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1.
Artículo en Chino | MEDLINE | ID: mdl-38599645

RESUMEN

Objective: To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR. Methods: A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m2 day 1, cisplatin 25 mg/m2 days 1-3, and capecitabine 800 mg/m2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results: A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm3. The T stage (OR=12.71, 95%CI: 1.4-112.5, P=0.022) and the volume (OR=7.1, 95%CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion: The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Masculino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Femenino , Docetaxel/uso terapéutico , Cisplatino/uso terapéutico , Carcinoma de Células Escamosas/patología , Capecitabina/uso terapéutico , Estudios Prospectivos , Fluorouracilo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Taxoides/efectos adversos , Resultado del Tratamiento , Carcinoma de Células Escamosas de Cabeza y Cuello , Quimioterapia de Inducción
2.
PLoS One ; 19(4): e0299742, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38635652

RESUMEN

BACKGROUND: In Japan, preoperative adjuvant chemotherapy followed by surgical resection is the standard treatment for patients with locally advanced esophageal squamous cell carcinoma. However, the risk of recurrence after surgical resection remains high. Although a randomized controlled trial evaluating the efficacy of nivolumab, a fully human monoclonal anti-programmed death 1 antibody, as postoperative adjuvant therapy after neoadjuvant chemoradiotherapy and surgery established its superior efficacy as adjuvant therapy, the efficacy for patients who received preoperative adjuvant chemotherapy has not been demonstrated. This study aims to elucidate the efficacy and safety of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. METHODS: This study is a multi-institutional, single-arm, Phase II trial. We plan to recruit 130 esophageal squamous cell carcinoma patients, who have undergone preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. If the patient did not have a pathological complete response, nivolumab is started as a postoperative adjuvant therapy within 4-16 weeks after surgery. The nivolumab dose is 480 mg/day every four weeks. Nivolumab is administered for up to 12 months. The primary endpoint is disease-free survival; the secondary endpoints are overall survival, distant metastasis-free survival, and incidence of adverse events. DISCUSSION: To our knowledge this study is the first trial establishing the efficacy of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. In Japan, preoperative adjuvant chemotherapy followed by surgery is a well-established standard treatment for resectable, locally advanced esophageal squamous cell carcinoma. Therefore, developing an effective postoperative adjuvant therapy has been essential for improving oncological outcomes.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Cisplatino/efectos adversos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Docetaxel/uso terapéutico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/etiología , Nivolumab/uso terapéutico , Taxoides/uso terapéutico , Resultado del Tratamiento , Fluorouracilo/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia Neoadyuvante , Ensayos Clínicos Controlados Aleatorios como Asunto , Ensayos Clínicos Fase II como Asunto
4.
Medicine (Baltimore) ; 103(9): e37338, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38428887

RESUMEN

BACKGROUND: Buyang Huanwu Decoction (BYHWD) is a traditional Chinese prescription, originally derived from Yi Lin Gai Cuo during the Qing Dynasty. This study aimed to evaluate the efficacy and safety of BYHWD in the prevention of taxane-induced peripheral neuropathy (TIPN) in patients with breast cancer. METHODS: This single-center, statistician-blinded, parallel-group, simple randomized, no-treatment controlled study was conducted at the China-Japan Friendship Hospital in Beijing. Sixty breast cancer patients scheduled to receive nab-paclitaxel-based chemotherapy were randomly assigned to either the BYHWD group (N = 30) or the control group (N = 30) using simple randomization procedures. The data analysts were unaware of the treatment allocation. The primary efficacy endpoints were the incidence and severity of TIPN in the 2 groups, assessed using the Common Terminology Criteria for Adverse Events (CTCAE) and Patients' Neurotoxicity Questionnaire (PNQ). The secondary efficacy endpoint was the score of Functional Assessment of Cancer Therapy-Breast for both groups. The primary safety endpoints were routine blood test results and liver and renal functions. Both groups were subjected to 4 chemotherapy cycles. Efficacy and safety analyses were conducted on an intention-to-treat basis. RESULTS: The incidence of TIPN in the BYHWD group was 50.0%, which was lower than the 80.0% incidence in the control group (ß = -1.881 [95%CI -3.274, -.488]; P = .008, adjusted). The probability of TIPN in the BYHWD group was 15.2% of that in the control group, representing a significant reduction in incidence (odds ratio = .152, [95%CI .038, 0.614]; P = .008, adjusted). The CTCAE and PNQ grades of the BYHWD group were 1.527 and 1.495 points lower than those of the control group at the same cycle, respectively (CTCAE: ß = -1.527 [95%CI -2.522, -.533]; P = .003, adjusted; PNQ: ß = -1.495 [95%CI -2.501, -.489]; P = .004, adjusted, respectively). After treatment, the Functional Assessment of Cancer Therapy-Breast scores in the BYHWD group were significantly better than those in the control group (P = .003), especially in the physiological, functional, and additional concerns domains. CONCLUSION: Buyang Huanwu decoction (BYHWD) can effectively prevent TIPN and improve the quality of life in patients with breast cancer.


Asunto(s)
Neoplasias de la Mama , Hidrocarburos Aromáticos con Puentes , Medicamentos Herbarios Chinos , Síndromes de Neurotoxicidad , Enfermedades del Sistema Nervioso Periférico , Humanos , Femenino , Medicina Tradicional China , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/inducido químicamente , Calidad de Vida , Estudios Prospectivos , Medicamentos Herbarios Chinos/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/prevención & control , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Taxoides/efectos adversos
5.
BMJ Open ; 14(1): e076391, 2024 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-38195173

RESUMEN

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of neurotoxic chemotherapy. Acute symptoms of CIPN during treatment can lead to dose reduction and cessation. Trials using electroacupuncture (EA) to treat established CIPN postchemotherapy have shown some efficacy. The current trial aims to assess the feasibility and preliminary efficacy of using EA to treat CIPN during chemotherapy. METHODS AND ANALYSIS: The current study is a single-centre, 1:1 randomised, sham-controlled pilot study set in a tertiary cancer hospital in Sydney, Australia, and will recruit 40 adult patients with early breast cancer undergoing adjuvant or neoadjuvant paclitaxel chemotherapy. Patients who develop CIPN within the first 6 weeks of chemotherapy will receive either true EA or sham-EA once a week for 10 weeks. The coprimary endpoints are recruitment and adherence rate, successful blinding of patients and compliance with the follow-up period. Secondary endpoints are mean change of CIPN symptoms from randomisation to end of treatment, sustained change in CIPN symptoms at 8-week and 24-week follow-up postchemotherapy, proportion of subjects attaining completion of 12 weeks of chemotherapy without dose reduction or cessation, change in acupuncture expectancy response pretreatment, during treatment and posttreatment. The primary assessment tool for the secondary endpoints will be a validated patient-reported outcome measure (European Organisation for Research and Treatment of Cancer Quality of Life Chemotherapy-Induced Peripheral Neuropathy) captured weekly from randomisation to week 12 of chemotherapy. ETHICS AND DISSEMINATION: The study protocol (2021/ETH12123) has been approved by the institutional Human Research Ethics Committee at St Vincent's Hospital Sydney and Chris O'Brien Lifehouse. Informed consent will be obtained prior to starting study-related procedures. The results will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: ACTRN12622000081718.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Electroacupuntura , Enfermedades del Sistema Nervioso Periférico , Adulto , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Calidad de Vida , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/terapia , Taxoides/efectos adversos , Antineoplásicos/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto
6.
Molecules ; 28(23)2023 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-38067476

RESUMEN

Taxanes are the best-known compounds in Taxus cuspidata owing to their strong anticancer effects. However, the traditional taxanes extraction method is the solid-liquid extraction method, which is limited by a large energy consumption and low yield. Therefore, it is urgent to find an efficient method for taxanes extraction. The ultrasonic microwave synergistic extraction (UME) method integrates the cavitation effect of ultrasound and the intensifying heat transfer (ionic conduction and dipole rotation of molecules) effect of microwave to accelerate the release of intracellular compounds and is used in active ingredient extractions. This study aimed to evaluate the performance of UME in extracting taxanes from T. cuspidata needles (dichloromethane-ethanol as extractant). A single-factor experiment, Plackett-Burman design, and the response surface method showed that the optimal UME parameters for taxanes extraction were an ultrasonic power of 300 W, a microwave power of 215 W, and 130 sieve meshes. Under these conditions, the taxanes yield was 570.32 µg/g, which increased by 13.41% and 41.63% compared with the ultrasound (US) and microwave (MW) treatments, respectively. The reasons for the differences in the taxanes yield were revealed by comparing the physicochemical properties of T. cuspidata residues after the UME, US, and MW treatments. The cell structures were significantly damaged after the UME treatment, and numerous tiny holes were observed on the surface. The absorption peaks of cellulose, hemicellulose, and lignin increased significantly in intensity, and the lowest peak temperature (307.40 °C), with a melting enthalpy of -5.19 J/g, was found after the UME treatment compared with the US and MW treatments. These results demonstrate that UME is an effective method (570.32 µg/g) to extract taxanes from T. cuspidata needles by destroying cellular structures.


Asunto(s)
Taxoides , Taxus , Taxoides/química , Taxus/química , Ultrasonido , Microondas , Extractos Vegetales/química
7.
In Vivo ; 37(3): 1275-1280, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37103108

RESUMEN

BACKGROUND/AIM: Chemoradiotherapy (CRT) with high-dose cisplatin has become the standard of care for larynx preservation in patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, the long-term results are unsatisfactory. Induction chemotherapy (ICT) with docetaxel/cisplatin/5-fluorouracil (TPF) is associated with hematologic toxicity, and a safer therapy with comparable efficacy is desired. We conducted a pilot study to investigate the efficacy and safety of 5-fluorouracil/cisplatin/cetuximab (FPE) therapy as a candidate regimen for ICT in comparison with TPF. PATIENTS AND METHODS: Patients with stage cN2/3 LA-SCCHN of the larynx/oropharynx/hypopharynx were treated with FPE or TPF followed by radiotherapy. We reviewed patients' medical records and evaluated treatment efficacy and safety retrospectively. RESULTS: The response rates for ICT and ICT-radiotherapy were 71% and 93%, respectively, in the FPE group and 90% and 89%, respectively, in the TPF group. The 1-year progression-free and overall survival rates were 57% and 100%, respectively, in the FPE group and 70% and 90%, respectively, in the TPF group. TPF was linked to significantly higher rates of Grade 3/4 hematologic toxicity during ICT. The rates of Grade 3 or higher toxicity did not differ between the two groups during radiotherapy. CONCLUSION: The efficacy of ICT was comparable between the FPE and TPF groups, whereas FPE was associated with less toxicity. It is suggested that FPE therapy is an alternative ICT regimen to TPF therapy, but further long-term follow-up is needed.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Cetuximab/efectos adversos , Fluorouracilo/efectos adversos , Cisplatino , Carcinoma de Células Escamosas/patología , Quimioterapia de Inducción/métodos , Estudios Retrospectivos , Proyectos Piloto , Taxoides/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Docetaxel , Quimioradioterapia , Neoplasias de Cabeza y Cuello/tratamiento farmacológico
8.
Altern Ther Health Med ; 29(4): 177-183, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36947649

RESUMEN

Objective: To evaluate the safety of the combination of pegylated liposomal doxorubicin and docetaxel in neoadjuvant therapy for breast cancer (BC) with axillary lymph nodes metastasis. Methods: In this single-arm study, 91 patients with clinical stage IIA-IIIc BC received 6 cycles of pegylated liposomal doxorubicin plus docetaxel as neoadjuvant chemotherapy (NAC). Trastuzumab was allowed in patients with human epidermal growth factor receptor 2-positive tumors. The effects of new anthracycline-polyethylene glycol liposomal doxorubicin on the patients' hearts were studied. The changes in left ventricular ejection fraction (LVEF) before and after treatment were evaluated by echocardiography, and the levels of cardiac-specific biomarker troponin I (cTnI) and N terminal B natriuretic peptide (NT-pro-BNP) were noted before and after treatment. Result: In our study, 88 patients completed 6 cycles of neoadjuvant chemotherapy. LVEF was within normal range; average LVEF was 67% at baseline, 66% after NAC. The difference was not statistically significant. However, LVEF decreased by more than 10% in 44.4% of patients. There was no significant difference in troponin I or NT-pro-BNP levels before or after treatment. No cardiac events with clinical symptoms were reported. Conclusion: The combination of polyethylene glycol liposome adriamycin and docetaxel in neoadjuvant chemotherapy in patients with early BC with axillary lymph node metastasis has certain cardiac safety. And in the human epidermal growth factor receptor-2 (HER-2) positive population, polyethylene glycol liposome adriamycin combined with docetaxel and trastuzumab also has certain cardiac safety.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Docetaxel/uso terapéutico , Terapia Neoadyuvante/efectos adversos , Liposomas/uso terapéutico , Metástasis Linfática , Volumen Sistólico , Troponina I , Taxoides/efectos adversos , Función Ventricular Izquierda , Doxorrubicina/efectos adversos , Trastuzumab/efectos adversos , Polietilenglicoles/uso terapéutico
9.
Inflammopharmacology ; 31(1): 451-464, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36595125

RESUMEN

The needle powder of Taxus wallichiana is in use for the management of diabetes and inflammation-related complications in the Indian and Chinese Systems of Traditional Medicine but the lack of proper pharmacological intervention has prompted us to investigate the pharmacological mechanism against inflammation-induced insulin resistance in high-fat diet-fed C57BL/6 mice. Hexane (Tw-H), chloroform (Tw-C), and ethyl acetate (Tw-EA) extracts were prepared from a needle of T. wallichiana and its effect on glucose uptake against TNF-α-induced insulin resistance in skeletal muscle cells was studied. Among all, Tw-EA extract has shown promising glucose uptake potential. Tw-EA treatment is also able to decrease the lipid accumulation in adipocytes. Chemical signature of Tw-EA using HPLC showed the presence of taxoids. Efficacy of taxoids-rich extract from T. wallichiana (Tw-EA) was further validated in in vivo system against high-fat diet (HFD)-induced insulin resistance in C57BL/6 mice. Oral treatment of Tw-EA showed significant reduction in blood glucose, pro-inflammatory cytokine production and body weight gain when compared with vehicle-treated HFD-induced insulin resistance in C57BL/6 mice. Histopathology and immunohistochemistry study in skeletal muscle and adipose tissue revealed that oral treatment of Tw-EA is able to reduce the infiltration of inflammatory cells in skeletal muscles, ameliorate the hypertrophy in adipose tissue and upregulate the GLUT4 protein expression. Treatment with Tw-EA significantly up-regulated mRNA expression of insulin signaling pathway (IRS-1, PI3K, AKT, GLUT 4). This study suggested the beneficial effect of taxoids-rich extract from Taxus wallichiana against the inflammation-associated insulin resistance condition.


Asunto(s)
Resistencia a la Insulina , Taxus , Ratones , Animales , Resistencia a la Insulina/fisiología , Dieta Alta en Grasa , Taxus/metabolismo , Taxoides/uso terapéutico , Ratones Endogámicos C57BL , Inflamación/tratamiento farmacológico , Insulina/metabolismo , Glucemia/metabolismo
10.
Int J Gynecol Cancer ; 33(5): 792-801, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36600535

RESUMEN

OBJECTIVE: To compare the effectiveness of acupuncture alone or with additional integrative oncology modalities for taxane-induced peripheral neuropathy-related symptoms in patients with gynecological and breast cancer. METHODS: The study was a prospective evaluation of patients undergoing twice-weekly treatments with either acupuncture alone (single-modality, group A) or with additional manual-movement and mind-body therapies (multimodality, group B), for 6 weeks. Symptom severity was assessed at baseline, 6 weeks, and 9 weeks using the Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) tool; and von Frey perception thresholds. Additional symptoms were also assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the Measure Yourself Concerns and Wellbeing (MYCaW) study tool. RESULTS: For the 120 participants (60 in each study arm), baseline to 6-week scores were similar in both groups for improved FACT-Tax physical wellbeing and scores for hand numbness/tingling; EORTC physical functioning and global health status; and MYCaW scores. FACT-Tax taxane subscales and scores for foot numbness/tingling improved only in group A (p=0.038), while emotional wellbeing FACT-Tax (p=0.02) and EORTC pain (p=0.005) improved only in group B. Group B showed greater improvement for FACT-Tax neuropathy-related concerns than group A at 24 hours (p=0.043) and 7 days (p=0.009) after the first treatment. CONCLUSION: Acupuncture alone or with additional integrative oncology modalities may help reduce neuropathy-related symptoms. The single-modality group demonstrated greater improvement for foot numbness/tingling, and the multimodality group demonstrated improvement for pain and improved emotional wellbeing and neuropathy-related concerns in the first week of treatment. TRIAL REGISTRATION NUMBER: NCT03290976.


Asunto(s)
Terapia por Acupuntura , Oncología Integrativa , Enfermedades del Sistema Nervioso Periférico , Humanos , Calidad de Vida/psicología , Hipoestesia , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Taxoides/efectos adversos , Dolor , Encuestas y Cuestionarios
11.
Esophagus ; 20(2): 281-289, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36484900

RESUMEN

BACKGROUND: Neoadjuvant docetaxel plus cisplatin and 5-FU (NAC-DCF) and adjuvant nivolumab monotherapy are the standard care for locally advanced resectable esophageal squamous cell carcinoma (ESCC). However, no effective biomarkers have been found in perioperative setting. We investigated how programmed death-ligand 1 (PD-L1) changes before and after NAC-DCF and how it relates to the therapeutic effect of NAC-DCF in resectable ESCC. METHODS: PD-L1 expression in paired diagnostic biopsy and surgically resected tissues from ESCC patients who underwent surgical resection after receiving two or three NAC-DCF cycles was evaluated. PD-L1 positivity was defined as a combined positive score (CPS) of 10% ≤ . Gene expression analysis was conducted using samples before NAC-DCF. RESULTS: Sixty-six paired samples from 33 patients were included in PD-L1 expression analysis, and 33 Pre-NAC samples acquired by diagnostic biopsy were included in gene expression analysis. Pretreatment, 3 (9%), 13 (39%), and 17 (52%) patients harbored tumors with CPS ranges of < 1%, 1%-10%, and 10% ≤ , respectively. After NAC-DCF, 5 (15%), 15 (45%), and 13 (39%) tumors presented CPS ranges of < 1%, 1%-10%, and 10% ≤ , respectively. The concordance rate between Pre-and Post-NAC-DCF samples was 45%. Patients with PD-L1-negative tumors both before and after NAC-DCF (n = 9) had shorter survival and different gene expression profile characterized by upregulation in WNT signaling or neutrophils. CONCLUSIONS: A substantial PD-L1 expression alteration was observed, resulting in low concordance rate before and after NAC-DCF. Tumors persistently lacking PD-L1 had distinct gene expression profile with worse clinical outcomes, raising the need for further investigation.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Cisplatino/uso terapéutico , Docetaxel/uso terapéutico , Antígeno B7-H1/genética , Neoplasias Esofágicas/patología , Terapia Neoadyuvante/métodos , Fluorouracilo/uso terapéutico , Taxoides/uso terapéutico
12.
Int J Mol Sci ; 23(24)2022 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-36555256

RESUMEN

Biologically active taxanes, present in small- to medium-sized evergreen conifers of various Taxus species, are widely used for their antioxidant, antimicrobial and anti-inflammatory effects, but mostly for their antitumour effects used in the treatment of solid tumours of the breast, ovary, lung, bladder, prostate, oesophagus and melanoma. More of the substances found in Taxus plant extracts have medical potential. Therefore, at the beginning of this review, we describe the methods of isolation, identification and determination of taxanes in different plant parts. One of the most important taxanes is paclitaxel, for which we summarize the pharmacokinetic parameters of its different formulations. We also describe toxicological risks during clinical therapy such as hypersensitivity, neurotoxicity, gastrointestinal, cardiovascular, haematological, skin and renal toxicity and toxicity to the respiratory system. Since the effect of the drug-form PTX is enhanced by various Taxus spp. extracts, we summarize published clinical intoxications and all fatal poisonings for the Taxus baccata plant. This showed that, despite their significant use in anticancer treatment, attention should also be focused on the risk of fatal intoxication due to ingestion of extracts from these plants, which are commonly found in our surroundings.


Asunto(s)
Neoplasias , Taxus , Masculino , Femenino , Humanos , Taxoides/farmacología , Paclitaxel , Extractos Vegetales/farmacología , Neoplasias/tratamiento farmacológico
13.
Eur J Med Res ; 27(1): 239, 2022 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-36352476

RESUMEN

BACKGROUND: Neoadjuvant chemotherapy (NAC) for locally advanced gastric and gastroesophageal junction adenocarcinoma (LAGC) has been recommended in several guidelines. However, there is no global consensus about the optimum of NAC regimens. We aimed to determine the optimal NAC regimen for LAGC. METHODS: A systematic review and Bayesian network meta-analysis was performed. The literature search was conducted from inception to June 2022. The odds ratio (OR) value and 95% confidence interval (95% CI) were used for assessment of R0 resection rate and pathological complete response rate (pCR) as primary outcomes. The hazard ratio (HR) value and 95% CI were interpreted for the assessment of overall survival (OS) and disease-free survival (DFS) as second outcomes. The risk ratio (RR) value and 95% CI were used for safety assessment. RESULTS: Twelve randomized controlled trials were identified with 3846 eligible participants. The network plots for R0 resectability, OS, and DFS constituted closed loops. The regimens of TPF (taxane and platinum plus fluoropyrimidine), ECF (epirubicin and cisplatin plus fluorouracil), and PF (platinum plus fluoropyrimidine) showed a meaningful improvement of R0 resectability, as well as OS and/or DFS, compared with surgery (including surgery-alone and surgery plus postoperative adjuvant chemotherapy). Importantly, among these regimens, TPF regimen showed significant superiority in R0 resection rate (versus ECF regimen), OS (versus ECF regimen), DFS (versus PF and ECF regimens), and pCR (versus PF regimen). CONCLUSIONS: The taxane-based triplet regimen of TPF is likely the optimal neoadjuvant chemotherapy regimen for LAGC patients.


Asunto(s)
Adenocarcinoma , Neoplasias Gástricas , Humanos , Terapia Neoadyuvante , Metaanálisis en Red , Teorema de Bayes , Platino (Metal)/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Taxoides/uso terapéutico , Unión Esofagogástrica/patología , Quimioterapia Adyuvante , Fluorouracilo/uso terapéutico
14.
Breast Cancer Res Treat ; 196(2): 329-339, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36114940

RESUMEN

PURPOSE: The impact of elevated body mass index (BMI) on overall survival (OS) in patients receiving modern anthracycline-taxane chemotherapy for early breast cancer (EBC) has not yet been well established. The purpose of our study was to examine overall survival (OS) by BMI category in women with EBC receiving either doxorubicin (A), cyclophosphamide (C) + paclitaxel (P) or fluorouracil (F), epirubicin (E), cyclophosphamide (C) + docetaxel (D). METHODS: This was a retrospective cohort study in patients ≥ 18 years with resected stage I-III BC diagnosed between 2007 and 2017 in Ontario, identified through linkage of administrative databases. Patients were classified according to baseline BMI into underweight (< 18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (≥ 30 kg/m2) World Health Organization (WHO) categories. The primary outcome was OS. Univariable and multivariable analyses were used to examine the association between clinico-pathologic characteristics and OS among BMI categories. RESULTS: Our cohort included 11,601 women, of whom 3890 (33.5%) were normal weight, 3696 (31.9%) overweight, and 3847 (33.1%) obese. Median OS was 7.9 years. There were no statistically significant differences in OS according to BMI (p = 0.66) in the overall study cohort or among the BMI categories after adjusting for age, nodal status, stage, grade, ER and HER2 status for either AC-P or FEC-D- treated patients (p = 0.45 and p = 0.97, respectively). CONCLUSIONS: Our large population-based retrospective cohort analysis of EBC patients receiving adjuvant anthracycline-taxane chemotherapy found no significant impact of BMI on OS. Further investigation is warranted to confirm these findings in prospective patient cohorts.


Asunto(s)
Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/tratamiento farmacológico , Índice de Masa Corporal , Epirrubicina/uso terapéutico , Docetaxel/uso terapéutico , Estudios Retrospectivos , Sobrepeso , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante , Taxoides/uso terapéutico , Fluorouracilo/uso terapéutico , Ciclofosfamida/uso terapéutico , Antraciclinas/uso terapéutico , Obesidad/tratamiento farmacológico , Paclitaxel/uso terapéutico
15.
Front Endocrinol (Lausanne) ; 13: 950345, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36120434

RESUMEN

Due to the lack of symptoms and detection biomarkers at the early stage, most patients with ovarian cancer (OC) are diagnosed at an advanced stage and often face chemoresistance and relapse. Hence, defining detection biomarkers and mechanisms of chemoresistance is imperative. A previous report of a cDNA microarray analysis shows a potential association of carnitine O-octanoyltransferase (CROT) with taxane resistance but the biological function of CROT in OC remains unknown. The current study explored the function and regulatory mechanism of CROT on cellular behavior and paclitaxel (PTX)-resistance in OC. We found that CROT was downregulated in OC tissues and PTX-resistant cells. Furthermore, CROT expression was negatively correlated with the prognosis of OC patients. Overexpression of CROT inhibited the OC cell proliferation, migration, invasion, and colony formation, arrested the cell cycle at the G2/M phase, and promoted cell apoptosis. In addition, miR-33a-5p bound directly to the 3'UTR of CROT to negatively regulate the expression of CROT and promoted OC cell growth. Finally, overexpression of CROT decreased the phosphorylation of Smad2, whereas knockdown of CROT increased the nuclear translocation of Smad2 and Smad4, two transducer proteins of TGF-ß signaling, indicating that CROT is a tumor suppressor which mediates OC cell behaviors through the TGF-ß signaling pathway. Thus, targeting the miR-33a-5p/CROT axis may have clinical potential for the treatment of patients with OC.


Asunto(s)
MicroARNs , Neoplasias Ováricas , Regiones no Traducidas 3' , Carnitina , Línea Celular Tumoral , ADN Complementario/uso terapéutico , Resistencia a Antineoplásicos/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Recurrencia Local de Neoplasia/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Transducción de Señal , Taxoides/uso terapéutico , Factor de Crecimiento Transformador beta
16.
BMJ Open ; 12(9): e065045, 2022 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-36167383

RESUMEN

INTRODUCTION: Lymphoedema associated with breast cancer is caused by an interruption of the lymphatic system, together with factors such as total mastectomy, axillary dissection, positive lymph nodes, radiotherapy, use of taxanes and obesity. Physiotherapy treatment consists of complex decongestive therapy, manual lymphatic drainage and exercises, among other interventions. Currently, there are several systematic review and randomised controlled trials that evaluate the efficacy of these interventions. However, at present, there are no studies that compare the effectiveness of all these physical therapy interventions. The purpose of this study is to determine which physical therapy treatment is most effective in reducing breast cancer-related lymphoedema, improving quality of life and reducing pain. METHODS AND ANALYSIS: MEDLINE, PEDro, CINAHL, EMBASE, LILACS and Cochrane Central Register of Controlled Trials will be searched for reports of randomised controlled trials published from database inception to June 2022. We will only include studies that are written in English, Spanish and Portuguese. We will also search grey literature, preprint servers and clinical trial registries. The primary outcomes are reduction of secondary lymphoedema associated with breast cancer, improvements in quality of life and pain reduction. The risk of bias of individual studies will be evaluated using the Cochrane Risk of Bias 2.0 Tool. A network meta-analysis will be performed using a random-effects model. First, pairs will be directly meta-analysed and indirect comparisons will be made between the different physical therapy treatments. The GRADE system will be used to assess the overall quality of the body of evidence associated with the main results. ETHICS AND DISSEMINATION: This protocol does not require approval from an ethics committee. The results will be disseminated via peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CDR42022323541.


Asunto(s)
Neoplasias de la Mama , Linfedema , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/terapia , Enfermedad Crónica , Femenino , Humanos , Linfedema/cirugía , Linfedema/terapia , Mastectomía/efectos adversos , Metaanálisis como Asunto , Metaanálisis en Red , Dolor/complicaciones , Modalidades de Fisioterapia , Calidad de Vida , Revisiones Sistemáticas como Asunto , Taxoides
17.
Cancer ; 128(20): 3641-3652, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35960141

RESUMEN

BACKGROUND: To explore the impact of acupuncture with other complementary and integrative medicine (CIM) modalities on chemotherapy-induced peripheral neuropathy (CIPN) and quality of life (QoL) in oncology patients. METHODS: In this prospective, pragmatic, and patient-preference study, patients with CIPN were treated with acupuncture and CIM therapies (intervention group) or standard care alone (controls) for 6 weeks. Patients in the intervention arm were randomized to twice-weekly acupuncture-only (group A) or acupuncture with additional manual-movement or mind-body CIM therapies (group B). Severity of CIPN was assessed at baseline and at 6 weeks using the Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) tool. Other QoL-related outcomes were assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC); and the Measure Yourself Concerns and Well-being questionnaire. Von Frey measurements examined perception thresholds. RESULTS: Of 168 participants, 136 underwent the study intervention (group A, 69; group B, 67), with 32 controls. Baseline-to-6-week assessment scores improved significantly in the intervention arm (vs controls) on FACT-Tax (p = .038) and emotional well-being (p = .04) scores; FACT-TAX scores for hand numbness/tingling (p = .007) and discomfort (p < .0001); and EORTC physical functioning (p = .045). Intervention groups A and B showed improved FACT-Tax physical well-being (p < .001), FACT-TAX total score (p < .001), FACT-TAX feet discomfort (p = .003), and EORTC pain (p = .017) scores. CONCLUSIONS: Acupuncture, with or without CIM modalities, can relieve CIPN-related symptoms during oncology treatment. This is most pronounced for hand numbness, tingling, pain, discomfort, and for physical functioning.


Asunto(s)
Terapia por Acupuntura , Antineoplásicos , Neoplasias , Enfermedades del Sistema Nervioso Periférico , Antineoplásicos/efectos adversos , Humanos , Hipoestesia/inducido químicamente , Neoplasias/tratamiento farmacológico , Dolor/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/terapia , Estudios Prospectivos , Calidad de Vida , Taxoides/uso terapéutico
18.
Eur J Oncol Nurs ; 60: 102171, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35952460

RESUMEN

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose limiting toxicity posing a major clinical challenge for managing patients receiving specific chemotherapy regimens (e.g., Taxanes). There is a growing body of literature suggesting acupuncture can improve CIPN symptoms. The purpose of the ACUFOCIN trial was to collect preliminary data on the safety, feasibility, acceptability and initial effectiveness of acupuncture as a treatment for CIPN, comparing use of acupuncture plus standard care (Acupuncture) against standard care alone (Control). METHOD: At a tertiary cancer centre, a pragmatic, randomised, parallel group design study was used to investigate the effectiveness of a 10-week course of acupuncture. Participants experiencing CIPN of ≥ Grade II, recording a 'Most Troublesome' CIPN symptom score of ≥3 using the "Measure Yourself Medical Outcome Profile" (MYMOP 2), were randomised to 'Acupuncture' or 'Control' arms. Clinicians were blinded to allocated groups, however as it was not possible to blind participants, it cannot be guaranteed they did not disclose study allocation within their clinic assessments. The primary outcome measure was the number of patients reporting a ≥ 2-point improvement (success) in their MYMOP2 score at week 10. 100 participants (120 to allow for attrition) were required for a hypothesised improvement in success proportions from 30% to 55% using a primary analysis model with logistic regression adjusted for stratification factors and baseline MYMOP2 scores. Feasibility and acceptability of study design was addressed through percentage return of primary outcome, retention rate and a nested qualitative study. RESULTS: Primary MYMOP2 outcome data at week 10 was available for 108/120 randomised participants; this is greater than the 100 participants required to adequately power the study. There were 36/53 (68%) successes in 'Acupuncture' compared to 18/55 (33%) in 'Control'. Beneficial effects were seen in the secondary outcome data, including clinicians' grading of neuropathy, EORTC, QLQ-CIPN20, QLQ-C30 summary scores and patient reported pain scores. There were no serious adverse events reported within the study and only 16 acupuncture associated events, none of which required intervention. CONCLUSION: A 10-week course of acupuncture resulted in measurable improvement in participants symptoms of CIPN. The results warrant further investigation.


Asunto(s)
Terapia por Acupuntura , Antineoplásicos , Enfermedades del Sistema Nervioso Periférico , Terapia por Acupuntura/efectos adversos , Terapia por Acupuntura/métodos , Antineoplásicos/efectos adversos , Humanos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/terapia , Calidad de Vida , Proyectos de Investigación , Taxoides/efectos adversos
20.
PLoS One ; 17(7): e0266777, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35802666

RESUMEN

Light emitting diode (LED) lamps are increasingly being studied in cultivation of horticultural, ornamental and medicinal plants as means to increase yield, quality, stress resistance, and bioactive compounds content. Enhancing the production of metabolites for medicinal or pharmaceutical use by regulating LED intensity and spectra is a challenging subject, where promising results have been achieved. Nevertheless, some species have been poorly investigated, despite their interest as a source of medicinally active substances, with particular reference to LED effects at the plant cultivation level. This study evaluates the effects of supplementary top-light LED treatments on Taxus baccata, one of the main sources of taxane precursors. Blue, red and mixed red-and-blue spectra were tested at 100 µM m-2 s-1. Moreover, 50 and 150 µM m-2 s-1 intensities were tested for the mixed spectrum. All treatments were set for 14 hours a day and were tested against natural light as control treatment, in a controlled environment, from 19 August to 9 December 2019, this latter date representing 112 days after treatment (DAT) began. A smart monitoring and control system powered by environmental and proximal sensors was implemented to assure homogeneity of temperature, humidity, and base natural light for all the treatments. It resulted in negligible deviations from expected values and reliable exclusion of confusing factors. Biometric measurements and 1H-NMR based metabolomic analysis were performed to investigate growth and phytochemical profile throughout the trial. One-way ANOVA showed that supplemental LED lighting increased plant height and number of sprouts. Considering the mixed red-and-blue spectrum, plant height increased almost proportionally from control to 100 µM m-2 s-1 (+20% at 112 DAT), with no further increase at higher intensity. The number of sprouts was strongly enhanced by LED treatments only in the early phase (48.9 vs. 7.5 sprouts in the averaged 50, 100 and 150 µM m-2 s-1 vs. the control at 28 DAT), with no differences related to intensity in the very early stage, and more persisting effects (up to 56 DAT) for higher intensities. After the very early growth stages (28 DAT), plant vigor showed a modest although significant increase over time compared to the control, with no differences related to light intensity (0.81 vs. 0.74 of NDVI in the averaged 50, 100 and 150 µM m-2 s-1 vs. the control, across 56, 84 and 112 DAT). The different spectra tested at 100 µM m-2 s-1 showed no significant differences in growth parameters, except for a slight beneficial influence of blue (alone or with red) compared to only red for sprouting. According to the metabolomic analysis, treated plants at 28 DAT were characterized by the highest content of sucrose and aromatic compounds. Signals of a putative taxane were detected in the 1H NMR profiles of plants, which were compared to the spectrum of baccatin III standard. However, the intensity of these spectral signals was not affected by the treatment, while they increased only slightly during time. Light at 150 µM m-2 s-1 induced the strongest variation in the metabolome. Conversely, light composition did not induce significant differences in the metabolome.


Asunto(s)
Plantas Medicinales , Taxus , Luz , Iluminación/métodos , Taxoides
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