Cultures of cells from normal and busulfan-treated immature mice induced the development of pre-meiotic (Vasa), meiotic (Boule), and post-meiotic (acrosin) cells. However, the percentage of developed Boule and acrosin cells was significantly lower in cultures of busulfan-treated mice compared to normal mice. Adding IL-1β to both cultures significantly increased the percentages of Vasa, Boule, and acrosin cells compared to their controls. However, the percentage of Boule and acrosin cells was significantly lower from cultures of busulfan-treated mice that were treated with IL-1β compared to cultures treated with IL-1β from normal mice. Furthermore, addition of IL-1β to cultures from normal mice significantly increased only the expression of androgen receptor and transferrin but no other factors of Sertoli cells compared to their CT. However, the addition of IL-1β to cultures from busulfan-treated mice significantly increased only the expression of androgen-binding protein and the FSH receptor compared to their CT. Adding IL-1β to cultures of normal mice did not affect the expression of 3βHSD compared to the CT, but it significantly reduced its expression in cultures from busulfan-treated mice compared to the CT. Our findings demonstrate the development of different stages of spermatogenesis in vitro from busulfan-treated mice and that IL-1β could potentiate this development in vitro.
Topics: Animals; Busulfan; Spermatogenesis; Male; Interleukin-1beta; Mice; Sertoli Cells; Testis; Leydig Cells; Seminiferous Tubules; Cells, Cultured
PubMed: 38732137
DOI: 10.3390/ijms25094926 -
Scientific Reports May 2024While some clinics have adopted abbreviated neoadjuvant treatment for HER2-positive breast cancer, there remains a shortage of comprehensive clinical data to support... (Comparative Study)
Comparative Study
While some clinics have adopted abbreviated neoadjuvant treatment for HER2-positive breast cancer, there remains a shortage of comprehensive clinical data to support this practice. This is a retrospective, multicenter study. A total of 142 patients were included in the study who are HER2-positive breast cancer, aged ≤ 65 years, with left ventricular ejection fraction ≥ 50%, received neoadjuvant chemotherapy and underwent surgery at 10 different oncology centers in Türkiye between October 2016 and December 2022. The treatment arms were divided into 4-6 cycles of docetaxel/trastuzumab/pertuzumab for arm A, 4 cycles of adriamycin/cyclophosphamide followed by 4 cycles of taxane/TP for arm B. There were 50 patients (35.2%) in arm A and 92 patients (64.8%) in arm B. The median follow-up of all of the patients was 19.9 months (95% CI 17.5-22.3). The 3-year DFS rates for treatment arms A and B were 90.0% and 83.8%, respectively, and the survival outcomes between the groups were similar (p = 0.34). Furthermore, the pathologic complete response rates were similar in both treatment arms, at 50.0% and 51.1%, respectively (p = 0.90). This study supports shortened neoadjuvant treatment of HER2-positive breast cancer, a common practice in some clinics.
Topics: Humans; Breast Neoplasms; Female; Middle Aged; Neoadjuvant Therapy; Receptor, ErbB-2; Anthracyclines; Adult; Antineoplastic Combined Chemotherapy Protocols; Retrospective Studies; Trastuzumab; Cyclophosphamide; Docetaxel; Taxoids; Doxorubicin; Bridged-Ring Compounds; Treatment Outcome; Aged; Antibodies, Monoclonal, Humanized
PubMed: 38724585
DOI: 10.1038/s41598-024-61562-w -
Therapeutic Drug Monitoring Jun 2024
Topics: Tandem Mass Spectrometry; Humans; Busulfan; Chromatography, High Pressure Liquid; Polyethylene Glycols; Drug Monitoring; Immunosuppressive Agents
PubMed: 38723116
DOI: 10.1097/FTD.0000000000001212 -
Pediatric Blood & Cancer Aug 2024The addition of rituximab to standard regimens for primary mediastinal large B-cell lymphoma (PMBCL) has significantly improved overall survival. However, the optimal...
The addition of rituximab to standard regimens for primary mediastinal large B-cell lymphoma (PMBCL) has significantly improved overall survival. However, the optimal management of isolated central nervous system (CNS) relapse and role of CNS prophylaxis remains undefined. We present cases of two adolescents with PMBCL who developed isolated CNS relapses. While isolated CNS relapse may be managed with high-dose chemotherapy and autologous stem cell transplant with or without CNS radiotherapy, review of these cases and the literature highlight the need for further work to define risk factors for CNS relapse, and identify patients who may benefit from CNS prophylaxis.
Topics: Humans; Mediastinal Neoplasms; Adolescent; Lymphoma, Large B-Cell, Diffuse; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Male; Rituximab; Vincristine; Etoposide; Doxorubicin; Cyclophosphamide; Female; Prednisone; Neoplasm Recurrence, Local
PubMed: 38721853
DOI: 10.1002/pbc.31065 -
International Journal of Gynecological... May 2024
Durable response in platinum refractory small cell carcinoma of the ovary hypercalcemic type treated with combination pembrolizumab, oral cyclophosphamide, and bevacizumab.
Topics: Humans; Female; Bevacizumab; Cyclophosphamide; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Ovarian Neoplasms; Carcinoma, Small Cell; Hypercalcemia; Middle Aged
PubMed: 38719275
DOI: 10.1136/ijgc-2024-005321 -
The New England Journal of Medicine May 2024
Topics: Humans; Male; Polyarteritis Nodosa; Middle Aged; Tomography, X-Ray Computed; Angiography; Arteries; Abdomen; Glucocorticoids; Cyclophosphamide; Immunosuppressive Agents; Administration, Oral
PubMed: 38718361
DOI: 10.1056/NEJMicm2309365 -
PloS One 2024M-type phospholipase A2 receptor (PLA2R) is a major auto-antigen of primary membranous nephropathy(PMN). Anti-PLA2R antibody levels are closely associated with disease...
BACKGROUND
M-type phospholipase A2 receptor (PLA2R) is a major auto-antigen of primary membranous nephropathy(PMN). Anti-PLA2R antibody levels are closely associated with disease severity and therapeutic effectiveness. Analysis of PLA2R antigen epitope reactivity may have a greater predictive value for remission compared with total PLA2R-antibody level. This study aims to elucidate the relationship between domain-specific antibody levels and clinical outcomes of PMN.
METHODS
This retrospective analysis included 87 patients with PLA2R-associated PMN. Among them, 40 and 47 were treated with rituximab (RTX) and cyclophosphamide (CTX) regimen, respectively. The quantitative detection of -immunoglobulin G (IgG)/-IgG4 targeting PLA2R and its epitope levels in the serum of patients with PMN were obtained through time-resolved fluorescence immunoassays and served as biomarkers in evaluating the treatment effectiveness. A predictive PMN remission possibility nomogram was developed using multivariate logistic regression analysis. Discrimination in the prediction model was assessed using the area under the receiver operating characteristic curve (AUC-ROC).Bootstrap ROC was used to evaluate the performance of the prediction model.
RESULTS
After a 6-month treatment period, the remission rates of proteinuria, including complete remission and partial remission in the RTX and CTX groups, were 70% and 70.21% (P = 0.983), respectively. However, there was a significant difference in immunological remission in the PLA2R-IgG4 between the RTX and CTX groups (21.43% vs. 61.90%, P = 0.019). Furthermore, we found differences in PLA2R-CysR-IgG4(P = 0.030), PLA2R-CTLD1-IgG4(P = 0.005), PLA2R-CTLD678-IgG4(P = 0.003), and epitope spreading (P = 0.023) between responders and non-responders in the CTX group. Multivariate logistic analysis showed that higher levels of urinary protein (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.26-0.95; P = 0.035) and higher levels of PLA2R-CTLD1-IgG4 (OR, 0.79; 95%CI,0.62-0.99; P = 0.041) were independent risk factors for early remission. A multivariate model for estimating the possibility of early remission in patients with PMN is presented as a nomogram. The AUC-ROC of our model was 0.721 (95%CI, 0.601-0.840), in consistency with the results obtained with internal validation, for which the AUC-ROC was 0.711 (95%CI, 0.587-0.824), thus, demonstrating robustness.
CONCLUSIONS
Cyclophosphamide can induce immunological remission earlier than rituximab at the span of 6 months. The PLA2R-CTLD1-IgG4 has a better predict value than total PLA2R-IgG for remission of proteinuria at the 6th month.
Topics: Humans; Glomerulonephritis, Membranous; Receptors, Phospholipase A2; Male; Female; Retrospective Studies; Middle Aged; Rituximab; Remission Induction; Autoantibodies; Adult; Immunoglobulin G; Cyclophosphamide; Aged; ROC Curve; Treatment Outcome
PubMed: 38718066
DOI: 10.1371/journal.pone.0302100 -
Revista Da Associacao Medica Brasileira... 2024We aimed to investigate the effect of coenzyme q10 on cyclophosphamide-induced kidney damage in rats.
OBJECTIVE
We aimed to investigate the effect of coenzyme q10 on cyclophosphamide-induced kidney damage in rats.
METHODS
A total of 30 female Wistar-Albino rats were utilized to form three groups. In group 1 (control group) (n=10), no drugs were given. In group 2 (cyclophosphamide group) (n=10), 30 mg/kg intraperitoneal cyclophosphamide was administered for 7 days. In group 3 (cyclophosphamide+coenzyme q10 group) (n=10), 30 mg/kg cyclophosphamide and 10 mg/kg coenzyme q10 were given for 7 days via intraperitoneal route. Right kidneys were removed in all groups. Blood malondialdehyde levels and activities of catalase and superoxide dismutase were measured. Histopathological damage was evaluated by examining the slides prepared from kidney tissue using a light microscope.
RESULTS
Tissue damage was significantly higher in the cyclophosphamide group than in the cyclophosphamide+coenzyme q10 group (p<0.05). The malondialdehyde levels were significantly higher and the activities of superoxide dismutase and catalase were lower in the cyclophosphamide group than in the cyclophosphamide+coenzyme q10 group (p<0.05).
CONCLUSION
Coenzyme q10 may be a good option to prevent cyclophosphamide-induced kidney damage.
Topics: Animals; Ubiquinone; Cyclophosphamide; Female; Rats, Wistar; Malondialdehyde; Catalase; Superoxide Dismutase; Kidney; Rats; Kidney Diseases; Antioxidants; Oxidative Stress
PubMed: 38716935
DOI: 10.1590/1806-9282.20230990 -
Revista Da Associacao Medica Brasileira... 2024Anticipatory nausea and vomiting are unpleasant symptoms observed before undergoing chemotherapy sessions. Less is known about the occurrence of symptoms since the...
OBJECTIVE
Anticipatory nausea and vomiting are unpleasant symptoms observed before undergoing chemotherapy sessions. Less is known about the occurrence of symptoms since the advent of the new neurokinin-1 antagonist.
METHODS
This prospective cohort study was performed at a single Brazilian Institution. This study included breast cancer patients who received doxorubicin and cyclophosphamide chemotherapy and an appropriate antiemetic regimen (dexamethasone 10 mg, palonosetron 0.56 mg, and netupitant 300 mg in the D1 followed by dexamethasone 10 mg 12/12 h in D2 and D4). Patients used a diary to record nausea, vomiting, and use of rescue medication in the first two cycles of treatment. The prevalence of anticipatory nausea and vomiting was assessed before chemotherapy on day 1 of C2.
RESULTS
From August 4, 2020, to August 12, 2021, 60 patients were screened, and 52 patients were enrolled. The mean age was 50.8 (28-69) years, most had stage III (53.8%), and most received chemotherapy with curative intent (94%). During the first cycle, the frequency of overall nausea and vomiting was 67.31%, and that of severe nausea and vomiting (defined as grade>4 on a 10-point visual scale or use of rescue medication) was 55.77%. Ten patients had anticipatory nausea and vomiting (19.23%). The occurrence of nausea and vomiting during C1 was the only statistically significant predictor of anticipatory nausea and vomiting (OR=16, 95%CI 2.4-670.9, p=0.0003).
CONCLUSION
The prevalence of anticipatory nausea is still high in the era of neurokinin-1 antagonists, and failure of antiemetic control in C1 remains the main risk factor. All efforts should be made to control chemotherapy-induced nausea or nausea and vomiting on C1 to avoid anticipatory nausea.
Topics: Humans; Female; Breast Neoplasms; Middle Aged; Prospective Studies; Adult; Antiemetics; Aged; Nausea; Prevalence; Brazil; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Vomiting, Anticipatory; Vomiting; Dexamethasone; Palonosetron
PubMed: 38716933
DOI: 10.1590/1806-9282.20230937 -
Zhonghua Xue Ye Xue Za Zhi = Zhonghua... Mar 2024To analyze the efficacy of allo-HSCT with total body irradiation (TBI) and chemotherapy alone in the treatment of adult ALL and to explore the factors affecting...
To analyze the efficacy of allo-HSCT with total body irradiation (TBI) and chemotherapy alone in the treatment of adult ALL and to explore the factors affecting prognosis. The clinical data of 95 adult patients with ALL who underwent allo-HSCT from January 2015 to August 2022 were included. According to the conditioning regimen, the patients were divided into two groups: the TBI plus cyclophosphamide (TBI/Cy) group (=53) and the busulfan plus cyclophosphamide (Bu/Cy) group (=42). Hematopoietic reconstitution after transplantation, GVHD, transplantation-related complications, relapse rate (RR), non-relapse mortality (NRM), OS, and LFS were compared, and the factors related to prognosis were analyzed. The median time of neutrophil engraftment was 14 (10-25) days in the TBI/Cy group and 14 (10-24) days in the Bu/Cy group (=0.106). The median time of megakaryocyte engraftment was 17 (10-42) days in the TBI/Cy group and 19 (11-42) days in the Bu/Cy group (=0.488). The incidence of grade Ⅱ-Ⅳ acute GVHD (aGVHD) in the TBI/Cy and Bu/Cy groups was 41.5% and 35.7%, respectively (=0.565). The incidence of grade Ⅲ-Ⅳ aGVHD in these two groups was 24.5% and 4.8%, respectively (=0.009). The incidence of severe chronic GVHD in the two groups was 16.7% and 13.5%, respectively (=0.689). The incidence of cytomegalovirus infection, Epstein-Barr virus infection, severe infection, and hemorrhagic cystitis in the two groups was 41.5% and 35.7% (=0.565), 34.0% and 35.7% (=0.859), 43.4% and 33.3% (=0.318), and 20.8% and 50.0% (=0.003), respectively. The median follow-up time was 37.1 months and 53.3 months in the TBI/Cy and Bu/Cy groups, respectively. The 2-year cumulative RR was 17.0% in the TBI/Cy group and 42.9% in the Bu/Cy group (=0.017). The 2-year cumulative NRM was 24.5% and 7.1%, respectively (=0.120). The 2-year LFS was 58.5% and 50.0%, respectively (=0.466). The 2-year OS rate was 69.8% and 64.3%, respectively (=0.697). In the multivariate analysis, the conditioning regimen containing TBI was a protective factor for relapse after transplantation (=0.304, 95% 0.135-0.688, =0.004), whereas the effect on NRM was not significant (=1.393, 95% 0.355-5.462, =0.634). Infection was an independent risk factor for OS after allo-HSCT in adult patients with ALL. allo-HSCT based on TBI conditioning regimen had lower relapse rate and lower incidence of hemorrhagic cystitis for adult ALL, compared with chemotherapy regimen. While the incidence o grade Ⅲ/Ⅳ aGVHD was hgher in TBI conditioning regimen than that in chemotherapy regimen.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Whole-Body Irradiation; Transplantation Conditioning; Transplantation, Homologous; Prognosis; Adult; Survival Rate; Graft vs Host Disease; Cyclophosphamide; Male; Female; Middle Aged
PubMed: 38716596
DOI: 10.3760/cma.j.cn121090-20230822-00084