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Arch. argent. pediatr ; 122(1): e202310061, feb. 2024. tab, ilus
Article in English, Spanish | BINACIS, LILACS | ID: biblio-1525854


El síndrome de Wiskott-Aldrich es un error innato de la inmunidad de herencia ligada al cromosoma X, producido por variantes en el gen que codifica la proteína del síndrome de Wiskott-Aldrich (WASp). Reportamos el caso clínico de un paciente de 18 meses con diagnóstico de Wiskott-Aldrich que no presentaba donante antígeno leucocitario humano (HLA) idéntico y recibió un trasplante de células progenitoras hematopoyéticas (TCPH) con donante familiar haploidéntico. La profilaxis para enfermedad de injerto contra huésped incluyó ciclofosfamida (PT-Cy). El quimerismo del día +30 fue 100 % del donante y la evaluación postrasplante de la expresión de la proteína WAS fue normal. Actualmente, a 32 meses del trasplante, presenta reconstitución hematológica e inmunológica y quimerismo completo sin evidencia de enfermedad injerto contra huésped. El TCPH haploidéntico con PT-Cy se mostró factible y seguro en este caso de síndrome de WiskottAldrich en el que no se disponía de un donante HLA idéntico.

Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder caused by mutations in the gene that encodes the Wiskott-Aldrich syndrome protein (WASp). Here, we report the clinical case of an 18-month-old boy diagnosed with Wiskott-Aldrich syndrome, who did not have an HLA-matched related or unrelated donor and was treated successfully with a hematopoietic stem cell transplant (HSCT) from a haploidentical family donor. Graft-versus-host disease (GvHD) prophylaxis included post-transplant cyclophosphamide (PT-Cy). At day +30, the peripheral blood-nucleated cell chimerism was 100% and the WAS protein had a normal expression. Currently, at month 32 post-transplant, the patient has hematological and immune reconstitution and complete donor chimerism without evidence of GvHD. HSCT with PT-Cy was a feasible and safe option for this patient with WAS, in which an HLA matched donor was not available.

Humans , Male , Infant , Wiskott-Aldrich Syndrome/diagnosis , Wiskott-Aldrich Syndrome/genetics , Wiskott-Aldrich Syndrome/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/etiology , Bone Marrow Transplantation/adverse effects , Cyclophosphamide
Chinese Journal of Hematology ; (12): 321-327, 2023.
Article in Chinese | WPRIM | ID: wpr-984622


Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.

Male , Adult , Humans , Prognosis , Retrospective Studies , Myeloid Differentiation Factor 88 , China/epidemiology , Testicular Neoplasms/drug therapy , Cyclophosphamide , Rituximab/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Prednisone/therapeutic use , Doxorubicin/therapeutic use , Vincristine/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Immediate-Early Proteins/therapeutic use , Tumor Suppressor Proteins
Chinese Journal of Internal Medicine ; (12): 819-825, 2023.
Article in Chinese | WPRIM | ID: wpr-985992


Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.

Male , Humans , Female , Multiple Myeloma/diagnosis , Hematopoietic Stem Cell Transplantation/adverse effects , Retrospective Studies , Creatinine , Hematopoietic Stem Cell Mobilization , Transplantation, Autologous , Dexamethasone/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Heterocyclic Compounds/therapeutic use , Bortezomib/therapeutic use , Cyclophosphamide/therapeutic use , Stomatitis/etiology
Journal of Experimental Hematology ; (6): 125-129, 2023.
Article in Chinese | WPRIM | ID: wpr-971113


OBJECTIVE@#To investigate the in vivo intervention and relative mechanism of Genistein (GEN) on tumor-associated inflammatory and tumor thrombophilia in lymphoma-bearing mice.@*METHODS@#Forty female Balb/c mice aged 5-6 weeks were injected with murine-derived Pro B-cell lymphoma cell line 38B9 to establish a lymphoma mouse model, which was randomly divided into control group, tumor-bearing group, GEN drug intervention group and cyclophosphamide (CTX)drug intervention group. Histopathologic was used to evaluate the tumorigenesis. Tumor formation was observed, and tumor tissues were collected of HE and immunohistochemical staining. ELISA and flow cytometry were used to detect the expression of inflammatory factors and the changes of thrombus indices in plasma after intervention of GEN and Cyclophosphamide (CTX) respectively. Immunohistochemistry method was used to detect the expression of CD19 in tomor tissues of tummor bearing mice.@*RESULTS@#After 14 days of tumor bearing, the mice were tumorigenic. The lymphoma cells were diffusely distributed in the tumor tissue and the expression of CD19 in the tumor tissue was positive. The inflammatory factors such as IL-6, NETs and CLEC-2, and thrombotic indices such as TF, FIB and D-D in lymphoma-bearing mice were significantly higher than those before tumor-injection and lower than those after drug-intervention (all P<0.05). The levels of CLEC-2 and D-D in GEN group were significantly lower than those in CTX group (P<0.05).@*CONCLUSION@#Tumor-associated inflammation and thrombophilia exist in lymphoma-bearing mice. GEN shows better anti-inflammatory and anti-thrombotic effects compared with CTX by interfering with tumor inflammatory factors.

Mice , Female , Animals , Genistein , Lymphoma , Cyclophosphamide , Thrombophilia , Inflammation , Lectins, C-Type
Chinese Medical Journal ; (24): 167-175, 2023.
Article in English | WPRIM | ID: wpr-970048


BACKGROUND@#To compare the efficacy and safety of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in Waldeyer's ring diffuse large B-cell lymphoma (WR-DLBCL) at a single institution.@*METHODS@#This retrospective study included 115 newly diagnosed patients with WR-DLBCL, of whom 68 patients received R-CHOP, and 47 patients received DA-EPOCH-R as their first-line treatment. The baseline features of the two groups were well balanced using a 1:1 propensity score matching method, and a total of 84 cases were obtained, including respective 42 cases in the R-CHOP and DA-EPOCH-R groups, for further survival and prognosis analysis. The primary objectives included progression-free survival (PFS) and overall survival (OS).@*RESULTS@#During a median follow-up of 45 months, there were nine (21.4%) deaths in the R-CHOP group and two (4.8%) in the DA-EPOCH-R group. Kaplan-Meier analysis showed statistically significant improvements in PFS and OS in patients with DA-EPOCH-R compared with those treated with R-CHOP (log-rank test, P  = 0.025 and P  = 0.035, respectively). The 2-year PFS and OS rates in the DA-EPOCH-R group were 90.1% (95% confidence interval [CI]: 81.4-99.8%) and 95.2% (95% CI: 89.0-100.0%), respectively, and 80.5% (95% CI: 69.3-93.6%) and 90.5% (95% CI: 52.8-99.8%) in the R-CHOP group. Patients without B symptoms and elevated lactate dehydrogenase levels had a higher PFS in the DA-EPOCH-R group, with P values of 0.038 (hazard ratio [HR]: 0.11; 95% CI: 0.01-0.88) and 0.042 (HR: 0.19; 95% CI: 0.04-0.94), respectively. There were no statistically significant differences in clinical responses and treatment-related toxicities between the two groups.@*CONCLUSION@#Compared with patients received R-CHOP, those treated by DA-EPOCH-R had superior PFS, OS, and controlled toxicity in patients with WR-DLBCL.

Humans , Rituximab/therapeutic use , Vincristine/therapeutic use , Retrospective Studies , Prednisone/therapeutic use , Etoposide/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use
Chinese Critical Care Medicine ; (12): 431-434, 2023.
Article in Chinese | WPRIM | ID: wpr-982607


Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) has a wide range of symptoms, and it is difficult for clinicians to make a quick and correct diagnosis. On November 11, 2021, a 36-year-old male patient with AAV was admitted to the emergency and critical care department of Yichang Central People's Hospital. He was admitted to the emergency intensive care unit (EICU) with gastrointestinal symptoms (abdominal pain, black stool) as the main physical signs, and was initially diagnosed as AAV with gastrointestinal hemorrhage (GIH). No bleeding point was found after repeated gastroscopy and colonoscopy. Abdominal emission CT (ECT) showed diffuse hemorrhage in the ileum, ascending colon and transverse colon. Multi-disciplinary consultation in the whole hospital considered the diffuse hemorrhage caused by small vascular lesions in the digestive tract caused by AAV. Pulse therapy with methylprednisolone 1 000 mg/d and immunosuppressive therapy with cyclophosphamide (CTX) 0.2 g/d were administered. The patient's symptoms quickly relieved and transferred out of the EICU. After 17 days of treatment, the patient finally died of massive gastrointestinal bleeding. A systematic review of relevant literatures combined with the case diagnosis and treatment process found that only a minority of AAV patients present with gastrointestinal symptoms as their first symptoms, and patients with GIH were very rare. Such patients had a poor prognosis. This patient delayed the use of induced remission and immunosuppressive agents due to the treatment of gastrointestinal bleeding, which may be the main cause of life-threatening GIH secondary to AAV. Gastrointestinal bleeding is a rare and fatal complication of vasculitis. Timely and effective induction and remission treatment is the key to survival. Whether patients should receive maintenance therapy, the duration of maintenance therapy, and the search for markers of disease diagnosis and treatment response are directions and challenges for further research.

Male , Humans , Adult , Gastrointestinal Hemorrhage , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Critical Care , Cyclophosphamide , Death
Arq. ciências saúde UNIPAR ; 26(3): 1412-1426, set-dez. 2022.
Article in Portuguese | LILACS | ID: biblio-1414674


cistite hemorrágica e a cistite intersticial expressam uma etiologia variável, desde idiopática à provocada por fármacos, dentre eles a ciclofosfamida. A cistite apresenta tratamento multifatorial, e o potencial efeito satisfatório do uso da medicina complementar, vem ganhando espaço na prática médica. Assim o objetivo do presente estudo foi avaliar o efeito protetivo do extrato bruto de Echinodorus grandiflorus sobre a bexiga de ratos induzidos a cistite por ciclofosfamida. Utilizou-se neste estudo, 35 ratos, machos, Wistar, com peso médio de 321g, que foram submetidos a indução de cistite com uso de ciclofosfamida por via intraperitoneal e tratados com diferentes doses de extrato de Echinodorus grandiflorus (30, 100, 300mg) e o grupo controle com o fármaco Mesna. Todos os animais foram mortos no décimo sétimo dia e suas bexigas urinarias foram ressecadas para avaliação macro e microscópica, além da análise de hemograma e leucograma. A análise do sangue mostrou leucopenia com diferença significativa em todos os animais que receberam a ciclofosfamida. Observou-se que a dose de 300mg/kg do extrato bruto da planta, apresentou efeito protetivo no urotélio vesical, porém, inferior ao uso de Mesna. Diante dos resultados apresentados neste estudo sugere-se que o extrato de Echinodorus grandiflorus apresenta efeito protetivo no urotélio vesical na dose de 300mg/kg, porém estudos futuros quanto a dose e também a uma possível associação terapêutica ao Mesna devam ser realizados. Por se tratar de uma patologia com prevalência importante e ser muitas vezes desagradável e limitante à vida, faz-se necessário o empenho em métodos terapêuticos alternativos aos atuais, afim de, diminuírem os custos e efeitos colaterais dos métodos já documentados.

Hemorrhagic cystitis and interstitial cystitis have a variable etiology, from idiopathic to drug-induced, including cyclophosphamide. Cystitis has a multifactorial treatment, and the potential satisfactory effect of the use of complementary medicine has been gaining ground in medical practice. Thus, the aim of the present study was to evaluate the protective effect of the crude extract of Echinodorus grandiflorus on the bladder of rats induced to cystitis by cyclophosphamide. In this study, 35 male Wistar rats, with an average weight of 321g, were submitted to cystitis induction with intraperitoneal use of cyclophosphamide and treated with different doses of Echinodorus grandiflorus extract (30, 100, 300mg) and the control group with the drug Mesna. All animals were killed on the seventeenth day and their urinary bladders were resected for macro and microscopic evaluation, in addition to the analysis of blood count and leukogram. Blood analysis showed leukopenia with a significant difference in all animals that received cyclophosphamide. It was observed that the dose of 300mg/kg of the crude extract of the plant had a protective effect on the vesical urothelium, however, it was inferior to the use of Mesna. In view of the results presented in this study, it is suggested that the Echinodorus grandiflorus extract has a protective effect on the vesical urothelium at a dose of 300mg/kg, but future studies regarding the dose and also a possible therapeutic association with Mesna should be carried out. Because it is a pathology with significant prevalence and is often unpleasant and life-limiting, it is necessary to commit to alternative therapeutic methods to the current ones, in order to reduce the costs and side effects of the methods already documented.

cistitis hemorrágica y la cistitis intersticial tienen una etiología variable, desde idiopática hasta inducida por fármacos, incluida la ciclofosfamida. La cistitis tiene un tratamiento multifactorial, y el potencial efecto satisfactorio del uso de la medicina complementaria ha ido ganando terreno en la práctica médica. Así, el objetivo del presente estudio fue evaluar el efecto protector del extracto crudo de Echinodorus grandiflorus sobre la vejiga de ratas inducidas a cistitis por ciclofosfamida. En este estudio, 35 ratas Wistar macho, con un peso promedio de 321g, fueron sometidas a inducción de cistitis con uso intraperitoneal de ciclofosfamida y tratadas con diferentes dosis de extracto de Echinodorus grandiflorus (30, 100, 300mg) y el grupo control con el fármaco Mesna. Todos los animales fueron sacrificados al decimoséptimo día y sus vejigas urinarias fueron resecadas para evaluación macro y microscópica, además del análisis de hemograma y leucograma. El análisis de sangre mostró leucopenia con una diferencia significativa en todos los animales que recibieron ciclofosfamida. Se observó que la dosis de 300 mg/kg del extracto crudo de la planta tuvo un efecto protector sobre el urotelio vesical, sin embargo, fue inferior al uso de Mesna. En vista de los resultados presentados en este estudio, se sugiere que el extracto de Echinodorus grandiflorus tiene un efecto protector sobre el urotelio vesical a una dosis de 300 mg/kg, pero se deben realizar estudios futuros sobre la dosis y también una posible asociación terapéutica con Mesna. llevado a cabo. Por tratarse de una patología con una prevalencia importante y muchas veces desagradable y

Animals , Rats , Rats, Wistar , Urothelium , Cyclophosphamide , Cystitis , Alismataceae , Urinary Bladder , Pharmaceutical Preparations , Leukopenia
Arq. ciências saúde UNIPAR ; 26(3): 1398-1411, set-dez. 2022.
Article in Portuguese | LILACS | ID: biblio-1414511


Pelas características anatômicas e fisiológicas dos rins, a lesão renal aguda tem sua origem nefrotóxica pela alta circulação local, o que favorece a alta concentração de substâncias tóxicas e seus metabólitos no tecido. A lesão renal aguda é uma complicação comum em internações hospitalares e principalmente em internações em unidades de terapia intensiva. A ciclofosfamida, um quimioterápico utilizado no tratamento de doenças autoimunes e neoplasias sólidas, pode causar nefrotoxicidade com disfunção glomerular e tubular. O uso de plantas medicinais, pelas suas potentes ações antioxidantes, tem sido usado para prevenção ou tratamento de lesões celulares induzidas pelo desequilíbrio entre enzimas antioxidantes e oxidantes. Por esse motivo, o objetivo do experimento foi avaliar o potencial efeito protetor da Echinodorus grandiflorus na prevenção da nefrotoxidade induzida pela ciclofosfamida. Para isso, foi realizado o experimento com a utilização de 35 ratos machos, Wistar, divididos em seis grupos experimentais, sendo administrado a ciclofosfamida na dose de 150mg/kg nos grupos G2 a G6 e diferentes doses da Echinodorus grandiflorus, com posterior análise de parâmetros sanguíneos e histológicos. A administração de ciclofosfamida na dose de 150mg/kg de massa corporal, em dose única, foi capaz de induzir a nefrotoxicidade aguda em todos os ratos. O extrato bruto de Echinodorus grandiflorus apresentou potencial efeito renoprotetor ao uso da ciclofosfamida, na dose de 300mg/kg de massa corporal, sendo possível observar redução dos efeitos nefrotóxicos do quimioterápico, pela redução dos danos tubulares e pela diminuição dos espaços capsulas, nitidamente encontradas alterados no grupo que recebeu apenas ciclofosfamida, denotando resultados promissores para utilização desta planta medicinal na prevenção da nefrotoxicidade induzida pelo fármaco. Contudo, novos estudos dos efeitos renoprotetor do chapéu de couro, poderão elucidar os mecanismos envolvidos na ação do extrato bruto do chapéu de couro. A utilização de extrato bruto de plantas medicinais torna-se um adjuvante aos tratamentos pelo baixo custo e pela facilidade de acesso das diferentes populações as plantas desde que devidamente orientados pelos profissionais habilitados.

Due to the anatomical and physiological characteristics of the kidneys, acute kidney injury has its nephrotoxic origin due to the high local circulation, which favors the high concentration of toxic substances and their metabolites in the tissue. Acute kidney injury is a common complication in hospital admissions and especially in intensive care unit admissions. Cyclophosphamide, a chemotherapy drug used in the treatment of autoimmune diseases and solid neoplasms, can cause nephrotoxicity with glomerular and tubular dysfunction. The use of medicinal plants, due to their potent antioxidant actions, has been used for the prevention or treatment of cellular injuries induced by the imbalance between antioxidant and oxidant enzymes. For this reason, the aim of the experiment was to evaluate the potential protective effect of Echinodorus grandiflorus in preventing cyclophosphamide-induced nephrotoxicity. For this, the experiment was carried out with the use of 35 male Wistar rats, divided into six experimental groups, being administered cyclophosphamide at a dose of 150mg/kg in groups G2 to G6 and different doses of Echinodorus grandiflorus, with subsequent analysis of parameters blood and histology. The administration of cyclophosphamide at a dose of 150mg/kg of body weight, in a single dose, was able to induce acute nephrotoxicity in all rats. The crude extract of Echinodorus grandiflorus showed a potential renoprotective effect with the use of cyclophosphamide, at a dose of 300mg/kg of body mass, and it was possible to observe a reduction in the nephrotoxic effects of the chemotherapy, due to the reduction of tubular damage and the reduction of capsule spaces, clearly found altered in the group that received only cyclophosphamide, showing promising results for the use of this medicinal plant in the prevention of drug-induced nephrotoxicity. However, further studies of the renoprotective effects of the leather hat may elucidate the mechanisms involved in the action of the crude extract of the leather hat. The use of raw extract of medicinal plants becomes an adjuvant to treatments due to the low cost and ease of access of different populations to plants, provided that they are properly guided by qualified professionals.

Debido a las características anatómicas y fisiológicas de los riñones, la lesión renal aguda tiene su origen nefrotóxico por la elevada circulación local, que favorece la alta concentración de sustancias tóxicas y sus metabolitos en el tejido. La lesión renal aguda es una complicación frecuente en los ingresos hospitalarios y principalmente en las unidades de cuidados intensivos. La ciclofosfamida, un quimioterápico utilizado en el tratamiento de enfermedades autoinmunes y neoplasias sólidas, puede causar nefrotoxicidad con disfunción glomerular y tubular. El uso de plantas medicinales, debido a sus potentes acciones antioxidantes, se ha utilizado para la prevención o el tratamiento de lesiones celulares inducidas por el desequilibrio entre enzimas antioxidantes y oxidantes. Por este motivo, el objetivo del experimento era evaluar el posible efecto protector del Echinodorus grandiflorus en la prevención de la nefrotoxicidad inducida por la ciclofosfamida. Para ello, se realizó el experimento utilizando 35 ratas Wistar macho, divididas en seis grupos experimentales, administrándoseles ciclofosfamida a una dosis de 150mg/kg en los grupos G2 a G6 y diferentes dosis de Echinodorus grandiflorus, con posterior análisis de sangre y parámetros histológicos. La administración de ciclofosfamida a una dosis de 150mg/kg de masa corporal, en dosis única, fue capaz de inducir nefrotoxicidad aguda en todas las ratas. El extracto crudo de Echinodorus grandiflorus presentó un potencial efecto renoprotector al uso de ciclofosfamida, a una dosis de 300mg/kg de masa corporal, siendo posible observar una reducción de los efectos nefrotóxicos de la quimioterapia, por la reducción del daño tubular y por la disminución de los espacios capsulares, encontrándose claramente alterados en el grupo que recibió solamente ciclofosfamida, denotando resultados promisorios para el uso de esta planta medicinal en la prevención de la nefrotoxicidad inducida por el fármaco. Sin embargo, nuevos estudios sobre los efectos renoprotectores del sombrero de cuero podrían dilucidar los mecanismos implicados en la acción del extracto crudo de sombrero de cuero. El uso de extractos crudos de plantas medicinales se convierte en un coadyuvante de los tratamientos por su bajo coste y la facilidad de acceso de las diferentes poblaciones a las plantas desde que son guiadas adecuadamente por profesionales cualificados.

Animals , Rats , Cyclophosphamide/analysis , Alismataceae/toxicity , Acute Kidney Injury/drug therapy , Plants, Medicinal/drug effects , Body Weight/drug effects , Pharmaceutical Preparations/analysis , Mesna/toxicity , Rats, Wistar
Biomédica (Bogotá) ; 42(2): 253-263, ene.-jun. 2022. tab, graf
Article in English | LILACS | ID: biblio-1403579


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.

Propolis , Cystitis , Cyclophosphamide , Models, Animal
Rev. urug. cardiol ; 37(1): e706, jun. 2022. ilus
Article in Spanish | LILACS, BNUY, UY-BNMED | ID: biblio-1415403


El término miocarditis hace referencia a una inflamación del miocardio, que puede tener diversas causas (infecciones, tóxicos, enfermedades autoinmunes). Su diagnóstico es desafiante debido al gran espectro de presentaciones clínicas que puede adoptar, muchas veces imitando patologías más prevalentes como el infarto agudo de miocardio. La miocarditis asociada a enfermedades autoinmunes es poco frecuente, y la importancia de reconocerla radica en que el diagnóstico e inicio temprano del tratamiento son cruciales para mejorar su pronóstico. Presentamos aquí un caso clínico de una perimiocarditis lúpica.

Myocarditis refers to an inflammation of the myocardium, which can have various causes (infections, toxic substances, autoimmune diseases). Its diagnosis is challenging due to the wide spectrum of clinical presentations, often mimicking more prevalent pathologies such as acute myocardial infarction. Myocarditis associated with autoimmune diseases is rare, and the importance of recognizing is that early diagnosis and initiation of treatment are crucial to improve its prognosis. We present here a clinical case of lupus perimyocarditis.

O termo miocardite refere-se a uma inflamação do miocárdio, que pode ter várias causas (infecções, substâncias tóxicas, doenças autoimunes). Seu diagnóstico é desafiador devido ao amplo espectro de apresentações clínicas que pode ter, muitas vezes mimetizando patologias mais prevalentes como o infarto agudo do miocárdio. A miocardite associada a doenças autoimunes é rara, e a importância de reconhecê-la reside no fato de que o diagnóstico precoce e o início do tratamento são cruciais para melhorar seu prognóstico. Apresentamos aqui um caso clínico de perimiocardite lúpica.

Humans , Female , Adult , Heart Failure/therapy , Myocarditis/diagnostic imaging , Chest Pain , Methylprednisolone/therapeutic use , Treatment Outcome , Immunoglobulins, Intravenous/therapeutic use , Cyclophosphamide/therapeutic use , Hydroxychloroquine/therapeutic use , Immunologic Factors/therapeutic use , Immunosuppressive Agents/therapeutic use , Lupus Erythematosus, Systemic/complications , Myocarditis/etiology , Myocarditis/drug therapy
Hematol., Transfus. Cell Ther. (Impr.) ; 44(2): 163-168, Apr.-June 2022. tab, graf
Article in English | LILACS | ID: biblio-1385054


Abstract Introduction Hemorrhagic cystitis (HC) is a common complication of haploidentical hematopoietic stem cell transplantation (haplo-HSCT), characterized by irritative symptoms of the urinary tract and a higher morbidity and mortality rate. The worldwide incidence is reported between 10% and 70%. The use of alkylating agents and BK viral infection are the most frequent etiologies. The aim of this study was to report the HC incidence in an outpatient haplo-HCST program with a reduced intensity-conditioning (RIC) regimen, cataloguing risk factors, complications and final outcomes. Methods The medical database of patients who received a haplo-HSCT between January 2012 and November 2017 was retrospectively analyzed. Demographic variables, general characteristics and HC incidence were included. Results One hundred and eleven patients were included, 30 (27%) of whom developed HC, most of them (70%) being grade II, with a 30-day (7-149) median time of post-transplant HC onset. The BK virus was detected in 71% of the urine samples analyzed. All HC patients responded to treatment, except two (6.6%), who died due to HC complications. Conclusions There was no difference in the HC incidence or severity, compared to that reported when performing haplo-HSCT in hospitalized patients, although the donor-recipient sex mismatch did relate to a higher HC incidence.

Humans , Male , Female , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Young Adult , BK Virus , Hematopoietic Stem Cell Transplantation , Cystitis , Transplantation, Haploidentical , Incidence , Cyclophosphamide
Journal of Experimental Hematology ; (6): 516-521, 2022.
Article in Chinese | WPRIM | ID: wpr-928746


OBJECTIVE@#To investigate the efficacy and safety of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in combination of ATG and post-transplant cyclophosphamide (PTCy) -induced immune tolerance after transplantation in treatment of childhood myelodysplastic syndromes(MDS).@*METHODS@#From July 2016 to November 2020, a total of 8 children with MDS receiving the haploidentical allo-HSCT combined with ATG and PTCy-induced immune tolerance after transplantation in our hospital were enrolled, whose clinical data were retrospected and analyzed.@*RESULTS@#Median age at diagnosis of the 8 children (1 male and 7 females) was 6.4 (range, 10 months to 15 years) years old. The median medical history of MDS was 2.7 years (range, 3 months to 8 years). Among the 8 patients, 7 cases were diagnosed with refractory cytopenia of childhood and one with refractory anemia with excess of blasts. The HSC donors were father, mother or brother of patients and HLA matching in 6-9/12 loci were identical. All the donors were healthy and didn't carry the same pathogenic genes as the recipients. The median age of donors was 36.4 (range, 25 to 49) years old. The median mononuclear cell (MNC) number of the graft was 19.8, ranging in (13.2-47.3)×108/kg, and the median CD34+ cell number was 11.8×106/kg, ranging in (5.0-18.3)×106/kg. Graft-versus-host disease prophylactic regimen was started on day 3 and 4 after transplantation, in which cyclophosphamide (50 mg/kg·d) was administered by intravenous infusion. From day 5 after transplantation, low-dose tacrolimus was administered by intravenous infusion and mycophenolate mofetil was administered orally. The median time of neutrophil and platelet engraftment was 12.6 (rang, 11 to 15) days and 13.3 (rang, 11 to 18) days, respectively. All the patients achieved full donor chimerism on neutrophil engraftment after transplantation. The median follow-up time was 1 032 (rang, 747 to 1 536) days. Both overall survival rate and disease-free survival rate were 100%.@*CONCLUSION@#Haplo-HSCT combined with ATG and PTCy-induced immune tolerance after transplantation is a safe and effective treatment for children with MDS.

Adult , Child , Female , Humans , Male , Middle Aged , Cyclophosphamide , Graft vs Host Disease/drug therapy , Hematopoietic Stem Cell Transplantation , Myelodysplastic Syndromes/drug therapy , Transplantation Conditioning , Treatment Outcome
Acta Medica Philippina ; : 72-76, 2022.
Article in English | WPRIM | ID: wpr-988169


@#We report two Filipino women with systemic lupus erythematosus (SLE) who developed diffuse alveolar hemorrhage (DAH), a rare, life-threatening complication associated with a high mortality rate. DAH should be suspected in patients with SLE presenting with new pulmonary infiltrates, a decline in hemoglobin, hemoptysis, dyspnea, and persistent desaturation. The first patient is 23 years old and was diagnosed with SLE 8 years ago; initially presenting with malar rash, oral ulcers, nephritis, and positive antinuclear antibodies (ANA). She had a poorly controlled disease and was admitted for facial and bipedal edema due to lupus nephritis. She was given 1 gram of methylprednisolone intravenously (IV) for three consecutive days. She then became tachypneic producing bloody secretions, with desaturation and sudden decline in hemoglobin. She was given cyclophosphamide 1 gram IV and referred for plasmapheresis but eventually succumbed. The second patient is 56 years old with generalized body weakness. Laboratory workup showed nephritis, anemia, ANA, low C3, and high anti-dsDNA titers. Pulse methylprednisolone 1000 mg was initiated. However, there was new-onset hemoptysis and desaturation and the patient was intubated. Bronchoscopy revealed diffuse bleeding on the right middle lobe and she eventually expired. Both patients with active SLE nephritis presented in this study died within days of DAH diagnosis. Hence, aside from early recognition to improve outcomes we should anticipate its possible occurrence in patients with high disease activity.

Lupus Erythematosus, Systemic , Cyclophosphamide , Nephritis , Methylprednisolone
Chinese Journal of Hematology ; (12): 287-292, 2022.
Article in Chinese | WPRIM | ID: wpr-929637


Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.

Adult , Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/therapeutic use , Cytarabine/therapeutic use , Hematopoietic Stem Cell Transplantation , Idarubicin/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Neutropenia , Prospective Studies , Recurrence , Retrospective Studies
Chinese Journal of Hematology ; (12): 203-208, 2022.
Article in Chinese | WPRIM | ID: wpr-929558


Objective: This study aimed to look into the clinical characteristics and prognosis of patients with human immunodeficiency virus (HIV) -associated diffuse large B-cell lymphoma (DLBCL) . Methods: Retrospective review of the clinical data of 63 HIV-infected patients with DLBCL diagnosed at Chongqing University Cancer Hospital between July 2008 and August 2021. The Kaplan-Meier method was used to calculate survival curves, and the log-rank test method was used to compare survival between groups. The Cox proportional hazards model was used for multivariate analysis. Results: In 63 patients with HIV-associated DLBCL, 57 (90.5% ) were men, and the median age was 49 (23-87) years. The most common pathological subtype was the germinal center B-cell-like lymphoma (74.6% ) ; 46.0% (29/63) were combined with extranodal lesions. Seventeen of 63 (27.0% ) patients had large masses (≥7.5 cm) . Twenty of 63 (31.7% ) patients had B symptoms. The median CD4(+) T cell count was 203 (4-1022) ×10(6)/L. A total of 49% (25/51) patients had CD4(+) cell count <200×10(6)/L, 56.9% (33/58) had high (3-5) International Prognostic Index (IPI) scores, and 43.1% (25/58) had low (0-2) IPI scores. Further, 78% (46/59) were diagnosed with Ann Arbor Stage Ⅲ/Ⅳ, and 25.4% (16/63) didn't receive chemotherapy. A total of 22.2% (14/63) of patients received less than four cycles of chemotherapy, and 52.4% (33/63) received four or more cycles of chemotherapy. Among patients undergoing chemotherapy, 61.7% (29/47) received R-CHOP-like regimens, and 38.3% (18/47) used CHOP-like regimens. The 1-, 2-, 3-, and 5-year overall survival (OS) rates were 65.0% , 53.8% , 47.1% , and 43.5% , respectively. Univariate analysis revealed that age ≥ 60 years (P=0.012) , Eastern Cooperative Oncology Gruop Performance Status (ECOG-PS) score 2-4 points (P=0.043) , IPI score 3-5 points (P=0.001) , β(2)-MG elevation (≥5.5 mg/L) (P=0.007) , and systemic chemotherapy cycles less than four times (P<0.001) were the negative prognostic factors affecting the OS of patients. The Cox multivariate analysis depicted that age ≥60 years (HR=2.272, 95% CI 1.110-4.651, P=0.025) , IPI score 3-5 points (HR=3.562, 95% CI 1.794-7.074, P<0.001) , ECOG-PS score 2-4 points (HR=2.675, 95% CI 1.162-6.153, P=0.021) , and number of cycles of chemotherapy<4 (HR=0.290, 95% CI 0.176-0.479, P<0.001) were independent risk factors for adverse prognosis of OS. Conclusion: HIV-associated DLBCL is the most common HIV-related tumor, is most commonly seen in men, and has a high 1-year mortality rate. Chemotherapy combined with antiretroviral therapy can improve patient prognosis.

Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , HIV Infections , Lymphoma, Large B-Cell, Diffuse/drug therapy , Prednisone/therapeutic use , Prognosis , Retrospective Studies , Rituximab/therapeutic use , Survival Rate , Vincristine/therapeutic use
Chinese Journal of Oncology ; (12): 581-586, 2022.
Article in Chinese | WPRIM | ID: wpr-940926


Objective: To investigate the pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma (cHL-NS2) in our cancer center. Methods: A retrospective collection of 23 cases of cHL-NS2 admitted in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from July 2008 to April 2019 was performed. Fifty-five cases of nodular sclerosis grade 1 of classical Hodgkin's lymphoma (cHL-NS1) during the same period were selected as control group. Survival curves were plotted using the Kaplan-Meier method, and Cox regression model was used to analyze the influencing factors for survival. Results: The median age of 23 cases of cHL-NS2 was 30 years old. Five cases had extra nodal invasion, and 19 cases were Ⅰ-Ⅱ stage based on Ann Arbor system. The pathological morphology of cHL-NS2 showed that the lymph node structure was completely destroyed and was divided into nodules by thick collagen. The tumor cells in the nodules were abundant and proliferated in sheets. The boundaries between the tumor cells were not clear. The incidence of tumor necrosis in cHL-NS2 was 43.5% (10/23), which was significantly higher than 18.2% (10/55) in cHL-NS1 (P=0.040). The 3-year progression-free survival (PFS) rate of patients in the cHL-NS2 group was 58.1%, which was significantly lower than 89.7% in the cHL-NS1 group (P=0.002). In all of 78 cases, the 3-year PFS rate of patients who did not obtain complete response (CR) was 67.1%, which was significantly lower than 92.2% in patients who achieved CR (P=0.030). Multivariate Cox regression analysis demonstrated that both cHL-NS2 and failure to obtain CR by first-line treatment were independent indicators for short PFS time (P<0.05). Conclusions: In cHL-NS2, the morphology of tumor cells are diverse, and tumor necrosis can be easily found. Under the current first-line treatments of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), cHL-NS2 is an independent indicator for worse PFS.

Adult , Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin/therapeutic use , Cyclophosphamide/therapeutic use , Dacarbazine/therapeutic use , Doxorubicin/therapeutic use , Etoposide/therapeutic use , Hodgkin Disease/drug therapy , Necrosis/drug therapy , Prednisone/therapeutic use , Prognosis , Retrospective Studies , Sclerosis/drug therapy , Vinblastine/therapeutic use , Vincristine/therapeutic use
Journal of Integrative Medicine ; (12): 348-354, 2022.
Article in English | WPRIM | ID: wpr-939896


OBJECTIVE@#Salvadora persica (SP) is used as a food additive and is a common ingredient in folk medicine. This study investigates the antioxidant, anti-inflammatory, and beneficial effects of SP against cyclophosphamide (CYP) toxicity in rats.@*METHODS@#In a 10-day study, 32 male rats were equally allocated into 4 groups (8 rats/group) as follows: the normal control (NC group), normal rats that only received oral aqueous extract of SP (100 mg/[kg·d]; SP group), animals treated with intraperitoneal CYP injections (30 mg/[kg·d]; CYP group), and the CYP + SP group that concurrently received CYP with SP aqueous extract. Serum samples were collected to measure the liver and renal biochemical profiles, as well as antioxidant and oxidative stress markers and the concentrations of interleukin-1β (IL-1β), IL-6, IL-10, tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) and adenosine 5'-monophosphate-activated protein kinase (AMPK). Hepatic and renal tissues were also harvested for histopathology and to measure apoptosis using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique, alongside tissue levels of oxidative stress markers.@*RESULTS@#Liver enzymes, total bilirubin, creatinine and urea, as well as serum IL-1β, IL-6, TNF-α and NF-κB increased significantly, whilst total protein, albumin, calcium, IL-10 and AMPK declined in serum of the CYP group relative to the NC group. The hepatorenal concentrations of glutathione, glutathione peroxidase and catalase declined markedly in the CYP group, whereas malondialdehyde, protein adducts, and apoptosis index increased compared with the NC group. By contrast, the hepatorenal biochemistry and apoptosis index of the SP group were comparable to the NC group. Interestingly, the CYP + SP group had significant improvements in the liver and renal biochemical parameters, enhanced anti-oxidative and anti-inflammatory effects, and marked declines in hepatic and renal apoptosis relative to the CYP group. Moreover, all monitored parameters were statistically indistinguishable between the CYP + SP group and the NC group.@*CONCLUSION@#This study suggests that the aqueous extract of SP could be a potential remedy against CYP-induced hepatorenal damage and may act by modulating the AMPK/NF-κB signaling pathway and promoting anti-oxidative and anti-inflammatory activities.

Animals , Male , Rats , AMP-Activated Protein Kinases/metabolism , Anti-Inflammatory Agents/pharmacology , Antioxidants/metabolism , Apoptosis , Biomarkers , Cyclophosphamide , Inflammation/drug therapy , Interleukin-10 , Interleukin-6/metabolism , Liver , NF-kappa B/metabolism , Oxidative Stress , Salvadoraceae/metabolism , Tumor Necrosis Factor-alpha/metabolism
Journal of Experimental Hematology ; (6): 784-789, 2022.
Article in Chinese | WPRIM | ID: wpr-939689


OBJECTIVE@#To analyze the relationship between serum miR-34a level and thrombocytopenia after chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL).@*METHODS@#A total of 69 eligible DLBCL patients who received chemotherapy in our hospital from January 2018 to January 2020 were prospectively included as the research subjects, all patients received R-CHOP 21 regimen (rituximab + cyclophosphamide + adriamycin + vincristine + prednisone) for chemotherapy, 3 weeks was 1 cycle, and 2 cycles of chemotherapy were used. The patients were divided into a reduction group and a non reduction group according to whether there was thrombocytopenia after chemotherapy, the general data and laboratory indexes of the two groups were investigated and compared, the relationship between serum miR-34a before chemotherapy and thrombocytopenia after chemotherapy in patients was analyzed.@*RESULTS@#Among the 69 DLBCL patients, 36 patients developed thrombocytopenia after 2 cycles of R-CHOP 21 regimen for chemotherapy, the incidence was 52.17%; the level of serum IL-11 and the relative expression of miR-34a mRNA in the reduction group were significantly lower than the non reduction group (P<0.05), compared other data between groups, there was no statistical significant difference (P>0.05); after Logistic regression analysis, the results showed that the level of serum IL-11 and the relative expression of miR-34a mRNA were related to thrombocytopenia after chemotherapy in DLBCL patients, low expression of each index may be a risk factor of thrombocytopenia after chemotherapy in DLBCL patients (OR>1, P<0.05); ROC curve was drawn, and the results showed that the AUC of serum IL-11 level and miR-34a mRNA relative expression before chemotherapy alone and in combination predicted the risk of thrombocytopenia after chemotherapy in DLBCL patients were all >0.80, and the predictive value was ideal, when the cut-off value of serum IL-11 level before chemotherapy was 42.094 pg/ml, and the cut-off value of miR-34a mRNA relative expression was 3.894, the combined prediction value was the best.@*CONCLUSION@#The relative expression of miR-34a mRNA is associated with thrombocytopenia after chemotherapy in DLBCL patients, which may be a risk factor for thrombocytopenia in patients after chemotherapy, has certain value in predicting the risk of thrombocytopenia of patients after chemotherapy.

Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide , Doxorubicin , Interleukin-11/therapeutic use , Lymphoma, Large B-Cell, Diffuse/genetics , MicroRNAs/genetics , Prednisone/therapeutic use , Prognosis , RNA, Messenger , Rituximab/therapeutic use , Thrombocytopenia , Vincristine
Journal of Experimental Hematology ; (6): 760-764, 2022.
Article in Chinese | WPRIM | ID: wpr-939685


OBJECTIVE@#To analyze clinical response of the Rituximab-based chemotherapy and prognostic features in patients with primary gastric diffuse large B-cell lymphoma (PGDLBCL).@*METHODS@#From June 2008 to December 2020, the data of 53 PGDLBCL patients were analyzed retrospectively.@*RESULTS@#The median age was 46(25-77) years old in 53 patients including 35 males and 18 females. Stomachache is the most common symptom. The diagnosis were confirmed in 47 patients by endoscopic biopsy and 6 patients by surgery. Twenty-six patients had Ⅰ/Ⅱ1 stage (Lugano staging system) disease and 27 cases had II2/IV stage disease. All patients were treated with chemotherapy, including RCHOP (25/53) and R-DA-EPOCH (28/53). Complete remission rate was 79.2%(42/53). The 3-year and 5-year overall survival (OS) rates were 77.4% and 69.8%. Univariate analysis showed that lactate dehydrogenase(LDH), Lugano stage and lesion size affected OS. Multivariate Cox regression analysis revealed that IPI score and Lugano stage were independent prognosis risk factors affecting OS. The patients in the R-DA-EPOCH group presented better survival outcomes than those in the RCHOP group with late stage (P5-year OS=0.035).@*CONCLUSION@#Rituximab in combination with chemotherapy is the backbone of therapy for PGDLBCL. IPI score and Lugano stage are independent prognosis risk factors affecting OS of PGDLBCL. R-DA-EPOCH can be superior to R-CHOP as a first-line regimen in PGDLBCL patients with late stage.

Adult , Aged , Female , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/therapeutic use , Disease-Free Survival , Doxorubicin/therapeutic use , L-Lactate Dehydrogenase , Lymphoma, Large B-Cell, Diffuse/pathology , Prednisone/therapeutic use , Prognosis , Retrospective Studies , Rituximab/therapeutic use , Vincristine/therapeutic use
Journal of Southern Medical University ; (12): 538-545, 2022.
Article in Chinese | WPRIM | ID: wpr-936345


OBJECTIVE@#To investigate the therapeutic effects of total saponins from Panax notognseng (PNS) combined with cyclophosphamide (CTX) in mice bearing hepatocellular carcinoma H22 cell xenograft.@*METHODS@#We examined the effects of treatment with different concentrations of PNS on H22 cell proliferation for 24 to 72 h in vitro using CCK8 colorimetric assay. Annexin V/PI double fluorescence staining was used to detect the effect of PNS on apoptosis of H22 cells. Mouse models bearing H22 cell xenograft were established and treated with CTX (25 mg/kg), PNS (120, 240 or 480 mg/kg), alone or in combinations. After treatments for consecutive 10 days, the mice were euthanized for examinations of carbon clearance ability of the monocytes and macrophages, splenic lymphocyte proliferation, tumor necrosis factor (TNF-α), interleukin-2 (IL-2), serum hemolysin antibody level, blood indicators, and the tumor inhibition rate.@*RESULTS@#Treatment with PNS concentration-dependently inhibited the proliferation and significantly promoted apoptosis of cultured H22 cells (P < 0.01). In the tumor-bearing mouse models, PNS alone and its combination with CTX both resulted in obvious enhancement of phagocytosis of the monocyte-macrophages, stimulated the proliferation of splenic lymphocytes, promoted the release of TNF-α and IL-2 and the production of serum hemolysin antibody, and increased the number of white blood cells, red blood cells and lymphocytes in the peripheral blood. Treatment with 480 mg/kg PNS combined with CTX resulted in a tumor inhibition rate of 83.28% (P < 0.01) and a life prolonging rate of 131.25% in the mouse models (P < 0.05).@*CONCLUSION@#PNS alone or in combination with CTX can improve the immunity and tumor inhibition rate and prolong the survival time of H22 tumor-bearing mice.

Animals , Humans , Mice , Carcinoma, Hepatocellular/pathology , Cyclophosphamide/therapeutic use , Hemolysin Proteins , Heterografts , Interleukin-2 , Liver Neoplasms/pathology , Panax notoginseng , Saponins/therapeutic use , Tumor Necrosis Factor-alpha