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1.
Ann Palliat Med ; 10(8): 9122-9135, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34488398

RESUMO

BACKGROUND: Primary fallopian tube carcinoma (PFTC) is a rare malignancy. In recent years the incidence of PFTC has been rising. This study retrospectively analyzed 46 cases of PFTC to identify prognostic factors that may impact the survival of patients with PFTC and explored the clinical characteristics. METHODS: The clinical data of patients who had undergone surgery and adjuvant chemotherapy in Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University from 1995 to 2015 were retrospectively analyzed. We analyzed clinical data. Cox proportional hazards model was used for univariate and multivariate survival analysis. RESULTS: The level of CA125 increased in almost all patients with advanced-stage (stage III-IV) carcinoma and about half the patients with early stage (stage I-II) carcinoma. On ultrasound examination, 41 cases had pelvic mass, and five cases had intrauterine space-occupying lesion. Nine patients underwent curettage (19.6%). By the International Federation of Gynecology and Obstetricians (FIGO) staging system, the distribution of patients was 18 at stage I, 16 at stage II, 10 at stage III, and 2 at stage IV. The mainstay of treatment was surgical cytoreduction and platinum-based chemotherapy. Four patients had residual tumors diameter ≤1 cm (R1), 10 had residual tumors diameter >1 cm, and 32 had no macroscopic residual tumor (R0). Forty patients received postoperative intravenous (IV) chemotherapy. The five-year overall survival (OS) was 94.7% in stage I, 80.0% in stage II, 44.4% in stage III, and 0% in stage IV. Univariate and multivariate analysis revealed that residual tumor was independent prognostic variable for OS. Univariate and multivariate analysis revealed that ascites tumor cells and residual tumor were independent prognostic variables for progression free survival (PFS). CONCLUSIONS: Any postmenopausal women with vaginal bleeding, vaginal discharge, or lower abdominal pain should be alert to PFTC. Complete tumor markers and imaging examination should be conducted as soon as possible to improve the early diagnosis rate of the disease. Regardless of whether the operation is a comprehensive staging operation or cytoreductive surgery (CRS), achieving satisfactory R0 can improve OS and PFS. It is important the ascitic fluid is tested for tumor markers in order to predict PFS.


Assuntos
Carcinoma , Tubas Uterinas , Carcinoma/patologia , China , Tubas Uterinas/patologia , Feminino , Seguimentos , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
2.
Int J Mol Sci ; 22(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34445547

RESUMO

Gangliosides serve as antitumor therapy targets and aberrations in their composition strongly correlate with tumor growth and invasiveness. Anaplastic ganglioglioma is a rare, poorly characterized, malignant neuronal-glial tumor type. We present the first comparative characterization of ganglioside composition in anaplastic ganglioglioma vs. peritumoral and healthy brain tissues by combining mass spectrometry and thin-layer chromatography. Anaplastic ganglioglioma ganglioside composition was highly distinguishable from both peritumoral and healthy tissue despite having five to six times lower total content. Ten out of twelve MS-identified ganglioside classes, defined by unique glycan residues, were represented by a large number and considerable abundance of individual species with different fatty acid residues (C16-C24) in ceramide portions. The major structurally identified class was tumor-associated GD3 (>50%) with 11 species; GD3 (d18:1/24:0) being the most abundant. The dominant sphingoid base residue in ganglioside ceramides was sphingosine (d18:1), followed by eicosasphingosine (d20:1). The peritumoral tissue ganglioside composition was estimated as normal. Specific ganglioside composition and large variability of ganglioside ceramide structures determined in anaplastic ganglioglioma demonstrate realistic ganglioside expression patterns and correspond to the profile of high-grade malignancy brain tumors.


Assuntos
Neoplasias Encefálicas/patologia , Encéfalo/patologia , Carcinoma/patologia , Cromatografia em Camada Delgada/métodos , Ganglioglioma/patologia , Gangliosídeos/metabolismo , Espectrometria de Massas/métodos , Idoso , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Carcinoma/metabolismo , Feminino , Ganglioglioma/metabolismo , Gangliosídeos/análise , Humanos , Pessoa de Meia-Idade
3.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361031

RESUMO

Human leukocyte antigen-G (HLA-G) conveys immunological tolerance at the maternal-foetal interface. HLA-G expression by tumour cells may also play such a role, resulting in tumour immune evasion, making HLA-G a potential target for immunotherapies. The aim of this review was to determine to what extent it is justified that HLA-G expression is considered as a target for immune checkpoint inhibiting therapy by critically assessing the association between HLA-G expression by carcinomas and clinical outcome of patients. The used HLA-G-detecting mAb, HLA-G quantification methods and statistically significant HLA-G-associated clinicopathological parameters are discussed. Tumour HLA-G expression correlated with poor clinical outcome in breast, esophageal, gastric and hepatocellular carcinoma patients. Tumour HLA-G expression was not associated with clinical outcome in ovarian and oral carcinoma patients. Cervical, colorectal, lung, and pancreatic carcinoma patients presented discrepant and therefore inconclusive results regarding the association between tumour HLA-G expression and clinical outcome. These disparities might partly be the result of differences in the methodological approach to quantify HLA-G expression between studies. Therefore, implementation of universal methodological procedures is strongly advised. Overall, HLA-G expression did not univocally result in poor clinical outcome of carcinoma patients. This implies that tumour HLA-G expression is not necessarily part of an inhibited tumour-immune response and tumour progression. Consequently, it remains elusive whether HLA-G expression by carcinomas functions as an immune checkpoint molecule affecting a tumour-immune response. It may also reflect derailed control of gene expression in tumours, with no real functional consequences.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Carcinoma/genética , Neoplasias do Sistema Digestório/genética , Antígenos HLA-G/genética , Neoplasias Pulmonares/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma/metabolismo , Carcinoma/patologia , Neoplasias do Sistema Digestório/metabolismo , Neoplasias do Sistema Digestório/patologia , Antígenos HLA-G/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia
4.
Tuberk Toraks ; 69(2): 247-252, 2021 Jun.
Artigo em Turco | MEDLINE | ID: mdl-34256516

RESUMO

The lung is the most common site of metastasis for many malignancies. Especially the gastrointestinal system, gynecological malignancies and osteosarcomas frequently metastasize to the lung. It accounts for less than 0.5% of all ovarian neoplasms. The frequency of recurrence and metastasis is less than 5%. In most cases, they are stage I tumors, limited to the ovary and carry a good prognosis. Here, while investigating the nodules in the lung that were detected incidentally at the age of 64, the rare Sertoli-Leydig cell tumor of the lung is discussed clinically, radiologically and pathologically in the presence of a 64-year-old patient who was found to have undergone ovarian surgery 9 years ago. Since imaging methods and tumor markers did not yield significant results in terms of primary malignancy, wedge resection was performed from the left lung nodules. The histology of the lung nodule was the same as the poorly differentiated foci of the ovarian tumor. The immunohistochemical profiles of the two tumors were also similar. As a result of the evaluation of the patient's old materials belonging to the ovary and the samples taken from the lung together; The diagnosis was reached by obtaining similar results with the primary tumor in the immunohistochemical examination performed for the metastatic focus. Sex cord stromal tumors of the ovary, which rarely cause lung metastasis and have a tendency to recur and metastasis in a very long time after the first diagnosis, should also be kept in mind in the elderly woman and the patient with a gynecological history.


Assuntos
Carcinoma/patologia , Neoplasias Pulmonares/secundário , Neoplasias Ovarianas/patologia , Tumor de Células de Sertoli-Leydig/patologia , Feminino , Humanos , Pessoa de Meia-Idade
5.
Am J Surg Pathol ; 45(7): 969-978, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34105518

RESUMO

The 2019 World Health Organization (WHO) classification of colorectal carcinoma (CRC) profoundly reclassified CRC subtypes and introduces tumor budding as a second major grading criterion, while condensing conventional grade into a 2-tiered system. So far it remains largely unexplored how these parameters interact with each other and whether they truly have an independent impact on patient prognosis. We reclassified a large single-center cohort of 1004 CRCs spanning 2 decades for adjusted WHO grade (low vs. high), tumor budding (Bd1/Bd2/Bd3), and CRC subtype (adenocarcinoma not otherwise specified, micropapillary, mucinous, serrated, medullary, adenoma-like, signet-ring cell, mixed adenoneuroendocrine carcinoma/neuroendocrine carcinoma, undifferentiated) according to the criteria of the 2019 WHO classification. We investigated the interaction of these parameters, their connection to stage/microsatellite status, and their significance for patient survival in the different subgroups. Specific subtypes other than adenocarcinoma not otherwise specified represented one third of all CRCs and were unevenly distributed throughout stage and microsatellite subgroups. Subtypes, WHO grade and tumor budding profoundly impacted all survival parameters (P<0.001 for all analyses), with CRC subtypes and tumor budding-but not WHO grade-being stage-independent prognosticators for all survival comparisons. WHO grade had very limited prognostic value in CRC subtypes, while tumor budding retained its strong prognostic impact in most scenarios. Accurate delineation of CRC subtypes introduced in the 2019 WHO classification provides strong stage-independent prognostic information, arguing that they should be considered in pathology reports and in clinical trials. Of the morphology-based grading schemes included in the 2019 WHO, tumor budding outperforms WHO grade.


Assuntos
Carcinoma/patologia , Movimento Celular , Neoplasias Colorretais/patologia , Idoso , Biópsia , Carcinoma/classificação , Carcinoma/mortalidade , Carcinoma/cirurgia , Colectomia , Neoplasias Colorretais/classificação , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Instabilidade de Microssatélites , Gradação de Tumores , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Organização Mundial da Saúde
7.
Virus Genes ; 57(4): 358-368, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34146250

RESUMO

The eukaryotic translation initiation factor 4E (eIF4E) is a component of the eukaryotic translation initiation factor 4F, a significant complex in the protein translation process. It has been found to be closely related to many human tumors, such as gastric carcinoma. It is known that the Epstein-Barr virus (EBV) upregulates eIF4E in various ways in nasopharyngeal carcinoma. However, there are very few studies on eIF4E in EBV-associated gastric carcinoma. We found that the expression level of eIF4E in EBV-associated gastric carcinoma was lower than other types of gastric carcinoma, and the downregulation of eIF4E could lead to increased apoptosis of gastric carcinoma cells, retardation at S phase, and decreased cell migration. The dual luciferase reporter experiment showed that EBV-miR-BART11-3p could directly target the 3'-UTR region of eIF4E, and BART11-3p is the key factor leading to the downregulation of eIF4E. It could provide a new evidence for EBV-regulating host gene to affect the development of gastric carcinoma.


Assuntos
Carcinoma/genética , Fator de Iniciação 4E em Eucariotos/genética , MicroRNAs/genética , Neoplasias Gástricas/genética , Apoptose/genética , Carcinoma/patologia , Carcinoma/virologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Regulação Neoplásica da Expressão Gênica/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/patogenicidade , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/virologia
8.
J Cancer Res Clin Oncol ; 147(8): 2199-2207, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34115239

RESUMO

Colorectal cancer is an important public health concern leading to significant cancer associate mortality. A vast majority of colon cancer arises from polyp which later follows adenoma, adenocarcinoma, and carcinoma sequence. This whole process takes several years to complete and recent genomic and proteomic technologies are identifying several targets involved in each step of polyp to carcinoma transformation in a large number of studies. Current text presents interaction network of targets involved in polyp to carcinoma transformation. In addition, important targets involved in each step according to network biological parameters are also presented. The functional overrepresentation analysis of each step targets and common top biological processes and pathways involved in carcinoma indicate several insights about this whole mechanism. Interaction networks indicate TP53, AKT1, GAPDH, INS, EGFR, and ALB as the most important targets commonly involved in polyp to carcinoma sequence. Though several important pathways are known to be involved in CRC, the central common involvement of PI3K-AKT indicates its potential for devising CRC management strategies. The common and central targets and pathways involved in polyp to carcinoma progression can shed light on its mechanism and potential management strategies. The data-driven approach aims to add valuable inputs to the mechanism of the years-long polyp-carcinoma sequence.


Assuntos
Carcinoma/prevenção & controle , Transformação Celular Neoplásica , Neoplasias do Colo/prevenção & controle , Pólipos do Colo/terapia , Terapia de Alvo Molecular/métodos , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/prevenção & controle , Adenoma/genética , Adenoma/metabolismo , Adenoma/patologia , Adenoma/prevenção & controle , Pólipos Adenomatosos/genética , Pólipos Adenomatosos/metabolismo , Pólipos Adenomatosos/patologia , Pólipos Adenomatosos/prevenção & controle , Antineoplásicos/uso terapêutico , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/patologia , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Pólipos do Colo/genética , Pólipos do Colo/metabolismo , Pólipos do Colo/patologia , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Redes Reguladoras de Genes/fisiologia , Genes de Troca/efeitos dos fármacos , Humanos , Mapas de Interação de Proteínas/efeitos dos fármacos , Mapas de Interação de Proteínas/genética , Proteômica , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
9.
Molecules ; 26(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068314

RESUMO

The Myrteacae family is known as a rich source of phloroglucinols, a group of secondary metabolites with notable biological activities. Leaves of Psidium cattleianum were extracted with chloroform: methanol 8:2 to target the isolation of phloroglucinol derivatives. Isolated compounds were characterized using different spectroscopic methods: nuclear magnetic resonance (NMR), ultra-violet (UV) and mass spectrometry (MS). Two new phloroglucinols were evaluated for cytotoxicity against a panel of six human cancer cell lines, namely colorectal adenocarcinoma cells (HT-29 and HCT-116); hepatocellular carcinoma cells (HepG-2); laryngeal carcinoma (Hep-2); breast adenocarcinoma cells (MCF7 and MDA-MB231), in addition to normal human melanocytes HFB-4. Additionally, cell cycle analysis and annexin-V/FITC-staining were used to gain insights into the mechanism of action of the isolated compounds. The new phloroglucinol meroterpenoids, designated cattleianal and cattleianone, showed selective antiproliferative action against HT-29 cells with IC50's of 35.2 and 32.1 µM, respectively. Results obtained using cell cycle analysis and annexin-V/FITC-staining implicated both necrosis and apoptosis pathways in the selective cytotoxicity of cattleianal and cattleianone. Our findings suggest that both compounds are selective antiproliferative agents and support further mechanistic studies for phloroglucinol meroterpenoids as scaffolds for developing new selective chemotherapeutic agents.


Assuntos
Carcinoma/patologia , Folhas de Planta/química , Psidium/química , Terpenos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Necrose , Terpenos/isolamento & purificação
10.
Lancet Oncol ; 22(6): 872-882, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33991512

RESUMO

BACKGROUND: Locally advanced or metastatic urothelial carcinoma is generally incurable and has scarce treatment options, especially for cisplatin-ineligible patients previously treated with PD-1 or PD-L1 therapy. Enfortumab vedotin is an antibody-drug conjugate directed at Nectin-4, a protein highly expressed in urothelial carcinoma. We aimed to evaluate the efficacy and safety of enfortumab vedotin in the post-immunotherapy setting in cisplatin-ineligible patients. METHODS: EV-201 is a multicentre, single-arm, phase 2 study of enfortumab vedotin in patients with locally advanced or metastatic urothelial carcinoma previously treated with PD-1 or PD-L1 inhibitors. Cohort 2 included adults (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status score of 2 or less who were considered ineligible for cisplatin at enrolment and who had not received platinum-containing chemotherapy in the locally advanced or metastatic setting. Enfortumab vedotin was given intravenously at a dose of 1·25 mg/kg on days 1, 8, and 15 of every 28-day cycle. The primary endpoint was confirmed objective response rate per Response Evaluation Criteria in Solid Tumours version 1.1 assessed by blinded independent central review. Efficacy and safety were analysed in all patients who received at least one dose of enfortumab vedotin. EV-201 is an ongoing study and the primary analysis is complete. This study is registered with Clinicaltrials.gov, NCT03219333. FINDINGS: Between Oct 8, 2017, and Feb 11, 2020, 91 patients were enrolled at 40 sites globally, of whom 89 received treatment. Median follow-up was 13·4 months (IQR 11·3-18·9). At data cutoff (Sept 8, 2020), the confirmed objective response rate was 52% (46 of 89 patients; 95% CI 41-62), with 18 (20%) of 89 patients achieving a complete response and 28 (31%) achieving a partial response. 49 (55%) of 89 patients had grade 3 or worse treatment-related adverse events. The most common grade 3 or 4 treatment-related adverse events were neutropenia (eight [9%] patients), maculopapular rash (seven [8%] patients), and fatigue (six [7%] patients). Treatment-related serious adverse events occurred in 15 (17%) patients. Three (3%) patients died due to acute kidney injury, metabolic acidosis, and multiple organ dysfunction syndrome (one [1%] each) within 30 days of first dose and these deaths were considered by the investigator to be related to treatment; a fourth death from pneumonitis occurred more than 30 days after the last dose and was also considered to be related to treatment. INTERPRETATION: Treatment with enfortumab vedotin was tolerable and confirmed responses were seen in 52% of cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma who were previously treated with PD-1 or PD-L1 inhibitors. These patients have few treatment options, and enfortumab vedotin could be a promising new therapy for a patient population with a high unmet need. FUNDING: Astellas Pharma Global Development and Seagen.


Assuntos
Antígeno B7-H1/genética , Carcinoma/tratamento farmacológico , Moléculas de Adesão Celular/genética , Receptor de Morte Celular Programada 1/genética , Neoplasias Urológicas/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Carcinoma/genética , Carcinoma/patologia , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Critérios de Avaliação de Resposta em Tumores Sólidos , Neoplasias Urológicas/genética , Neoplasias Urológicas/patologia , Urotélio/efeitos dos fármacos , Urotélio/patologia
11.
Lancet Oncol ; 22(7): 931-945, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34051178

RESUMO

BACKGROUND: PD-1 and PD-L1 inhibitors are active in metastatic urothelial carcinoma, but positive randomised data supporting their use as a first-line treatment are lacking. In this study we assessed outcomes with first-line pembrolizumab alone or combined with chemotherapy versus chemotherapy for patients with previously untreated advanced urothelial carcinoma. METHODS: KEYNOTE-361 is a randomised, open-label, phase 3 trial of patients aged at least 18 years, with untreated, locally advanced, unresectable, or metastatic urothelial carcinoma, with an Eastern Cooperative Oncology Group performance status of up to 2. Eligible patients were enrolled from 201 medical centres in 21 countries and randomly allocated (1:1:1) via an interactive voice-web response system to intravenous pembrolizumab 200 mg every 3 weeks for a maximum of 35 cycles plus intravenous chemotherapy (gemcitabine [1000 mg/m2] on days 1 and 8 and investigator's choice of cisplatin [70 mg/m2] or carboplatin [area under the curve 5] on day 1 of every 3-week cycle) for a maximum of six cycles, pembrolizumab alone, or chemotherapy alone, stratified by choice of platinum therapy and PD-L1 combined positive score (CPS). Neither patients nor investigators were masked to the treatment assignment or CPS. At protocol-specified final analysis, sequential hypothesis testing began with superiority of pembrolizumab plus chemotherapy versus chemotherapy alone in the total population (all patients randomly allocated to a treatment) for the dual primary endpoints of progression-free survival (p value boundary 0·0019), assessed by masked, independent central review, and overall survival (p value boundary 0·0142), followed by non-inferiority and superiority of overall survival for pembrolizumab versus chemotherapy in the patient population with CPS of at least 10 and in the total population (also a primary endpoint). Safety was assessed in the as-treated population (all patients who received at least one dose of study treatment). This study is completed and is no longer enrolling patients, and is registered at ClinicalTrials.gov, number NCT02853305. FINDINGS: Between Oct 19, 2016 and June 29, 2018, 1010 patients were enrolled and allocated to receive pembrolizumab plus chemotherapy (n=351), pembrolizumab monotherapy (n=307), or chemotherapy alone (n=352). Median follow-up was 31·7 months (IQR 27·7-36·0). Pembrolizumab plus chemotherapy versus chemotherapy did not significantly improve progression-free survival, with a median progression-free survival of 8·3 months (95% CI 7·5-8·5) in the pembrolizumab plus chemotherapy group versus 7·1 months (6·4-7·9) in the chemotherapy group (hazard ratio [HR] 0·78, 95% CI 0·65-0·93; p=0·0033), or overall survival, with a median overall survival of 17·0 months (14·5-19·5) in the pembrolizumab plus chemotherapy group versus 14·3 months (12·3-16·7) in the chemotherapy group (0·86, 0·72-1·02; p=0·0407). No further formal statistical hypothesis testing was done. In analyses of overall survival with pembrolizumab versus chemotherapy (now exploratory based on hierarchical statistical testing), overall survival was similar between these treatment groups, both in the total population (15·6 months [95% CI 12·1-17·9] with pembrolizumab vs 14·3 months [12·3-16·7] with chemotherapy; HR 0·92, 95% CI 0·77-1·11) and the population with CPS of at least 10 (16·1 months [13·6-19·9] with pembrolizumab vs 15·2 months [11·6-23·3] with chemotherapy; 1·01, 0·77-1·32). The most common grade 3 or 4 adverse event attributed to study treatment was anaemia with pembrolizumab plus chemotherapy (104 [30%] of 349 patients) or chemotherapy alone (112 [33%] of 342 patients), and diarrhoea, fatigue, and hyponatraemia (each affecting four [1%] of 302 patients) with pembrolizumab alone. Six (1%) of 1010 patients died due to an adverse event attributed to study treatment; two patients in each treatment group. One each occurred due to cardiac arrest and device-related sepsis in the pembrolizumab plus chemotherapy group, one each due to cardiac failure and malignant neoplasm progression in the pembrolizumab group, and one each due to myocardial infarction and ischaemic colitis in the chemotherapy group. INTERPRETATION: The addition of pembrolizumab to first-line platinum-based chemotherapy did not significantly improve efficacy and should not be widely adopted for treatment of advanced urothelial carcinoma. FUNDING: Merck Sharp and Dohme, a subsidiary of Merck, Kenilworth, NJ, USA.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Urotélio/efeitos dos fármacos , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/uso terapêutico , Carcinoma/imunologia , Carcinoma/mortalidade , Carcinoma/patologia , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Progressão da Doença , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Fatores de Tempo , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Urotélio/imunologia , Urotélio/patologia
12.
Adv Anat Pathol ; 28(4): 228-250, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34009777

RESUMO

Renal neoplasms largely favor male patients; however, there is a growing list of tumors that are more frequently diagnosed in females. These tumors include metanephric adenoma, mixed epithelial and stromal tumor, juxtaglomerular cell tumor, mucinous tubular and spindle cell carcinoma, Xp11.2 (TFE3) translocation-associated renal cell carcinoma, and tuberous sclerosis complex (somatic or germline) associated renal neoplasms. The latter category is a heterogenous group with entities still being delineated. Eosinophilic solid and cystic renal cell carcinoma is the best-described entity, whereas, eosinophilic vacuolated tumor is a proposed entity, and the remaining tumors are currently grouped together under the umbrella of tuberous sclerosis complex/mammalian target of rapamycin-related renal neoplasms. The entities described in this review are often diagnostic considerations when evaluating renal mass tissue on biopsy or resection. For example, Xp11.2 translocation renal cell carcinoma is in the differential when a tumor has clear cell cytology and papillary architecture and occurs in a young or middle-aged patient. In contrast, tuberous sclerosis complex-related neoplasms often enter the differential for tumors with eosinophilic cytology. This review provides an overview of the clinical, gross, microscopic, immunohistochemical, genetic, and molecular alterations in key renal neoplasms occurring more commonly in females; differential diagnoses are also discussed regardless of sex predilection.


Assuntos
Adenoma/patologia , Carcinoma/patologia , Neoplasias Renais/patologia , Biomarcadores Tumorais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Fatores Sexuais
13.
Clin Immunol ; 227: 108753, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33945871

RESUMO

Neutrophils are conspicuous components of gastric cancer (GC) tumors, increasing with tumor progression and poor patient survival. However, the phenotype, regulation and clinical relevance of neutrophils in human GC are presently unknown. Most intratumoral neutrophils showed an activated CD54+ phenotype and expressed high level B7-H3. Tumor tissue culture supernatants from GC patients induced the expression of CD54 and B7-H3 on neutrophils in time-dependent and dose-dependent manners. Locally enriched CD54+ neutrophils and B7-H3+ neutrophils positively correlated with increased granulocyte-macrophage colony stimulating factor (GM-CSF) detection ex vivo; and in vitro GM-CSF induced the expression of CD54 and B7-H3 on neutrophils in both time-dependent and dose-dependent manners. Furthermore, GC tumor-derived GM-CSF activated neutrophils and induced neutrophil B7-H3 expression via JAK-STAT3 signaling pathway activation. Finally, intratumoral B7-H3+ neutrophils increased with tumor progression and independently predicted reduced overall survival. Collectively, these results suggest B7-H3+ neutrophils to be potential biomarkers in GC.


Assuntos
Antígenos B7/metabolismo , Carcinoma/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Ativação de Neutrófilo , Neutrófilos/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Carcinoma/patologia , Progressão da Doença , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Técnicas In Vitro , Molécula 1 de Adesão Intercelular/metabolismo , Janus Quinases/efeitos dos fármacos , Janus Quinases/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Prognóstico , Fator de Transcrição STAT3/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Adulto Jovem
14.
BMC Cancer ; 21(1): 499, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947352

RESUMO

BACKGROUND: Genetic alterations for epithelial ovarian cancer are insufficiently characterized. Previous studies are limited regarding included histologies, gene numbers, copy number variant (CNV) detection, and interpretation of pathway alteration patterns of individual patients. METHODS: We sequenced 410 genes to analyze mutations and CNV of 82 ovarian carcinomas, including high-grade serous (n = 37), endometrioid (n = 22) and clear cell (n = 23) histologies. Eligibility for targeted therapy was determined for each patient by a pathway-based approach. The analysis covered DNA repair, receptor tyrosine kinase, PI3K/AKT/MTOR, RAS/MAPK, cell cycle, and hedgehog pathways, and included 14 drug targets. RESULTS: Postulated PARP, MTOR, and CDK4/6 inhibition sensitivity were most common. BRCA1/2 alterations, PTEN loss, and gain of PIK3CA and CCND1 were characteristic for high-grade serous carcinomas. Mutations of ARID1A, PIK3CA, and KRAS, and ERBB2 gain were enriched in the other histologies. PTEN mutations and high tumor mutational burden were characteristic for endometrioid carcinomas. Drug target downstream alterations impaired actionability in all histologies, and many alterations would not have been discovered by key gene mutational analysis. Individual patients often had more than one actionable drug target. CONCLUSIONS: Genetic alterations in ovarian carcinomas are complex and differ among histologies. Our results aid the personalization of therapy and biomarker analysis for clinical studies, and indicate a high potential for combinations of targeted therapies.


Assuntos
Carcinoma Epitelial do Ovário/genética , Carcinoma/genética , Mutação , Neoplasias Ovarianas/genética , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/terapia , Carcinoma/patologia , Carcinoma/terapia , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/terapia , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/terapia , Ciclo Celular/genética , Variações do Número de Cópias de DNA , Análise Mutacional de DNA/métodos , Reparo do DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas Hedgehog/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Medicina de Precisão , Estudos Retrospectivos
15.
BMC Cancer ; 21(1): 484, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933005

RESUMO

BACKGROUND: The assessment of retroperitoneal lymph node status in patients with locally advanced cervical cancer is still a problem. This study aimed to explore the choice of these assessment methods. METHODS: Laparoscopic retroperitoneal lymphadenectomy was performed in 96 patients with advanced cervical cancer. The positive rates of lymph node metastasis were analyzed. The values of computed tomography lymph node minimum axial diameter (MAD) and squamous cell carcinoma antigen (SCC-Ag), and their combination in predicting retroperitoneal lymph node metastasis were compared. High-risk factors for common iliac lymph node (CILN) and/or para-aortic lymph node (PALN) metastasis were analyzed. RESULTS: The lymph node metastasis rate was 62.50% and the CILN and/or PALN metastasis rate was 31.25%. Overall, 96 patients had 172 visible lymph nodes. The positive rate of lymph node metastasis was significantly higher in the MAD ≥1.0 cm group (83.33%) than in the 0.5 cm ≤ MAD < 1.0 cm group (26.82%). The critical values of MAD and SCC-Ag in determining lymph node metastasis were 1.0 cm and 5.2 ng/mL, respectively. The accuracy, specificity, and Youden index of MAD ≥1.0 cm combined with SCC-Ag ≥ 5.2 ng/mL for evaluating lymph node metastasis were 75.71%, 100%, and 0.59, respectively, and were significantly different from the values for the MAD ≥1.0 cm (72.09%, 80.56%, and 0.47, respectively) and SCC-Ag ≥ 5.2 ng/mL (71.43%, 68.97%, and 0.42, respectively) groups. Correlation analysis showed that non-squamous cell carcinoma, pelvic lymph node (PLN) MAD ≥1.0 cm plus number ≥ 2, and 1 PLN MAD ≥1.0 cm with CILN and/or PALN MAD 0.5-1.0 cm were risk factors for CILN and/or PALN metastasis. CONCLUSION: Patients with MAD ≥1.0 cm and SCC-Ag ≥ 5.2 ng/mL, as well as high risk factors for CILN and/or PALN metastasis, should undergo resection of enlarged lymph nodes below the common iliac gland and lymphadenectomy of CILN/PALN to reduce tumor burden and to clarify lymph node metastasis status for accurate guidance in follow-up treatment. Patients with MAD < 1.0 cm and SCC-Ag < 5.2 ng/mL may be treated with chemoradiotherapy directly based on imaging, given the low lymph node metastasis rate.


Assuntos
Linfonodos/patologia , Metástase Linfática/patologia , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Antígenos de Neoplasias/sangue , Área Sob a Curva , Carcinoma/sangue , Carcinoma/diagnóstico por imagem , Carcinoma/patologia , Carcinoma/terapia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Feminino , Humanos , Laparoscopia , Excisão de Linfonodo/métodos , Linfonodos/diagnóstico por imagem , Linfonodos/imunologia , Pessoa de Meia-Idade , Radioterapia de Intensidade Modulada , Espaço Retroperitoneal , Fatores de Risco , Sensibilidade e Especificidade , Serpinas/sangue , Tomografia Computadorizada Espiral , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/terapia , Adulto Jovem
16.
Pan Afr Med J ; 38: 180, 2021.
Artigo em Francês | MEDLINE | ID: mdl-33995786

RESUMO

The purpose of this study was to describe the clinical, radiological, histological and therapeutic features of breast cancer diagnosed during pregnancy. We performed a review of all medical records of patients with breast cancer diagnosed during pregnancy in the Maternity and Neonatal Center, Monastir-Tunisia, over the period 2004-2019. We collected data on 15 cases. The average age of patients was 34 years; most pregnancy-associated breast cancers (PABCs) had been diagnosed during the postpartum period. Invasive ductal carcinoma was the major histological type (93% of cases), a rare case of secretory breast carcinoma had been observed. The main clinical stages were T2 and T4 breast cancer. Hormone receptor (HR)-negative breast cancers had been reported in 40% of cases, HER2-positive breast cancers in 26.6% of cases. Treatment included surgery, radiotherapy, chemotherapy and palliative chemotherapy. The median overall survival was 32.2 months. Pregnancy-associated breast cancer is a rare entity. Patients' prognosis is generally poor due to the young age at onset and a usually delayed diagnosis. Patients should participate in therapeutic decision making, which is difficult and multidisciplinary. Targeted therapy is the great hope for new therapies.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Complicações Neoplásicas na Gravidez/patologia , Adulto , Fatores Etários , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Carcinoma/diagnóstico , Carcinoma/patologia , Carcinoma/terapia , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/terapia , Feminino , Humanos , Estadiamento de Neoplasias , Período Pós-Parto , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Tunísia
17.
Anticancer Res ; 41(5): 2501-2509, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952478

RESUMO

BACKGROUND/AIM: Pulmonary pleomorphic carcinoma (PPC) is a rare and aggressive tumor that is resistant to treatment. The expression and prognostic value of programmed cell death-ligand 1 (PD-L1) and its association with epithelial-mesenchymal transition (EMT) in PPC remains unclear. PATIENTS AND METHODS: The expression of PD-L1 and EMT markers, such as E-cadherin, vimentin, zinc finger E-box-binding homeobox 1 (ZEB-1), and cellular mesenchymal-epithelial transition (c-Met) was evaluated by immuno - histochemistry in 16 patients with PPC who underwent surgical resection. RESULTS: The expression of PD-L1 varied between carcinomatous and sarcomatous areas. Positive correlations between PD-L1 and vimentin expression in carcinomatous areas (r=0.668, p=0.005) and PD-L1 and ZEB-1 expression in sarcomatous areas (r=0.562, p=0.023) were found. High PD-L1 and ZEB-1 expression in sarcomatous areas predicted poor survival (p=0.045 and p=0.012, respectively). CONCLUSION: PD-L1 expression associated with ZEB1 expression in the sarcomatoid component of patients with PPC may be useful for predicting patient prognosis.


Assuntos
Antígeno B7-H1/genética , Carcinoma/genética , Neoplasias Pulmonares/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Carcinoma/patologia , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Pulmonares/patologia , Análise de Sobrevida
18.
Anticancer Res ; 41(5): 2719-2726, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952503

RESUMO

BACKGROUND/AIM: We present a case of uterine dedifferentiated mesonephric-like adenocarcinoma (MLA). CASE REPORT: A 54-year-old woman underwent total hysterectomy for a uterine mass under the impression of a uterine sarcoma. Histologically, MLA exhibited various growth patterns including tubular and glandular architecture. Undifferentiated carcinoma (UC) displayed discohesive tumor cells without any obvious architecture. Immunohistochemically, UC was positive for epithelial markers in very few scattered tumor cells. MLA exhibited the wild-type p53 expression pattern, whereas UC showed a uniform and strong p53 immunoreactivity. Targeted sequencing analysis revealed an identical Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in both components. A pathogenic missense tumor protein 53 (TP53) mutation was detected in UC, but not in MLA. CONCLUSION: The mutant p53 expression pattern exclusively detected in UC was concordant with the presence of missense TP53 mutation. Our observations suggested that TP53 mutation is associated with the possible transformation from MLA to UC.


Assuntos
Adenocarcinoma/diagnóstico , Carcinoma/diagnóstico , Sarcoma/diagnóstico , Doenças Uterinas/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Carcinoma/genética , Carcinoma/patologia , Carcinoma/cirurgia , Desdiferenciação Celular/genética , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Sarcoma/genética , Sarcoma/patologia , Sarcoma/cirurgia , Doenças Uterinas/patologia , Doenças Uterinas/cirurgia , Ductos Mesonéfricos/diagnóstico por imagem , Ductos Mesonéfricos/patologia , Ductos Mesonéfricos/cirurgia
19.
J Cardiothorac Surg ; 16(1): 128, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980268

RESUMO

BACKGROUND: The aim of this study was to assess the ability of using mean computed tomography (mCT) values to predict non-small cell lung cancer (NSCLC) tumor recurrence. METHODS: A retrospective study was conducted on 494 patients with stage IA NSCLC. Receiver operating characteristics analysis was used to assess the ability to use mCT value, C/T ratio, tumor size, and SUV to predict tumor recurrence. Multiple logistic regression analyses were performed to determine the independent variables for the prediction of tumor recurrence. RESULTS: The m-CT values were - 213.7 ± 10.2 Hounsfield Units (HU) for the recurrence group and - 594.1 ± 11.6 HU for the non-recurrence group (p < 0.0001). Recurrence occurred in 45 patients (9.1%). The tumor recurrence group was strongly associated with a high CT attenuation value, high C/T ratio, large solid tumor size, and SUV. The diagnostic value of mCT value was more accurate than the C/T ratio, excluding the pure ground-glass opacity and pure solid (0 < C/T ratio < 100) groups. The SUV and mCT are independent predictive factors of tumor recurrence. CONCLUSIONS: The evaluation of mCT values was useful for predicting recurrence after the limited resection of small-sized NSCLC, and may potentially contribute to the selection of suitable treatment strategies.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Pneumonectomia , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Carcinoma/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Seguimentos , Humanos , Modelos Logísticos , Pulmão/patologia , Pulmão/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento
20.
Cancer Med ; 10(10): 3188-3196, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33931987

RESUMO

BACKGROUND: The benefits of pembrolizumab in patients with advanced urothelial carcinoma (UC) and impaired performance status (PS) remain unknown. This study assessed the safety and efficacy of pembrolizumab in patients with platinum-refractory UC and Eastern Cooperative Oncology Group PS ≥2 to identify which subgroups may benefit from this drug. METHODS: This retrospective nationwide cohort study collected clinicopathological information for 755 patients from 59 institutions. The overall response rate (ORR) and overall survival (OS) were compared among the patients with PS 0-1, 2, and 3-4. Multivariate analysis was conducted to identify factors predicting OS in patients with PS ≥2. RESULTS: The numbers of patients with PS 0-1, 2, and 3-4 were 602, 98, and 55, respectively; the ORRs in these groups were 29.5, 15.3, and 9.1%, respectively, and the median OS times were 14.3, 3.1, and 2.4 months, respectively. In multivariate Cox regression analysis, a neutrophil-lymphocyte ratio (NLR) ≥3.5 (hazard ratio [HR] = 1.897) and liver metastasis (HR = 2.072) were associated with OS in the PS ≥2 subgroup. The median OS of patients with PS ≥2 without either risk factor was 6.8 months, compared with 3.1 months for patients with one risk factor and 2.3 months for patients with both risk factors. CONCLUSIONS: PS ≥2 portended worse ORR and OS than PS ≤1 despite a comparable safety profile. Among the patients with impaired PS, patients with NLR <3.5 and no liver metastasis may most greatly benefit from pembrolizumab therapy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias Urológicas/tratamento farmacológico , Urotélio/efeitos dos fármacos , Idoso , Grupo com Ancestrais do Continente Asiático , Carcinoma/patologia , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Estudos Retrospectivos , Fatores de Risco , Neoplasias Urológicas/patologia , Urotélio/patologia
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