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BACKGROUND: Survivin has been recently identified as a promising novel therapeutic target and prognostic marker in different types of cancer. Here we conducted a comprehensive meta-analysis to better clarify they the precise prognostic and diagnostic value of survivin in head and neck squamous cell carcinoma (HNSCC). METHODS: Database of PubMed (Medline), Embase, and Web of Science were systematically searched for related published literature up to September 2020. Pooled hazards ratios (HR) and related 95% confidence intervals (CI) were used to estimate the association of survivin expression and survival outcomes in HNSCC patients. RESULTS: Twenty eight studies with 4891 patients were finally included in this meta-analysis, the pooled analysis indicated that the survivin expression was significantly correlated with poorer overall survival (OS) (HR, 2.02; 95% CI, 1.65-2.47, P < 0.001), and poorer disease-free survival (DFS)/ disease-specific survival (DSS) (HR = 2.03, 95%CI: 1.64-2.52, P < 0.001; HR = 1.92, 95%CI: 1.41-2.60, P < 0.001, receptively). Similar results were observed in subgroup analysis stratified by different cancer types, such as laryngeal squamous cell carcinoma (LSCC) (HR = 1.35, 95%CI: 1.05-1.74, P < 0.001), oral squamous cell carcinomas (OSCC) (HR = 2.45, 95%CI: 1.89-3.17, P < 0.001), nasopharyngeal carcinoma (NPC) (HR = 2.53, 95%CI: 1.76-3.62, P < 0.001) and HNSCC (HR = 1.52, 95%CI: 1.25-1.86, P < 0.001). Furthermore, ethnicity-stratified analysis indicated that survivin was significantly associated with poorer OS among both Asian and Non- Asian HNSCC patients (HR = 2.16, 95%CI: 1.76-2.66; HR = 1.56, 95%CI: 1.33-1.82, respectively). CONCLUSIONS: Our results suggested that survivin is predictors of worse prognosis in HNSCC patients. Hence, survivin is a potential therapeutic target for HNSCC.
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Biomarcadores de Tumor , Expresión Génica , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Survivin/genética , Humanos , Grupos de Población , Pronóstico , Sesgo de Publicación , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnósticoRESUMEN
Glutamate (Glu) is the major afferent excitatory neurotransmitter in the auditory system, and excessive Glu may play an important role in cochlear dysfunction. It is unclear how excessive Glu plays roles in cochlear dysfunction in cochlear organotypic cultures. In this study neonatal rat cochlear organotypic cultures were prepared, and then the cochlear tissues were incubated with a new medium containing specific concentrations of Glu (0.1, 0.5, 1, 10 or 20 mmol/L) for 24 h, or incubated with the medium containing a concentration of 20 mmol/L Glu for 6, 12, 24 or 72 h, respectively. It was found that when the cochlear tissues were cultured for 24 h, the inner hair cells (IHCs) were damaged at the concentration of 0.5 mmol/L Glu, and with the increases of the concentrations, the injury was gradually aggravated, and 20 mmol/L Glu resulted in the significant loss of IHCs. In the 20 mmol/L Glu groups, the stereocilia bundles were missing or disarrayed on a few IHCs after culture for 6 h and the damage effect was time-dependent. The missing of IHCs was more significant in the basal turn of the cochlea than in the middle turn of the cochlea under the same concentration of Glu exposure. These results suggest that excessive exogenous Glu affects the morphology of IHCs, but not affects the outer hair cells (OHCs) in cochlear organotypic cultures, and the excitotoxic effects are different on IHCs of different parts of the cochlea under the same concentration of Glu exposure.
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Cóclea/efectos de los fármacos , Ácido Glutámico/toxicidad , Animales , Relación Dosis-Respuesta a Droga , Ratas , Ratas Sprague-DawleyRESUMEN
Neurosynovial tumors, originating from Schwann cells within nerve sheaths, are benign entities, with 25% to 45% manifesting in the head and neck region. However, occurrences in the pterygopalatine fossa (PPF) are exceptionally rare, and only a handful of cases have been documented. In this report, we present the unique case of a 6-year-old child exhibiting a sizable soft tissue mass in the left PPF, extending into the inferior orbital fissure. The patient underwent successful intranasal endoscopic removal of PPF schwannoma utilizing the prelacrimal recess approach, with postoperative pathology confirming the diagnosis of schwannoma. Schwannomas within the PPF are particularly uncommon, and instances of such tumors in pediatric patients are even more exceptional. This case highlights the diagnostic and therapeutic challenges associated with PPF schwannomas in children, emphasizing the significance of a multidisciplinary approach for optimal management. In addition, a comprehensive literature review is presented to provide insights into the existing knowledge on this rare entity, further contributing to the understanding of pediatric PPF schwannomas.
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It is known that the medial vestibular nucleus (MVN) and the cerebellar flocculus are the key areas, which contribute to the behavioral recovery ("vestibular compensation") after unilateral labyrinthectomy (UL). In these areas, how the genetic activities of the metabotropic glutamate receptors mGluR2 and mGluR7 performance after UL is unknown. With the means of quantitative real-time PCR, Western blotting, and immunohistochemistry, we analyzed the expression of mGluR2 and mGluR7 in the bilateral MVN and the flocculus of rats in different stages after UL (the 1st, 3rd, and 7th day). Our results show that in the MVN, the mRNA, and protein expressions of mGluR7 were ipsilaterally decreased at the 1st day following UL. However, in the MVN, no change was observed in the mRNA and protein expressions of mGluR2. On the other hand, the mRNA and protein expression of mGluR2 were enhanced in the ipsilateral flocculus at the 1st day following UL, while in the flocculus no change was shown in mGluR7 mRNA and protein expressions. Our results suggest that mGluR2 and mGluR7 may contribute to the early rebalancing of spontaneous resting activity in the MVN.
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Receptores de Glutamato Metabotrópico/biosíntesis , Vestíbulo del Laberinto/cirugía , Animales , Regulación de la Expresión Génica , ARN Mensajero/biosíntesis , Ratas , Núcleos Vestibulares/metabolismoRESUMEN
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous tumor that is highly aggressive and ranks fifth among the most common cancers worldwide. Although, the researches that attempted to construct a diagnostic model were deficient in HNSCC. Currently, the gold standard for diagnosing head and neck tumors is pathology, but this requires a traumatic biopsy. There is still a lack of a noninvasive test for such a high-incidence tumor. In order to screen genetic markers and construct diagnostic model, the methods of random forest (RF) and artificial neural network (ANN) were utilized. The data of HNSCC gene expression was accessed from Gene Expression Omnibus (GEO) database; we selected three datasets totally, and we combined 2 datasets (GSE6631 and GSE55547) for screening differentially expressed genes (DEGs) and chose another dataset (GSE13399) for validation. Firstly, the 6 DEGs (CRISP3, SPINK5, KRT4, MMP1, MAL, SPP1) were screened by RF. Subsequently, ANN was applied to calculate the weights of 6 genes. Besides, we created a diagnostic model and nominated it as neuralHNSCC, and the performance of neuralHNSCC by area under curve (AUC) was verified using another dataset. Our model achieved an AUC of 0.998 in the training cohort, and 0.734 in the validation cohort. Furthermore, we used the Cell-type Identification using Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm to investigate the difference in immune cell infiltration between HNSCC and normal tissues initially. The selected 6 DEGs and the constructed novel diagnostic model of HNSCC would make contributions to the diagnosis.
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Neoplasias de Cabeza y Cuello , Bosques Aleatorios , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Biomarcadores de Tumor/genética , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/genética , Redes Neurales de la ComputaciónRESUMEN
Salivary duct carcinoma (SDC) is an uncommon but highly aggressive tumor with a poor prognosis. SDC mainly arises from the major salivary glands, typically the parotid gland. Here, we report a rare case of sinonasal SDC in a 54-year-old male patient that might have originated from the inferior turbinate. The patient presented with left nasal congestion and rhinorrhea. Following an endoscopic intervention, the histopathological examination revealed a diagnosis of SDC, characterized by the formation of solid cancer nests and central comedo-type necrosis. Given the highly aggressive nature and unfavorable prognosis of SDC, it is essential to consider it as a differential diagnosis for unilateral nasal tumors.
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Pleomorphic adenoma (PA) is the most prevalent benign tumor of the salivary glands, characterized by both epithelial and mesenchymal differentiation. It primarily originates within the parotid and submandibular glands, with only rare occurrences in the minor salivary glands. PA in the sinonasal area is extremely rare. Herein, we present a case of a 61-year-old female with a large soft tissue mass in the paranasal sinus and nasal cavity, as evidenced by computed tomography imaging. The patient suffered from repeated nasal congestion for more than 6 months. Eventually, the mass was completely resected using an endoscopic endonasal prelacrimal approach under general anesthesia. Postoperative pathological examination revealed the presence of PA in the nasal sinus.
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BACKGROUND: Obstructive sleep apnea (OSA) as an independent cardiovascular risk factor has been proposed, but the mechanisms underlying cardiovascular disease is far from being completely elucidated. Leptin, an inflammatory cytokine produced by adipocytes, contributes to the modulation of metabolism, respiratory control, and inflammation, which are factors associated with cardiovascular disease. Serum levels of leptin in children with OSA have shown conflicting results in previous studies. METHODS: We performed a meta-analysis to clarify the correlation between leptin expression of the OSA patients following the PRISMA. PubMed, Embase, and Web of Science were systematically searched for relevant studies, and then independently screened by two researchers, and analyzed the data through STATA version 12.0. RESULTS: In a total of 5 articles including 469 participants, the data analysis showed that serum leptin levels were elevated in children with OSA (MD, 6.36; 95% CI, 0.24-12.49, Pâ <â .001), compared to the control group. Subgroup analysis were performed based on body mass index. The results of subgroup analysis demonstrated that the serum leptin concentration was correlated with body mass index in children with OSA (MD, 9.70; 95% CI, 0.22-11.18, Pâ <â .001). CONCLUSIONS: The serum leptin levels were elevated in children with OSA, compared to the control group. It could add to our developing understanding of the pathogenesis and potential treatments for children with OSA, and help us to recognize the relevance of OSA in determining cardiovascular issues among children.
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Enfermedades Cardiovasculares , Apnea Obstructiva del Sueño , Índice de Masa Corporal , Enfermedades Cardiovasculares/complicaciones , Niño , Citocinas , Humanos , Leptina , Apnea Obstructiva del Sueño/complicacionesRESUMEN
Background: Head and neck squamous cell carcinomas (HNSCCs) are derived from the mucosal linings of the upper aerodigestive tract, salivary glands, thyroid, oropharynx, larynx, and hypopharynx. The present study aimed to identify the novel genes and pathways underlying HNSCC. Despite the advances in HNSCC research, diagnosis, and treatment, its incidence continues to rise, and the mortality of advanced HNSCC is expected to increase by 50%. Therefore, there is an urgent need for effective biomarkers to predict HNSCC patients' prognosis and provide guidance to the personalized treatment. Methods: Both HNSCC clinical and gene expression data were abstracted from The Cancer Genome Atlas (TCGA) database. Intersecting analysis was adopted between the gene expression matrix of HNSCC patients from TCGA database to extract TME-related genes. Differential gene expression analysis between HNSCC tissue samples and normal tissue samples was performed by R software. Then, HNSCC patients were categorized into clusters 1 and 2 via NMF. Next, TME-related prognosis genes (p < 0.05) were analyzed by univariate Cox regression analysis, LASSO Cox regression analysis, and multivariate Cox regression analysis. Finally, nine genes were selected to construct a prognostic risk model and a prognostic gene signature. We also established a nomogram using relevant clinical parameters and a risk score. The Kaplan-Meier curve, survival analysis, time-dependent receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and the concordance index (C-index) were carried out to assess the accuracy of the prognostic risk model and nomogram. Potential molecular mechanisms were revealed by gene set enrichment analysis (GSEA). Additionally, gene correlation analysis and immune cell correlation analysis were conducted for further enriching our results. Results: A novel HNSCC prognostic model was established based on the nine genes (GTSE1, LRRN4CL, CRYAB, SHOX2, ASNS, KRT23, ANGPT2, HOXA9, and CARD11). The value of area under the ROC curves (AUCs) (0.769, 0.841, and 0.816) in TCGA whole set showed that the model effectively predicted the 1-, 3-, and 5-year overall survival (OS). Results of the Cox regression assessment confirmed the nine-gene signature as a reliable independent prognostic factor in HNSCC patients. The prognostic nomogram developed using multivariate Cox regression analysis showed a superior C-index over other clinical signatures. Also, the calibration curve had a high level of concordance between estimated OS and the observed OS. This showed that its clinical net can precisely estimate the one-, three-, and five-year OS in HNSCC patients. The gene set enrichment analysis (GSEA) to some extent revealed the immune- and tumor-linked cascades. Conclusion: In conclusion, the TME-related nine-gene signature and nomogram can effectively improve the estimation of prognosis in patients with HNSCC.
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Background: ß-Catenin has been recently identified as a promising novel therapeutic target and prognostic marker in different types of cancer. Here, we conduct a meta-analysis to better clarify the correlation between ß-Catenin expression and survival outcomes in nasopharyngeal carcinoma (NPC) patients. Patients/methods: Following the Preferred Reporting Items or Systematic Reviews Meta Analyses (PRISMA) 2020 guidelines, the PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases were systematically searched for relevant studies to explore the prognostic significance of ß-Catenin in NPC. Pooled hazards ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the association of ß-Catenin expression with survival outcomes in NPC patients. Odd ratios (ORs) and 95% CIs for clinicopathological characteristics were also statistically analyzed. Results: Eight studies involving 1,179 patients with NPC were ultimately included in the meta-analysis. Pooled analysis indicated that elevated ß-Catenin expression was significantly associated with poor OS (HR = 2.45, 95% CIs: 1.45-4.16, p = 0.001) and poor DFS/PFS (HR 1.79, 95% CIs: 1.29-2.49, p = 0.000). Furthermore, ß-cadherin was signifcantly associated with higher TMN stages (OR = 5.10, 95% CIs 2.93-8.86, p = 0.000), clinical stages (OR = 5.10, 95% CIs 2.93-8.86, p = 0.000) and lymph node metastasis (LNM) (OR = 5.01, 95% CIs 2.40-10.44, p = 0.000). Conclusions: This study demonstrated that for NPC, patients with elevated ß-Catenin expression are more likely to have poor survival.
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N6-methyladenosine (m6A) modifications play an essential role in tumorigenesis. These modifications modulate RNAs, including mRNAs and lncRNAs. However, the prognostic role of m6A-related lncRNAs in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Based on LASSO Cox regression, enrichment analysis, univariate and multivariate Cox regression analysis, a prognostic risk model, and consensus clustering analysis, we analyzed 12 m6A-related lncRNAs in HNSCC sample data from The Cancer Genome Atlas (TCGA) database. We found 12 m6A-related lncRNAs in the training cohort and validated them in all cohorts by Kaplan-Meier and Cox regression analyses, revealing their independent prognostic value in HNSCC. Moreover, ROC analysis was conducted, confirming the strong predictive ability of this signature for HNSCC survival. GSEA and detailed immune infiltration analyses revealed specific pathways associated with m6A-related lncRNAs. In this study, a novel risk model including twelve genes (SAP30L-AS1, AC022098.1, LINC01475, AC090587.2, AC008115.3, AC015911.3, AL122035.2, AC010226.1, AL513190.1, ZNF32-AS1, AL035587.1 and AL031716.1) was built. It could accurately predict HNSCC outcomes and could provide new therapeutic targets for HNSCC patients.
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Adenosina/análogos & derivados , Neoplasias de Cabeza y Cuello/diagnóstico , ARN Largo no Codificante/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Adenosina/metabolismo , Anciano , Estudios de Cohortes , Biología Computacional , Femenino , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Microambiente TumoralRESUMEN
Chronic inflammation may promote the incidence and development of neoplasms. As a pro-inflammatory death pathway, pyroptosis could induce normal cells to transform into cancerous cells, but the potential effect of pyroptosis in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study developed and evaluated a pyroptosis-related gene signature to predict the prognosis and immune status of patients with HNSCC. The gene expression, mutation information, and clinical characteristics of HNSCC were extracted from TCGA to establish a comprehensive genome database (GEO). Based on LASSO Cox regression model, nine pyroptosis-related genes (TTLL1, TRIML2, DYNC1I1, KLHL35, CAMK2N1, TNFRSF18, GLDC, SPINK5, and DKK1) were used to construct a pyroptosis-related gene signature, which had good ability to predict the prognosis of HNSCC. Furthermore, the expression of nine pyroptosis-related genes in HNSCC and paracancerous tissues was detected by quantitative real-time PCR (qRT-PCR). The potential immunotherapeutic features and drug sensitivity prediction of this signature were also explored. Because pyroptosis regulators play an important role in HNSCC development and prognoses, further exploration might assist in identifying new biomarkers and predictors of prognosis to benefit clinical identification and management.
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Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms that were initially identified in the pleura. SFTs in the nasal or paranasal sinuses are especially rare. Most SFTs exhibit indolent behavior, with a low local recurrence rate. A 39-year-old man complained of bilateral nasal congestion, hyposmia, and occasional right eye tears six months prior to hospitalization. Based on MRI and CT imaging, a total gross surgical resection was achieved. Subsequently, postsurgical histopathological examinations were conducted. Under the microscope, pathological mitotic bodies were visible (<5 mitoses per 2 mm2). The immunohistochemical staining results revealed that tumor cells were positive for CD34, BCL-2, STAT-6, and Ki-67 (<5%) but negative for EMA, S-100, PR, GFAP, and SMA. Based on these findings, the patient was diagnosed with SFT.
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Fibroblast growth factor receptor 1 (FGFR1) has recently been identified as a promising novel therapeutic target and prognostic marker in different types of cancer. In the present study, a meta-analysis was performed to clarify the correlation between FGFR1 and the survival outcomes of head and neck squamous cell carcinoma (HNSCC) patients. PubMed, Embase, and Web of Science were systematically searched for relevant studies in order to explore the prognostic significance of FGFR1 in HNSCC. Hazards ratios (HR) and 95% confidence intervals (CI) were collected to estimate the correlation between overexpression and amplification of FGFR1 and survival outcomes of HNSCC patients. Nine studies including 2708 patients with HNSCC were finally selected for the meta-analysis. The results indicated that FGFR1 predicted poor overall survival (OS) (HR, 1.97; 95% CI, 1.49-2.61, P<0.001) in HNSCC patients. Futhermore, FGFR1 was related to poor OS in human papillomavirus (HPV) negative HNSCC not in HPV positive HNSCC patients. Subgroup analysis stratified by molecular abnormalities, such as overexpression or amplification showed the similar results. The present study demonstrated that HNSCC patients with FGFR1 overexpression and amplification were more likely to exhibit poorer survival.
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Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Amplificación de Genes/genética , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Persona de Mediana Edad , Pronóstico , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Adulto JovenRESUMEN
BACKGROUND: Isolated fungus ball (FB) in a single cell of the left ethmoid roof is a very rare condition. CASE SUMMARY: We report the case of a 51-year-old female patient whose computed tomography presented a soft tissue mass filling in the left ethmoid roof cell. The patient did not complain of any specific sinonasal symptoms, such as nasal discharge, nasal obstruction, and loss of smell, apart from headache in the left retro-orbital region. CONCLUSION: The patient underwent functional endoscopic sinus surgery under general anesthesia, and the inflammatory material collected was histologically diagnosed as a rare case of a FB in a single cell of the left ethmoid roof.
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The medial vestibular nucleus (MVN) and the cerebellar flocculus have been known to be the key areas involved in vestibular compensation (VC) following unilateral labyrinthectomy (UL). In this study, we examined the role of gephyrin and glycine receptor (GlyR) in VC using Sprague-Dawley rats, in an aim to gain deeper insight into the mechanisms responsible for VC. The expression of the α1 and ß subunits of GlyR and gephyrin was immunohistochemically localized in rat MVN and flocculi. The mRNA and protein expression of GlyR (α1 and ß subunits) and gephyrin was quantitatively determined by RT-qPCR and western blot analysis at 8 h, and at 1, 3 and 7 days following UL. It was found that in the ipsilateral MVN, the mRNA and protein expression of the ß subunit of GlyR was significantly increased in comparison to the sham-operated (P<0.01) rats, and in comparison to the contralateral side (P<0.01) at 8 h following UL. In the ipsilateral flocculi, GlyR ß protein expression was significantly elevated (P<0.01 for all), as compared to the sham-operated rats at 8 h, and at 1 and 3 days and to the contralateral side 8 h, 1 and 3 days following UL. No significant differences were observed in the mRNA and protein expression of GlyR α1 and gephyrin in the MVN or flocculi between the two sides (ipsilateral and contralateral) in the UL group, and between the sham-operated group and the UL group at any time point. The findings of our study thus suggest that GlyR plays a major role in the recovery of the resting discharge of the deafferented MVN neurons in the central vestibular system.
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Proteínas Portadoras/genética , Regulación de la Expresión Génica , Proteínas de la Membrana/genética , Receptores de Glicina/genética , Núcleos Vestibulares/metabolismo , Vestíbulo del Laberinto/cirugía , Animales , Western Blotting , Proteínas Portadoras/metabolismo , Inmunohistoquímica , Masculino , Proteínas de la Membrana/metabolismo , Modelos Biológicos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Receptores de Glicina/metabolismoRESUMEN
PURPOSE: The CD38 cell surface antigen is expressed in diverse hematologic malignancies including multiple myeloma, B-cell non-Hodgkin lymphoma (NHL), B-cell chronic lymphocytic leukemia, B-cell acute lymphoblastic leukemia (ALL), and T-cell ALL. Here, we assessed the antitumor activity of the anti-CD38 antibody SAR650984. EXPERIMENTAL DESIGN: Activity of SAR650984 was examined on lymphoma, leukemia and multiple myeloma cell lines, primary multiple myeloma samples, and multiple myeloma xenograft models in immunodeficient mice. RESULTS: We identified a humanized anti-CD38 antibody with strong proapoptotic activity independent of cross-linking agents, and potent effector functions including complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cellular phagocytosis (ADCP), equivalent in vitro to rituximab in CD20+ and CD38+ models. This unique antibody, termed SAR650984, inhibited the ADP-ribosyl cyclase activity of CD38, likely through an allosteric antagonism as suggested by 3D structure analysis of the complex. In vivo, SAR650984 was active in diverse NHL, ALL, and multiple myeloma CD38+ tumor xenograft models. SAR650984 demonstrated single-agent activity comparable with rituximab or cyclophosphamide in Daudi or SU-DHL-8 lymphoma xenograft models with induction of the proapoptotic marker cleaved capase-7. In addition, SAR650984 had more potent antitumor activity than bortezomib in NCI-H929 and Molp-8 multiple myeloma xenograft studies. Consistent with its mode of action, SAR650984 demonstrated potent proapoptotic activity against CD38+ human primary multiple myeloma cells. CONCLUSION: These results validate CD38 as a therapeutic target and support the current evaluation of this unique CD38-targeting functional antibody in phase I clinical trials in patients with CD38+ B-cell malignancies.