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Background: Ovarian cancer is a leading cause of death from gynecological cancer in the world and in India. This study aims to evaluate the efficacy and toxicity profile of oral metronomic chemotherapy (MCT) in the form of etoposide, cyclophosphamide, and tamoxifen in recurrent and metastatic ovarian cancer. Methods: This was a retrospective observational study that included those post?treatment patients who had the recurrent or metastatic disease after completion of treatment in 2018 at Regional Cancer Centre, Bikaner, Rajasthan. Forty patients who were unfit for further intensive intravenous chemotherapy were included. The oral MCT constituted etoposide, cyclophosphamide, and tamoxifen. Descriptive statistics and Kaplan?Meier analyses were performed. Progression?free survival (PFS) and overall survival (OS) were assessed. Results: Forty women with a median age of 62 (range: 35?80) years were enrolled in the study to receive oral MCT. The Eastern Cooperative Oncology Group?Performance Status (ECOG?PS) was 0�in 28 patients and 2�in 12 patients. The best clinical response rate post?oral MCT was seen in the first 4 months. Objective response was observed in 24 (60%) of patients in the form of stable disease (19, 47.5%) and partial response (5, 12.5%). Disease progression was observed in 10 (25%) of patients. The median follow?up was 6.4 months (4.5�2 months). The median estimated OS was 6.5 months. The median estimated PFS was 3.7 months. Nineteen (47.5%) patients had grade?I/II mucositis. Grade?III/IV mucositis were observed in 9 (22.5%) patients. Thirty?seven (92.5%) patients died at the end of the study at 1 year. Dose reduction was required in 15 (37.5%) patients. Conclusion: Oral MCT was found to be an effective and well?tolerated regime with good symptomatic control and low?moderate toxicity profile in patients with relapsed and metastatic ovarian cancer. However, 22% of patients showed grade?III/IV thrombocytopenia.
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ABSTRACT Membranous nephropathy is a glomerulopathy, which main affected target is the podocyte, and has consequences on the glomerular basement membrane. It is more common in adults, especially over 50 years of age. The clinical presentation is nephrotic syndrome, but many cases can evolve with asymptomatic non-nephrotic proteinuria. The mechanism consists of the deposition of immune complexes in the subepithelial space of the glomerular capillary loop with subsequent activation of the complement system. Great advances in the identification of potential target antigens have occurred in the last twenty years, and the main one is the protein "M-type phospholipase-A2 receptor" (PLA2R) with the circulating anti-PLA2R antibody, which makes it possible to evaluate the activity and prognosis of this nephropathy. This route of injury corresponds to approximately 70% to 80% of cases of membranous nephropathy characterized as primary. In the last 10 years, several other potential target antigens have been identified. This review proposes to present clinical, etiopathogenic and therapeutic aspects of membranous nephropathy in a didactic manner, including cases that occur during kidney transplantation.
RESUMO A nefropatia membranosa é uma glomerulopatia, cujo principal alvo acometido é o podócito, e acarreta consequências na membrana basal glomerular. Tem maior frequência em adultos, principalmente acima dos 50 anos. A apresentação clínica é a síndrome nefrótica, mas muitos casos podem evoluir com proteinúria não nefrótica assintomática. O mecanismo consiste na deposição de complexos imunes no espaço subepitelial da alça capilar glomerular com subsequente ativação do sistema do complemento. Grandes avanços na identificação de potenciais antígenos alvo têm ocorrido nos últimos vinte anos, e o principal é a proteína "M-type phospholipase-A2 receptor" (PLA2R) com o anticorpo anti-PLA2R circulante, o que possibilita avaliar a atividade e o prognóstico dessa nefropatia. Essa via de lesão corresponde aproximadamente a 70% a 80% dos casos da nefropatia membranosa caracterizada como primária. Nos últimos 10 anos vários outros antígenos alvo potenciais têm sido identificados. Esta revisão se propõe a apresentar de modo didático aspectos clínicos, etiopatogênicos e terapêuticos da nefropatia membranosa, incluídos os casos com ocorrência no transplante renal.
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Abstract Background Dexamethasone-cyclophosphamide pulse (DCP) and dexamethasone pulse (DP) have been successfully used to treat pemphigus, but DCP/DP outcomes comparing pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are scarce. Objective To compare DCP/DP outcomes in a Brazilian cohort of PV and PF patients according to demographic and clinical data. Methods Retrospective analytical cohort study, reviewing medical charts of PV and PF patients (for DCP/DP Phases I‒IV consult Pasricha et al.16‒18). Results 37 PV and 41 PF patients non responsive to usual treatments were included similarly for DCP or DP therapy. Disease duration was longer among PF before DCP/DP prescription (p < 0.001); PF required a higher number of monthly pulses to acquire remission in Phase I (median 10 and 6 pulses, respectively; p = 0.005). DCP/DP outcomes were similar in both groups: remission in 37.8% of PV and 34.1% of PF after completed DCP/DP cycles following a median of 13 months (1-56 months follow-up); failure occurred in 13.5% of PV and 14.6% of PF in Phase I; relapse in 13.5% of PV and 12.2% of PF, and dropout in 27% of PV and 24.4% of PF in Phases II to IV. Mild side effects were documented. Study limitations The severity of PV and PF disease was not assessed by score indexes. Conclusions PV and PF patients presented similar DCP/DP outcomes. DCP/DP should be initiated earlier in PF patients due to the longer duration of their disease in order to decrease the number of pulses and the duration of Phase I to acquire remission.
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Resumen ANTECEDENTES: Durante el embarazo es más común el linfoma de Hodking que el no Hodking; afecta, en promedio, a mujeres de 30 años (18-44 años) y más. Suele diagnosticarse alrededor de las 28 semanas de embarazo y está documentado que puede llegarse al término. Los esquemas de tratamiento pueden iniciarse en el posparto inmediato o, incluso, antes. La incidencia mundial del linfoma no Hodking es de 0.8 por cada 100,000 mujeres; se desconoce la supervivencia durante el embarazo. CASO CLINICO: Paciente de 34 años, con antecedentes obstétricos de tres embarazos, una cesárea y un aborto y el embarazo actual en curso de las 29 semanas, referida de la ciudad de Colima debido a un reporte de BI-RADS 3 en el ultrasonido de mama y un nódulo mamario palpable, con evidencia de múltiples tumoraciones en la zona hepática, esplénica y peripancreática. La biopsia tomada de las zonas de la lesión reportó: linfoma de células B de alto grado de malignidad, con morfología blastoide y expresión de C-MYC y BCL2. Además, la paciente se encontró con: anemia, dolor abdominal, múltiples nódulos hepáticos y adenopatías abdominales. Se decidió la interrupción del embrazo a las 30 semanas, con la obtención de un recién nacido, sin complicaciones. Enseguida se inició el tratamiento con rituximab-etopósido-prednisolona-vincristina-ciclofosfamida-doxorrubicina (R-EPOCH) con adecuada adaptación por la paciente. CONCLUSION: Puesto que la información bibliográfica de linfoma y embarazo es escasa el caso aquí reportado es relevante por su aporte. La atención multidisciplinaria favorecerá siempre el pronóstico de las pacientes.
Abstract BACKGROUND: Hodking's lymphoma is more common during pregnancy than non-Hodking's lymphoma; it affects, on average, women aged 30 years (18-44 years) and older. It is usually diagnosed around 28 weeks of pregnancy and is documented to be carried to term. Treatment regimens can be initiated in the immediate postpartum period or even earlier. The worldwide incidence of non-Hodking's lymphoma is 0.8 per 100,000 women; survival during pregnancy is unknown. CLINICAL CASE: 34-year-old patient, with obstetric history of three pregnancies, one cesarean section and one abortion and the current pregnancy in progress at 29 weeks, referred from the city of Colima due to a report of BI-RADS 3 on breast ultrasound and a palpable breast nodule, with evidence of multiple tumors in the hepatic, splenic and peripancreatic area. Biopsy taken from the lesion areas reported: high grade malignant B-cell lymphoma, with blastoid morphology and expression of C-MYC and BCL2. In addition, the patient was found to have: anemia, abdominal pain, multiple hepatic nodules and abdominal adenopathies. It was decided to terminate the pregnancy at 30 weeks, with the delivery of an uncomplicated newborn. Rituximab-Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (R-EPOCH) therapy was started immediately with adequate adaptation by the patient. CONCLUSION: Since bibliographic information on lymphoma and pregnancy is scarce, the case reported here is relevant for its contribution. Multidisciplinary care will always favor the prognosis of patients.
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ABSTRACT Objective To assess the incidence of febrile neutropenia without primary granulocyte colony-stimulating factor prophylaxis in patients undergoing chemotherapy with adjuvant docetaxel and cyclophosphamide, and to evaluate the toxicity profile of brand-name docetaxel (Taxotere ® ) and the generic formulation. Methods This retrospective study was conducted using data obtained from electronic medical records of patients treated at a Brazilian cancer center. Patients with breast cancer who underwent adjuvant treatment between January 2016 and June 2019 were selected. Data were analyzed using chi-square and Fisher correlation of variables, and multivariate analyses were adjusted for propensity score. Results A total of 231 patients with a mean age of 55.9 years at the time of treatment were included in the study. The majority (93.9%) had luminal histology, 84.8% were at clinical stage I, and 98.2% had a good performance status. The overall incidence of febrile neutropenia in the study population was 13.4% (31 cases). The use of brand-name docetaxel (Taxotere ® ) was the only factor associated with febrile neutropenia occurrence (OR= 3.55, 95%CI= 1.58-7.94, p=0.002). Conclusion In patients with breast cancer who require treatment with adjuvant docetaxel and cyclophosphamide regimen, the toxicity profile differs between brand-name and generic docetaxel. Regardless of the formulation used, the incidence of febrile neutropenia was less than 20%, which may allow for the omission of primary prophylactic granulocyte colony-stimulating factor use in this setting.
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The study aims to explore the effects and mechanisms of water extract of Potentilla anserina (PA) on myelosuppression mice induced by cyclophosphamide based on metabonomics. The myelosuppressive mouse model was established by injected with cyclophosphamide and treated with water extract of PA. Thymus and spleen indexes, peripheral hemogram and bone marrow nucleated cells of each group was detected. Bone marrow pathology analysis was performed by hematoxylin-eosin staining. The levels of interleukin 3 (IL-3), interleukin 6 (IL-6), erythropoietin (EPO), granulocyte colony stimulating factor (GM-CSF), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were measured. The changes of biomarkers and related metabolic pathways were analyzed by UPLC-Q-TOF/MS-based metabonomics. Animal experiments were approved by the Animal Ethics Committee of Southwest Minzu University. The high doses of PA could significantly improve the decrease of white blood cell (WBC), red blood cell (RBC) counts and hemoglobin (HGB) levels of mice induced by cyclophosphamide (P < 0.05), and significantly increase the number of nucleated cells and the area of hematopoietic tissue in femoral bone marrow. The medium and high doses of PA could significantly improve the serum levels of SOD, CAT, MDA, IL-6 and GM-CSF (P < 0.05), and have no significant effect on the expression of IL-3 and EPO (P > 0.05). Serum metabolomics analysis showed that the aqueous extracts of PA could alleviate myrosuppression by regulating the aminoacyl-tRNA, valine, leucine and isoleucine biosynthesis mediated by 13 different metabolites such as valine, leucine, asparagine and hydroxyisohexic acid. PA improve the inhibition of hematopoietic function in myelosuppression mouse, and its mechanisms may be related to anti-oxidation and promoting the expression of hematopoietic-related cytokines and regulating the related metabolic pathways.
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Severe aplastic anemia (SAA) is a severe bone marrow failure syndrome caused by multiple causes, which is clinically manifested with severe anemia, infection and bleeding. The complex pathogenesis of SAA has not been fully understood. SAA is characterized with acute onset, severe disease condition and rapid progression. At present, with the in-depth study of SAA and the improvement of diagnosis and treatment, the therapeutic strategy for SAA has been evolved from classical immunosuppressive therapy based on antithymocyte globulin and cyclosporine to the application of thrombopoietin receptor agonist and combined treatment based on allogeneic hematopoietic stem cell transplantation, which may promote the reconstruction of hematopoietic function of SAA patients to varying degree and significantly improve survival and clinical prognosis, becoming the research hotspot of SAA treatment. In this article, new advances in the treatment of SAA at home and abroad were reviewed.
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Objective To evaluate the feasibility of secondary transplantation for patients with acute leukemia after failure of the first haploidentical hematopoietic stem cell transplantation. Methods Two acute leukemia patients underwent the first haploidentical hematopoietic stem cell transplantation from two donors with thalassemia, and the number of collected CD34+ cells was 2.57×106/kg and 1.99×106/kg per donor, respectively. The first haploidentical hematopoietic stem cell transplantation failed. Secondary transplantation was performed from two non-thalassemia donors, and the number of collected CD34+ cells was 4.28×106/kg and 5.75×106/kg per donor, respectively. A reduced-intensity conditioning regimen consisting of fludarabine (Flu), busulfan (Bu) and antithymocyte globulin (ATG) was adopted for the secondary transplantation. Results For two recipients, the time of secondary transplantation of neutrophil and platelet was +12 d and +10 d, +10 d and +10 d, respectively. Up to the final follow-up (+1 062 d and +265 d after secondary transplantation), the primary diseases of both two recipients have been completely relieved without evident post-transplantation complications. Conclusions Secondary transplantation with reduced-intensity conditioning regimen may successfully treat acute leukemia after failure of the first haploidentical hematopoietic stem cell transplantation.
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OBJECTIVE To compare the efficacy， safety and economy of tacrolimus （TAC）， cyclosporin A （CsA）， cyclophosphamide （CTX） and rituximab （RTX） in the treatment of membranous nephropathy （MN）. METHODS Retrieved from Pubmed， the Cochrane Library， Wanfang data， CNKI and health technology assessment （HTA） official website， HTA reports， systematic reviews/meta-analysis and pharmacoeconomic studies about TAC， CsA， CTX and RTX combined with glucocorticoid in the treatment of MN were collected during the inception and Mar. 2022. After data extraction and quality evaluation， descriptive analysis was performed on the results of the included studies. RESULTS A total of 15 articles were included， involving 13 systematic reviews/meta-analysis and 2 pharmacoeconomic studies. In terms of efficacy， TAC and CsA showed significant advantages in increasing the response rate， and could improve the levels of urine protein， serum albumin， serum creatinine and serum total cholesterol. In terms of safety， the incidence of adverse reaction induced by TAC， CsA and RTX was low and the symptoms were mild. In terms of economics， CTX cost lower but caused severe adverse reaction； TAC cost higher but showed higher remission rate and good safety. CONCLUSIONS TAC combined with glucocorticoid may be the recommended scheme for MN.
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@#Choriocarcinoma is a malignant subtype of gestational trophoblastic disease that follows any type of pregnancy. It is characterized by rapid hematogenous spread to multiple organs, associated with high human chorionic gonadotropin levels with good response to chemotherapy. We present the case of a 31‑year‑old Filipina who initially presented with severe headaches and blurring of vision 3 years after an unremarkable term pregnancy. The transvaginal ultrasound was normal. After a series of diagnostic tests, the initial working impression was a primary brain tumor with metastases to the lungs, adrenal, kidney, and vulva. Emergency craniotomy was done due to deteriorating status secondary to an intracranial hemorrhage. The histopathology report showed choriocarcinoma. Chemotherapy using Etoposide‑Methotrexate‑Actinomycin D‑Cyclophosphamide‑Vincristine with high‑dose methotrexate and concomitant whole‑brain irradiation was then instituted with good response. This case highlights the importance of having a high index of suspicion for gestational trophoblastic neoplasia to prevent the performance of unnecessary procedures, leading to a delay in diagnosis and the institution of the appropriate treatment.
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Gestational Trophoblastic DiseaseABSTRACT
ObjectiveTo compare the regulatory effects of five plant polysaccharides on immune function of cyclophosphamide （CTX）-induced immunosuppressed mice by network Meta-analysis， to provide evidence for the clinical application of polysaccharides and the development of effective polysaccharides and oligosaccharides. MethodSeven databases including PubMed， Embase and Web of Science were searched， and studies that met the inclusion criteria were selected. The methodological quality of the included studies was evaluated using the risk of bias tool of Systematic Review Centre for Laboratory Animal Experimentation （SYRCLE）， and the data were analyzed using RStudio and StataSE 17. ResultA total of 62 randomized controlled trials （RCTs） were included， involving 1 512 mice and five plant polysaccharides： Astragalus polysaccharide （APS）， lentinan （LNT）， Ganoderma lucidum polysaccharide （GLP）， Poria cocos polysaccharide （PCC）， and Codonopsis pilosula polysaccharide （CPP）. The network Meta-analysis showed that APS ranked first in increasing spleen index （mean deviation （MD）=3.54， 95% confidence interval （CI） ［2.10， 5.96］）， thymus index （MD=1.98， 95%CI ［1.55， 2.54］） and T helper cells （CD4+）/T suppressor cells （CD8+） （MD=1.63， 95%CI ［1.13， 2.37］）， while CPP ranked first in up-regulating the number of peripheral blood leukocytes （MD=24.16， 95%CI ［8.21， 71.12］）， macrophage phagocytosis index （MD=2.52， 95%CI ［1.32， 4.82］） and immunoglobulin M （IgM） content （MD=1.79， 95%CI ［1.12， 2.85］）. ConclusionAll the five plant polysaccharides can regulate the immune function of immunosuppressed mice. Among them， APS has advantages in elevating spleen index， thymus index and CD4+/CD8+， while CPP focuses on increasing the number of peripheral blood leukocytes， macrophage phagocytosis index and IgM content. Due to limited number and quality of included studies， the conclusions needs to be further verified with large samples and high-quality studies.
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OBJECTIVE@#To observe the effect of wheat-grain moxibustion at "Dazhui" (GV 14), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) on Wnt/β-catenin signaling pathway in bone marrow cell in mice with bone marrow inhibition, and to explore the possible mechanism of wheat-grain moxibustion in treating bone marrow inhibition.@*METHODS@#Forty-five SPF male CD1(ICR) mice were randomly divided into a blank group, a model group and a wheat-grain moxibustion group, 15 mice in each group. The bone marrow inhibition model was established by intraperitoneal injection of 80 mg/kg of cyclophosphamide (CTX). The mice in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6), 3 moxa cones per acupoint, 30 s per moxa cone, once a day, for 7 consecutive days. The white blood cell count (WBC) was measured before modeling, before intervention and 3, 5 d and 7 d into intervention. After intervention, the general situation of mice was observed; the number of nucleated cells in bone marrow was detected; the serum levels of interleukin-3 (IL-3), interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF) were measured by ELISA; the protein and mRNA expression of β-catenin, cyclinD1 and C-Myc in bone marrow cells was measured by Western blot and real-time PCR method.@*RESULTS@#Compared with the blank group, the mice in the model group showed sluggish reaction, unstable gait, decreased body weight, and the WBC, number of nucleated cells in bone marrow as well as serum levels of IL-3, IL-6, GM-CSF were decreased (P<0.01), and the protein and mRNA expression of β-catenin, cyclinD1 and C-Myc was decreased (P<0.01). Compared with the model group, the mice in the wheat-grain moxibustion group showed better general condition, and WBC, the number of nucleated cells in bone marrow as well as serum levels of IL-3, IL-6, GM-CSF were increased (P<0.01, P<0.05), and the protein and mRNA expression of β-catenin, cyclinD1 and C-Myc was increased (P<0.05).@*CONCLUSION@#Wheat-grain moxibustion shows therapeutic effect on bone marrow inhibition, and its mechanism may be related to activating Wnt/β-catenin signaling pathway in bone marrow cells, improving bone medullary hematopoiesis microenvironment and promoting bone marrow cell proliferation.
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Animals , Male , Mice , beta Catenin/metabolism , Bone Marrow/physiopathology , Bone Marrow Cells/physiology , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Interleukin-3/metabolism , Interleukin-6/metabolism , Mice, Inbred ICR , Moxibustion/methods , RNA, Messenger/metabolism , Triticum , Wnt Signaling Pathway , HematopoiesisABSTRACT
The battle against SARS-COV-2 is rising and the hope in the safety and effectiveness of immunization against this virus is growing up, even though serious and severe adverse events are scarcely observed. In this article, we report a case of mRNA vaccine induced an autoimmune dermatomyositis with features of severity that are managed by immunosuppressants medications and still in regular follow-up. Inflammatory dermatomyositis can be triggered after vaccination with COVID vaccine in the same mechanism that COVID-19 infection-induced myositis.
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Introduction: Scleroderma is a multisystem autoimmune connective tissue disease with approximately 90% of patients having lung involvement. It is the leading cause of morbidity and mortality in scleroderma. There is no effective treatment once there is lung involvement in the form of fibrosis. Study setting: Conducted in a tertiary care center between January 2017 and December 2019. Aim: To evaluate the efficacy of intravenous cyclophosphamide in patients with scleroderma-associated interstitial lung disease (ILD). Study population: Symptomatic patient with scleroderma with high-resolution computed tomography (HRCT)-proven non-specific interstitial pneumonia (NSIP)-pattern ILD. Methodology: Patients received 12 cycles of cyclophosphamide at a dose of 10 mg/kg every 4 weeks. Patients were followed up for 1 year after treatment completion. A six-minute walk test (6MWT) and spirometry were done at baseline and then every 6 months up to 2 years. Diffusing capacity of lung for carbon monoxide (DLCO) was done at baseline and then yearly for up to 2 years. Results: A total of 38 patients completed the study. The majority of patients had diffuse cutaneous type of systemic sclerosis. Throughout the study period, there was a gradual worsening of dyspnea as measured by the Modified Medical Research Council (mMRC) scale. Mean forced vital capacity (FVC) improved with 1 year of treatment, but later steadily decreased during follow-up. Similarly, DLCO also improved during 1-year treatment, but the improvement was not sustained during follow-up. There was a statistically significant improvement in 6MWD at the end of 6 months. This was followed by a gradual fall in 6MWD during follow-up. The only adverse event noted was persistent leukopenia in one patient. Conclusion: Intravenous pulse cyclophosphamide therapy in patients with scleroderma-associated ILD is associated with stabilization of pulmonary function during the treatment period, but not maintained during follow-up.
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Introduction. Cyclophosphamide (CP) is used to treat malignant neoplasias and control autoimmune diseases. Still, one of its metabolites, acrolein, is toxic to the urothelium and can lead to hemorrhagic cystitis and severe discomfort. Objective.To evaluate the ability of red propolis to prevent and treat CP-induced hemorrhagic cystitis in rats. Materials and methods. Red propolis was extracted in 1% gum arabic and administered subcutaneously (sc). In the first experiment, groups IA, IIA, and IIIA and groups IB, IIB, and IIIB received water, gum arabic (GA), or propolis, respectively, for 30 days. Then water (controls) or CP (treatment) was administered i.p. In the second experiment, groups IVA, VA, and VIA received water i.p. while groups IVB, VB, and VIB received CP i.p. This was followed by 5 injections at 2-hour intervals with either water, GA, or propolis. Bladder tissue was examined according to Gray's criteria. Results. The total inflammatory histology score was significantly smaller in group VIB (11.33 ± 2.07). Mild inflammation predominated in group VIB while most of the animals in group IVB had severe inflammation (p=0.0375). Ulcers were predominantly multiple in Groups IVA and VB but rare or absent in Group VIB (p=0.0118). Urothelial cells were mostly absent in groups IVB and VB and present/normal in group VIB (p=0.0052). Fibrin was abundant in groups IVB and VA but mostly absent in group VIB (p=0.0273). Conclusions. Red propolis can reduce inflammation in CP-induced hemorrhagic cystitis in rats.
Introducción. La ciclofosfamida se usa para tratar neoplasias malignas y controlar enfermedades autoinmunitarias, pero uno de sus metabolitos, la acroleína, es tóxico para el urotelio y puede provocar cistitis hemorrágica y malestar grave. Objetivo. Evaluar la capacidad del propóleos rojo para prevenir y tratar la cistitis hemorrágica inducida por ciclofosfamida en ratas. Materiales y métodos. Se extrajo propóleos rojo en goma arábiga al 1 % y se administró por vía subcutánea. En el primer experimento, los grupos IA, IIA, IIIA, IB, IIB y IIIB recibieron agua, goma arábiga y propóleos, respectivamente, durante 30 días. Luego se les administró agua (controles) o el tratamiento (ciclofosfamida) por inyección intraperitoneal. En el segundo experimento, los grupos IVA, VA, VIA recibieron agua por vía intraperitoneal, y los grupos IVB, VB, VIB recibieron el tratamiento por la misma vía, a lo que le siguieron cinco inyecciones con intervalos de dos horas entre ellas, con agua, goma arábiga o propóleos. El tejido de la vejiga se examinó de acuerdo con los criterios de Gray. Resultados. La puntuación total de la inflamación según la histología fue significativamente menor en el grupo VIB (11,33 ± 2,07). La inflamación leve predominó en este grupo, en tanto que la mayoría de los animales del IVB presentó inflamación grave (p=0,0375). Predominaron las úlceras múltiples en los grupos IVA y VB, pero fueron raras o estuvieron ausentes en el VIB (p=0,0118). En general, no se observaron células uroteliales en los grupos IVB y VB, pero sí en el VIB (p=0,0052). La fibrina fue abundante en los grupos IVB y VA, pero predominantemente ausente en el VIB (p=0,0273). Conclusiones. El propóleos rojo puede reducir la inflamación en la cistitis hemorrágica inducida por ciclofosfamida en ratas.
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Propolis , Cystitis , Cyclophosphamide , Models, AnimalABSTRACT
OBJECTIVE@#To establish a stable mouse model of acquired aplastic anemia.@*METHODS@#Female BALB/C mice aged 6 months were intraperitoneally injected with cyclophosphamide and cyclosporine for 14 days. The number of peripheral blood cells, the concentration of hemoglobin, the number of bone marrow nucleated cells, bone marrow smear, bone marrow pathological sections and other indexes were observed.@*RESULTS@#In BALB/C mice injected intraperitoneally with cyclophosphamide and cyclosporine, the number of peripheral blood cells and the concentration of hemoglobin were significantly decreased, especially the white blood cells and platelets. Bone marrow smear showed a significant decrease in the number of nucleated cells and bone marrow hyperplasia. Bone marrow pathology showed decreased hematopoietic cells and increased non-hematopoietic cells such as adipocytes.@*CONCLUSION@#The mouse model with intraperitoneal injection of cyclophosphamide and cyclosporine can meet the diagnostic criteria of acquired aplastic anemia, which can be used as a mouse model for the study of the pathogenesis and treatment of acquired aplastic anemia.
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Animals , Female , Mice , Anemia, Aplastic , Bone Marrow , Cyclophosphamide , Cyclosporine , Mice, Inbred BALB CABSTRACT
Objective:To investigate the effects of ribonucleic acid for injection Ⅱ, often called RNA Ⅱ for short, combined with chemotherapeutic drug cyclophosphamide (CTX) on the tumor inhibition and survival of sarcoma cell S180 tumor-bearing mice.Methods:The solid transplanted tumor mouse model of sarcoma cell S180 and peritoneal fluid tumor mouse model were established respectively. CTX (25 mg/kg, once for 2 days) alone or combined with low-dose (25 mg/kg, once a day) and medium-dose (50 mg/kg, once a day) RNA Ⅱ were injected intraperitoneally into solid transplanted tumor mice for 10 d. CTX (25 mg/kg, once for 2 days) alone, medium-dose (50 mg/kg, once a day) or high-dose (100 mg/kg, once a day) RNA Ⅱ alone or combined with CTX were injected intraperitoneally into peritoneal effusion tumor mice until all mice died. The two models were set up for modeling groups without drug treatment, 8 mice in each group. The body mass of solid transplanted tumor mice after administration was weighed, the tumor tissue in vivo was taken out and weighed after the mice were executed, and the tumor inhibition rate was calculated. The body mass of peritoneal effusion tumor mice after administration was weighed, the growth rate of body mass was calculated, the survival curve of each group was drawn, and the life extension rate was calculated.Results:(1) Solid transplanted tumor mice: the body mass of mice in each administration group was lower than that in the modeling group after administration. During the administration period, the tumor volume in the modeling group was much higher than that in each administration group. From the 8th day of administration, the tumor volume in vivo in the CTX group began to be larger compared with that in the two combined administration groups. After stopping the administration and killing the mice, the weighing showed that the tumor mass of each administration group was lower than that in the modeling group (all P < 0.01), the tumor mass of CTX + RNA Ⅱ low-dose group and CTX + RNA Ⅱ medium-dose group was lower than that of CTX group (all P < 0.05), and the tumor inhibition rate of the two groups was higher than that of CTX group (83.6%, 77.2% vs. 58.5%). (2) Peritoneal effusion tumor mice: after administration for 12 d, the body mass growth rate of mice in CTX group was increased rapidly and reached the highest, and the body mass growth rate of mice in the two combined administration groups was lower than that in other groups. The life prolongation rates of RNA Ⅱ high-dose group and CTX group were 48.2% and 53.2% respectively, which had the same effect on life prolongation. The life prolongation rate in RNA Ⅱ medium-dose group was 20.9%. The life prolongation rates of CTX + RNA Ⅱ medium-dose group and CTX + RNA Ⅱ high-dose group were 94.2% and 105.0% respectively. Conclusions:RNA Ⅱ combined with CTX can significantly prolong the survival time of sarcoma cell S180 tumor-bearing mice, increase the tumor inhibition rate and improve the quality of life of the mice. Both of them have a synergistic effect.
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Objective:To evaluate the effectiveness and safety of rituximab (RTX) and cyclophosphamide/azathioprine (CYC/AZA) in the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis (AAV).Methods:After setting up the search strategy, the inclusion and screening criteria of the literature were determined, the Pubmed, Cochrane Library, Embase, China Biomedical Literature Database, CNKI, Wanfang Database, Weipu Database were searched for RTX and CYC/AZA treatment for AAV. For randomized controlled studies, in which the experimental group was RTX for AAV, and the control group was CYC/AZA for AAV were included. The retrieval time span was from January 2000 to June 2021, and the data obtained were analyzed using Revman 5.3 software.Results:A total of 9 articles and 4 studies were included, with a total of 384 patients, including 203 cases in the experimental group and 181 cases in the control group. In the treatment of AAV, the difference in the remission rate of RTX and CYC/AZA treatment of AAV was statistically significant, and the remission rate of the RTX group was higher [ OR(95% CI)=1.58(1.03, 2.40), P=0.03]. For the remission rates of different types of AAV, RTX and CYC/AZA were benefit for the treatment of granulomatous vasculitis, microscopic polyangiitis, eosinophilic granulomatous vasculitis, there was no statistically significant difference in the remission rate of patients with protease 3-related vasculitis and myeloperoxidase-related vasculitis. The incidence of granulocytopenia in the RTX group was significantly lower than that in the CYC/AZA group, and RTX treatment could reduce the incidence of other serious adverse reactions. Conclusion:For the remission induction therapy, RTX is not inferior to CYC for all subtypes of AAV. In the maintenance treatment phase, RTX has a higher remission rate and a lower recurrence rate. During the entire treatment process, patients who were treated with RTX had a higher long-term remission rate than patients who were not treated with RTX. RTX can effectively reduce the occurrence of adverse reactions such as neutropenia.
ABSTRACT
Objective: He-Wei Granule (HWKL) is a modern product derived from the modified formulation of traditional Chinese medicine Banxia Xiexin Decoction (BXD), which remarkedly enhanced the anti-proliferation activity of cyclophosphamide (CTX) on HepG2 and SGC-7901 cell lines in vitro in our previous research. The aim of the study was to investigate the synergistic effects of HWKL and CTX using a transplanted H22 hepatocellular carcinoma mouse model. Methods: The CTX-toxic-reducing efficacy of HWKL was evaluated by hematology indexes, organ indexes and marrow DNA detection. To investigate the underlying mechanisms, histopathology test, immunohistochemistry test and TUNEL staining were conducted. The efficacy of HWKL on the micro-vessel density (MVD) in tumor tissue was also evaluated by measuring CD34 level. Results: High dose HWKL (6.75 g/kg) markedly attenuated CTX-induced hepatotoxicity and myelosuppression while significantly enhanced CTX anticancer efficacy in vivo. Further mechanism investigation suggested that high dose HWKL significantly increased cleaved Caspase 3 level and promoted apoptosis in tumor tissue by up-regulating Bax expression and down-regulating Bcl-2 and FasL expressions. Compared with CTX alone group, the decrease in LC-3B and Beclin 1 levels suggested that the autophagy in H22 carcinoma was significantly inhibited with addition of high dose HWKL. ELISA assay results indicated that the autophagy inhibition was achieved by decreasing p53 expression, blocking PI3K/AKT/mTOR pathway and recovering Th1/Th2 cytokine balance. In addition, CD34 and EGFR immunohistochemistry assay suggest that high dose HWKL could significantly decrease micro-vessel density (MVD) and inhibit angiogenesis in H22 carcinoma. Conclusion: It can be concluded that high-dose HWKL enhanced CTX efficacy by promoting apoptosis, inhibiting autophagy and angiogenesis in tumor tissue while significantly alleviated CTX-induced toxicity, and could be applied along with CTX in clinical treatment as a supplement agent.
ABSTRACT
A 71-year-old woman was referred to our hospital with complaints of gross hematuria. She had been administered 50mg/day of cyclophosphamide for 13 years to treat idiopathic thrombocytopenic purpura (ITP). Cystoscopy revealed irregular surface of bladder mucosa. On suspicion of bladder cancer, we performed transurethral resection of bladder tumor (TURBT). The pathological examination showed polypoid cyst, and we diagnosed hemorrhagic cystitis. Two months after the operation, gross hematuria was observed again. Although we administered choreitogoshimotsuto and then saireito, both were ineffective. Then we administered kamikihito, considering the findings of deficiency of ki (qi) and ketsu (blood) in Kampo diagnosis and the underlying disease ITP. One month after administering kamikihito, gross hematuria disappeared, urinary sediment test showed RBC 1-4/HPF. After one year of follow-up, bladder tumor was suspected by cystoscopy, but the pathological result of the second TUR-BT was inflammatory change. Since then, kamikihito was continued during the 44-month observation period, and no gross hematuria was observed.