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BACKGROUND: The present meta-analysis was updated with randomized controlled trials (RCTs) to revaluate the efficacy and safety of cetuximab vs. cisplatin combined with radiotherapy in patients of head and neck squamous cell carcinoma (HNSCC). METHODS: A meta-analysis containing RCTs that compared the efficacy or toxicity of cetuximab and cisplatin in HNSCC patients was conducted. RESULTS: Seven RCTs were included in the final analysis. The patients treated by cetuximab plus radiotherapy showed an inferior overall survival (OS) and locoregional control (LRC) compared to cisplatin plus radiotherapy. The tendency of progression-free survival (PFS) was in agreement with OS and LRC. Subgroup analysis showed that cetuximab had poorer OS relative to cisplatin in the absence of induction chemotherapy. The profile of severe adverse events (SAEs) varied between the two groups, no significant difference in total SAEs was shown for the two arms. DISCUSSION: Cetuximab combined with radiotherapy shows significantly reduced therapeutic efficacy compared to cisplatin plus radiotherapy in HNSCC patients.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Cetuximab/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Cisplatino , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
BACKGROUND: Tumor-infiltrating B lymphocytes (TIL-Bs) is a heterogeneous population of lymphocytes. The prognostic value of TIL-Bs in patients with breast cancer remains controversial. Here we conducted this meta-analysis to clarify the association of TIL-Bs with outcomes of patients with breast cancer. METHODS: We searched PubMed, Embase, and Web of Science to identify relevant studies assessing the prognostic significance of TIL-Bs in patients with breast cancer. Fixed- or random-effects models were used to evaluate the pooled hazard ratios (HRs) for overall survival (OS), breast cancer-specific survival (BCSS), disease-free survival (DFS), and relapse-free survival (RFS) in breast cancer. RESULTS: A total of 8 studies including 2628 patients were included in our study. Pooled analyses revealed that high level of TIL-Bs was associated with longer OS (pooled HR = 0.42, 95% CI 0.24-0.60), BCSS (pooled HR = 0.66, 95% CI 0.47-0.85), and DFS/RFS (pooled HR = 0.41, 95% CI 0.27-0.55). CONCLUSIONS: This meta-analysis suggests that TIL-Bs could be a promising prognostic marker for breast cancer. Novel therapeutic strategies for breast cancer treatment could be developed by enhancement of B cell-mediated antitumor immunity.
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Existing evidence has shown that circulating Epstein-Barr virus (EBV)-miR-BART13-3p is highly expressed in plasma of nasopharyngeal carcinoma (NPC) patients, especially among patients with advanced diseases. However, the exact role that EBV-miR-BART13-3p plays in the development of NPC remains poorly understood. Here we show that up-regulated expression of EBV-miR-BART13-3p leads to increased capacity in migration and invasion of NPC cells in vitro and causes tumor metastasis in vivo. Furthermore, we find that EBV-miR-BART13-3p directly targets ABI2, known as a tumor suppressor and a cell migration inhibitor, drives epithelial-mesenchymal transition (EMT) by activating c-JUN/SLUG signaling pathway. Silencing ABI2 shows similar effects to overexpression of EBV-miR-BART13-3p, whereas reconstitution of ABI2 resulted in a phenotypic reversion, highlighting the role of ABI2 in EBV-miR-BART13-3p-driven metastasis in NPC. Besides, expression levels of ABI2 in NPC tissue samples correlate with N stages of NPC patients. Taken together, these results suggest a novel mechanism by which ABI2 downregulation by EBV-miR-BART13-3p promotes EMT and metastasis of NPC via upregulating c-JUN/SLUG signaling pathway.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/genética , MicroRNAs/genética , Carcinoma Nasofaríngeo/etiologia , Carcinoma Nasofaríngeo/metabolismo , RNA Viral , Transdução de Sinais , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Transição Epitelial-Mesenquimal/genética , Infecções por Vírus Epstein-Barr/virologia , Técnicas de Silenciamento de Genes , Humanos , Modelos Biológicos , Carcinoma Nasofaríngeo/patologia , Proteínas Proto-Oncogênicas c-jun/metabolismo , Fatores de Transcrição da Família Snail/metabolismoRESUMO
The authors have retracted this article because of numerous errors in the figures.
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Hypofractionated radiotherapy is a new and highly effective mode of radiation therapy. For this study we used biologically equivalent dose (BED), the dose required to give the same log cell kill as the schedule being studied. BED has been widely accepted to transform its dose to conventionally fractionated ones. However, actual differential effects beyond the clone-forming ability between hypofractionation and conventional radiation treatment remain unknown. We hypothesize that hypofractionation has some advantages over conventional treatment in in vitro radiobiology, excluding influences of the tumor microenvironment in angiogenesis and potential immune-stimulatory effects. For this study, two non-small cell lung cancer (NSCLC) cell lines with different α/ß values were chosen: A549 (α/ß = 12.4) and H460 (α/ß = 2.95). We designed the following two fractionation regimens with equal BED: A549-HRT (10 Gy/1 fraction) and A549-CRT (16 Gy/8 fractions) as well as H460-HRT (10 Gy/1 fraction) and H460-CRT (26 Gy/13 fractions). After irradiation, we performed cell counting, MTT assay, flow cytometry analysis of apoptosis and cell cycle, immunocytofluorescence of γ-H2AX and Hoechst 33258, and senescence-associated ß-galactosidase assay to identify differential effects. Glucose consumption and lactic acid production per cell were tested using glucose and lactate assays. Two weeks postirradiation, we collected early-passage cells of the colony cells after both conventional and fractionated irradiations for further investigation. Then, we used the side population (SP) assay, cell-counting assay and Transwell assay to test the proliferation and invasion capability, the MTT assay to identify the drug resistance of cisplatin, pemetrexed and docetaxel, the Western blot assay to test the stem cell-related proteins of NANOG, CD133, OCT4, SOX2, BMI1 and KLF4. After irradiation, the total cell count and cell viability in both cell lines gradually decreased in a similar manner. However, more senescent, necrotic cells and apoptotic cells were found in the conventionally-treated cells at an early time point postirradiation. Contrarily, a higher percentage of G2/M cell cycle arrest and more γ-H2AX foci were found in the cell lines that received hypofractionated treatment. Glucose consumption and lactic acid production per cell were lower in the cell lines that received hypofractionated irradiation. Early-passage cells in the conventional-treated cell line showed more SP cells with higher expressions of NANOG, OCT4 and BMI1 proteins. Early-passage cells in the conventional-treated cell line also revealed higher proliferative ability, drug resistance and invasion ability. Although we detected some radiobiological differences between the two fractionation treatments, there was no obvious advantage for hypofractionation in the early days postirradiation. However, there were some advantages for hypofractionation compared to conventional treatment in early-passage cells in vitro, which may partially contribute to its clinical advantages. Moreover, the damage to healthy tissue should also be addressed to fully elucidate the implications of radiotherapy addressed in this work.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Hipofracionamento da Dose de Radiação , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Humanos , Fator 4 Semelhante a Kruppel , Neoplasias Pulmonares/patologia , Microambiente TumoralRESUMO
Cardamonin has been demonstrated to have an inhibitory effect in many cancers, but its underlying mechanism remains elusive. Here, we studied, for the first time, the mechanism of cardamonin-induced nasopharyngeal carcinoma cell death both in vitro and in vivo. In our study, we showed that cardamonin inhibited cancer cell growth by inducing G2/M phase cell cycle arrest and apoptosis via accumulation of ROS. NF-κB activation was involved in breaking cellular redox homeostasis. Therefore, our results provided new insight into the mechanism of the antitumor effect of cardamonin, supporting cardamonin as a prospective therapeutic drug in nasopharyngeal carcinoma by modulating intracellular redox balance.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma/tratamento farmacológico , Chalconas/farmacologia , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , NF-kappa B/genética , Neoplasias Nasofaríngeas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/genética , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/metabolismo , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , NF-kappa B/agonistas , NF-kappa B/metabolismo , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
RATIONALE: Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant neoplasm of which intracranial EMC is the rarest. PATIENT CONCERNS: We present an unusual case report of a 41-year-old woman who was sent to the emergency department for a sudden headache and other symptoms related to increased intracranial pressure. INTERVENTIONS: Emergent CT revealed an occupying lesion in the left cerebellum with surrounding edema. A complete surgical excision of the lesion through a transcortical approach was performed. After the operation, this patient received adjuvant radiotherapy and temozolomide treatment. DIAGNOSES: Pathology diagnosis was an intracranial EMC. OUTCOMES: The patient survives with no tumor recurrence as of the last follow-up. Progression-free survival exceeded 20 months. LESSONS: We have reviewed the literature and here summarize the diagnosis and treatment options for intracranial EMC. Diagnosis and treatment options of this rare disease are discussed.