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1.
N Engl J Med ; 391(1): 44-55, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38959480

RESUMEN

BACKGROUND: Recurrent cervical cancer is a life-threatening disease, with limited treatment options available when disease progression occurs after first-line combination therapy. METHODS: We conducted a phase 3, multinational, open-label trial of tisotumab vedotin as second- or third-line therapy in patients with recurrent or metastatic cervical cancer. Patients were randomly assigned, in a 1:1 ratio, to receive tisotumab vedotin monotherapy (2.0 mg per kilogram of body weight every 3 weeks) or the investigator's choice of chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed). The primary end point was overall survival. RESULTS: A total of 502 patients underwent randomization (253 were assigned to the tisotumab vedotin group and 249 to the chemotherapy group); the groups were similar with respect to demographic and disease characteristics. The median overall survival was significantly longer in the tisotumab vedotin group than in the chemotherapy group (11.5 months [95% confidence interval {CI}, 9.8 to 14.9] vs. 9.5 months [95% CI, 7.9 to 10.7]), results that represented a 30% lower risk of death with tisotumab vedotin than with chemotherapy (hazard ratio, 0.70; 95% CI, 0.54 to 0.89; two-sided P = 0.004). The median progression-free survival was 4.2 months (95% CI, 4.0 to 4.4) with tisotumab vedotin and 2.9 months (95% CI, 2.6 to 3.1) with chemotherapy (hazard ratio, 0.67; 95% CI, 0.54 to 0.82; two-sided P<0.001). The confirmed objective response rate was 17.8% in the tisotumab vedotin group and 5.2% in the chemotherapy group (odds ratio, 4.0; 95% CI, 2.1 to 7.6; two-sided P<0.001). A total of 98.4% of patients in the tisotumab vedotin group and 99.2% in the chemotherapy group had at least one adverse event that occurred during the treatment period (defined as the period from day 1 of dose 1 until 30 days after the last dose); grade 3 or greater events occurred in 52.0% and 62.3%, respectively. A total of 14.8% of patients stopped tisotumab vedotin treatment because of toxic effects. CONCLUSIONS: In patients with recurrent cervical cancer, second- or third-line treatment with tisotumab vedotin resulted in significantly greater efficacy than chemotherapy. (Funded by Genmab and Seagen [acquired by Pfizer]; innovaTV 301 ClinicalTrials.gov number, NCT04697628.).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Recurrencia Local de Neoplasia , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/mortalidad , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estimación de Kaplan-Meier , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/administración & dosificación , Análisis de Supervivencia , Supervivencia sin Progresión , Anciano de 80 o más Años
2.
Int J Gynecol Cancer ; 32(2): 141-146, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34969827

RESUMEN

OBJECTIVES: Cervical cancer is the fourth most common cancer in women worldwide. Epidemiological and quality of life (QoL) data in patients with cervical cancer from low- and middle-income countries are scarce. We aimed to describe sociodemographic and clinicopathological characteristics and quality of life of patients with cervical cancer at diagnosis in Brazil. METHODS: EVITA is a prospective cohort study of newly diagnosed patients with cervical cancer from May 2016 to December 2017, stages I-IVB, from 16 Brazilian sites representing the five Brazilian regions. At baseline, medical evaluation was performed and European Organization for Research and Treatment of Cancer (EORTC) QLQ-CX24/C30 questionnaires were administered. RESULTS: A total of 631 patients were included. Mean±SD age was 49.3±13.9 years; skin color was non-white in 65.3%, and 68.0% had ≤8 years of formal education. In total, 85.1% of patients had a Pap smear. The main reasons reported by patients for not having a Pap smear were: lack of interest (46.9%), shame or embarrassment (19.7%), lack of knowledge (19.7%), and difficulty with access (9.1%). Most patients were diagnosed with locally advanced or metastatic disease (FIGO clinical stage II-IV in 81.8%- stage II in 35.2%, stage III in 36.1%, and stage IV in 10.5%). Patients with clinical stage III-IV had worse physical functioning and role functioning. CONCLUSIONS: Cervical cancer in Brazil is usually diagnosed at an advanced stage. Most patients have low formal education and are unemployed. Lack of interest was identified as a main reason for not having a screening test, and limited access was reported as a reason by <10% of the patients. Awareness campaigns must be a governmental priority, specially focused on the needy population, along with wide access to treatment.


Asunto(s)
Carcinoma de Células Escamosas/epidemiología , Conocimientos, Actitudes y Práctica en Salud , Tamizaje Masivo/estadística & datos numéricos , Neoplasias del Cuello Uterino/epidemiología , Adulto , Brasil/epidemiología , Carcinoma de Células Escamosas/psicología , Femenino , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Humanos , Persona de Mediana Edad , Prueba de Papanicolaou/estadística & datos numéricos , Estudios Prospectivos , Calidad de Vida , Factores Socioeconómicos , Encuestas y Cuestionarios , Neoplasias del Cuello Uterino/psicología
3.
BMC Urol ; 22(1): 86, 2022 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-35706024

RESUMEN

BACKGROUND: Active surveillance (AS) is the preferred treatment for patients with very low-and low-risk prostate cancer (PCa), but it is underperformed worldwide. This study aimed to report knowledge, attitudes, and practices (KAP) of AS for PCa among urologists in Brazil. METHODS: This cross-sectional study used a questionnaire with 50 questions divided into participant characteristics, knowledge regarding inclusion criteria for AS, follow-up, intervention triggers, acceptance, and practice for an index patient. Data analysis comprises absolute and relative frequencies of the variables. After that, a logistic regression was performed in order to verify possible patterns of answers provided by the respondents in the index patient questionnaire. RESULTS: Questionnaires were sent through the SurveyMonkey® platform to 5,015 urologists using email addresses and through social media. A total of 600 (12%) questionnaires returned and 413 (8.2%) were completed and included in the analysis. Only 53% of urologists adopt AS for low- and very-low-risk PCa. Inclusion criteria were patients with age > 50 years (32.2%), prostate specific antigen (PSA) < 10 ng/mL (87.2%), T1 clinical stage (80.4%), Biopsy Gleason score ≤ 6, positive cores ≤ 2 (44.3%), positive core involvement < 50% (45.3%), and magnetic resonance imaging findings (38.7%). The PSA doubling time was still used by 60.3%. Confirmatory biopsy (55.9%), PSA level (36.6%), and digital rectal examination (34.4%) were considered by most urologists for follow-ups. Patient preference (85.7%), upgrade of Gleason score (73.4%), and increased number of positive cores (66.8%) were associated with conversion to definitive treatment. In an index patient, non-acceptance and active treatment request were the most cited reasons for not performing AS. CONCLUSION: There is significant variability in the KAP of AS in Brazil, which indicates the need to reinforce AS, its inclusion and follow-up criteria, and the benefits for physicians and the general population. TRIAL REGISTRATION: Not applicable.


Asunto(s)
Antígeno Prostático Específico , Neoplasias de la Próstata , Brasil , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Encuestas y Cuestionarios , Urólogos , Espera Vigilante/métodos
4.
Neurogenetics ; 22(2): 105-115, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33937968

RESUMEN

Dravet syndrome (DS) is a rare and severe epileptic syndrome of childhood with prevalence between 1/22,000 and 1/49,900 of live births. Approximately 80% of patients with this syndrome present SCN1A pathogenic variants, which encodes an alpha subunit of a neural voltage-dependent sodium channel. There is a correlation between PCDH19 pathogenic variants, encodes the protocadherin 19, and a similar disease to DS known as DS-like phenotype. The present review aims to clarify the differences between DS and DS-like phenotype according to the SCN1A and PCDH19 variants. A systematic review was conducted in PubMed and Virtual Health Library (VHL) databases, using "Dravet Syndrome" and "Severe Myoclonic Epilepsy in Infancy (SMEI)" search words, selecting cohort of studies published in journal with impact factor of two or greater. The systematic review was according to the Preferred Reporting Items for Systematic Review and Meta-Analysis recommendations. Nineteen studies were included in the present review, and a significant proportion of patients with DS-carrying SCN1A was greater than patients with DS-like phenotype-harboring PCDH19 variants (76.6% versus 23.4%). When clinical and genetic data were correlated, autism was predominantly observed in patients with DS-like-carrying PCDH19 variants compared to SCN1A variant carriers (62.5% versus 37.5%, respectively, P-value = 0.044, P-value corrected = 0.198). In addition, it was noticed a significant predisposition to hyperthermia during epilepsy crisis in individuals carrying PCDH19 variants (P-value = 0.003; P-value corrected = 0.027). The present review is the first to point out differences between the DS and DS-like phenotype according to the SCN1A and PCDH19 variants.


Asunto(s)
Epilepsias Mioclónicas/genética , Heterogeneidad Genética , Mutación , Canal de Sodio Activado por Voltaje NAV1.1/genética , Protocadherinas/genética , Trastorno Autístico/genética , Humanos , Hipertermia/genética , Canal de Sodio Activado por Voltaje NAV1.1/deficiencia , Estudios Observacionales como Asunto , Fenotipo , Protocadherinas/deficiencia , Convulsiones Febriles/genética , Síndrome
5.
Int Braz J Urol ; 47(2): 359-373, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33284538

RESUMEN

BACKGROUND: Non-metastatic castration resistant prostate cancer (M0 CRPC) has seen important developments in drugs and diagnostic tools in the last two years. New hormonal agents have demonstrated improvement in metastasis free survival in M0 CRPC patients and have been approved by regulatory agencies in Brazil. Additionally, newer and more sensitive imaging tools are able to detect metastasis earlier than before, which will impact the percentage of patients staged as M0 CRPC. Based on the available international guidelines, a group of Brazilian urology and medical oncology experts developed and completed a survey on the diagnosis and treatment of M0 CRPC in Brazil. These results are reviewed and summarized and associated recommendations are provided. OBJECTIVE: To present survey results on management of M0 CRPC in Brazil. DESIGN, SETTING, AND PARTICIPANTS: A panel of six Brazilian prostate cancer experts determined 64 questions concerning the main areas of interest: 1) staging tools, 2) treatments, 3) side effects of systemic treatment/s, and 4) osteoclast-targeted therapy. A larger panel of 28 Brazilian prostate cancer experts answered these questions in order to create country-specific recommendations discussed in this manuscript. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on the predefined questions. These answers are the panelists' opinions, not a literature review or meta-analysis. Therapies not yet approved in Brazil were excluded from answer options. Each question had five to seven relevant answers including two non-answers. Results were tabulated in real time. CONCLUSIONS: The results and recommendations presented can be used by Brazilian physicians to support the management of M0 CRPC patients. Individual clinical decision making should be supported by available data, however, for Brazil, guidelines for diagnosis and management of M0 CRPC patients have not been developed. This document will serve as a point of reference when confronting this disease stage.


Asunto(s)
Consenso , Médicos , Neoplasias de la Próstata Resistentes a la Castración , Brasil , Humanos , Masculino , Selección de Paciente , Percepción , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Resultado del Tratamiento
6.
BMC Cancer ; 19(1): 487, 2019 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-31122212

RESUMEN

BACKGROUND: Testosterone suppression is the standard treatment for advanced prostate cancer, and it is associated with side-effects that impair patients' quality of life, like sexual dysfunction, osteoporosis, weight gain, and increased cardiovascular risk. We hypothesized that abiraterone acetate with prednisone (AAP) and apalutamide, alone or in combination, can be an effective hormonal therapy also possibly decreasing castration-associated side effects. METHODS: Phase II, open-label, randomized, efficacy trial of abiraterone acetate plus prednisone (AAP) and Androgen Deprivation Therapy (ADT) versus apalutamide versus the combination of AAP (without ADT) and apalutamide. Key eligibility criteria are confirmed prostate adenocarcinoma; biochemical relapse after definitive treatment (PSA ≥ 4 ng/ml and doubling time less than 10 months, or PSA ≥ 20 ng/ml); newly diagnosed locally advanced or metastatic prostate cancer; asymptomatic to moderately symptomatic regarding bone symptoms. Patients with other histology besides adenocarcinoma or previous use of hormonal therapy or chemotherapy were excluded. DISCUSSION: There is an urgent need to study and validate regimens such as new hormonal agents that may add benefit to castration with an acceptable safety profile. We aim to evaluate if apalutamide in monotherapy or in combination with AAP is an effective and safety hormonal treatment that can spare patients of androgen deprivation therapy. TRIAL REGISTRATION: This trial was registered in ClinicalTrials.gov on October 16, 2017, under Identifier: NCT02867020.


Asunto(s)
Acetato de Abiraterona/uso terapéutico , Adenocarcinoma/tratamiento farmacológico , Antagonistas de Receptores Androgénicos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Goserelina/uso terapéutico , Prednisona/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Tiohidantoínas/uso terapéutico , Acetato de Abiraterona/administración & dosificación , Antagonistas de Receptores Androgénicos/administración & dosificación , Antineoplásicos Hormonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica , Supervivencia sin Enfermedad , Goserelina/administración & dosificación , Humanos , Masculino , Medición de Resultados Informados por el Paciente , Prednisona/administración & dosificación , Calidad de Vida , Testosterona/sangre , Tiohidantoínas/administración & dosificación , Resultado del Tratamiento
7.
Future Oncol ; 15(4): 401-408, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30620220

RESUMEN

AIM: Prognostic differences between major histologic gastric cancer groups, intestinal and diffuse are uncertain, since cellular components in each of them possibly have different behaviors. MATERIALS & METHODS: We reviewed 198 gastric cancer patients charts diagnosed from January 2003 to December 2015 in a tertiary hospital. Multivariate Cox proportional survival models were used to evaluate the impact of histologic groups on overall survival. RESULTS: About a third had the signet-ring cell carcinoma (SRCC). In a comparison of the different histologic subtypes, SRCC had the worst prognosis of all. The median durations of survival for patients with stage III and stage IV were 19.7 and 7.7 months, respectively. CONCLUSION: Signet-ring cell component seem to have a relevant role in defining prognosis for gastric cancer.


Asunto(s)
Carcinoma de Células en Anillo de Sello/mortalidad , Carcinoma de Células en Anillo de Sello/patología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Anciano , Anciano de 80 o más Años , Carcinoma de Células en Anillo de Sello/terapia , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Neoplasias Gástricas/terapia , Tasa de Supervivencia
8.
Int Braz J Urol ; 45(3): 449-458, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31038861

RESUMEN

Prostate cancer is the second most common cancer and the fi fth leading cause of cancer deaths. In Brazil, it is likewise the second most common cancer among men, second only to non-melanoma skin cancers. The aim of this consensus is to align different opinions and interpretations of the medical literature in a practical and patient-oriented approach. The fi rst Brazilian Consensus on the Treatment of Advanced Prostate Cancer was published in 2017, with the goal of reducing the heterogeneity of therapeutic conduct in Brazilian patients with metastatic prostate cancer. We acknowledge that in Brazil the incorporation of different technologies is a big challenge, especially in the Sistema Único de Saúde (SUS), which allows for the disparity in the options available to patients treated in different institutions. In order to update the recommendations and to make them objective and easily accessible, once more a panel of specialists was formed in order to discuss and elaborate a new Brazilian Consensus on Advanced Prostate Cancer. This Consensus was written through a joint initiative of the Brazilian Society of Clinical Oncology (SBOC) and the Brazilian Society of Urology (SBU) to support the clinical decisions of physicians and other health professionals involved in the care of patients with prostate cancer.


Asunto(s)
Consenso , Guías de Práctica Clínica como Asunto , Neoplasias de la Próstata/terapia , Antineoplásicos/uso terapéutico , Brasil , Toma de Decisiones Clínicas , Humanos , Masculino , Metástasis de la Neoplasia , Neoplasias de la Próstata/patología , Sociedades Médicas
9.
J BUON ; 23(4): 925-935, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30358195

RESUMEN

PURPOSE: Over 50% of metastatic colorectal cancers harbor RAS mutations. It is unclear if different mutation variants have an impact on survival. The purpose of this study was to evaluate the impact of these mutations on colorectal cancer survival. METHODS: The charts of all cases of metastatic colorectal cancer diagnosed between January 2005 and January 2016 in a tertiary hospital in Brazil were reviewed. Inclusion criteria were complete data on clinical staging, treatments received and all-RAS testing. Multivariate Cox proportional survival models were used to evaluate the impact of specific RAS variants on survival. RESULTS: There were 151 eligible patients and 61.6% had RAS alterations, the most common G12D (11.9%) and G12A (8.6%). Most patients received chemotherapy, including oxaliplatin (79%), irinotecan (53%) and bevacizumab (59%). Among RAS-wild type patients, 46% received anti-EGFR therapy. Median survival was 39.2 months for RAS-wildtype, 18.8 months for RAS G12A and 34.6 for other RASmutant patients (multivariate analysis for G12A vs RASwild type HR 1.94; 95% CI 0.83-5.51; p=0.12). CONCLUSION: Patients with metastatic colorectal cancer who have RAS mutations have shorter overall survival. Regarding the impact of specific KRAS alterations, G12A mutations have a worse prognosis.


Asunto(s)
Adenocarcinoma/genética , Neoplasias Colorrectales/genética , Genes ras , Proteínas ras/genética , Adenocarcinoma/patología , Anciano , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Mutación , Metástasis de la Neoplasia , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento
10.
Int Braz J Urol ; 43(3): 407-415, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28199075

RESUMEN

INTRODUCTION: Prostate cancer still represents a major cause of morbidity, and still about 20% of men with the disease are diagnosed or will progress to the advanced stage without the possibility of curative treatment. Despite the recent advances in scientific and technological knowledge and the availability of new therapies, there is still considerable heterogeneity in the therapeutic approaches for metastatic prostate cancer. OBJECTIVES: This article presents a summary of the I Brazilian Consensus on Advanced Prostate Cancer, conducted by the Brazilian Society of Urology and Brazilian Society of Clinical Oncology. MATERIALS AND METHODS: Experts were selected by the medical societies involved. Forty issues regarding controversial issues in advanced disease were previously elaborated. The panel met for consensus, with a threshold established for 2/3 of the participants. RESULTS AND CONCLUSIONS: The treatment of advanced prostate cancer is complex, due to the existence of a large number of therapies, with different response profiles and toxicities. The panel addressed recommendations on preferred choice of therapies, indicators that would justify their change, and indicated some strategies for better sequencing of treatment in order to maximize the potential for disease control with the available therapeutic arsenal. The lack of consensus on some topics clearly indicates the absence of strong evidence for some decisions.


Asunto(s)
Consenso , Guías de Práctica Clínica como Asunto , Neoplasias de la Próstata/terapia , Brasil , Humanos , Masculino , Próstata/patología , Neoplasias de la Próstata/diagnóstico
12.
Acta Crystallogr D Biol Crystallogr ; 71(Pt 6): 1257-71, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26057666

RESUMEN

The sequences of all seven polypeptide chains from the giant haemoglobin of the free-living earthworm Glossoscolex paulistus (HbGp) are reported together with the three-dimensional structure of the 3.6 MDa complex which they form. The refinement of the full particle, which has been solved at 3.2 Å resolution, the highest resolution reported to date for a hexagonal bilayer haemoglobin composed of 12 protomers, is reported. This has allowed a more detailed description of the contacts between subunits which are essential for particle stability. Interpretation of features in the electron-density maps suggests the presence of metal-binding sites (probably Zn(2+) and Ca(2+)) and glycosylation sites, some of which have not been reported previously. The former appear to be important for the integrity of the particle. The crystal structure of the isolated d chain (d-HbGp) at 2.1 Å resolution shows different interchain contacts between d monomers compared with those observed in the full particle. Instead of forming trimers, as seen in the complex, the isolated d chains associate to form dimers across a crystallographic twofold axis. These observations eliminate the possibility that trimers form spontaneously in solution as intermediates during the formation of the dodecameric globin cap and contribute to understanding of the possible ways in which the particle self-assembles.


Asunto(s)
Hemoglobinas/química , Oligoquetos/química , Secuencia de Aminoácidos , Animales , Cristalografía por Rayos X , Datos de Secuencia Molecular , Conformación Proteica , Homología de Secuencia de Aminoácido
15.
Gynecol Oncol ; 138(2): 272-7, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26026738

RESUMEN

OBJECTIVES: The primary objective was to evaluate the clinical efficacy of hu3S193, a humanized monoclonal antibody against the Lewis-Y antigen, in patients with platinum resistant/refractory ovarian, fallopian tube and primary peritoneal carcinoma. Secondary objectives were safety and pharmacokinetics. In addition, we sought to determine the potential interaction of clinical benefit and patient characteristics. METHODS: This two-stage, multicenter, single arm, phase II trial enrolled eligible patients to receive hu3S193 weekly at a dose of 20mg/m(2) intravenously for 8 weeks (1 cycle) to a maximum of 3 cycles. Efficacy was measured as clinical benefit rate (objective response or stable disease for at least 24 weeks). RESULTS: 26 of 31 patients were eligible for efficacy analysis. No complete/partial responses were observed. Six patients had stable disease for 24+weeks [clinical benefit rate 23% (95% CI=9.77%-46.71%)]. Median PFS was 8.4 weeks (95% CI=6.0 to 16.1). Median PFS differed between patients with no ascites and no visceral disease and patients with ascites and/or visceral disease [16.1 vs. 8.1 weeks (p=0.0058)]. The most commonly reported treatment-related adverse events were fatigue (19.3%) and nausea (16.2%). Allergic reactions occurred in 6 patients (5 with Grade 1/2; 1 with Grade 3). CONCLUSIONS: Hu3S193 lacked sufficient activity in the first stage of the study to open enrollment to the second stage. However, based on the longer PFS in patients with no ascites and no visceral disease, consolidation strategies in platinum sensitive disease are currently being tested.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias de las Trompas Uterinas/terapia , Neoplasias Glandulares y Epiteliales/terapia , Neoplasias Ováricas/terapia , Neoplasias Peritoneales/terapia , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/inmunología , Anticuerpos Monoclonales Humanizados/farmacocinética , Carcinoma Epitelial de Ovario , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Neoplasias de las Trompas Uterinas/inmunología , Neoplasias de las Trompas Uterinas/metabolismo , Femenino , Humanos , Antígenos del Grupo Sanguíneo de Lewis/inmunología , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/inmunología , Neoplasias Glandulares y Epiteliales/metabolismo , Compuestos Organoplatinos/farmacología , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/metabolismo , Neoplasias Peritoneales/inmunología , Neoplasias Peritoneales/metabolismo , Adulto Joven
16.
Nanomedicine ; 11(2): 351-8, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25461288

RESUMEN

Several synthetic metallated protoporphyrins (M-PPIX) were tested for their ability to block the cell cycle of the lethal human malaria parasite Plasmodium falciparum. After encapsulating the porphyrin derivatives in micro- and nanocapsules of marine atelocollagen, their effects on cultures of red blood cells infected (RBC) with P. falciparum were verified. RBCs infected with synchronized P. falciparum incubated for 48 h showed a toxic effect over a micromolar range. Strikingly, the IC50 of encapsulated metalloporphyrins reached nanomolar concentrations, where Zn-PPIX showed the best antimalarial effect, with an IC50=330 nM. This value is an 80-fold increase in the antimalarial activity compared to the antimalarial effect of non-encapsulated Zn-PPIX. These findings reveal that the incubation of P. falciparum infected-RBCs with 20 µM Zn-PPIX reduced the size of hemozoin crystal by 34%, whereas a 28% reduction was noticed with chloroquine, confirming the importance of heme detoxification pathway in drug therapy. FROM THE CLINICAL EDITOR: In this study, synthetic metalloporphyrins were tested as therapeutics that target Plasmodium falciparum. The IC50 of encapsulated metalloporphyrins was found to be in the nanomolar concentration range, with encapsulated Zn-PPIX showing an 80-fold increase in its antimalarial activity compared to the non-encapsulated form.


Asunto(s)
Antimaláricos/administración & dosificación , Malaria Falciparum/tratamiento farmacológico , Metaloporfirinas/administración & dosificación , Plasmodium falciparum/efectos de los fármacos , Animales , Antimaláricos/química , Colágeno/administración & dosificación , Colágeno/química , Humanos , Malaria Falciparum/parasitología , Nanocápsulas/administración & dosificación , Nanocápsulas/química
17.
J Cancer Res Clin Oncol ; 150(4): 183, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594593

RESUMEN

PURPOSE: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. METHODS: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. RESULTS: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. CONCLUSION: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , América Latina , Consenso , Sunitinib
18.
J Cancer Policy ; 37: 100429, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37391094

RESUMEN

BACKGROUND: Cancer is a public health issue in Brazil. To mitigate exposure to risk factors, change habits and ensure access to cancer care, an increasing number of bills are presented every year. This article analyzes the changes proposed in these bills, portraying how the representatives perceive and respond to the challenges imposed by cancer on the healthcare system and society. METHODS: Through a systematic search on the Brazilian House of Representatives website, this exploratory study examines cancer-related bills presented up to 2022. RESULTS: Of 1311 bills identified, 310 met the inclusion criteria and were categorized based on their content. The increasing annual number of cancer bills reflects the interest of representatives on the topic. The cancer types addressed correspond to the most prevalent ones, except for the colorectal. The most common strategy is primary prevention (n: 129), proposing the reduction of risk factors exposure or the promotion of protective ones, followed by tertiary (n: 106) and secondary (n: 36) strategies, targeting, respectively, cancer treatment/management and its early diagnosis/detection. On the nature of proposed changes, most seek to implement increased healthcare access (n: 125), production/sale (dis)incentives for goods containing carcinogens (n: 60), and fiscal/financial (dis)incentives (n: 53). CONCLUSION: The identified gaps - such as the limited use of data and evidence to support what is proposed, overlapping but fragmented efforts with previous bills, scarce efforts directly addressing the determinants of health, and the low rate of conversion to law - entails opportunities to advance the Legislative propositions. POLICY SUMMARY: To effectively respond to cancer-related challenges, is essential that the Legislative branch takes into account what is already being proposed or being left out, inputs from society, real-world data, and the results produced by the multisectoral policies in place.


Asunto(s)
Política de Salud , Neoplasias , Brasil/epidemiología , Salud Pública , Factores de Riesgo , Accesibilidad a los Servicios de Salud , Neoplasias/diagnóstico
19.
Sci Rep ; 13(1): 12886, 2023 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-37558765

RESUMEN

We aimed to investigate changes in olfactory bulb volume and brain network in the white matter (WM) in patients with persistent olfactory disfunction (OD) following COVID-19. A cross-sectional study evaluated 38 participants with OD after mild COVID-19 and 24 controls, including Sniffin' Sticks identification test (SS-16), MoCA, and brain magnetic resonance imaging. Network-Based Statistics (NBS) and graph theoretical analysis were used to explore the WM. The COVID-19 group had reduced olfactory bulb volume compared to controls. In NBS, COVID-19 patients showed increased structural connectivity in a subnetwork comprising parietal brain regions. Regarding global network topological properties, patients exhibited lower global and local efficiency and higher assortativity than controls. Concerning local network topological properties, patients had reduced local efficiency (left lateral orbital gyrus and pallidum), increased clustering (left lateral orbital gyrus), increased nodal strength (right anterior orbital gyrus), and reduced nodal strength (left amygdala). SS-16 test score was negatively correlated with clustering of whole-brain WM in the COVID-19 group. Thus, patients with OD after COVID-19 had relevant WM network dysfunction with increased connectivity in the parietal sensory cortex. Reduced integration and increased segregation are observed within olfactory-related brain areas might be due to compensatory plasticity mechanisms devoted to recovering olfactory function.


Asunto(s)
COVID-19 , Sustancia Blanca , Humanos , Imagen de Difusión Tensora/métodos , Estudios Transversales , COVID-19/patología , Encéfalo/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Imagen por Resonancia Magnética
20.
Front Oncol ; 13: 1133277, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36969061

RESUMEN

Background: Endometrial cancer is of increasing concern in several countries, including Brazil, in part because of an ageing population, declines in fertility, and the increasing prevalence of obesity. Although endometrial tumors had lagged behind other cancer types in terms of treatment improvements, molecular characterization of these tumors is paving the way for novel therapies and an expansion of the therapeutic arsenal. We aimed to help medical oncologists who manage patients with recurrent or metastatic endometrial cancer in the Brazilian healthcare setting. Methods: The panel, composed of 20 medical oncologists, convened in November 2021 to address 50 multiple-choice questions on molecular testing and treatment choices. We classified the level of agreement among panelists as (1) consensus (≥75% choosing the same answer), (2) majority vote (50% to <75%), or (3) less than majority vote (<50%). Results: Consensus was present for 25 of the 50 questions, whereas majority vote was present for an additional 23 questions. Key recommendations include molecular testing for every patient with recurrent/metastatic endometrial cancer; choice of first-line treatment according to microsatellite instability and HER2, with the addition of programmed death ligand 1 (PD-L1) and hormone receptors (HRs) for second-line therapy; carboplatin and paclitaxel as the preferred option in first-line treatment of HER2-negative disease, with the addition of trastuzumab in HER2-positive disease; pembrolizumab plus lenvatinib as a key option in second line, regardless of HER2, PD-L1 or HRs; and various recommendations regarding treatment choice for patients with distinct comorbidities. Conclusion: Despite the existing gaps in the current literature, the vast majority of issues addressed by the panel provided a level of agreement sufficient to inform clinical practice in Brazil and in other countries with similar healthcare environments.

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