RESUMEN
Cancer immunotherapy frequently fails because most carcinomas have few T cells, suggesting that cancers can suppress T cell infiltration. Here, we show that cancer cells of human pancreatic ductal adenocarcinoma (PDA), colorectal cancer, and breast cancer are coated with transglutaminase-2 (TGM2)-dependent covalent CXCL12-keratin-19 (KRT19) heterodimers that are organized as filamentous networks. Since a dimeric form of CXCL12 suppresses the motility of human T cells, we determined whether this polymeric CXCL12-KRT19 coating mediated T cell exclusion. Mouse tumors containing control PDA cells exhibited the CXCL12-KRT19 coating, excluded T cells, and did not respond to treatment with anti-PD-1 antibody. Tumors containing PDA cells not expressing either KRT19 or TGM2 lacked the CXCL12-KRT19 coating, were infiltrated with activated CD8+ T cells, and growth was suppressed with anti-PD-1 antibody treatment. Thus, carcinomas assemble a CXCL12-KRT19 coating to evade cancer immune attack.
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Carcinoma/etiología , Carcinoma/metabolismo , Quimiocina CXCL12/metabolismo , Citotoxicidad Inmunológica , Queratina-19/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Animales , Neoplasias de la Mama , Carcinoma/patología , Línea Celular Tumoral , Quimiocina CXCL12/química , Femenino , Humanos , Queratina-19/química , Masculino , Ratones , Repeticiones de Microsatélite , Neoplasias Pancreáticas , Unión Proteica , Multimerización de Proteína , Neoplasias PancreáticasRESUMEN
Laparoscopic-assisted vaginal radical hysterectomy (LARVH) and abdominal radical hysterectomy (ARH) have been widely applied to treat cervical carcinoma. But LARVH and ARH have not been fully investigated in treating cervical carcinoma after injury associated with injury. This research is intended to provide an up-to-date basis for comparing LARVH with ARH in early stage cervical carcinoma. Comparison between LARVH and ARH in cervical carcinoma was carried out through a combination of related research. Eligible articles from databases such as PubMed and Embase were screened using an established search strategy. This report covered the results of LARVH versus ARH in cervical carcinoma. The average difference and the 95% confidence interval (CI) were used for the combination of consecutive variables. The combination of categorical variables was performed with the odds ratio (OR) 95% confidence interval. Through the identification of 1137 publications, eight of them were chosen to be analysed. Among them, 363 were treated with LARVH and 326 were treated with ARH. Eight trials showed that LARVH was associated with a reduced risk of postoperative wound infection than ARH (OR, 0.23; 95% CI, 0.1-0.55, p = 0.0009). Five trials showed that there was no difference in the risk of postoperative bleeding after surgery (OR, 1.17; 95% CI, 0.42-3.29, p = 0.76). We also did not differ significantly in the duration of the surgery (OR, 1.79; 95% CI, -6.58 to 10.15, p = 0.68). So, the two surgical methods differ significantly only in the risk of postoperative wound infection.
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Carcinoma , Laparoscopía , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/etiología , Neoplasias del Cuello Uterino/patología , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/cirugía , Laparoscopía/efectos adversos , Laparoscopía/métodos , Estadificación de Neoplasias , Histerectomía/efectos adversos , Histerectomía/métodos , Carcinoma/etiología , Carcinoma/patología , Carcinoma/cirugía , Estudios Retrospectivos , Complicaciones Posoperatorias/etiologíaRESUMEN
OBJECTIVE: The present study assessed the diagnostic and prognostic significance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for suspected intrathoracic metastasis after HNC treatment. METHODS: A retrospective analysis was conducted on 75 patients with a prior history of head and neck cancer treatment who underwent EBUS-TBNA for suspected intrathoracic metastases between March 2012 and December 2021. RESULTS: A total of 126 targeted lesions, including 107 mediastinal/hilar lymph nodes and 19 intrapulmonary/mediastinal masses, were sampled. The metastatic head and neck cancer (HNC) cases detected by EBUS-TBNA consisted of nasopharyngeal carcinoma (n = 24), oropharyngeal carcinoma (n = 3), hypopharynx carcinoma (n = 6), laryngeal carcinoma (n = 6), and oral cavity carcinoma (n = 6). Cases with negative EBUS-TBNA results consisted of tuberculosis (n = 9), sarcoidosis (n = 3), anthracosis (n = 9), and reactive lymphadenitis (n = 9). Six false-negative cases were found among the 75 patients with suspected intrathoracic metastases. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the EBUS-TBNA procedure for metastatic HNC were 88.2, 100.0, 100.0, 80, and 92.0%, respectively. The diagnosis of HNC intrathoracic metastasis by EBUS-TBNA correlated with an adverse prognosis in terms of overall survival (OS) (P = .008). The log-rank univariate analysis and Cox regression multivariate analysis results indicated that the detection of metastatic HNC through EBUS-TBNA was a significant independent prognostic factor for patients with HNC who had received prior treatment. CONCLUSIONS: Endobronchial ultrasound-guided transbronchial needle aspiration is a safe, effective, and minimally invasive procedure for assessing suspected intrathoracic metastasis in HNC patients after treatment. The intrathoracic metastasis detected by EBUS-TBNA has crucial prognostic significance in previously treated HNC patients.
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Carcinoma , Neoplasias de Cabeza y Cuello , Neoplasias Pulmonares , Humanos , Pronóstico , Estudios Retrospectivos , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Mediastino , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/patología , Carcinoma/etiología , Carcinoma/patología , Neoplasias Pulmonares/patologíaRESUMEN
PURPOSE: Minimally invasive surgery (MIS) for thymic tumors is now accepted widely, in line with improved surgical techniques; however, we occasionally encounter complicated cases of large tumors or of total thymectomy requiring prolonged operative duration or conversion to an open procedure (OP). We reviewed patients registered in a nationwide database to identify the technical feasibility of MIS for thymic epithelial tumors. METHODS: Data on patients treated surgically between 2017 and 2019 were extracted from the National Clinical Database of Japan. Clinical factors and operative outcomes were calculated by tumor diameter using trend analyses. Perioperative outcomes of MIS for non-invasive thymoma were investigated using propensity score-matched analyses. RESULTS: MIS was performed in 46.2% of the patients. The operative duration and conversion rate increased with the tumor diameter (p < .001). After propensity score-matching, operative duration and postoperative hospital stay were shorter (p < .001), and the transfusion rate was lower (p = .007) in patients who underwent MIS than in those who underwent OP for thymomas ≥ 5 cm. Among patients who underwent total thymectomy, blood loss was less (p < .001) and the postoperative hospital stay was shorter (p < .001) in those who underwent MIS than in those who underwent OP. There were no significant differences in postoperative complications and mortality. CONCLUSIONS: MIS is technically feasible even for large non-invasive thymomas or for total thymectomy, although the operative duration and open conversion rate increase with the tumor diameter.
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Carcinoma , Neoplasias Glandulares y Epiteliales , Timoma , Neoplasias del Timo , Humanos , Carcinoma/etiología , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Neoplasias Glandulares y Epiteliales/cirugía , Estudios Retrospectivos , Timectomía/métodosRESUMEN
BACKGROUND AND AIMS: Endoscopic resection has been established as curative therapy for superficial cancer arising from Barrett's oesophagus (BE); recurrences are very rare. Based on a case series with unusual and massive early recurrences, we analyse the issue of tumour cell reimplantation. METHODS: This hypothesis was developed on the basis of two out of seven patients treated by circumferential (n=6) or nearly circumferential (n=1) en bloc and R0 endoscopic resection of T1 neoplastic BE. Subsequently, a prospective histocytological analysis of endoscope channels and accessories was performed in 2 phases (cytohistological analysis; test for cell viability) in 22 different oesophageal carcinoma patients undergoing endoscopy. Finally, cultures from two oesophageal adenocarcinoma cell lines were incubated with different triamcinolone concentrations (0.625-10 mg/mL); cell growth was determined on a Multiwell plate reader. RESULTS: Cancer regrowth in the two suspicious cases (male, 78/71 years) occurred 7 and 1 months, respectively, after curative tumour resection. Subsequent surgery showed advanced tumours (T2) with lymph node metastases; one patient died. On cytohistological examinations of channels and accessories, suspicious/neoplastic cells were found in 4/10 superficial and in all 5 advanced cancers. Further analyses in seven further advanced adenocarcinoma cases showed viable cells in two channel washing specimens. Finally, cell culture experiments demonstrated enhanced tumour cell growth by triamcinolone after 24 hours compared with controls. CONCLUSIONS: Tumour cell reimplanation from contaminated endoscopes and accessories is a possible cause of local recurrence after curative endoscopic therapy for superficial Barrett carcinoma; also, corticosteroid injection could have promoted tumour regrowth in these cases.
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Esófago de Barrett/cirugía , Carcinoma/cirugía , Neoplasias Esofágicas/cirugía , Esofagoscopía/efectos adversos , Recurrencia Local de Neoplasia/etiología , Siembra Neoplásica , Anciano , Anciano de 80 o más Años , Esófago de Barrett/patología , Carcinoma/etiología , Carcinoma/patología , Estudios de Cohortes , Neoplasias Esofágicas/etiología , Neoplasias Esofágicas/patología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Factores de RiesgoRESUMEN
BACKGROUND: The most frequently reported malignancies after solid organ transplant are cutaneous, but data on the risk in pediatric populations varies across studies. OBJECTIVES: To perform a systematic review including reported features and outcomes of skin cancers in pediatric solid organ transplant recipients. METHODS: EMBASE and MEDLINE were systematically searched (Prospero CRD42020201659). RESULTS: The review summarizes data from 20 studies on 337 patients, with a median age ranging from 15.0 to 19.5 years as reported in 4 studies, who developed skin malignancies after pediatric solid organ transplantation. Median ages at transplant and skin cancer diagnosis ranged from 1.5 to 17.0 years and 15.3 to 33.5 years, respectively. Squamous cell carcinoma (SCC) was most commonly reported (218 cases), followed by basal cell carcinoma (BCC) (91 cases), melanoma (18 cases), and unspecified keratinocyte carcinomas (2 cases). The median latency period between transplantation and cancer diagnosis ranged from 2.2 to 21.0 years. Overall, 4 studies reported 17 cases of metastasis in total, and recurrence was reported in one case. Six deaths were reported in one study related to SCC and melanoma metastases. The incidence rate of skin cancer after pediatric transplantation per 100 person-years of follow-up was 2.1 based on 5 studies. CONCLUSION: The most frequent post-transplant malignancy in pediatric organ transplant recipients was SCC.
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Carcinoma/etiología , Melanoma/etiología , Trasplante de Órganos , Complicaciones Posoperatorias , Neoplasias Cutáneas/etiología , Adolescente , Carcinoma/epidemiología , Niño , Preescolar , Humanos , Incidencia , Lactante , Melanoma/epidemiología , Complicaciones Posoperatorias/epidemiología , Neoplasias Cutáneas/epidemiologíaRESUMEN
To compare the impact of transoral radiofrequency microsurgery (TRM) and radiotherapy (RT) on long-term swallowing function in patients with T1 glottic carcinoma. A total of 41 cases of T1 glottic carcinoma treated with TRM or RT alone more than 5 years ago were collected, including 17 cases treated with TRM (TRM group) and 24 cases treated with RT (RT group). The Chinese version of the Swallowing Quality-of-Life Questionnaire (CSWAL-QOL) and videofluoroscopic swallowing study results at the last follow-up (more than 5 years after TRM or RT) were assessed. The TRM group scored significantly better than the RT group on overall CSWAL-QOL, the Frequency score, and 6 out of 10 CSWAL-QOL dimensions. The RT group scored significantly better than the TRM group only on the Communication dimension. The dysphagia score (DS) and penetration-aspiration scale (PAS) score of the TRM group were better than those of the RT group. The overall CSWAL-QOL score, the Frequency score, DS, and PAS scores were not significantly different between patients who received conventional radiotherapy and patients who received intensity-modulated radiation therapy. The RT dose was correlated with the DS. TRM provides better swallowing outcomes as compared to RT in management of early glottic cancer. In addition, there is a correlation between RT dose and dysphagia. Prospective studies should be conducted to further evaluate the impact of TRM and RT on swallowing function.
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Carcinoma , Trastornos de Deglución , Neoplasias Laríngeas , Terapia por Láser , Carcinoma/etiología , Carcinoma/cirugía , Deglución , Humanos , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/cirugía , Terapia por Láser/efectos adversos , Terapia por Láser/métodos , Microcirugia/métodos , Estudios Prospectivos , Calidad de Vida , Resultado del TratamientoRESUMEN
Beset by poor prognosis, pancreatic ductal adenocarcinoma is classified as familial or sporadic. This review elaborates on the known genetic syndromes that underlie familial pancreatic cancer, where there are opportunities for genetic counseling and testing as well as clinical monitoring of at-risk patients. Such subsets of familial pancreatic cancer involve germline cationic trypsinogen or PRSS1 mutations (hereditary pancreatitis), BRCA2 mutations (usually in association with hereditary breast-ovarian cancer syndrome), CDKN2 mutations (familial atypical mole and multiple melanoma), or DNA repair gene mutations (e.g., ATM and PALB2, apart from those in BRCA2). However, the vast majority of familial pancreatic cancer cases have yet to have their genetic underpinnings elucidated, waiting in part for the results of deep sequencing efforts.
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Carcinoma/genética , Neoplasias Pancreáticas/genética , Carcinoma/etiología , Neoplasias del Colon/complicaciones , Neoplasias del Colon/genética , Reparación del ADN/genética , Humanos , Melanoma/complicaciones , Melanoma/genética , Mutación/genética , Neoplasias Pancreáticas/etiología , Pancreatitis Crónica/complicaciones , Pancreatitis Crónica/genética , Neoplasias Cutáneas , Síndrome , Melanoma Cutáneo MalignoRESUMEN
Arsenic in drinking water is one of the major etiological factors in urinary bladder carcinoma (BlCa). Here, high-resolution CGH-SNP microarray analysis in arsenic accumulated BlCa tissues showed significant (p < 0.05) association of chromosomal alterations with high arsenic (≥112 ng/g) accumulation, further corroborated by high γH2AX nuclear expression. Cytobands 5q11-35, 9p24.3-21.5, 18q11.1-25, etc. showed deletion, whereas 12q was amplified in high arsenic samples (AsH). Consecutively, IPA® found FA-BRCA pathway to be exclusively altered in AsH group. Validation of several key regulatory genes (RAD50, BRIP1, UIMC1, FANCD2, BRCA2 and BRCA1) of the pathway, were performed in independent BlCa cases (n = 81). UIMC1, RAD50 and BRIP1 were differentially deleted and associated with poor survival of AsH samples. Moreover, reduced nuclear expression with diffused cytoplasmic expression of FANCD2 was higher in AsH samples. Collectively, frequent deregulation of RAD50, UIMC1 and BRIP1 may result in reduced nuclear translocation of FANCD2, which may cause more chromosomal aberrations among AsH samples.
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Arsénico/toxicidad , Carcinoma/genética , Neoplasias de la Vejiga Urinaria/genética , Arsénico/metabolismo , Carcinoma/etiología , Carcinoma/metabolismo , Carcinoma/mortalidad , Aberraciones Cromosómicas , Variaciones en el Número de Copia de ADN , Reparación del ADN , Proteína del Grupo de Complementación D2 de la Anemia de Fanconi/genética , Proteínas del Grupo de Complementación de la Anemia de Fanconi/metabolismo , Perfilación de la Expresión Génica , Genes BRCA1 , Genes BRCA2 , Genómica , Redes y Vías Metabólicas , Repeticiones de Microsatélite , Transducción de Señal , Neoplasias de la Vejiga Urinaria/etiología , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/mortalidadRESUMEN
Despite research efforts, current knowledge of the etiology of thyroid carcinoma remains limited. To explore the potential role of diet-induced inflammation, we examined the association between differentiated thyroid cancer risk and the energy-adjusted Dietary Inflammatory Index (E-DII) in a population-based case-control study conducted in New Caledonia, a Pacific archipelago with one of the highest recorded thyroid cancer incidence rates in the world. The E-DII was computed from food frequency questionnaire information on usual dietary intake. Logistic regression analyses were performed on data from 324 histologically confirmed cases of papillary or follicular carcinoma, diagnosed from 1993 to 1999, and 402 controls. Positive associations between E-DII and thyroid cancer risk were observed (comparing extreme tertiles, odds ratio = 1.67, 95% confidence interval: 1.08, 2.58; P for trend = 0.002), with stronger associations found for larger carcinomas (P for trend = 0.0005). Stratified analyses showed an increased risk of thyroid cancer associated with the E-DII among Southern province residents (P for trend = 0.003), Melanesian women (P for trend = 0.02), obese participants (P for trend = 0.006), and ever-smokers (P for trend = 0.0005). Our results suggest that a proinflammatory diet-especially when concomitant with other inflammation-inducing conditions or habits (e.g., obesity, smoking)-is associated with increased risk of thyroid carcinoma.
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Carcinoma/epidemiología , Dieta Saludable/estadística & datos numéricos , Dieta/efectos adversos , Inflamación/epidemiología , Neoplasias de la Tiroides/epidemiología , Adulto , Anciano , Carcinoma/etiología , Estudios de Casos y Controles , Encuestas sobre Dietas , Femenino , Humanos , Inflamación/etiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Nueva Caledonia/epidemiología , Oportunidad Relativa , Factores de Riesgo , Neoplasias de la Tiroides/etiologíaRESUMEN
BACKGROUND AND AIMS: Colitis-associated cancer (CAC) is one of the most serious complications in patients with inflammatory bowel disease. Sphingosine kinase 1 (Sphk1) is a key enzyme in the sphingolipid pathway and has oncogene potential for inducing both initiation and progression of tumors. The aim of this work is to characterize the role of epithelial Sphk1 in mouse colitis and CAC models. METHODS: We investigated the roles of Sphk1 in CAC by conditional deletion of Sphk1 in intestinal epithelial cells (IECs). RESULTS: CAC was induced in both Sphk1ΔIEC/ApcMin/+ and Sphk1IEC/ApcMin/+ mice by administration of 2% dextran sodium sulfate (DSS) for 7 days. Genetic deletion of Sphk1 significantly reduced the number and size of tumors in ApcMin/+ mice. Histologic grade was more severe in Sphk1ΔIEC/ApcMin/+ mice compared with Sphk1IEC/ApcMin/+ mice (invasive carcinoma, 71% versus 13%, p < 0.05). Deletion of Sphk1 decreased mucosal proliferation and inhibited STAT3 activation and genetic expression of cyclin D1 and cMyc in tumor cells. Conditional deletion of Sphk1 using CRISPR-Cas9 in HCT 116 cells inhibited interleukin (IL)-6-mediated STAT3 activation. CONCLUSIONS: Epithelial conditional deletion of Sphk1 inhibits CAC in ApcMin/+-DSS models in mice by inhibiting STAT3 activation and its target signaling pathways.
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Carcinoma/etiología , Neoplasias del Colon/etiología , Fosfotransferasas (Aceptor de Grupo Alcohol)/fisiología , Factor de Transcripción STAT3/metabolismo , Animales , Carcinogénesis , Colitis/complicaciones , Sulfato de Dextran , Células Epiteliales/metabolismo , Células HCT116 , Humanos , Ratones NoqueadosRESUMEN
Nasopharyngeal carcinoma (NPC) most frequently occurs in southern China and southeast Asia. Epidemiology studies link NPC to genetic predisposition, Epstein-Barr virus (EBV) infection, and environmental factors. Genetic studies indicate that mutations in chromatin-modifying enzymes are the most frequent genetic alterations in NPC. Here, we used H3K27ac chromatin immune precipitation followed by deep sequencing (ChIP-seq) to define the NPC epigenome in primary NPC biopsies, NPC xenografts, and an NPC cell line, and compared them to immortalized normal nasopharyngeal or oral epithelial cells. We identified NPC-specific enhancers and found these enhancers were enriched with nuclear factor κB (NF-κB), IFN-responsive factor 1 (IRF1) and IRF2, and ETS family members ETS1 motifs. Normal cell-specific enhancers were enriched with basic leucine zipper family members and TP53 motifs. NPC super-enhancers with extraordinarily broad and high H3K27ac signals were also identified, and they were linked to genes important for oncogenesis including ETV6. ETV6 was also highly expressed in NPC biopsies by immunohistochemistry. High ETV6 expression correlated with a poor prognosis. Furthermore, we defined the EBV episome epigenetic landscapes in primary NPC tissue.
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Carcinoma/genética , Elementos de Facilitación Genéticos , Neoplasias Nasofaríngeas/genética , Proteínas Proto-Oncogénicas c-ets/genética , Proteínas Represoras/genética , Adolescente , Adulto , Anciano , Animales , Azepinas/farmacología , Carcinoma/etiología , Carcinoma/metabolismo , Proteínas de Ciclo Celular , Línea Celular Tumoral , Elementos de Facilitación Genéticos/efectos de los fármacos , Epigénesis Genética , Infecciones por Virus de Epstein-Barr/complicaciones , Femenino , Genoma Viral , Xenoinjertos , Secuenciación de Nucleótidos de Alto Rendimiento , Código de Histonas/genética , Humanos , Inmunohistoquímica , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/etiología , Neoplasias Nasofaríngeas/metabolismo , Proteínas Nucleares/antagonistas & inhibidores , Pronóstico , Proteínas Proto-Oncogénicas c-ets/metabolismo , Proteínas Represoras/metabolismo , Factores de Transcripción/antagonistas & inhibidores , Triazoles/farmacología , Adulto Joven , Proteína ETS de Variante de Translocación 6RESUMEN
Oral carcinogenesis is a complex and multifactorial process that involves cumulative genetic and molecular alterations, leading to uncontrolled cell proliferation, impaired DNA repair and defective cell death. At the early stages, the onset of potentially malignant lesions in the oral mucosa, or oral dysplasia, is associated with higher rates of malignant progression towards carcinoma in situ and invasive carcinoma. Efforts have been made to get insights about signaling pathways that are deregulated in oral dysplasia, as these could be translated into novel markers and might represent promising therapeutic targets. In this context, recent evidence underscored the relevance of the Wnt/ß-catenin signaling pathway in oral dysplasia, as this pathway is progressively "switched on" through the different grades of dysplasia (mild, moderate and severe dysplasia), with the consequent nuclear translocation of ß-catenin and expression of target genes associated with the maintenance of representative traits of oral dysplasia, namely cell proliferation and viability. Intriguingly, recent studies provide an unanticipated connection between active ß-catenin signaling and deregulated endosome trafficking in oral dysplasia, highlighting the relevance of endocytic components in oral carcinogenesis. This review summarizes evidence about the role of the Wnt/ß-catenin signaling pathway and the underlying mechanisms that account for its aberrant activation in oral carcinogenesis.
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Carcinogénesis/metabolismo , Carcinoma/etiología , Neoplasias de la Boca/etiología , Vía de Señalización Wnt , beta Catenina/metabolismo , Carcinoma/metabolismo , Humanos , Neoplasias de la Boca/metabolismoRESUMEN
Radiation-induced genomic instability (GI) is hypothesized to persist after exposure and ultimately promote carcinogenesis. Based on the absorbed dose to the breast, an increased risk of developing breast cancer was shown in the Swedish hemangioma cohort that was treated with radium-226 for skin hemangioma as infants. Here, we screened 31 primary breast carcinomas for genetic alterations using the OncoScan CNV Plus Assay to assess GI and chromothripsis-like patterns associated with the absorbed dose to the breast. Higher absorbed doses were associated with increased numbers of copy number alterations in the tumor genome and thus a more unstable genome. Hence, the observed dose-dependent GI in the tumor genome is a measurable manifestation of the long-term effects of irradiation. We developed a highly predictive Cox regression model for overall survival based on the interaction between absorbed dose and GI. The Swedish hemangioma cohort is a valuable cohort to investigate the biological relationship between absorbed dose and GI in irradiated humans. This work gives a biological basis for improved risk assessment to minimize carcinogenesis as a secondary disease after radiation therapy.
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Neoplasias de la Mama/genética , Carcinoma/genética , Inestabilidad Genómica , Hemangioma/radioterapia , Neoplasias Inducidas por Radiación/genética , Anciano , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/etiología , Carcinoma/epidemiología , Carcinoma/etiología , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Inducidas por Radiación/etiología , Radioterapia/efectos adversos , SueciaRESUMEN
OBJECTIVES: To determine the effectiveness of surveillance colonoscopy (SC) and optimize its use by assessing real-world surgically resected cases of ulcerative colitis (UC)-associated colorectal cancer (CRC) and dysplasia. METHODS: Clinicopathological data of 406 (238 CRC and 168 dysplasia) patients who underwent surgical resection in 10 UC specialized institutions were retrospectively reviewed. The overall survival (OS) rates were compared between the SC and non-SC groups. The incidence of and risk factors for early-onset CRC (<8 years after UC onset) were identified. The distribution of CRC lesions was also assessed. RESULTS: Cancer stages were significantly more advanced in the non-SC group than in the SC group (P < 0.001). The patients in the SC group showed significantly better OS than those in the non-SC group (5-year OS: 89% vs 70%; log-rank test: P = 0.001). Seventeen percent of patients developed CRC within 8 years after UC onset. The age at UC onset was a risk factor and a good predictor of early-onset CRC (<8 years) (P < 0.01; AUC: 0.85). The most common sites of CRC were the rectum (51%) and sigmoid colon (20%). Multiple CRC was identified in 16% of patients. CONCLUSIONS: Surveillance colonoscopy was effective and improved the OS in patients with UC. We recommend that patients with late-onset UC (>40 years) undergo SCs earlier because of the high incidence of CRC within 8 years of UC onset. Moreover, the rectum and sigmoid colon should be more thoroughly examined.
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Carcinoma/diagnóstico , Colitis Ulcerosa/terapia , Colonoscopía/métodos , Neoplasias Colorrectales/diagnóstico , Neoplasias Primarias Múltiples/diagnóstico , Adulto , Edad de Inicio , Carcinoma/etiología , Carcinoma/patología , Carcinoma/cirugía , Colitis Ulcerosa/complicaciones , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Manejo de la Enfermedad , Detección Precoz del Cáncer/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Primarias Múltiples/etiología , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/cirugía , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/etiología , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Factores de Riesgo , Neoplasias del Colon Sigmoide/diagnóstico , Neoplasias del Colon Sigmoide/etiología , Neoplasias del Colon Sigmoide/patología , Neoplasias del Colon Sigmoide/cirugía , Tasa de SupervivenciaRESUMEN
BACKGROUND: SMARCB1-deficient sinonasal carcinoma (SDSC) is an aggressive subtype of head and neck cancers that has a poor prognosis despite multimodal therapy. We present a unique case with next generation sequencing data of a patient who had SDSC with perineural invasion to the trigeminal nerve that progressed to a brain metastasis and eventually leptomeningeal spread. CASE PRESENTATION: A 42 year old female presented with facial pain and had resection of a tumor along the V2 division of the trigeminal nerve on the right. She underwent adjuvant stereotactic radiation. She developed further neurological symptoms and imaging demonstrated the tumor had infiltrated into the cavernous sinus as well as intradurally. She had surgical resection for removal of her brain metastasis and decompression of the cavernous sinus. Following her second surgery, she had adjuvant radiation and chemotherapy. Several months later she had quadriparesis and imaging was consistent with leptomeningeal spread. She underwent palliative radiation and ultimately transitioned quickly to comfort care and expired. Overall survival from time of diagnosis was 13 months. Next generation sequencing was carried out on her primary tumor and brain metastasis. The brain metastatic tissue had an increased tumor mutational burden in comparison to the primary. CONCLUSIONS: This is the first report of SDSC with perineural invasion progressing to leptomeningeal carcinomatosis. Continued next generation sequencing of the primary and metastatic tissue by clinicians is encouraged toprovide further insights into metastatic progression of rare solid tumors.
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Carcinoma/etiología , Carcinoma/patología , Neoplasias de los Senos Paranasales/etiología , Neoplasias de los Senos Paranasales/patología , Proteína SMARCB1/deficiencia , Adulto , Biomarcadores de Tumor , Carcinoma/diagnóstico por imagen , Progresión de la Enfermedad , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunohistoquímica , Carcinomatosis Meníngea/diagnóstico , Carcinomatosis Meníngea/secundario , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias de los Senos Paranasales/diagnóstico por imagen , Polimorfismo de Nucleótido Simple , Tomografía Computarizada por Rayos XRESUMEN
The therapies used to treat Ewing sarcoma are associated with a risk of second malignant neoplasm (SMN). We conducted a systematic review to pool available evidence on the risks, types, and outcomes after SMN. We obtained 52 articles that met inclusion criteria. Cumulative incidence rates of SMN ranged from 0.9 to 8.4% and 10.1 to 20.5% at 5 and 30 years after initial diagnosis. Of the 327 reported SMNs, 63.6% were solid tumors, although acute myeloid leukemia /myelodysplastic syndrome was the single most commonly diagnosed SMN, with generally poor outcomes. Patients treated for Ewing sarcoma are at substantial risk of SMN, with a broad range of reported secondary cancers.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Óseas , Neoplasias Inducidas por Radiación/etiología , Neoplasias Primarias Secundarias/etiología , Radioterapia/efectos adversos , Sarcoma de Ewing , Factores de Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/radioterapia , Neoplasias Óseas/cirugía , Carcinoma/epidemiología , Carcinoma/etiología , Carcinoma/terapia , Humanos , Incidencia , Leucemia Mieloide/epidemiología , Leucemia Mieloide/etiología , Leucemia Mieloide/terapia , Linfoma/epidemiología , Linfoma/etiología , Linfoma/terapia , Melanoma/epidemiología , Melanoma/etiología , Melanoma/terapia , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Inducidas por Radiación/terapia , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/terapia , Riesgo , Sarcoma/epidemiología , Sarcoma/etiología , Sarcoma/terapia , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma de Ewing/radioterapia , Sarcoma de Ewing/cirugía , Factores de Tiempo , Resultado del TratamientoRESUMEN
An inverse association exists between physical activity and breast cancer incidence and outcomes. An objective indicator of an individual's recent physical activity exposure is aerobic capacity. We took advantage of the fact that there is an inherited as well as inducible component of aerobic capacity to show that experimentally induced mammary cancer is inversely related to inherent aerobic capacity (IAC). The objective of this study was to determine whether cell signaling pathways involved in the development of mammary cancer differed in rats with low inherent aerobic capacity (LIAC, n = 55) versus high inherent aerobic capacity (HIAC, n = 57). Cancer burden was 0.21 ± 0.16 g/rat in HIAC versus 1.14 ± 0.45 in LIAC, p < 0.001. Based on protein expression, cancer in LIAC animals was associated with upregulated glucose utilization, and protein and fatty acid synthesis. Signaling in cancers from HIAC rats was associated with energy sensing, fatty acid oxidation and cell cycle arrest. These findings support the thesis that pro-glycolytic, metabolic inflexibility in LIAC favors not only insulin resistance and obesity but also tumor development and growth. This provides an unappreciated framework for understanding how obesity and low aerobic fitness, hallmarks of physical inactivity, are associated with higher cancer risk and poorer prognosis.
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Carcinoma/metabolismo , Neoplasias Mamarias Experimentales/metabolismo , Consumo de Oxígeno , Transducción de Señal , Animales , Carcinoma/etiología , Metabolismo Energético , Ácidos Grasos/biosíntesis , Femenino , Glucosa/metabolismo , Neoplasias Mamarias Experimentales/etiología , Biosíntesis de Proteínas , RatasRESUMEN
Urothelial carcinoma of the bladder (UCB) and upper tracts (UTUC) used to share management with similar principles. However, their genetic and epigenetic differences along with different responses to immunotherapy were recently identified, which are reminiscent of their distinct etiologies. Different from the variety of environmental factors relating to UCB, UTUC is best known for its close relationship with exposure to aristolochic acid (AA). AA is believed to cause its carcinogenicity through forming DNA adducts of deoxyadenosine-aristolactam, as well as A:T â T:A transversions in the TP53 tumor suppressor gene. Since recent findings suggested that cancers with higher somatic mutations are associated with better treatment responses upon immune checkpoint blockade, UTUC and AA-related biomarkers reasonably serve as good candidates, as well as a potential prognostic predictor for the flourishing immunotherapy. This review covers the current state of the literature on the clinical response of UTUC and UCB receiving immunotherapy and points out directions for refinement regarding patient selection.
Asunto(s)
Ácidos Aristolóquicos/toxicidad , Carcinógenos/toxicidad , Carcinoma/terapia , Inmunoterapia/métodos , Neoplasias de la Vejiga Urinaria/terapia , Animales , Carcinoma/etiología , Humanos , Neoplasias de la Vejiga Urinaria/etiología , Urotelio/efectos de los fármacos , Urotelio/metabolismo , Urotelio/patologíaRESUMEN
The liver and pancreas are closely associated organs that share a common embryological origin. They display amphicrine properties and have similar exocrine organization with parenchymal cells, namely, hepatocytes and acinar cells, secreting bile and pancreatic juice into the duodenum via a converging network of bile ducts and pancreatic ducts. Here we compare and highlight the similarities of molecular mechanisms leading to liver and pancreatic cancer development. We suggest that unraveling tumor development in an organ may provide insight into our understanding of carcinogenesis in the other organ.