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1.
Sci Total Environ ; 805: 150460, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34818796

RESUMO

Cyclophosphamide (CP) is a broad-spectrum anticancer drug and has been frequently detected in aquatic environments due to its incomplete removal by wastewater treatment facilities and slow degradation in waters. Its toxicity in fish remains largely unknown. In this study, zebrafish eggs <4 h post fertilization (hpf) were exposed to CP at the concentrations from 0.5 to 50.0 µg/L until 168 hpf, and its toxicity was evaluated by biochemical, transcriptomic, and behavioral approaches. The results showed that malformation and mortality rates increased with CP concentrations. The 7-day malformation EC50 and mortality (LC30) by CP were calculated to be 86.8 µg/L and 7.5 mg/L, respectively. Inhibited startle response (light to dark) (a minimal of 19%) and reduced swimming velocity (a minimal of 30%) were observed in the CP-exposed larvae. The thicknesses of retinal ganglion layer, inner plexiform layer, and inner nuclear layer in the retina were increased after exposure to CP. Meanwhile, exposure to CP increased karyorrhexis and karyolysis in the liver tissue. Transcriptomic analysis identified 607 differentially expressed genes (DEGs) (159 up-regulated and 448 down-regulated). A significant reduction in the transcripts of sgk1 (the FoxO pathway), jun (the MAPK pathway), and diabloa (apoptosis pathway) were observed in the CP-treated larvae. This study has demonstrated that low concentrations of CP cause malformation, reduced swimming capacity, histopathological alterations in the retina and liver tissues, and interference on transcriptional expressions of key genes associated with different pathways. The ecological risk of CP and other anticancer drugs to aquatic organisms merits future investigation.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Ciclofosfamida/toxicidade , Embrião não Mamífero , Larva , Locomoção , Poluentes Químicos da Água/toxicidade
2.
J Med Case Rep ; 15(1): 546, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34727993

RESUMO

BACKGROUND: Primary lymphoma of the prostate is an exceedingly rare disease, with diffuse large B-cell lymphoma being the most common known subtype in a small number of reported cases. Due to its low prevalence, there has been a chronic lack of targeted diagnostic guidelines and treatment procedures. CASE PRESENTATION: In this article, we report a case of primary diffuse large B-cell lymphoma of the prostate in a 70-year-old Asian man who presented with symptoms of urinary tract obstruction. Histological and immunocytochemical studies of transurethral biopsy of the prostate showed diffuse large B-cell lymphoma. The patient was managed by a combination of eight courses of chemotherapy with a regimen including rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone and radiotherapy. Post-chemotherapy computed tomography scans showed complete remission. He remained disease free, until now, 15 months after the end of therapy. We also reviewed and analyzed relevant literature to illustrate the diagnosis, treatment, and prognosis of this disease. CONCLUSION: Diffuse large B-cell non-Hodgkin's lymphoma originating in the prostate is a rare and highly aggressive disease that lacks specificity in its clinical presentation and is easily misdiagnosed. This disease should be considered clinically in patients with significant prostate enlargement and insignificant prostate-specific antigen elevation. The diagnosis can be clarified with a prostate puncture biopsy. Chemotherapy is the main treatment for patients and may be supplemented with surgical treatment and radiotherapy.


Assuntos
Linfoma Difuso de Grandes Células B , Próstata , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Vincristina/uso terapêutico
3.
F1000Res ; 10: 829, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646504

RESUMO

Background: Despite many studies on COVID-19, our knowledge of it remains incomplete. In some cases, treating SARS-CoV-2 infection concomitant with other diseases can be particularly challenging, as finding an appropriate treatment may involve some risks. Case presentation: A 34-year-old SARS-CoV-2 positive patient admitted due to fever, dyspnoea, haemoptysis and pneumonia, developed alveolar haemorrhage and acute kidney injury. Due to his severe state, abnormalities in laboratory tests and rapidly progressing loss of kidney function, kidney biopsy, as well as antibody panel were carried out, in which perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) were found with a high titer (>200; N: <1:20). The results of kidney biopsy, combined with clinical manifestation and laboratory findings prompted the diagnosis of rapidly progressing glomerulonephritis (RPGN) in the course of p-ANCA vasculitis. Initial treatment consisted of heamodialyses, remdesivir, plasmaphereses, intravenous immunoglobulins, antibiotics, corticosteroids and fraxiparine. Once the haemorrhage had subsided, kidney function had been partially retrieved and heamodialyses had no longer been necessary, cyclophosphamide treatment was initiated, despite being contraindicated in COVID-19 according to its summary of product characteristics. Immunotherapy is still continued. The patient has already received a total of 2.4g of cyclophosphamide (4 cycles of 600mg each every three weeks). Pulmonary and radiological regression, as well as improvement of renal parameters have been achieved.        Conclusions: We suspect that cyclophosphamide, the drug of choice in p-ANCA vasculitis, could be a potential factor providing regression of the radiological changes in the lungs and it could have prevented the patient from developing acute respiratory distress syndrome. COVID-19 diagnosis should not exclude searching for other diseases which can have a similar course. When treating a patient in a life-threatening condition, a departure from trying to find the perfect timing of cyclophosphamide delivery should be considered, as delaying it could cause potentially greater harm.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , COVID-19 , Adulto , Teste para COVID-19 , Contraindicações , Ciclofosfamida/uso terapêutico , Humanos , SARS-CoV-2
4.
Gan To Kagaku Ryoho ; 48(11): 1365-1368, 2021 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-34795128

RESUMO

Docetaxel and cyclophosphamide (TC) and epirubicin and cyclophosphamide (EC) therapies are postoperative chemotherapy regimens for breast cancer. However, a previous study reported on the development of adverse events, such as neutropenia, in Asian patients. In this study, we examined the occurrence of neutropenia during chemotherapy, assessed the symptoms, and investigated the dose-reduction/discontinuation of chemotherapy or admission in patients undergoing postoperative EC or TC therapy following breast cancer surgery at our hospital between April 2018 and March 2020. EC and TC therapies were performed in 29 and 23 patients, respectively. We observed a significant difference in the incidence of neutropenia between the two therapies, although this observation might have been influenced by the frequent use of pegfilgrastim. In the TC therapy group, edema and pain were frequently observed. We observed no significant differences in the dose-reduction/discontinuation of chemotherapy or admission. However, in the TC therapy group, 5 patients required admission.


Assuntos
Neoplasias da Mama , Neutropenia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Epirubicina/efeitos adversos , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Hospitais Urbanos , Humanos , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Neutropenia/epidemiologia , Resultado do Tratamento
5.
Pol Merkur Lekarski ; 49(293): 317-373, 2021 Oct 22.
Artigo em Polonês | MEDLINE | ID: mdl-34800027

RESUMO

Still disease is a rare systemic connective tissue disease of unknown etiology, which due to nonspecific symptoms, requires thorough diagnostics. Steroids are the basis treatment, while other immunosuppressive drugs should be applied for patients who are resistant to standard therapy. A CASE REPORT: A 36-year-old woman was admitted to the Department of Rheumatology due to a month history of persisting fever, arthralgia, cervical lymphadenopathy, soar throat, cutaneous lesions, liver transaminases elevation, hyperferritinemia and elevated inflamatory markers. Basing on the clinical presentation and additional diagnostic examinations the adult-onset Still's disease (AOSD) was diagnosed. Initially the patient was placed on steroids and cyclosporine but due to the severe clinical course requiring high doses of steroids and relapses triggered by the tapering of the dose, the decision to initate the treatment with cyclophosphamide was made. It eventually led to the fast and lasting remission and allowed tapering and subsequent discontinuation of the steroids. CONCLUSIONS: Treatment with cyclophosphamide may be a viable and efficient therapeutic option in severe and refractory cases of AOSD.


Assuntos
Doença de Still de Início Tardio , Adulto , Ciclofosfamida/uso terapêutico , Feminino , Febre , Humanos , Imunossupressores/uso terapêutico , Doença de Still de Início Tardio/tratamento farmacológico
6.
World J Gastroenterol ; 27(38): 6501-6510, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34720538

RESUMO

BACKGROUND: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare primary intestinal T-cell lymphoma, previously known as enteropathy-associated T-cell lymphoma type II. MEITL is an aggressive T-cell lymphoma with a poor prognosis and high mortality rate. The known major complications of MEITL are intestinal perforation and obstruction. Here, we present a case of MEITL that was diagnosed following upper gastrointestinal bleeding from an ulcerative duodenal lesion, with recurrence-free survival for 5 years. CASE SUMMARY: A 68-year-old female was admitted to our hospital with melena and mild anemia. An urgent esophagogastroduodenoscopy (EGD) revealed bleeding from an ulcerative lesion in the transverse part of the duodenum, for which hemostatic treatment was performed. MEITL was diagnosed following repeated biopsies of the lesion, and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy was administered. She achieved complete remission after eight full cycles of CHOP therapy. At the last follow-up examination, EGD revealed a scarred ulcer and 18Fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography showed no abnormal FDG accumulation. The patient has been in complete remission for 68 mo after initial diagnosis. CONCLUSION: To rule out MEITL, it is important to carefully perform histological examination when bleeding from a duodenal ulcer is observed.


Assuntos
Linfoma de Células T Associado a Enteropatia , Linfoma de Células T , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Melena/etiologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Vincristina/uso terapêutico
7.
Clin Adv Hematol Oncol ; 19(11): 698-709, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34807015

RESUMO

The emerging molecular and prognostic characterization of diffuse large B-cell lymphoma (DLBCL) has challenged the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment paradigm in recent years, with the identification of several DLBCL subtypes associated with significantly inferior survival after standard R-CHOP therapy. Efforts to improve upon the R-CHOP backbone have included dose intensification as well as the addition of new agents; the infusional dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH) regimen has been identified as a potential replacement for R-CHOP in high-risk DLBCL. In this review, we provide a historical perspective on the R-CHOP and DA-R-EPOCH regimens and summarize the clinical trial literature regarding the efficacy of each regimen in various risk groups of DLBCL. Further, we propose clinical management scenarios in which DA-R-EPOCH may be preferred, including some for patient populations in which the use of R-CHOP vs DA-R-EPOCH is controversial.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina/uso terapêutico
8.
Phytomedicine ; 92: 153752, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34601223

RESUMO

BACKGROUND: Cyclophosphamide (CTX), which has been used to treat common female cancers for several years, often causes ovarian damage, early menopause and infertility. However, strategies for the effective prevention and treatment of CTX-induced ovarian damage are still lacking. Epigallocatechin gallate (EGCG) and theaflavins (TFs), key molecules derived from green tea or black tea, have been shown to exert preventive effects on many ageing-related diseases. PURPOSE: We aimed to explore the potential preventive and protective effects of EGCG and TFs on CTX-induced ovarian damage and compare the two compounds. STUDY DESIGN: Six-week-old female mice were administered a low or high dose of EGCG or TFs. The low dose was equivalent to the average daily amount of tea consumed by a drinker. METHODS: We determined the oestrous cycle and serum hormone levels to evaluate ovarian endocrine function, and we performed mating tests for reproductivity. We also assessed the follicle count and AMH level to evaluate ovarian reserve, and we performed Masson's trichrome and Sirius red staining to evaluate ovarian fibrosis. We conducted γ-H2AX and TUNEL analyses to evaluate DNA damage, and we also measured the relevant indicators of oxidative stress and follicular activation, including NRF2, HO-1, SOD2, AKT, mTOR and RPS6. RESULTS: EGCG and TFs treatment independently improved the ovarian endocrine function and reproductivity of mice that were administered CTX. EGCG and TFs also increased the ovarian reserve of these animals. Furthermore, EGCG and TFs alleviated oxidation-induced damage to ovarian DNA in mice by activating the NRF2/HO-1 and SOD2 pathways and reducing the apoptosis of growing follicles. At the same time, EGCG and TFs reduced the overactivation of primordial follicles by inhibiting the AKT/mTOR/RPS6 pathway. CONCLUSION: The present study showed that EGCG and TFs independently improved ovarian function in mice with CTX-induced ovarian damage, thereby providing useful information for designing a potential clinical strategy that will protect against chemotherapy-induced ovarian damage.


Assuntos
Catequina , Atresia Folicular , Animais , Biflavonoides , Catequina/análogos & derivados , Catequina/farmacologia , Ciclofosfamida/toxicidade , Feminino , Camundongos
9.
Medicine (Baltimore) ; 100(40): e27359, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622835

RESUMO

ABSTRACT: Uterine diffuse large B-cell lymphoma (DLBCL) is a rare clinical condition. Most studies for uterine DLBCL are derived from case reports and series. Our main objective was to present a new case while also investigating the demographic, clinical characteristics, and survival of women with primary uterine DLBCL as compared to non-uterine DLBCL using the Surveillance, Epidemiology, and End Results incidence database. We queried the Surveillance, Epidemiology, and End Results database for women aged 18 years or older with a diagnosis of primary DLBCL from 1975 to 2017. The most common site of primary uterine DLBCL is the cervix uteri not otherwise specified, followed by endometrium, uterus not otherwise specified, corpus uteri, myometrium and isthmus uteri. Non-uterine DLBCL cases tend to be older than uterine DLBCL cases. Uterine DLBCL is most common among women aged 40 to 64 years. Patients with uterine DLBCL showed greater survival than non-uterine DLBCL patients, and patients treated in the rituximab era also exhibited a survival benefit. Both the elderly and African American cohorts experienced worse overall survival.


Assuntos
Linfoma Difuso de Grandes Células B/mortalidade , Neoplasias Uterinas/mortalidade , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Estudos Retrospectivos , Rituximab/uso terapêutico , Programa de SEER , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/tratamento farmacológico , Vincristina/uso terapêutico
10.
Medicina (Kaunas) ; 57(10)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34684063

RESUMO

Background and objectives: Hodgkin lymphoma (HL) is characterized by the presence of malignant Reed Sternberg cells. Although the current curability rate in patients with HL has increased, up to 30% of those in the advanced stages and 5% to 10% of those in limited stages of the disease, relapse. According to the studies, the relapse risk in HL decreases after 2 years. The purpose of this study is to evaluate the relapse risk and event free survival (EFS) in patients with HL treated with Doxorubicin, Bleomycin, Vinblastine and Dacarbazine (ABVD), or treated with Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisone (BEACOPP) regimens. Material and methods: In an observational, consecutive-case scenario, 71 patients (median age 32 years; range 16 to 80 years) diagnosed within a 4-year timeframe were enrolled; all patients were treated according to standards of care. The average follow-up duration was 26 months. Results: The risk of relapse, in patients older than 40 years, decreased after 1 year, OR = 0.707 (95% CI 0.506 to 0.988), and 2 years, OR = 0.771 (95% CI 0.459 to 1.295), respectively. Patients in the advanced stages had a higher International Prognostic Score (IPS) (score ≥ 4). The overall survival at 2 years was 57.74% and the disease-specific survival at 2 years was 71.83%. Regardless, the chemotherapy regimen and the EFS time, advanced stage, high IPS and bulky disease were still associated with an increased relapse risk in patients with HL. Conclusions: The use of ABVD chemotherapy regimen followed by 2 years EFS was associated with a reduced relapse risk.


Assuntos
Doença de Hodgkin , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Dacarbazina/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Recidiva , Taxa de Sobrevida , Resultado do Tratamento , Vimblastina/uso terapêutico , Adulto Jovem
11.
Adv Ther ; 38(12): 5752-5762, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34699004

RESUMO

INTRODUCTION: Concurrent anthracycline and taxane is an effective and efficient way to deliver neoadjuvant chemotherapy for HER2-negative breast cancers. Data on efficacy and tolerance to 6 cycles of concurrent docetaxel, epirubicin, and cyclophosphamide (TEC) is limited. METHOD: All patients with HER2-negative breast cancers who received neoadjuvant TEC from January 2013 to December 2019 were reviewed. RESULTS: A total of 71 patients [57 luminal B disease; 14 triple negative breast cancer (TNBC)] received neoadjuvant TEC with prophylactic granulocyte colony-stimulating factor (G-CSF). The pathological complete response (pCR) rate was 26.3% and 28.6% for luminal B and TNBC, respectively. With median follow-up of 48.9 months, 3 years disease-free survival was 85.9%, and 3 years overall survival was 89.6%. Non-hematological toxicities were common but the majority was grade 1 or 2. The most common grade 3 or 4 toxicity were hematological, including neutropenia (26.8%) and anemia (15.5%). There was no cardiotoxicity observed. Half of the patients had at least one dose reduction but all patients completed the planned 6 cycles and had breast surgery done. CONCLUSION: Six cycles of TEC with prophylactic G-CSF is an effective and tolerable neoadjuvant regime for HER2-negative breast cancers. Hematological toxicities were the most common toxicities. Although many patients required dose reduction, all patients completed treatment and there was no observed cardiotoxicity.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Docetaxel/uso terapêutico , Epirubicina , Feminino , Humanos , Terapia Neoadjuvante , Receptor ErbB-2/uso terapêutico , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
13.
Lancet Haematol ; 8(11): e818-e827, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34634256

RESUMO

BACKGROUND: Dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) is a front-line treatment for patients with aggressive B-cell lymphomas. Bcl-2 is associated with chemoresistance due to BCL2 gene rearrangement or protein overexpression and is antagonised by venetoclax. We aimed to assess the safety of venetoclax with dose-adjusted EPOCH-R as initial therapy in aggressive B-cell lymphoma. METHODS: We conducted a single-arm, phase 1 study across seven treatment centres in the USA. Eligible patients were aged 18-80 years with histologically confirmed, previously untreated diffuse large B-cell lymphoma, transformed indolent non-Hodgkin lymphoma, high-grade B-cell lymphoma with double-hit or not otherwise specified, or primary mediastinal B-cell lymphoma, with Ann Arbor stage II-IV and Eastern Cooperative Oncology Group performance status of 0-2. Participants received six cycles of oral venetoclax 400 mg, 600 mg, or 800 mg once daily for 10 days per cycle with dose-adjusted EPOCH-R (one cycle every 3 weeks; baseline doses were intravenous rituximab 375 mg/m2 on day 1, intravenous etoposide 50 mg/m2 on days 1-4, oral prednisone 60 mg/m2 twice daily on days 1-5, intravenous vincristine 0·4 mg/m2 on days 1-4, intravenous cyclophosphamide 750 mg/m2 on day 5, and intravenous doxorubicin 10 mg/m2 on days 1-4). A subsequent cohort received venetoclax 600 mg once daily for 5 days per cycle. The primary endpoints were the maximum tolerated dose, dose-limiting toxicities, and the recommended phase 2 dose of venetoclax. Analyses were done per protocol. This trial is registered with ClinicalTrials.gov, NCT03036904, and enrolment is now closed. FINDINGS: Between Feb 3, 2017, and June 4, 2019, 34 patients were assessed for eligibility, and 30 were enrolled and received venetoclax with dose-adjusted EPOCH-R. The median patient age was 64·0 years (IQR 51·6-69·4). The maximum tolerated dose was 800 mg for 10 days and the established recommended phase 2 dose was 600 mg for 5 days due to tolerability for treatment duration. One (3%) of 30 patients had a dose-limiting toxicity in cycle one (grade 4 thrombocytopenia with 800 mg dose). The most common grade 3-4 adverse events were cytopenias (28 [93%] of 30 patients); febrile neutropenia occurred in 19 (63%) patients. Grade 3-4 non-haematological adverse events included hypophosphataemia (n=10), hypokalaemia (n=7), and hyperglycaemia (n=5). Serious adverse events included infection (n=7) and gastrointestinal toxicities including abdominal pain (n=3), colonic perforation (n=1), and small intestinal obstruction (n=1). There was one treatment-related death (sepsis). Overall response rate was 96·7% (95% CI 82·8-99·9); 28 (93·3% [77·9-99·2]) of 30 patients had complete response and one (3·3% [0·1-17·2]) had a partial response. INTERPRETATION: Venetoclax with dose-adjusted EPOCH-R showed an acceptable safety profile at the recommended phase 2 dose and had encouraging preliminary activity in this population at high risk of adverse outcomes, and is worthy of further study. The combination is being investigated in Alliance 051701 (NCT03984448). FUNDING: Genentech.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Sulfonamidas/uso terapêutico , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Etoposídeo/uso terapêutico , Feminino , Humanos , Linfoma de Células B/patologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Vincristina/uso terapêutico
14.
Pril (Makedon Akad Nauk Umet Odd Med Nauki) ; 42(2): 109-115, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34699711

RESUMO

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy, caused by dysregulation of the complement alternative pathway. Deletion of the complement factor H-related genes, CFHR1 and CFHR3, together with the presence of CFH autoantibodies are reported in aHUS patients, representing 10% of cases of patients with aHUS. Case presentation: We report here on a case of 4-year-old girl with anti-CFH antibody-associated aHUS. The measurement of complement factors and anti-factor H antibodies, was the main guideline for making an accurate diagnosis and providing the appropriate therapy, with the patient responding positively to plasma exchanges (PEs) and cyclophosphamide pulses. We then, one year after disease onset, continued with glucocorticoids and mycophenolate mofetil (MMF), as maintenance therapy. There were no complications during the therapy other than neutropenia. Now, one year after the cessation of the immune suppression therapy, she is in remission with normal kidney function, no signs of hemolysis, normal C3 levels, and normal range proteinuria. The anti-factor H autoantibody titer decreased but still remained positive, the factor H antigen values remained low all throughout. Close follow-up is applied with frequent urine testing and complete blood count with an intention for early detection of relapse of the disease. Conclusion: The purpose of this case report is to emphasize the value of complement factor measurements and also to separate anti-CFH antibody-associated aHUS as an entity, because immunosuppressive therapy provides an excellent response..


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Fator H do Complemento , Síndrome Hemolítico-Urêmica Atípica/genética , Autoanticorpos , Pré-Escolar , Fator H do Complemento/genética , Proteínas do Sistema Complemento , Ciclofosfamida , Feminino , Humanos
15.
Int J Mol Sci ; 22(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34638621

RESUMO

Previously, we showed that mice treated with cyclophosphamide (CTX) 4 days before intravenous injection of breast cancer cells had more cancer cells in the lung at 3 h after cancer injection than control counterparts without CTX. At 4 days after its injection, CTX is already excreted from the mice, allowing this pre-treatment design to reveal how CTX may modify the lung environment to indirectly affect cancer cells. In this study, we tested the hypothesis that the increase in cancer cell abundance at 3 h by CTX is due to an increase in the adhesiveness of vascular wall for cancer cells. Our data from protein array analysis and inhibition approach combined with in vitro and in vivo assays support the following two-prong mechanism. (1) CTX increases vascular permeability, resulting in the exposure of the basement membrane (BM). (2) CTX increases the level of matrix metalloproteinase-2 (MMP-2) in mouse serum, which remodels the BM and is functionally important for CTX to increase cancer abundance at this early stage. The combined effect of these two processes is the increased accessibility of critical protein domains in the BM, resulting in higher vascular adhesiveness for cancer cells to adhere. The critical protein domains in the vascular microenvironment are RGD and YISGR domains, whose known binding partners on cancer cells are integrin dimers and laminin receptor, respectively.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/farmacologia , Metaloproteinase 2 da Matriz/sangue , Microambiente Tumoral/efeitos dos fármacos , Animais , Membrana Basal/efeitos dos fármacos , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Permeabilidade Capilar/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Humanos , Integrina beta1/metabolismo , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Camundongos Knockout , Domínios Proteicos , Microambiente Tumoral/fisiologia
16.
DNA Cell Biol ; 40(11): 1356-1368, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34704810

RESUMO

In this study, we aimed to explore cyclophosphamide (Cytoxan) response-associated genes and constructed a model to predict the prognosis of breast cancer (BRCA) patients. Samples obtained from TCGA and GEO databases were subjected to Weighted Gene Coexpression Network Analysis (WGCNA) and univariate Cox and LASSO Cox regression analysis to identify and validate the Cytoxan response-related prognostic signature. Moreover, multivariate Cox regression analysis was performed to analyze the independence of factors, and the nomogram model was constructed by including all the independent factors. WGCNA revealed that 159 genes are significantly correlated with Cytoxan response in BRCA samples, and the samples with a different prognosis could be effectively distinguished based on the expression of those 159 genes. Ten genes were further selected to be related to the prognosis of BRCA patients, including PCDHB2, GRIK2, FRMD7, CCSER1, PCDHGA1, PCDHA1, LRRC37A6P, PCDHGA12, ZNF486, and PCDHGB5, based on the Risk Score model. Among them, PCDHA1 expression was validated in cells and patient samples. Multivariate Cox regression analysis confirmed that the Risk Score is an independent factor. Furthermore, the nomogram model showed that the predicted survival probability is closely related to the actual survival probability. In conclusion, we identified 159 genes potentially correlated with the Cytoxan response of BRCA patients, which had prognostic value in BRCA.


Assuntos
Biomarcadores Farmacológicos/análise , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Proteínas do Citoesqueleto/genética , Bases de Dados Genéticas , Tratamento Farmacológico/métodos , Feminino , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes , Predisposição Genética para Doença/genética , Testes Genéticos/métodos , Humanos , Estimativa de Kaplan-Meier , Proteínas de Membrana/genética , Nomogramas , Prognóstico , Fatores de Risco , Transcriptoma/genética , Microambiente Tumoral
17.
Cells ; 10(10)2021 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-34685756

RESUMO

Protein hydrolysate injection (PH) is a sterile solution of hydrolyzed protein and sorbitol that contains 17 amino acids and has a molecular mass of 185.0-622.0 g/mol. This study investigated the effect of PH on hematopoietic function in K562 cells and mice with cyclophosphamide (CTX)-induced hematopoietic dysfunction. In these myelosuppressed mice, PH increased the number of hematopoietic cells in the bone marrow (BM) and regulated the concentration of several factors related to hematopoietic function. PH restored peripheral blood cell concentrations and increased the numbers of hematopoietic stem cells and progenitor cells (HSPCs), B lymphocytes, macrophages, and granulocytes in the BM of CTX-treated mice. Moreover, PH regulated the concentrations of macrophage colony stimulating factor (M-CSF), interleukin (IL)-2, and other hematopoiesis-related cytokines in the serum, spleen, femoral condyle, and sternum. In K562 cells, the PH-induced upregulation of hematopoiesis-related proteins was inhibited by transfection with M-CSF siRNA. Therefore, PH might benefit the BM hematopoietic system via the regulation of M-CSF expression, suggesting a potential role for PH in the treatment of hematopoietic dysfunction caused by cancer therapy.


Assuntos
Hematopoese/efeitos dos fármacos , Fator Estimulador de Colônias de Macrófagos/farmacologia , Hidrolisados de Proteína/administração & dosagem , Hidrolisados de Proteína/farmacologia , Aminoácidos/análise , Animais , Células da Medula Óssea/efeitos dos fármacos , Ciclofosfamida/farmacologia , Fêmur/efeitos dos fármacos , Fêmur/patologia , Humanos , Células K562 , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Peso Molecular , Esterno/efeitos dos fármacos , Esterno/patologia
18.
Molecules ; 26(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34641277

RESUMO

The effects of immunomodulatory activity of two types of carboxymethyl pachymaran (CMP-1 and CMP-2) on cyclophosphamide (CTX)-induced mice were investigated. Both CMP-1 and CMP-2 were found to restore the splenomegaly and alleviate the spleen lesions and the mRNA expressions of TLR4, MyD88, p65 and NF-κB in spleen were also increased. CMP-1 and CMP-2 could enhance the immunity by increasing the levels of TNF-α, IL-2, IL-6, IFN-γ, Ig-A and Ig-G in serum. In addition, CMP-1 could increase the relative abundance of Bacteroidetes and reduce the relative richness of Firmicutes at the phylum level. CMP-1 and CMP-2 could reduce the relative abundance Erysipelatoclostridum at the genus level. CMP-1 and CMP-2 might enhance the immune function of immunosuppression mice by regulating the gene expression in the TLR4/NF-κB signaling pathway and changing the composition and abundance of the intestinal microbiota. The results suggested that CMP-1 and CMP-2 would be as potential immunomodulatory agents in functional foods.


Assuntos
Ciclofosfamida/efeitos adversos , Glucanos/química , Hospedeiro Imunocomprometido/efeitos dos fármacos , Fatores Imunológicos/administração & dosagem , Polissacarídeos/administração & dosagem , Esplenomegalia/tratamento farmacológico , Animais , Bacteroidetes/classificação , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , Modelos Animais de Doenças , Feminino , Firmicutes/classificação , Firmicutes/genética , Firmicutes/isolamento & purificação , Alimento Funcional , Microbioma Gastrointestinal/efeitos dos fármacos , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Camundongos , Fator 88 de Diferenciação Mieloide/genética , Filogenia , Polissacarídeos/química , Polissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Esplenomegalia/induzido quimicamente , Esplenomegalia/genética , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética
19.
Nutrients ; 13(10)2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34684550

RESUMO

Aim: Recently, more attention has been paid to the role of nutritional intervention in preventing the side effects of chemotherapy in oncology patients. Therefore, the aim of the present study was to analyze the effects of oral nutritional supplements on the body composition and biochemical parameters in women with breast cancer receiving postoperative adjuvant chemotherapy. Patients and Methods: The study involved women diagnosed with breast cancer who underwent surgical treatment and were qualified for chemotherapy (doxorubicin and cyclophosphamide). Women were divided into two groups, depending on whether oral nutritional supplements were used during chemotherapy. Anthropometric and biochemical parameters were analyzed twice in all patients: before and after six weeks of chemotherapy. Propensity score (PS) matching was performed to select patients balanced in terms of age, BMI, and clinicopathological features of the tumor. Statistical comparisons were conducted in a propensity-matched cohort of patients. Results: The value of BMI was maintained constant in the supplemented women older than 56 years after six weeks of chemotherapy. Regardless of age in the supplemented women, a significant increase in muscle mass, fat free mass (FFM), and fat free mass index (FFMI) was demonstrated. An increase in fat mass (FM) including visceral fat was observed only in the non-supplemented control. Regardless of age or initial FM, supplemented women exhibited a constant level of albumin. Moreover, in the supplemented women with normal initial FM, the stable values of triglycerides and HDL cholesterol were maintained after six weeks of chemotherapy. Conclusion: The present study demonstrated that oral nutritional supplements could improve body composition and prevent hypoalbuminemia and lipid abnormalities in women with breast cancer undergoing chemotherapy.


Assuntos
Composição Corporal , Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/terapia , Quimioterapia Adjuvante , Suplementos Nutricionais , Antropometria , Antineoplásicos Alquilantes/uso terapêutico , Índice de Massa Corporal , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Lipídeos/sangue , Mastectomia , Pessoa de Meia-Idade , Período Pós-Operatório , Pontuação de Propensão , Albumina Sérica/metabolismo , Resultado do Tratamento
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