Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.434
Filtrar
2.
J Dev Orig Health Dis ; 15: e10, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38724487

RESUMO

Premature infants have a risk of neurodevelopmental deficits. Little is known, however, about how retinopathy of prematurity (ROP) affects visual motor integration (VMI), which is necessary for both fine motor skills and further school abilities. Due to the systemic escape of bevacizumab in the treatment of ROP, concerns regarding the long-term neurodevelopmental effect of the drug have arisen. The aim is to evaluate VMI and motor development long-term outcomes after intravitreal bevacizumab (IVB) injection and laser treatment for ROP. Two groups of premature children were included: Bevacizumab group - 16 premature children who received IVB treatment and laser group - 23 premature children who underwent laser photocoagulation treatment in this single center cross-sectional study. At 2-6 years of age, VMI (Beery-Buktenica Developmental Test), motor development (Peabody Developmental Motor Scales-2), visual acuity, and refractive status were assessed. The incidence of abnormal visual function was significantly higher in bevacizumab group than in laser group (p = 0.022). The incidence of abnormal VMI skill was significantly higher in bevacizumab group than in laser group (p = 0.024). Incidences of abnormal gross, fine, and total motor skills were significantly higher in bevacizumab group compared to laser group (p < 0.05). Premature children who received bevacizumab for ROP demonstrated significantly lower VMI and motor development features than those with laser treatment at preschool age. Although our results suggest the relevance of bevacizumab injection in impaired VMI and motor development outcomes, general level of sickness rather than treatment might be the cause of delayed motor development.


Assuntos
Bevacizumab , Desenvolvimento Infantil , Retinopatia da Prematuridade , Humanos , Retinopatia da Prematuridade/terapia , Retinopatia da Prematuridade/fisiopatologia , Retinopatia da Prematuridade/cirurgia , Masculino , Feminino , Bevacizumab/administração & dosagem , Bevacizumab/uso terapêutico , Pré-Escolar , Estudos Transversais , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Desenvolvimento Infantil/fisiologia , Recém-Nascido , Recém-Nascido Prematuro , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Destreza Motora/fisiologia , Injeções Intravítreas
3.
Artigo em Inglês | MEDLINE | ID: mdl-38701802

RESUMO

A 17-year-old Appaloosa mare was referred for evaluation of presumed refractory keratitis of the left eye. Gross examination revealed ocular discomfort and corneal neovascularization with a nasal focal opacification affecting approximately 40% of the corneal surface. On ophthalmic examination, extensive subepithelial to mid-stromal vascular branching accompanied by a homogeneous white, dense opacification, which affected up to 80% of the total corneal thickness, were apparent. Signs of concurrent uveitis were absent. Deep-stromal lamellar keratectomy with a conjunctival pedicle graft was performed under general anesthesia. Histopathology confirmed a poorly differentiated corneal stromal invasive squamous cell carcinoma (SI-SCC) with neoplastic cell extension to the surgical margins. Postoperatively, 4 topical mitomycin C 0.04% chemotherapy cycles combined with oral firocoxib therapy were initiated. Seven months after surgery, regrowth of the SI-SCC was clinically suspected. A total volume of 1 ml bevacizumab 2.5% was administered in the standing sedated horse via 3 mid-stromal corneal injections. Four weeks later, intrastromal bevacizumab injections (ISBIs) were repeated, however, this time the solution was injected directly into the main corneal vessel branches.Seven weeks after the second ISBIs, the left eye was comfortable and significant remission of corneal vascularization and opacity was recognized. No recurrence has been noted for a follow-up period of more than 53 months.Equine SI-SCC usually has a very poor prognosis for globe maintenance. To the authors' knowledge this is the first report of well-tolerated intrastromal antivascular endothelial growth factor adjunctive therapy with bevazicumab 2.5% and SI-SCC resolution after a multimodal treatment approach.


Assuntos
Bevacizumab , Carcinoma de Células Escamosas , Neoplasias Oculares , Doenças dos Cavalos , Cavalos , Animais , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Doenças dos Cavalos/tratamento farmacológico , Feminino , Carcinoma de Células Escamosas/veterinária , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Oculares/veterinária , Neoplasias Oculares/tratamento farmacológico , Neoplasias Oculares/patologia , Neoplasias Oculares/cirurgia , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/administração & dosagem , Substância Própria/efeitos dos fármacos , Substância Própria/patologia
4.
Am J Manag Care ; 30(2 Suppl): S31-S35, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38701364

RESUMO

Numerous advances in the standard of care for metastatic colorectal cancer (mCRC), including the approval of several new treatments indicated for treatment in the third line or later (3L+), have been made, yet data and appropriate guidance on the optimal sequencing and treatment strategies for these lines of therapy are lacking. Four treatments-regorafenib, trifluridine/tipiracil alone or with bevacizumab, and fruquintinib-are FDA-approved and recommended by the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for the treatment of mCRC in the 3L+. When considering sequencing of treatment options for patients in the 3L+, the goal of treatment is to improve survival, but also maintain quality of life, a goal that requires consideration of relative efficacy and cumulative toxicity such as persistent myelosuppression.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Timina , Trifluridina , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Trifluridina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Piridinas/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Pirrolidinas/uso terapêutico , Combinação de Medicamentos , Metástase Neoplásica , Qualidade de Vida
6.
BMC Pediatr ; 24(1): 301, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704544

RESUMO

BACKGROUND: We present a patient with retinopathy of prematurity (ROP) who developed worsening plus disease after complete regression of stage 3 ROP. The use of fundus fluorescein angiography (FFA) aided the visualization of occult neovascularization that caused the disease progression. CASE PRESENTATION: The patient was at high risk for ROP due to low birth weight of 690 g and gestational age of 25 weeks. After the diagnosis of stage 3 ROP in zone I without plus disease, she was treated initially with bilateral intravitreal bevacizumab (IVB) and followed by laser photocoagulation 5 weeks later. Despite the resolution of ROP stage, the plus disease worsened. Neither systemic risk factors nor skip laser areas were observed. Hence, FFA was performed and subsequently identified occult neovascularization with active leakage. Additional IVB and laser treatment in the capillary dropout area inside vascularized retina were added. The plus disease improved but mild arteriolar tortuosity persisted. CONCLUSIONS: Worsening of plus disease after completion of laser ablation and IVB with complete regression of stage 3 ROP is rare. Systemic risk factors such as continuous oxygen therapy and cardiovascular disease should be ruled out. FFA aided in identifying occult neovascularization and prompted further treatment.


Assuntos
Inibidores da Angiogênese , Bevacizumab , Angiofluoresceinografia , Injeções Intravítreas , Fotocoagulação a Laser , Neovascularização Retiniana , Retinopatia da Prematuridade , Humanos , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Recém-Nascido , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/administração & dosagem , Feminino , Fotocoagulação a Laser/métodos , Neovascularização Retiniana/etiologia , Neovascularização Retiniana/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Terapia Combinada
7.
Eur J Cancer ; 204: 114089, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38703618

RESUMO

OBJECTIVES: The development of reliable biomarkers for the prediction of immune checkpoint inhibition (ICI) response in patients with metastatic renal cell carcinoma (mRCC) and urothelial carcinoma (mUC) remains an unresolved challenge. Conventional ICI biomarkers typically focus on tumor-related factors such as PD-L1 expression. However, a comprehensive evaluation of the predictive value of serum electrolyte levels, a so far widely unexplored area, is still pending. METHODS: We conducted a post-hoc analysis of baseline sodium, potassium, chloride, magnesium and calcium levels in two independent phase 3 clinical trials: IMvigor211 for mUC comparing atezolizumab to chemotherapy, and IMmotion151 for mRCC comparing atezolizumab+bevacizumab to sunitinib. This analysis aimed to evaluate the prognostic and predictive value of these electrolyte levels in these clinical settings. A total of 1787 patients (IMvigor211 n = 901; IMmotion151 n = 886) were analyzed. RESULTS: We found a linear correlation of baseline serum sodium and chloride with prognosis across both trials, which was not found for potassium, magnesium and calcium. In multivariate analysis, the prognostic capacity of sodium was limited to patients receiving ICI as compared to the control group. Interestingly, in both studies, the chance of achieving an objective response was highest in the patient subgroup with high baseline serum sodium levels of > 140 mmol/L (IMmotion151: Complete response in 17.9% versus 2.0% in patients with mRCC with baseline sodium < 135 mmol/L). Serum sodium outperformed tumor PD-L1 expression as a predictor for immunotherapy efficacy. CONCLUSIONS: Patients exhibiting elevated serum sodium levels derive the greatest benefit from immunotherapy, suggesting that baseline serum concentration could serve as a valuable and cost-effective predictive biomarker for immunotherapy across entities.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Sódio , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/sangue , Neoplasias Renais/patologia , Neoplasias Renais/imunologia , Masculino , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/patologia , Feminino , Sódio/sangue , Idoso , Pessoa de Meia-Idade , Imunoterapia/métodos , Anticorpos Monoclonais Humanizados/uso terapêutico , Bevacizumab/uso terapêutico , Biomarcadores Tumorais/sangue , Inibidores de Checkpoint Imunológico/uso terapêutico , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sunitinibe/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/sangue , Carcinoma de Células de Transição/secundário , Carcinoma de Células de Transição/imunologia
8.
Dermatol Online J ; 30(1)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38762867

RESUMO

Osteonecrosis of the jaw is a recognized complication associated with bevacizumab. Here, we present a patient with squamous cell carcinoma of the tonsil who experienced minimal skin fibrosis following intensity-modulated radiation therapy. Subsequently, the patient developed rectal adenocarcinoma and encountered osteonecrosis of the jaw after receiving two cycles of bevacizumab. Close monitoring, accompanied by thorough examination to detect early signs of osteonecrosis of the jaw, should be considered for patients who have undergone radiation therapy in the head and neck region and are receiving bevacizumab or other medications known to be associated with osteonecrosis of the jaw.


Assuntos
Bevacizumab , Carcinoma de Células Escamosas , Radioterapia de Intensidade Modulada , Neoplasias Tonsilares , Humanos , Bevacizumab/efeitos adversos , Bevacizumab/uso terapêutico , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Radioterapia de Intensidade Modulada/efeitos adversos , Neoplasias Tonsilares/radioterapia , Neoplasias Tonsilares/tratamento farmacológico , Masculino , Osteonecrose/induzido quimicamente , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Antineoplásicos Imunológicos/efeitos adversos , Pessoa de Meia-Idade , Doenças Maxilomandibulares/induzido quimicamente
9.
JCO Precis Oncol ; 8: e2300693, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38754056

RESUMO

PURPOSE: To report the results of OPAL (ClinicalTrials.gov identifier: NCT03574779) cohort A, a single-arm substudy of niraparib plus dostarlimab and bevacizumab for the treatment of advanced, platinum-resistant ovarian cancer (PROC). METHODS: Participants with PROC who received 1-2 previous lines of therapy were treated with niraparib (200 or 300 mg once daily), dostarlimab (500 mg once every 3 weeks for four 21-day cycles, followed by 1,000 mg once every 6 weeks), and bevacizumab (15 mg/kg once every 3 weeks). The primary end point was investigator-assessed objective response rate (ORR) per RECIST v1.1. Safety was also assessed. Exploratory biomarker end points included evaluation of changes in the tumor molecular profile and microenvironment using baseline and on-treatment tumor samples. RESULTS: Of 41 enrolled participants (median age, 66.0 years [range, 37-83 years]), 9.8% had tumors that were BRCA-mutated, 19.5% were homologous recombination (HR)-deficient, and 17.1% were HR repair (HRR)-mutated. As of the cutoff date, all participants discontinued treatment. The ORR was 17.1% (80% CI, 9.8 to 27.0), including one complete response (2.4%); the disease control rate was 73.2% (80% CI, 62.3 to 82.2). Two participants withdrew before first postbaseline scan because of adverse events (AEs). Grade ≥3 treatment-emergent AEs were reported in 92.7% of participants, with the most common being hypertension (26.8%). Response was not correlated with BRCA, HRR, HR deficiency (HRD), or PD-L1 status. Changes suggesting immune activation were observed in on-treatment samples after triplet therapy. CONCLUSION: Results demonstrated modest activity of niraparib, dostarlimab, and bevacizumab in participants with PROC, many of whom had prognostic factors for poor treatment response. Most participants with response were bevacizumab-naïve. No association was found with HRD, BRCA, or PD-L1 status. AEs were consistent with previous monotherapy reports, except that hypertension was reported more frequently.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Resistencia a Medicamentos Antineoplásicos , Indazóis , Neoplasias Ovarianas , Piperidinas , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Idoso , Bevacizumab/uso terapêutico , Adulto , Indazóis/uso terapêutico , Idoso de 80 Anos ou mais , Piperidinas/uso terapêutico , Piperidinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Estudos de Coortes
11.
JAMA Netw Open ; 7(4): e245552, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38592722

RESUMO

Importance: Testing for homologous recombination deficiency is required for the optimal treatment of high-grade epithelial ovarian cancer. The search for accurate biomarkers is ongoing. Objective: To investigate whether progression-free survival (PFS) and overall survival (OS) of patients with high-grade epithelial ovarian cancer treated with maintenance olaparib or placebo differed between patients with a tumor BRCA-like genomic profile and patients without a tumor BRCA-like profile. Design, Setting, and Participants: This cohort study was a secondary analysis of the PAOLA-1 randomized clinical trial that compared olaparib plus bevacizumab with placebo plus bevacizumab as maintenance treatment in patients with advanced high-grade ovarian cancer after a good response to first-line platinum with taxane chemotherapy plus bevacizumab, irrespective of germline or tumor BRCA1/2 mutation status. All patients with available tumor DNA were included in the analysis. The current analysis tested for an interaction between BRCA-like status and olaparib treatment on survival outcomes. The original trial was conducted between July 2015 and September 2017; at the time of data extraction for analysis in March 2022, a median follow-up of 54.1 months (IQR, 28.5-62.2 months) and a total follow-up time of 21 711 months was available, with 336 PFS and 245 OS events. Exposures: Tumor homologous recombination deficiency was assessed using the BRCA-like copy number aberration profile classifier. Myriad MyChoice CDx was previously measured. The trial was randomized between the olaparib and bevacizumab and placebo plus bevacizumab groups. Main Outcomes and Measures: This secondary analysis assessed hazard ratios (HRs) of olaparib vs placebo among biomarker strata and tested for interaction between BRCA-like status and olaparib treatment on PFS and OS, using Cox proportional hazards regression. Results: A total of 469 patients (median age, 60 [range 26-80] years) were included in this study. The patient cohort consisted of women with International Federation of Gynaecology and Obstetrics stage III (76%) high-grade serous (95%) ovarian cancer who had no evaluable disease or complete remission at initial or interval debulking surgery (76%). Thirty-one percent of the tumor samples (n = 138) harbored a pathogenic BRCA mutation, and BRCA-like classification was performed for 442 patients. Patients with a BRCA-like tumor had a longer PFS after olaparib treatment than after placebo (36.4 vs 18.6 months; HR, 0.49; 95% CI, 0.37-0.65; P < .001). No association of olaparib with PFS was found in patients with a non-BRCA-like tumor (17.6 vs 16.6 months; HR, 1.02; 95% CI, 0.68-1.51; P = .93). The interaction was significant (P = .004), and HRs and P values (for interaction) were similar in the relevant subgroups, OS, and multivariable analyses. Conclusions and Relevance: In this secondary analysis of the PAOLA-1 randomized clinical trial, patients with a BRCA-like tumor, but not those with a non-BRCA-like tumor, had a significantly longer survival after olaparib plus bevacizumab treatment than placebo plus bevacizumab treatment. Thus, the BRCA1-like classifier could be used as a biomarker for olaparib plus bevacizumab as a maintenance treatment.


Assuntos
Carcinoma , Neoplasias Ovarianas , Ftalazinas , Piperazinas , Gravidez , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/genética , Bevacizumab/uso terapêutico , Proteína BRCA1/genética , Estudos de Coortes , Proteína BRCA2/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Genômica , Biomarcadores
12.
Signal Transduct Target Ther ; 9(1): 79, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38565886

RESUMO

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6-18.0) for the immunotherapy group compared with 9.9 months (8.0-11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40-0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3-32.8) for the control group (HR, 0.57 [95% CI, 0.33-0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Oxaloacetatos , Humanos , Bevacizumab/uso terapêutico , Capecitabina/uso terapêutico , Oxaliplatina , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Imunoterapia
13.
Int Ophthalmol ; 44(1): 166, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557801

RESUMO

PURPOSE: To evaluate the safety and effectiveness of various treatment modalities in patients with diabetic retinopathy (DR) who underwent cataract surgery. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted using the PubMed, Embase, Cochrane Library, and CNKI databases up to December 22, 2021. The safety and efficacy of treatment modalities were assessed using the risk ratio (RR) to compare the progression of DR and the mean difference to evaluate the best corrected visual acuity (BCVA) and macular thickness (MT). RESULTS: The meta-analysis of the RCTs revealed that anti-VEGF (anti-vascular endothelial growth factor) drugs significantly reduced the progression of DR [RR: 0.37 (95%CI 0.19, 0.70), P = 0.002] and improved BCVA [mean difference = - 0.06 (- 0.12, - 0.01), P = 0.03] in patients with pre-existing DR who underwent cataract surgery. Steroid drugs also showed a significant reduction in macular thickness [mean difference = - 55.63 (- 90.73, - 20.53), I2 = 56%, P = 0.002] in DR patients two weeks after cataract surgery compared to the control group. The safety profiles of different management options did not differ significantly. CONCLUSION: The present meta-analysis suggests that anti-VEGF drugs can effectively slow down the progression of diabetic retinopathy, improve BCVA, and reduce MT in DR patients who underwent cataract surgery. Steroid drugs also show promise in reducing MT. However, further studies with larger sample sizes are required to compare the efficacy and safety of different management options in a multi-center clinical setting.


Assuntos
Catarata , Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Retinopatia Diabética/complicações , Retinopatia Diabética/tratamento farmacológico , Ranibizumab/uso terapêutico , Bevacizumab/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Edema Macular/tratamento farmacológico , Esteroides/uso terapêutico
14.
Neurosurg Rev ; 47(1): 137, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564039

RESUMO

Despite 2-staged stereotactic radiosurgery (2-SSRS) has been reported to provide patients with improved survival and limited toxicity, 2-SSRS for brainstem metastases (BSM) larger than 2 cm3 remains challenging. We tried to find out the effectiveness and safety of 2-SSRS plus bevacizumab therapy for BSMs over 2 cm3 and prognostic factors that related to the tumor local control. Patients that received 2-SSRS plus bevacizumab therapy from four gamma knife center were retrospectively studied from Jan 2014 to December 2023. Patients' domestic characteristics and the tumor features were evaluated before and after the treatment. Cox regression model was used to find out prognostic factors for tumor local control. 53 patients with 63 lesions received the therapy. The median peri-tumor edema volume greatly reduced at the end of therapy (P < 0.01), the median tumor volume dramatically reduced (P < 0.01) and patients' KPS score improved significantly (P < 0.05) 3 months after the therapy. Patients' median OS was 12.8 months. The tumor local control rate at 3, 6, and 12 months was 98.4%, 93.4%, and 85.2%. The incidence side effects were mainly oral and nasal hemorrhage (5.7%, 3/53), and radiation necrosis (13.2%, 7/53). Patients with primary lung adenocarcinoma, therapeutic dose over 12 Gy at second-stage SRS, primary peri-tumor edema volume less than 2.3 cm³, primary tumor volume less than 3.7 cm³ would enjoy longer tumor local control. These results suggested that 2-SSRS plus bevacizumab therapy was effective and safe for BSMs over 2 cm3. However, it is important for patients with BSM to receive early diagnosis and treatment to achieve good tumor local control.


Assuntos
Tronco Encefálico , Neoplasias , Humanos , Bevacizumab/uso terapêutico , Estudos Retrospectivos , Edema
15.
Indian J Ophthalmol ; 72(5): 617-619, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38661271

RESUMO

Bevacizumab is a monoclonal, humanized, full-length antibody targeting vascular endothelial growth factor(VEGF-A), known for its anti-angiogenic properties. The off-label use of bevacizumab has stirred legal, financial, industrial, and ethical complexities. With its potential to treat diverse ocular conditions, this commentary delves into the multifaceted dimensions of bevacizumab's off-label utilization, encompassing clinical trials, regulatory frameworks, safety considerations, comparative effectiveness, and economic implications.


Assuntos
Inibidores da Angiogênese , Anticorpos Monoclonais Humanizados , Bevacizumab , Injeções Intravítreas , Uso Off-Label , Fator A de Crescimento do Endotélio Vascular , Humanos , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Bevacizumab/administração & dosagem , Bevacizumab/uso terapêutico , Saúde Global , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
16.
Cell Death Dis ; 15(4): 292, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658527

RESUMO

Although bevacizumab (BVZ), a representative drug for anti-angiogenesis therapy (AAT), is used as a first-line treatment for patients with glioblastoma (GBM), its efficacy is notably limited. Whereas several mechanisms have been proposed to explain the acquisition of AAT resistance, the specific underlying mechanisms have yet to be sufficiently ascertained. Here, we established that inhibitor of differentiation 1 (ID1)high/activin Ahigh glioblastoma cell confers resistance to BVZ. The bipotent effect of activin A during its active phase was demonstrated to reduce vasculature dependence in tumorigenesis. In response to a temporary exposure to activin A, this cytokine was found to induce endothelial-to-mesenchymal transition via the Smad3/Slug axis, whereas prolonged exposure led to endothelial apoptosis. ID1 tumors showing resistance to BVZ were established to be characterized by a hypovascular structure, hyperpermeability, and scattered hypoxic regions. Using a GBM mouse model, we demonstrated that AAT resistance can be overcome by administering therapy based on a combination of BVZ and SB431542, a Smad2/3 inhibitor, which contributed to enhancing survival. These findings offer valuable insights that could contribute to the development of new strategies for treating AAT-resistant GBM.


Assuntos
Ativinas , Inibidores da Angiogênese , Bevacizumab , Resistencia a Medicamentos Antineoplásicos , Glioblastoma , Proteína 1 Inibidora de Diferenciação , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/metabolismo , Glioblastoma/irrigação sanguínea , Humanos , Animais , Proteína 1 Inibidora de Diferenciação/metabolismo , Proteína 1 Inibidora de Diferenciação/genética , Camundongos , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Ativinas/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linhagem Celular Tumoral , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Camundongos Nus , Apoptose/efeitos dos fármacos
17.
In Vivo ; 38(3): 1338-1350, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38688599

RESUMO

BACKGROUND/AIM: Over the past several decades, new anti-cancer drugs have been developed for the treatment of epithelial ovarian cancer. The development of drugs has led to changes in improving the prognosis of ovarian cancer patients. One of these drugs, bevacizumab, is used for advanced or recurrent ovarian cancer. In this study, we aimed to evaluate survival improvement in patients with platinum-resistant relapsed epithelial ovarian cancer (PR-ROC) after introduction of bevacizumab in real world experience. PATIENTS AND METHODS: We retrospectively divided patients with PR-ROC into two groups: bevacizumab plus chemotherapy (BEV-CT group) and chemotherapy alone (CT group). Progression-free survival (PFS), the primary endpoint, between two groups was compared to evaluate whether survival outcomes were improved. In addition, overall survival (OS) was also compared. RESULTS: A total of 154 patients were included in the study: 57 and 97 patients in the BEV-CT and CT groups, respectively. OS was significantly longer in the BEV-CT group than in the CT group. The use of bevacizumab was identified as a favorable prognostic factor for OS. In a subgroup analysis confined to second-line chemotherapy, PFS and OS were statistically different between groups. More patients in the CT group suffered hematologic adverse events of grade 3 or above than patients in the BEV-CT group. CONCLUSION: In a real-world clinical setting, introduction of bevacizumab led to improvement of OS in patients with PR-ROC with a tolerable toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Resistencia a Medicamentos Antineoplásicos , Recidiva Local de Neoplasia , Neoplasias Ovarianas , Humanos , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Feminino , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Idoso , Recidiva Local de Neoplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Resultado do Tratamento , Prognóstico , Estudos Retrospectivos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/mortalidade , Platina/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem
18.
Brain Tumor Pathol ; 41(2): 61-72, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38619734

RESUMO

Glioblastoma multiforme (GBM) acquires resistance to bevacizumab (Bev) treatment. Bev affects angiogenic factors other than vascular endothelial growth factor (VEGF), which are poorly understood. We investigated changes in angiogenic factors under and after Bev therapy, including angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2), placental growth factor (PLGF), fibroblast growth factor 2, and ephrin A2 (EphA2). Fifty-four GBM tissues, including 28 specimens from 14 cases as paired specimens from the same patient obtained in three settings: initial tumor resection (naïve Bev), tumors resected following Bev therapy (effective Bev), and recurrent tumors after Bev therapy (refractory Bev). Immunohistochemistry assessed their expressions in tumor vessels and its correlation with recurrent MRI patterns. PLGF expression was higher in the effective Bev group than in the naïve Bev group (p = 0.024) and remained high in the refractory Bev group. ANGPT2 and EphA2 expressions were higher in the refractory Bev group than in the naïve Bev group (p = 0.047 and 0.028, respectively). PLGF expression was higher in the refractory Bev group compared with the naïve Bev group for paired specimens (p = 0.036). PLGF was more abundant in T2 diffuse/circumscribe patterns (p = 0.046). This is the first study to evaluate angiogenic factors other than VEGF during effective and refractory Bev therapy in patient-derived specimens.


Assuntos
Inibidores da Angiogênese , Angiopoietina-2 , Bevacizumab , Neoplasias Encefálicas , Glioblastoma , Neovascularização Patológica , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/cirurgia , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neovascularização Patológica/tratamento farmacológico , Adulto , Angiopoietina-2/metabolismo , Inibidores da Angiogênese/uso terapêutico , Fator de Crescimento Placentário/metabolismo , Antineoplásicos Imunológicos/uso terapêutico , Angiopoietina-1/metabolismo , Recidiva Local de Neoplasia
19.
Front Immunol ; 15: 1354613, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617840

RESUMO

Metastatic colon cancer remains an incurable disease, and it is difficult for existing treatments to achieve the desired clinical outcome, especially for colon cancer patients who have received first-line treatment. Although immune checkpoint inhibitors (ICIs) have demonstrated durable clinical efficacy in a variety of solid tumors, their response requires an inflammatory tumor microenvironment. However, microsatellite-stable (MSS) colon cancer, which accounts for the majority of colorectal cancers, is a cold tumor that does not respond well to ICIs. Combination regimens open the door to the utility of ICIs in cold tumors. Although combination therapies have shown their advantage even for MSS colon cancer, it remains unclear whether combination therapies show their advantage in patients with pretreated metastatic colon cancer. We report a patient who has achieved complete remission and good tolerance with sintilimab plus bevacizumab and platinum-based chemotherapy after postoperative recurrence. The patient had KRAS mutation and MSS-type colon cancer, and his PD-1+CD8+ and CD3-CD19-CD14+CD16-HLA-DR were both positive. He has achieved a progression-free survival of 43 months and is still being followed up at our center. The above results suggest that this therapeutic regimen is a promising treatment modality for the management of pretreated, MSS-type and KRAS-mutated metastatic colorectal cancer although its application to the general public still needs to be validated in clinical trials.


Assuntos
Anticorpos Monoclonais Humanizados , Neoplasias do Colo , Proteínas Proto-Oncogênicas p21(ras) , Masculino , Humanos , Bevacizumab/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)/genética , Resposta Patológica Completa , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Platina , Repetições de Microssatélites , Microambiente Tumoral
20.
Eur J Obstet Gynecol Reprod Biol ; 297: 72-77, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38581888

RESUMO

OBJECTIVE: This study aimed to develop and evaluate an anti-angiogenesis-based model for predicting the survival and the potential benefits of targeted therapy for patients with localized advanced cervical cancer. METHODS: We collected clinical data from 163 patients with cervical cancer who received paclitaxel and cisplatin (TP) or TP plus bevacizumab during or after radiotherapy from June 2017 to February 2023. We analyzed the clinical measures of recent efficacy and overall survival (OS) using univariate and logistic multivariate and Cox regression methods, respectively. We constructed a nomogram model and evaluated its efficacy using the c-index, the area under the curve (AUC), a calibration curve, and the clinical decision curve (DCA). RESULTS: We found that targeted agents and hemoglobin were independent determinants of near-term efficacy (P < 0.05), while targeted agents and stage were independent factors of OS (P < 0.05). We developed a predictive model for an OS prognostic nomogram and performed internal validation 1000 times using the Bootstrap re-sampling method. The c-index was 0.81, and the AUC was 0.84 (P < 0.01).The calibration curves showed a good agreement between the projected and actual values. The DCA curve indicated that the model had a high positive predictive accuracy. CONCLUSION: We developed a novel anti-angiogenesis-based survival prediction model for patients with locally advanced cervical cancer. This model could estimate the benefit of targeted therapy before treatment, and it had good validation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Cisplatino , Nomogramas , Paclitaxel , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia , Pessoa de Meia-Idade , Paclitaxel/uso terapêutico , Adulto , Bevacizumab/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Idoso , Prognóstico , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA