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  1. Article ; Online: Spectrum and Clinical Activity of PD-1/PD-L1 Inhibitors: Regulatory Approval and Under Development.

    Oliveira, Leandro Jonata Carvalho / Gongora, Aline Bobato Lara / Jardim, Denis Leonardo Fontes

    Current oncology reports

    2020  Volume 22, Issue 7, Page(s) 70

    Abstract: Purpose of review: The aim of this review is to highlight the clinical development of PD-1 and PD-L1 inhibitors in cancer therapy. We focus on detailing the registration trials that have led to FDA-approved indications of anti-PD-1 and anti-PD-L1 ... ...

    Abstract Purpose of review: The aim of this review is to highlight the clinical development of PD-1 and PD-L1 inhibitors in cancer therapy. We focus on detailing the registration trials that have led to FDA-approved indications of anti-PD-1 and anti-PD-L1 therapies and future strategies.
    Recent findings: The number of PD-1/PD-L1 inhibitors approved and in studies continues to grow, in different scenarios. Although the first wave of approvals included advanced cancers, localized disease is under growing interest in recent trials and approvals. Several of these agents are migrating from a monotherapy strategy to combinations (especially with targeted agents and chemotherapy). To date, several studies are being conducted for a better understanding of predictive biomarkers, mechanisms of resistance, optimal treatment duration, and immune-related toxicities. This article summarizes the recent history of modern cancer immunotherapy, provides an overview of novel drug-development considerations, and thus, illustrates the opportunities these new generations of immunotherapies represent.
    MeSH term(s) Biomarkers, Tumor ; Drug Approval ; Drug Development ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Immune Checkpoint Inhibitors/therapeutic use ; Neoplasms/drug therapy
    Chemical Substances Biomarkers, Tumor ; Immune Checkpoint Inhibitors
    Language English
    Publishing date 2020-06-12
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2057359-5
    ISSN 1534-6269 ; 1523-3790
    ISSN (online) 1534-6269
    ISSN 1523-3790
    DOI 10.1007/s11912-020-00928-5
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5521: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: TRK Inhibitors in Non-Small Cell Lung Cancer.

    Harada, Guilherme / Gongora, Aline Bobato Lara / da Costa, Cesar Martins / Santini, Fernando Costa

    Current treatment options in oncology

    2020  Volume 21, Issue 5, Page(s) 39

    Abstract: Opinion statement: Care should be taken to ensure that the diagnostic strategy for a recently diagnosed advanced non-small cell lung cancer includes NTRK fusion testing. RNA sequencing is the gold standard method of detection of NTRK fusion; however, ... ...

    Abstract Opinion statement: Care should be taken to ensure that the diagnostic strategy for a recently diagnosed advanced non-small cell lung cancer includes NTRK fusion testing. RNA sequencing is the gold standard method of detection of NTRK fusion; however, pan-TRK immunohistochemistry could be used as a screening method with good sensitivity. Larotrectinib and entrectinib are approved therapies for TRK fusion-positive lung cancers as first or subsequent lines of therapy. TRK inhibition has demonstrated clinically meaningful, deep, and durable systemic and central nervous system responses. Larotrectinib and entrectinib have a manageable safety profile, including some TRK-related adverse events, such as dizziness and weight gain. At disease progression on first-generation TRK inhibitors, enrollment on a clinical trial should be encouraged, as new-generation TRK inhibitors are being tested.
    MeSH term(s) Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor ; Carcinoma, Non-Small-Cell Lung/diagnosis ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/etiology ; Carcinoma, Non-Small-Cell Lung/mortality ; Disease Management ; Disease Susceptibility ; Humans ; Lung Neoplasms/diagnosis ; Lung Neoplasms/drug therapy ; Lung Neoplasms/etiology ; Lung Neoplasms/mortality ; Molecular Diagnostic Techniques ; Molecular Targeted Therapy/adverse effects ; Molecular Targeted Therapy/methods ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Receptor Protein-Tyrosine Kinases/antagonists & inhibitors ; Treatment Outcome
    Chemical Substances Antineoplastic Agents ; Biomarkers, Tumor ; Protein Kinase Inhibitors ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1)
    Language English
    Publishing date 2020-04-23
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2057351-0
    ISSN 1534-6277 ; 1527-2729
    ISSN (online) 1534-6277
    ISSN 1527-2729
    DOI 10.1007/s11864-020-00741-z
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    Zs.A 5523: Show issues Location:
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  3. Article: Expanding the phenotype of E318K (c.952G > A) MITF germline mutation carriers: case series and review of the literature.

    Oliveira, Leandro Jonata Carvalho / Gongora, Aline Bobato Lara / Lima, Fabiola Ambrosio Silveira / Canedo, Felipe Sales Nogueira Amorim / Quirino, Carla Vanessa / Pisani, Janina Pontes / Achatz, Maria Isabel / Rossi, Benedito Mauro

    Hereditary cancer in clinical practice

    2021  Volume 19, Issue 1, Page(s) 32

    Abstract: Background: The microphthalmia-associated transcription factor gene (MITF) belongs to the MYC supergene family and plays an important role in melanocytes' homeostasis. Individuals harboring MITF germline pathogenic variants are at increased risk of ... ...

    Abstract Background: The microphthalmia-associated transcription factor gene (MITF) belongs to the MYC supergene family and plays an important role in melanocytes' homeostasis. Individuals harboring MITF germline pathogenic variants are at increased risk of developing cancer, most notably melanoma and renal cell carcinoma.
    Case presentation: We describe a cohort of ten individuals who harbor the same MITF c.952G > A (p.Glu 318Lys), or p.E318K, germline pathogenic variant. Six carriers developed at least one malignancy (4 cases of breast cancer; 1 cervical cancer; 1 colon cancer; 1 melanoma; 1 ovarian/fallopian tube cancer). A significant phenotypic heterogeneity was found among these individuals and their relatives. Breast cancer was, overall, the most frequent malignancy observed in this case series, with 13 occurrences of 60 (21.67 %) total cancer cases described among the probands and their relatives.
    Conclusions: Our retrospective analysis data raise the hypothesis of a possible association of the MITF p.E318K pathogenic variant with an increased risk of breast cancer.
    Language English
    Publishing date 2021-07-21
    Publishing country Poland
    Document type Journal Article
    ZDB-ID 2252512-9
    ISSN 1897-4287 ; 1731-2302
    ISSN (online) 1897-4287
    ISSN 1731-2302
    DOI 10.1186/s13053-021-00189-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Emerging biomarkers in metastatic urothelial carcinoma: tumour mutational burden, PD-L1 expression and APOBEC polypeptide-like signature in a patient with complete response to anti-programmed cell death protein-1 inhibitor.

    Queiroz, Marcello Moro / de Souza, Zenaide Silva / Gongora, Aline Bobato Lara / de Galiza Barbosa, Felipe / Buchpiguel, Carlos Alberto / de Castro, Marilia Germanos / de Macedo, Mariana Petaccia / Coelho, Rafael Ferreira / Sokol, Ethan Samuel / Camargo, Anamaria Aranha / Bastos, Diogo Assed

    Ecancermedicalscience

    2021  Volume 15, Page(s) 1306

    Abstract: Immunotherapy has recently been incorporated into the treatment guidelines for metastatic urothelial carcinoma. Nevertheless, the role of prognostic and predictive biomarkers in this setting is not completely defined. To date, PD-L1 expression and a high ...

    Abstract Immunotherapy has recently been incorporated into the treatment guidelines for metastatic urothelial carcinoma. Nevertheless, the role of prognostic and predictive biomarkers in this setting is not completely defined. To date, PD-L1 expression and a high tumour mutational burden (TMB) seem to predict better responses to immune checkpoint inhibitors, but patients without these biomarkers may still respond to immunotherapy. There are some caveats regarding these biomarkers, such as lack of standardisation of techniques, tumour heterogeneity and other factors influencing the tumour microenvironment. Genomic signatures are other promising emerging strategies. We hereby discuss the management of a 70-year-old man with a metastatic recurrence of urothelial carcinoma within 1 year after neoadjuvant chemotherapy and radical cystectomy. Tumour next-generation sequencing showed a high TMB and a
    Language English
    Publishing date 2021-10-22
    Publishing country England
    Document type Case Reports
    ISSN 1754-6605
    ISSN 1754-6605
    DOI 10.3332/ecancer.2021.1306
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  5. Article ; Online: Alectinib activity in chemotherapy-refractory metastatic RET-rearranged non-small cell lung carcinomas: A case series.

    Ribeiro, Maurício Fernando Silva Almeida / Alessi, João Victor Machado / Oliveira, Leandro Jonata Carvalho / Gongora, Aline Bobato Lara / Sacardo, Karina Perez / Zucchetti, Bruna Migliavacca / Shimada, Andrea Kazumi / de Galiza Barbosa, Felipe / Feher, Olavo / Katz, Artur

    Lung cancer (Amsterdam, Netherlands)

    2019  Volume 139, Page(s) 9–12

    Abstract: Objectives: to report outcomes of four cases of chemo-refractory RET-rearranged non-small cell lung carcinomas (NSCLCs) treated with alectinib in a single center.: Materials and methods: we retrospectively assessed and reported the activity and ... ...

    Abstract Objectives: to report outcomes of four cases of chemo-refractory RET-rearranged non-small cell lung carcinomas (NSCLCs) treated with alectinib in a single center.
    Materials and methods: we retrospectively assessed and reported the activity and tolerability of alectinib 600 mg twice daily in advanced and chemo-refractory RET-rearranged NSCLC patients treated in a Brazilian institution. Identification of RET rearrangements was performed using the FoundationOne® next-generation sequencing (NGS) platform.
    Results: The four patients herein reported were white, female and non-smokers, ranging between 59-66 years of age. All patients had been previously treated with chemotherapy and were TKI naïve; three of them presented disease progression to nivolumab as well. Molecular tumor profiling showed a KIF5B-RET fusion in three patients and a CCDC6-RET in the fourth. One patient exhibited disease progression and clinical deterioration two months after treatment initiation. Disease control was documented in two patients with PFS ranging from 4 to 5 months (one partial metabolic response and one stable disease). In one of the cases, which developed oligoprogression on alectinib, radiation therapy plus post-progression alectinib were able to provide additional disease control for 9 more months. No grade 3/4 adverse events, dose reductions or discontinuation due to toxicity were documented.
    Conclusion: Although this is a small single center evaluation, alectinib was well tolerated and demonstrated clinical activity against advanced RET-rearranged NSCLCs, suggesting its potential role in this specific subset of malignancies. Clinical trials addressing its efficacy and the optimal dosing schedule in the present context are underway, and results are eagerly awaited.
    MeSH term(s) Aged ; Carbazoles/therapeutic use ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/secondary ; Drug Resistance, Neoplasm/drug effects ; Female ; Follow-Up Studies ; Gene Rearrangement ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Middle Aged ; Piperidines/therapeutic use ; Prognosis ; Protein Kinase Inhibitors/therapeutic use ; Proto-Oncogene Proteins c-ret/genetics ; Retrospective Studies
    Chemical Substances Carbazoles ; Piperidines ; Protein Kinase Inhibitors ; Proto-Oncogene Proteins c-ret (EC 2.7.10.1) ; RET protein, human (EC 2.7.10.1) ; alectinib (LIJ4CT1Z3Y)
    Language English
    Publishing date 2019-10-24
    Publishing country Ireland
    Document type Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 632771-0
    ISSN 1872-8332 ; 0169-5002
    ISSN (online) 1872-8332
    ISSN 0169-5002
    DOI 10.1016/j.lungcan.2019.10.020
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2135: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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    Zs.MO 423: Show issues

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  6. Article ; Online: Tumor Lysis Syndrome After Platinum-based Chemotherapy in Castration-resistant Prostate Cancer With a BRCA2 Mutation: A Case Report.

    Gongora, Aline Bobato Lara / Canedo, Felipe Sales Nogueira Amorim / de Melo, André Luis Alves / Bezerra, Regis Otaviano Franca / Asprino, Paula Fontes / Camargo, Anamaria Aranha / Bastos, Diogo Assed

    Clinical genitourinary cancer

    2018  Volume 17, Issue 1, Page(s) e61–e64

    MeSH term(s) Antineoplastic Combined Chemotherapy Protocols/adverse effects ; BRCA2 Protein/genetics ; Carboplatin/administration & dosage ; Etoposide/administration & dosage ; Humans ; Male ; Middle Aged ; Mutation ; Prognosis ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/genetics ; Prostatic Neoplasms, Castration-Resistant/pathology ; Tumor Lysis Syndrome/etiology ; Tumor Lysis Syndrome/pathology
    Chemical Substances BRCA2 Protein ; BRCA2 protein, human ; Etoposide (6PLQ3CP4P3) ; Carboplatin (BG3F62OND5)
    Language English
    Publishing date 2018-09-07
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 2225121-2
    ISSN 1938-0682 ; 1558-7673
    ISSN (online) 1938-0682
    ISSN 1558-7673
    DOI 10.1016/j.clgc.2018.09.001
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    Zs.A 6168: Show issues Location:
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  7. Article ; Online: Multicenter Database of Patients with Germ-Cell Tumors: A Latin American Cooperative Oncology Group Registry (LACOG 0515).

    Bastos, Diogo A / Gongora, Aline Bobato Lara / Dzik, Carlos / Jardim, Denis Leonardo / Piva, Marina / Carcano, Flavio Mavignier / Bertollo, Glaucio / Trindade, Karine / Fontes, Mariane Sousa / Soares, Andrey / Reinert, Tomas / De Cassia Costamilan, Rita / Villarroel, Rodrigo Ughini / Watarai, Gabriel / Gazola, Antonia Angeli / Preto, Daniel D Almeida / Mutti, Haila / Bonalumi Dos Santos, Marcela / Mariano, Rodrigo Coutinho /
    Binotto, Monique / Carvalho, Monique Maciel / Oliveira, Veronica Patrícia da Costa / Gomes, Rafaela / Rebelatto, Taiane F / Schutz, Fabio A / Smaletz, Oren / Fay, Andre P

    Clinical genitourinary cancer

    2022  Volume 21, Issue 3, Page(s) e104–e113

    Abstract: Introduction: Germ-cell tumors (GCTs) are the most common malignancy in young men. There is a paucity of data on GCTs in developing countries. LACOG 0515 study aimed to evaluate clinical characteristics and treatment outcomes in patients with GCTs from ... ...

    Abstract Introduction: Germ-cell tumors (GCTs) are the most common malignancy in young men. There is a paucity of data on GCTs in developing countries. LACOG 0515 study aimed to evaluate clinical characteristics and treatment outcomes in patients with GCTs from Brazilian cancer centers.
    Materials and methods: This is a retrospective cohort study evaluating male patients diagnosed with GCTs from 2000 to 2018 in 13 Brazilian hospitals. We described baseline characteristics, progression-free survival (PFS), and overall survival (OS).
    Results: A total of 1232 patients were included, with a median age of 30 years. Histology was seminoma in 47.1% and non-seminoma GCT (NSGCT) in 52.9%. The primary tumor site was testis in 96.5%. At diagnosis, clinical stage I was present in 68.1% and 34.7% and clinical stages IS/II/III in 31.9% and 65.2% of patients with seminoma and NSCGT, respectively. Following orchiectomy, 55.2% of patients with clinical stage I were managed with surveillance. The 5-year disease-free survival rates among patients with stage I were 98.0% in seminoma and 92.3% in NSGCT, with 5-year OS of 99.6% and 97.6%, respectively. Among patients with advanced disease (IS, II, and III), the 5-year PFS were 88.7% in seminoma and 68.7% in NSGCT, with 5y-OS of 97.6% and 82.8%, respectively.
    Conclusion: This is the largest Brazilian cohort of GCTs. Our results show a high rate of adjuvant chemotherapy in patients with clinical stage I. Although our data demonstrate slightly inferior PFS compared with the International Germ Cell Cancer Collaborative Group and other contemporary series, the OS rates were similar.
    MeSH term(s) Humans ; Male ; Adult ; Retrospective Studies ; Latin America/epidemiology ; Testicular Neoplasms/drug therapy ; Testicular Neoplasms/diagnosis ; Neoplasms, Germ Cell and Embryonal/drug therapy ; Seminoma/drug therapy ; Registries
    Language English
    Publishing date 2022-11-12
    Publishing country United States
    Document type Multicenter Study ; Journal Article
    ZDB-ID 2225121-2
    ISSN 1938-0682 ; 1558-7673
    ISSN (online) 1938-0682
    ISSN 1558-7673
    DOI 10.1016/j.clgc.2022.11.004
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