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1.
Ann Hematol ; 99(10): 2429-2436, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32839869

RESUMO

Patients receiving vinca alkaloids for hematological malignancies frequently experience constipation that is unresponsive to laxatives. Research on treatment of vinca alkaloid-induced constipation is limited. This study aimed to determine whether the chloride channel activator lubiprostone ameliorates vinca alkaloid-induced constipation in patients with hematological malignancies. In this retrospective cohort study, vinca alkaloid-induced constipation (grade ≥ 3 using the Common Terminology Criteria for Adverse Events) was investigated in patients treated for hematological malignancies between July 2014 and June 2019 who had already been prescribed osmotic laxatives and additionally received either a stimulant laxative or lubiprostone. Univariate and multivariate analyses were performed to identify the risk factors for persistent constipation after introduction of the second laxative. A propensity score model was used to match 67 patients taking a stimulant laxative and 67 treated with lubiprostone, and the occurrence of intractable constipation was compared between groups. Overall, 203 patients were included, among whom 50 (25%) had constipation. On multivariate analysis, body mass index, opioid use, and addition of lubiprostone were independently associated with constipation. Patients treated with lubiprostone were significantly less likely to experience intractable constipation than did those treated with stimulant laxatives (10% vs. 34%, P = 0.002). Moreover, post-constipation diarrhea was significantly less frequent among patients treated with lubiprostone (42% vs. 63%, P = 0.024). Lubiprostone was more effective than stimulant laxatives at treating vinca alkaloid-induced intractable constipation in patients with hematological malignancies, and its use could enable safe vinca alkaloid chemotherapy.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Agonistas dos Canais de Cloreto/uso terapêutico , Constipação Intestinal/tratamento farmacológico , Neoplasias Hematológicas/tratamento farmacológico , Lubiprostona/uso terapêutico , Linfoma/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Alcaloides de Vinca/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Constipação Intestinal/induzido quimicamente , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Avaliação de Medicamentos , Quimioterapia Combinada , Famotidina/uso terapêutico , Feminino , Humanos , Laxantes/farmacologia , Laxantes/uso terapêutico , Óxido de Magnésio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Entorpecentes/efeitos adversos , Prednisona/administração & dosagem , Pontuação de Propensão , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Senosídeos/uso terapêutico , Alcaloides de Vinca/administração & dosagem , Vincristina/administração & dosagem
2.
Life Sci ; 256: 117984, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32593707

RESUMO

Dealing with cancer is of importance due to enhanced incidence rate of this life-threatening disorder. Chemotherapy is an ideal candidate in overcoming and eradication of cancer. To date, various chemotherapeutic agents have been applied in cancer therapy and paclitaxel (PTX) is one of them. PTX is a key member of taxane family with potential anti-tumor activity against different cancers. Notably, PTX has demonstrated excellent proficiency in elimination of cancer in clinical trials. This chemotherapeutic agent is isolated from Taxus brevifolia, and is a tricyclic diterpenoid. However, resistance of cancer cells into PTX chemotherapy has endangered its efficacy. Besides, administration of PTX is associated with a number of side effects such as neurotoxicity, hepatotoxicity, cardiotoxicity and so on, demanding novel strategies in obviating PTX issues. Curcumin is a pharmacological compound with diverse therapeutic effects including anti-tumor, anti-oxidant, anti-inflammatory, anti-diabetic and so on. In the current review, we demonstrate that curcumin, a naturally occurring nutraceutical compound is able to enhance anti-tumor activity of PTX against different cancers. Besides, curcumin administration reduces adverse effects of PTX due to its excellent pharmacological activities. These topics are discussed with an emphasis on molecular pathways to provide direction for further studies in revealing other signaling networks.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Curcumina/administração & dosagem , Neoplasias/tratamento farmacológico , Paclitaxel/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linhagem Celular Tumoral , Curcumina/efeitos adversos , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Paclitaxel/efeitos adversos
3.
J Cancer Res Ther ; 16(1): 34-39, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362607

RESUMO

Background and Objective: Metformin (MET) has been used as an antidiabetic agent for type II diabetes. At the same time, recent researches have shown that the clinical improvement of MET is useful for nerve damage. In this study, we investigated the analgesic effect of MET in paclitaxel (PAC)-induced neuropathic pain. Materials and Methods: Forty-two adult, female rats, Wistar strain weighing 220 ± 10 g were randomly divided into 5 experimental groups. PAC was intraperitoneally (IP) administered (2.0 mg/kg) for 4 groups every other day (0, 2, 4, and 6 days). By the 30th day, MET (100, 200, and 400 mg/kg) was administered to 4 groups. Before and after treatment, basal pain threshold values were measured with Randall-Selitto analgesiometer test. At the end of experiment, pathological values were measured in selected regions including brain (motor cortex, M1), spinal cord (L4-L5), sciatic nerve, and muscle. Results: According to our results, PAC-induced neuropathic pain reached to highest level at 14th day. Four hundred milligram/kilogram concentration of MET remarkably decreased PAC-induced neuropathic pain. On the other hand, pathologic features have shown that PAC had significant pathological change in the brain and spinal cord while in the peripheral nerves and muscles had not shown any pathological change. Conclusion: The pathological results of the current study for the first time demonstrated that MET beside of its antidiabetic effects reversed neuropathic pain induced by PAC. Consequently, this research can be promising for cancer patients that suffering from neuropathic pain induced by anticancer drugs.


Assuntos
Analgésicos/farmacologia , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Neoplasias/complicações , Neuralgia/prevenção & controle , Paclitaxel/efeitos adversos , Limiar da Dor/efeitos dos fármacos , Animais , Antineoplásicos Fitogênicos/efeitos adversos , Modelos Animais de Doenças , Feminino , Neoplasias/patologia , Neuralgia/induzido quimicamente , Neuralgia/patologia , Ratos , Ratos Wistar
4.
Anesthesiology ; 132(6): 1540-1553, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32404819

RESUMO

BACKGROUND: Patients undergoing cancer treatment often experience chemotherapy-induced neuropathic pain at their extremities, for which there is no U.S. Food and Drug Administration-approved drug. The authors hypothesized that local sympathetic blockade, which is used in the clinic to treat various pain conditions, can also be effective to treat chemotherapy-induced neuropathic pain. METHODS: A local sympathectomy (i.e., cutting the ipsilateral gray rami entering the spinal nerves near the L3 and L4 dorsal root ganglia) was performed in mice receiving intraperitoneal injections every other day of the chemotherapeutic drug paclitaxel. Sympathectomy effects were then assessed in chemotherapy-induced pain-like behaviors (i.e., mechanical and cold allodynia) and neuroimmune and electrophysiologic responses. RESULTS: Local microsympathectomy produced a fast recovery from mechanical allodynia (mean ± SD: sympathectomy vs. sham at day 5, 1.07 ± 0.34 g vs. 0.51 ± 0.17g, n = 5, P = 0.030 in male mice, and 1.08 ± 0.28 g vs. 0.62 ± 0.16 g, n = 5, P = 0.036 in female mice) and prevented the development of cold allodynia in both male and female mice after paclitaxel. Mechanistically, microsympathectomy induced transcriptional increases in dorsal root ganglia of macrophage markers and anti-inflammatory cytokines, such as the transforming growth factor-ß. Accordingly, depletion of monocytes/macrophages and blockade of transforming growth factor-ß signaling reversed the relief of mechanical allodynia by microsympathectomy. In particular, exogenous transforming growth factor-ß was sufficient to relieve mechanical allodynia after paclitaxel (transforming growth factor-ß 100 ng/site vs. vehicle at 3 h, 1.21 ± 0.34g vs. 0.53 ± 0.14 g, n = 5, P = 0.001 in male mice), and transforming growth factor-ß signaling regulated neuronal activity in dorsal root ganglia. CONCLUSIONS: Local sympathetic nerves control the progression of immune responses in dorsal root ganglia and pain-like behaviors in mice after paclitaxel, raising the possibility that clinical strategies already in use for local sympathetic blockade may also offer an effective treatment for patients experiencing chemotherapy-induced neuropathic pain.


Assuntos
Hiperalgesia/induzido quimicamente , Hiperalgesia/prevenção & controle , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Paclitaxel/efeitos adversos , Simpatectomia , Animais , Antineoplásicos Fitogênicos/efeitos adversos , Temperatura Baixa , Modelos Animais de Doenças , Feminino , Masculino , Camundongos
5.
Zhonghua Zhong Liu Za Zhi ; 42(3): 170-179, 2020 Mar 23.
Artigo em Chinês | MEDLINE | ID: mdl-32252195

RESUMO

Taxanes are cornerstones of cancer chemotherapy and can be used for the treatment of various tumors, including breast cancer. Taxane-associated peripheral neuropathy is a common adverse effect of taxanes, leading to discontinuation of drug therapy, affecting drug treatment outcomes, and severely affecting patients' quality of life. This consensus addresses and recommends the pathogenesis, clinical features, associated risk factors, diagnostic evaluation, prevention, and treatment of taxane-related peripheral neuropathy. It is hoped that this consensus will standardize the current management of taxane-related peripheral neuropathy in China and improve clinicians' understanding of taxane-related peripheral neuropathy, thereby improving patient outcomes and improving patient quality of life.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Síndromes Neurotóxicas/diagnóstico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico , Taxoides/efeitos adversos , Taxoides/uso terapêutico , Neoplasias da Mama/patologia , Neoplasias da Mama/psicologia , Hidrocarbonetos Aromáticos com Pontes , China , Consenso , Humanos , Síndromes Neurotóxicas/etiologia , Guias de Prática Clínica como Assunto , Qualidade de Vida
6.
Artigo em Alemão | MEDLINE | ID: mdl-32211937

RESUMO

Mistletoe (Viscum album L.) continues to be the medical herb prescribed most frequently for cancer patients in German-speaking countries. Demand for this therapy often comes from patients themselves and requires careful consideration by the attending physician during consultation.In German-speaking countries, mistletoe extracts are available as approved drugs (based on monographs of the commissions C and E of the German Federal Institute for Drugs and Medical Devices). In Switzerland, treatment costs are generally covered by statutory health insurance. In Germany, coverage is limited to palliative care. In adjuvant cases, treating physicians can request coverage by the health insurance if patients suffer from side effects due to the antitumoral treatment.The spectrum of Viscum album extract includes mistletoe lectin I; II, and III, viscotoxins, flavonoids, amino acids, polysaccharides, and membrane lipids. Preclinical studies have demonstrated cytotoxic, apoptosis-inducing, and immunomodulatory effects.Many clinical studies indicate a supportive efficacy of mistletoe extracts in tumor patients, even though methodological quality is discussed controversially in many cases. Clinical data regarding effects on survival of patients is inconsistent; effects concerning quality of life as well as the tolerability of antitumoral treatments are evaluated more positively.In view of the high demand on the patient side and increasing scientific evidence, the general conditions for prescriptions should continue as well as the ongoing scientific evaluation.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Erva-de-Passarinho/química , Neoplasias/tratamento farmacológico , Fitoterapia/métodos , Viscum album , Antineoplásicos Fitogênicos/efeitos adversos , Alemanha , Humanos , Imunomodulação , Erva-de-Passarinho/metabolismo , Neoplasias/patologia , Neoplasias/psicologia , Extratos Vegetais/uso terapêutico , Qualidade de Vida , Suíça
7.
Lancet ; 395(10231): 1195-1207, 2020 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-32145827

RESUMO

BACKGROUND: Optimal treatment regimens for AIDS-associated Kaposi sarcoma, a frequent contributor to morbidity and mortality among people with HIV, have not been systematically evaluated in low-income and middle-income countries, where the disease is most common. In this study, we aimed to investigate optimal treatment strategies for advanced stage disease in areas of high prevalence and limited resources. METHODS: In this open-label, non-inferiority trial, we enrolled people with HIV and advanced stage AIDS-associated Kaposi sarcoma attending 11 AIDS Clinical Trials Group sites in Brazil, Kenya, Malawi, South Africa, Uganda, and Zimbabwe. Eligible participants were randomly assigned (1:1:1) with a centralised computer system to receive either intravenous bleomycin and vincristine or oral etoposide (the investigational arms), or intravenous paclitaxel (the control arm), together with antiretroviral therapy (ART; combined efavirenz, tenofovir disoproxil fumarate, and emtricitabine). The primary outcome was progression-free survival (PFS) at week 48, using a 15% non-inferiority margin to compare the investigational groups against the active control group. Safety was assessed in all eligible treated study participants. The study was registered with ClinicalTrials.gov, NCT01435018. FINDINGS: 334 participants were enrolled between Oct 1, 2013, and March 8, 2018, when the study was closed early due to inferiority of the bleomycin and vincristine plus ART arm, as per the recommendations of the Data and Safety Monitoring Board (DSMB). The etoposide plus ART arm also closed due to inferiority in March, 2016, following a DSMB recommendation. Week-48 PFS rates were higher in the paclitaxel plus ART arm than in both investigational arms. The absolute differences in PFS were -30% (95% CI -52 to -8) for the comparison of paclitaxel plus ART (week 48 PFS 50%, 32 to 67; n=59) and etoposide plus ART (20%, 6 to 33; n=59), and -20% (-33% to -7%) for the comparison of paclitaxel plus ART (64%, 55 to 73; n=138) and bleomycin and vincristine plus ART (44%, 35 to 53; n=132). Both CIs overlapped the non-inferiority margin. The most common adverse events, in 329 eligible participants who began treatment, were neutropenia (48 [15%]), low serum albumin (33 [10%]), weight loss (29 [9%]), and anaemia (28 [9%]), occurring at similar frequency across treatment arms. INTERPRETATION: Non-inferiority of either investigational intervention was not shown, with paclitaxel plus ART showing superiority to both oral etoposide plus ART and bleomycin and vincristine plus ART, supporting its use in treating advanced AIDS-associated Kaposi sarcoma in resource-limited settings. FUNDING: US National Institute of Allergy and Infectious Diseases and National Cancer Institute, National Institutes of Health.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antibióticos Antineoplásicos/efeitos adversos , Antineoplásicos Fitogênicos/efeitos adversos , Bleomicina/efeitos adversos , Sarcoma de Kaposi/tratamento farmacológico , Vincristina/efeitos adversos , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Adulto , África , Fármacos Anti-HIV/administração & dosagem , Antibióticos Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Antirretroviral de Alta Atividade/métodos , Bleomicina/administração & dosagem , Países em Desenvolvimento , Quimioterapia Combinada , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Masculino , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Intervalo Livre de Progressão , Sarcoma de Kaposi/mortalidade , Vincristina/administração & dosagem
8.
Lancet Gastroenterol Hepatol ; 5(3): 267-275, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31926918

RESUMO

BACKGROUND: Chemoprevention of colorectal adenoma and colorectal cancer remains an important public health goal. The present study aimed to investigate the clinical potential and safety of berberine for prevention of colorectal adenoma recurrence. METHODS: This double-blind, randomised, placebo-controlled trial was done in seven hospital centres across six provinces in China. Individuals aged 18-75 years who had at least one but no more than six histologically confirmed colorectal adenomas that had undergone complete polypectomy within the 6 months before recruitment were recruited and randomly assigned (1:1) to receive berberine (0·3 g twice daily) or placebo tablets via block randomisation (block size of six). Participants were to undergo a first follow-up colonoscopy 1 year after enrolment, and if no colorectal adenomas were detected, a second follow-up colonoscopy at 2 years was planned. The study continued until the last enrolled participant reached the 2-year follow-up point. All participants, investigators, endoscopists, and pathologists were blinded to treatment assignment. The primary efficacy endpoint was the recurrence of adenomas at any follow-up colonoscopy. Analysis was based on modified intention-to-treat, with the full analysis set including all randomised participants who received at least one dose of study medication and who had available efficacy data. The study is registered with ClinicalTrials.gov, number NCT02226185; the trial has ended and this report represents the final analysis. FINDINGS: Between Nov 14, 2014, and Dec 30, 2016, 553 participants were randomly assigned to the berberine group and 555 to the placebo group. The full analysis set consisted of 429 participants in the berberine group and 462 in the placebo group. 155 (36%) participants in the berberine group and 216 (47%) in the placebo group were found to have recurrent adenoma during follow-up (unadjusted relative risk ratio for recurrence 0·77, 95% CI 0·66-0·91; p=0·001). No colorectal cancers were detected during follow-up. The most common adverse event was constipation (six [1%] of 446 patients in the berberine group vs one [<0·5%] of 478 in the placebo group). No serious adverse events were reported. INTERPRETATION: Berberine 0·3 g twice daily was safe and effective in reducing the risk of recurrence of colorectal adenoma and could be an option for chemoprevention after polypectomy. FUNDING: National Natural Science Foundation of China.


Assuntos
Adenoma/prevenção & controle , Antineoplásicos Fitogênicos/uso terapêutico , Berberina/uso terapêutico , Neoplasias Colorretais/patologia , Adenoma/patologia , Adenoma/cirurgia , Adolescente , Adulto , Assistência ao Convalescente , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Berberina/administração & dosagem , Berberina/efeitos adversos , Quimioprevenção/métodos , China/epidemiologia , Colonoscopia/métodos , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/epidemiologia , Método Duplo-Cego , Humanos , Análise de Intenção de Tratamento/métodos , Pessoa de Meia-Idade , Placebos/administração & dosagem , Plantas Medicinais/efeitos adversos , Recidiva , Segurança , Adulto Jovem
11.
J Oncol Pharm Pract ; 26(1): 51-59, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30866715

RESUMO

BACKGROUND: Different international organizations recommend safety measures for the use of vincristine to prevent wrong route administrations. A central recommendation is to use infusion bags instead of syringes to prevent confusion with intrathecal chemotherapy. This study aimed to investigate the implementation of safety measures for vincristine and intrathecal chemotherapies in Switzerland. METHOD: We conducted a written survey among hospital pharmacies of all general care and pediatric hospitals in Switzerland (n = 102). A responsible person of each hospital pharmacy was invited by email to participate in the online survey in May 2018. RESULTS: Of 66 responding hospitals (response rate 65%), 27 have a hospital pharmacy preparing parenteral chemotherapy. All of these hospitals prepared vincristine in 2017, while 21 also prepared intrathecal chemotherapy. Of these 21, 16 hospitals prepared vincristine as syringes, with small volume syringes being the most widely distributed dosage form. A switch from syringes to infusion bags was discussed in seven hospitals, and discussions led to plans for switch in two. The most prevalent safety measures were labeling for vincristine and special delivery for intrathecal drugs. Of hospitals preparing both vincristine syringes and intrathecal chemotherapy, four reported to have no safety measures implemented neither for vincristine nor for intrathecal chemotherapy. CONCLUSION: International recommendations are not widely implemented in Swiss hospitals. Syringes are still in use and other safety measures are sparsely disseminated. Thus, Swiss vincristine patients are still at an increased risk for wrong route application. Recommendations have to be further disseminated and implementation could be enhanced.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Erros de Medicação/prevenção & controle , Serviço de Farmácia Hospitalar/normas , Inquéritos e Questionários , Vincristina/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Vias de Administração de Medicamentos , Feminino , Humanos , Masculino , Serviço de Farmácia Hospitalar/métodos , Suíça/epidemiologia , Seringas/normas , Vincristina/efeitos adversos
12.
J Pharm Pharmacol ; 72(1): 1-16, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31659754

RESUMO

OBJECTIVES: Annona muricata, also known as graviola, soursop and guanabana, has been widely utilised for the treatment of a range of cancers. The mechanism of action and the efficacy of A. muricata and its constituents in the treatment of cancer have been comprehensively reviewed. The aim of this systematic review was to summarise the available literature that reports on factors related to the safety and tolerability of A. muricata leaf extract and its acetogenins. METHODS: In-vitro, preclinical animal studies and human studies of any design written in any language were included. Studies that evaluated A. muricata leaf extract and its constituents were searched through the databases Pubmed, Medline and Embase from inception to April 2019. The elaborated item 4 of Consolidated Standards of Reporting Trials statement and Animals in Research: Reporting In vivo Experiments guidelines were used to evaluate the quality of the studies. KEY FINDINGS: The results suggest that A. muricata and its constituents have hepatoprotective, neurotoxic, antinociceptive, anti-ulcerative and chemopreventive effects. The dose and duration used in animal studies demonstrating toxicity may not directly translate into the effects in humans. Studies included in this review were judged to be of medium to high quality. CONCLUSIONS: The overall outcome of the current review suggests that A. muricata has a favourable safety and tolerability profile. Future studies investigating its use in people diagnosed with a range of cancers are warranted.


Assuntos
Annona , Antineoplásicos Fitogênicos/uso terapêutico , Folhas de Planta , Preparações de Plantas/uso terapêutico , Animais , Annona/efeitos adversos , Annona/química , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/farmacocinética , Humanos , Segurança do Paciente , Folhas de Planta/efeitos adversos , Folhas de Planta/química , Preparações de Plantas/efeitos adversos , Preparações de Plantas/farmacocinética , Medição de Risco
13.
Drug Deliv ; 27(1): 91-99, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31870182

RESUMO

Although cell-penetrating peptides (CPPs) has been proven to be efficient transporter for drug delivery, ideal peptide vectors for tumor therapy are still being urgently sought. Peptide antagonists have attracted substantial attention as targeting molecules because of their high tumor accumulation and antitumor activity compared with agonists. SPA, a derivative of substance P, is a potent antagonist that exhibits antitumor activity. Based on the amino acid composition of SPA, we speculate that it can translocate across cell membranes as CPPs do. In this study, our results demonstrated that SPA could enter cells similarly to a CPP. As a vector, SPA could efficiently deliver camptothecin and plasmids into cells. In addition, our results showed that SPA exhibited low toxicity to normal cells and high enzymatic stability. Taken together, our results validated the ability of SPA for efficient drug delivery. More importantly, our study opens a new avenue for designing ideal CPPs based on peptide antagonists.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Camptotecina/farmacologia , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/farmacocinética , Substância P/análogos & derivados , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Células CHO , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Peptídeos Penetradores de Células/administração & dosagem , Cricetulus , Sistemas de Liberação de Medicamentos
14.
Yakugaku Zasshi ; 139(12): 1601-1608, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31787650

RESUMO

Paclitaxel (PTX)-associated acute pain syndrome (P-APS) is characterized by disabling but transient arthralgia and myalgia in up to 80% of patients administered with PTX. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely administered to patients with cancer who have pain or fever, and are mainly used to manage P-APS. In this study, we investigated how P-APS appear in the patients who were administered NSAIDs prior to PTX injection. The incidence or severity and duration of P-APS in patients previously administered NSAIDs were compared to those of patients who were not administered NSAIDs. The relationship between previously administered NSAIDs and rescue administration for the relief of P-APS was also evaluated. It was revealed that the incidence and duration of P-APS were 72% and 4.67±2.30 d, respectively, in the control group and 84% and 6.19±3.30 d, respectively, in the NSAIDs group. There was no significant difference in the incidence and duration and the severity of P-APS between the two groups. Patients who were previously administered NSAIDs tended to obtain less pain relief from NSAIDs administered as rescue medications, and needed other medication. Univariate and multivariate analysis revealed no correlation between previously administered NSAIDs or patient characteristics and the incidence of P-APS. In this study, it was found that clinical condition that needs NSAIDs and previously administered NSAIDs prior to PTX injection do not affect the incidence, severity, and duration of P-APS. These results will help in educating patients about their medications and will contribute to the management of P-APS.


Assuntos
Dor Aguda/induzido quimicamente , Anti-Inflamatórios não Esteroides/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Miotoxicidade/etiologia , Paclitaxel/efeitos adversos , Adulto , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Educação de Pacientes como Assunto , Estudos Retrospectivos , Índice de Gravidade de Doença , Síndrome
15.
Mar Drugs ; 18(1)2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31877728

RESUMO

Chemotherapeutic drugs are widely utilized in the treatment of human cancers. Painful chemotherapy-induced neuropathy is a common, debilitating, and dose-limiting side effect for which there is currently no effective treatment. Previous studies have demonstrated the potential utility of peptides from the marine snail from the genus Conus for the treatment of neuropathic pain. α-Conotoxin RgIA and a potent analog, RgIA4, have previously been shown to prevent the development of neuropathy resulting from the administration of oxaliplatin, a platinum-based antineoplastic drug. Here, we have examined its efficacy against paclitaxel, a chemotherapeutic drug that works by a mechanism of action distinct from that of oxaliplatin. Paclitaxel was administered at 2 mg/kg (intraperitoneally (IP)) every other day for a total of 8 mg/kg. Sprague Dawley rats that were co-administered RgIA4 at 80 µg/kg (subcutaneously (SC)) once daily, five times per week, for three weeks showed significant recovery from mechanical allodynia by day 31. Notably, the therapeutic effects reached significance 12 days after the last administration of RgIA4, which is suggestive of a rescue mechanism. These findings support the effects of RgIA4 in multiple chemotherapeutic models and the investigation of α9α10 nicotinic acetylcholine receptors (nAChRs) as a non-opioid target in the treatment of chronic pain.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Conotoxinas/farmacologia , Neuralgia/tratamento farmacológico , Neuralgia/etiologia , Paclitaxel/efeitos adversos , Animais , Humanos , Hiperalgesia/tratamento farmacológico , Masculino , Antagonistas Nicotínicos/farmacologia , Ratos , Ratos Sprague-Dawley
16.
PLoS One ; 14(11): e0225302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31756221

RESUMO

Telomeric repeat-containing RNAs (TERRAs) are long noncoding RNAs transcribed from subtelomeres toward telomeric repeat tracts, which have been implicated in telomere protection and heterochromatin formation. Genotoxic stress leads to upregulation of TERRAs. However, the mechanism of DNA damage-mediated TERRA induction remains elusive. Here, we treated HeLa cells with etoposide, a DNA double-strand break-generating agent, for various times and monitored the levels of TERRAs. Etoposide treatment led to a gradual time-dependent increase in TERRAs. Etoposide-mediated induction was evident in many TERRAs arising from various chromosome loci, including 20q and XpYp. Chromatin immunoprecipitation assays revealed no significant changes in the occupancy of RNA polymerase II at telomeres upon etoposide treatment. Interestingly, TERRAs arising from 20q, XpYp, 10q, and 13q degraded at slower rates in cells treated with etoposide, while degradation rates of TERRAs from many loci tested were nearly identical in both etoposide- and mock-treated cells. Telomere damage occurred from early time points of etoposide treatment, but telomere lengths and abundance of telomeric repeat-binding factor 2 (TRF2) at telomeres remained unchanged. In summary, etoposide treatment led to telomere damage and TERRA accumulation, but telomere lengths and TRF2-mediated telomere integrity were maintained. Etoposide-mediated TERRA accumulation could be attributed partly to RNA stabilization. These findings may provide insight into the post-transcriptional regulation of TERRAs in response to DNA damage.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Dano ao DNA , Etoposídeo/efeitos adversos , RNA Longo não Codificante/genética , Telômero/genética , Sobrevivência Celular/efeitos dos fármacos , Cromossomos Humanos Par 20/genética , Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HeLa , Humanos , Estabilidade de RNA , RNA Longo não Codificante/química , Telômero/efeitos dos fármacos , Proteína 2 de Ligação a Repetições Teloméricas
17.
Taiwan J Obstet Gynecol ; 58(6): 877-879, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31759547

RESUMO

OBJECTIVE: Dermatological problems after chemotherapy are often neglected with gynecological oncologists. Since paclitaxel is one of most popular agents for gynecology organ-related cancers, dermatologic change after paclitaxel treatment is seldom reported before. CASE REPORT: Two patients with gynecological organ malignancy who underwent the postoperative dose-dense weekly schedule of paclitaxel 80 mg/m2 plus carboplatin (area of curve 5) every three weeks had repeat dermatological problems (skull, facial and upper trunk areas) during the treatment. They included dermatitis, eczema, and folliculitis. Topical use of anti-fungal cream and oral anti-histamine agents stopped the disease progression and all had completed their chemotherapy without interruption. CONCLUSION: Clinicians should be aware of paclitaxel-induced skin toxicities, especially on the skull, face and upper trunk areas to minimize the occurrence of severe morbidity and to provide the better quality of life when cure is our primary priority in the management of gynecological organs-related malignancies.


Assuntos
Alopecia/induzido quimicamente , Foliculite/induzido quimicamente , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/efeitos adversos , Pele/patologia , Neoplasias do Colo do Útero/tratamento farmacológico , Alopecia/diagnóstico , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/uso terapêutico , Feminino , Foliculite/diagnóstico , Humanos , Pessoa de Meia-Idade , Paclitaxel/uso terapêutico
18.
Pharm Res ; 36(12): 163, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31617004

RESUMO

PURPOSE: There is ongoing concern regarding increased toxicity from paclitaxel in elderly patients, particularly of severe neutropenia. Yet, data so far is controversial and this concern is not supported by a clinically relevant age-dependent difference in pharmacokinetics (PK) of paclitaxel. This study assessed whether age is associated with increased risk for paclitaxel-induced neutropenia. METHODS: Paclitaxel plasma concentration-time data, pooled from multiple different studies, was combined with available respective neutrophil count data during the first treatment cycle. Paclitaxel pharmacokinetic-pharmacodynamic (PK-PD) data was modeled using a non-linear mixed effects approach and a semiphysiological neutropenia model, where systemic paclitaxel exposure was linked to reduced proliferation of neutrophils. The impact of age was evaluated on relevant variables in the model, using a significance threshold of p < 0.005. RESULTS: Paclitaxel PK-PD data was evaluated from 300 patients, with a median age of 65 years (range 23-84 years), containing 116 patients ≥70 years (39%). First cycle neutrophil counts were adequately described by a threshold effect model of paclitaxel on the proliferation rate of neutrophils. Age as a continuous or dichotomous variable (≥70 versus <70 years) did not significantly impact sensitivity of the bone marrow to paclitaxel nor the average maturation time of neutrophils (both p > 0.005), causing a decline in the respective interindividual variability of <1%. CONCLUSION: Results from this large retrospective patient cohort do not suggest elderly patients to be at an increased risk of developing paclitaxel-associated neutropenia during the first treatment cycle. Reflexive dose reductions of paclitaxel in elderly patients are unlikely to improve the risk of severe neutropenia and may be deleterious.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Neutropenia/induzido quimicamente , Paclitaxel/efeitos adversos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Estudos Retrospectivos
19.
Breast ; 48: 89-97, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31590108

RESUMO

PURPOSE: This pilot trial aimed to assess if cooling hands and feet with crushed ice during receipt of paclitaxel helps prevent peripheral neuropathy. METHODS: This prospective, randomized trial compared cryotherapy to standard care in patients initiating paclitaxel weekly x 12. For those on cryotherapy, hands and feet were cooled starting 15 min prior to and ending 15 min after each paclitaxel dose. EORTC QLQ-CIPN20 was completed at baseline, weekly x12, then monthly x6. Area under the curve (AUC) was calculated for subscale scores, adjusting for baseline, and compared between arms (Wilcoxon rank-sum test). Cross-study comparisons used data from 2 prior similarly-conducted neuropathy trials. RESULTS: Forty-six patients were accrued. Three withdrew and one was ineligible. Of the remaining 42 (21 cryotherapy, 21 control), 39 (19 cryotherapy, 20 control) were analyzable for AUC. Cryotherapy was well tolerated, but the AUC of the CIPN20 sensory scores over 12 weeks of paclitaxel was not found to differ between the study arms (mean difference 3.45, 95% CI -3.13 to 10.02, p = 0.26). However, the control arm of the current trial experienced less neuropathy than did the placebo arms of two previous similar trials. When our cryotherapy arm was compared to the combined control arms from all three trials, the cryotherapy arm had less neuropathy (Wilcoxon Rank-Sum p = 0.01). CONCLUSION: While there was no difference in CIPN20 scores identified between the 2 study arms in the current phase II trial, further investigation is needed given that the control arm experienced less neuropathy than was expected.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Crioterapia , Paclitaxel/efeitos adversos , Doenças do Sistema Nervoso Periférico/prevenção & controle , Idoso , Feminino , , Mãos , Humanos , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Projetos Piloto , Estudos Prospectivos
20.
Biomed Pharmacother ; 120: 109401, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31622950

RESUMO

Patients with cancer survivors are at increased risk of cardiovascular disease(CVD). Cardio-oncology has developed as a new discipline with the advances in cancer treatment. There are many new challenges for the clinician and a new frontier for research and investigation. There is an urgent need for further study on the prevention of cardiovascular toxicity. Imperatorin (IMP) is a natural form of coumarin and extract from several plants with diver's pharmacokinetic effects, including antioxidant and anti-inflammatory properties. This review focus on the molecular mechanisms and pharmacological effects of Imperatorin maybe provide potential cancer and cardiovascular protection that targets IMP. Further studies are required to elucidate the entire spectrum of cytotoxic activities of these compounds to validate and expand their preclinical and clinical applications and to clarify the potential role of IMP.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Sistema Cardiovascular/efeitos dos fármacos , Furocumarinas/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Antineoplásicos Fitogênicos/efeitos adversos , Antioxidantes/uso terapêutico , Fármacos Cardiovasculares/efeitos adversos , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Furocumarinas/efeitos adversos , Humanos , Mediadores da Inflamação/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais
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