RESUMO
BACKGROUND: Tumor microenvironment (TME) characteristics including tumor stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) were examined in resected gastric cancer. These TME features have been shown to indicate metastatic potential in colon cancer, and intestinal-type gastric cancer (IGC) has pathological similarities with that malignancy. METHODS: TSR, TB, and TILs were quantified in routine histological sections from 493 patients with IGC who underwent radical resection at 2 university hospitals in China from 2010 to 2016. TME variables were dichotomized as follows: TSR (50%), TILs (median), TB per international guidelines (4 buds/0.785mm2), and platelet-lymphocyte ratio (PLR) per survival ROC. Association of TME features with patient clinicopathological characteristics, time-to-recurrence (TTR), and cancer-specific-survival (CSS) were examined using univariate and multivariate analysis, including a relative contribution analysis by Cox regression. RESULTS: Patients whose tumors showed high TSR or high TB or low TILs were each significantly associated with increased T and N stage, higher histological grade, and poorer TTR and CSS at 5 years. Only TSR and N stage were independently associated with TTR and CSS after adjustment for covariates. PLR was only independently associated with TTR after adjustment for covariates. Among the variables examined, only TSR was significantly associated with both TTR (HR 1.72, 95% CI, 1.14-2.60, Pâ =â .01) and CSS (HR 1.62, 95% CI, 1.05-2.51, Pâ =â .03) multivariately. Relative contribution to TTR revealed that the top 3 contributors were N stage (45.1%), TSR (22.5%), and PLR (12.9%), while the top 3 contributors to CSS were N stage (59.9%), TSR (14.7%), and PLR (10.9%). CONCLUSIONS: Among the examined TME features, TSR was the most robust for prognostication and was significantly associated with both TTR and CSS. Furthermore, the relative contribution of TSR to patient TTR and CSS was second only to nodal status.
RESUMO
Background: Our main objective is to apply bioinformatics in predicting the efficacy of digestive tumour immunotherapy target TIM-3 and its inhibitors. Methods: Our study used the gene expression omnibus (GEO) database to identify datasets associated with digestive tumours and the action of TIM-3. The GSE427729 dataset based on the GPL10192 platform. The dataset consisted of six samples of total RNA derived from TIM-3 control and knockdown RAW 264.7 cells. We used GEO2R tool to identify DEGs before performing Gene Ontology and identifying the kyoto encyclopedia of genes and genomes (KEGG) pathways. Lastly, we determined the PPI networks to identify hub genes. Results: Our study identified 57 differentially expressed genes based on an adjusted p-value of less than 0.05 and a log2 fold change of 2.0. There were 26 down-regulated genes with 31 up-regulated genes while 22, 404 genes were non-significant. The DEGs were enriched in biological pathways such as activating leukocytes, cells, and development of the immune system. Additionally, we identified four significant KEGG pathways that were implicated in digestive tumour immunotherapy and TIM-3; pathways of pancreatic cancer, NF-Kappa B signalling pathway, Toll-like receptor signalling pathway and C-type lectin receptor signalling pathway. The PPI networks identified 10 hub genes that were implicated in digestive tumour immunotherapy target TIM-3 (Myd88, Traf6, Irf7, Cdk4, Ccnd2, Mapkap1, Prr5, Mpp3, Serpinb6b and Pvrl3). Conclusion: Targeting these biological pathways, KEGG pathways, molecular functions and cellular processes can lead to novel therapeutic treatment and management in digestive tumours based on TIM-3 immunotherapy.
RESUMO
Monoubiquitination of FANCD2 is a central step in the activation of the Fanconi anemia (FA) pathway after DNA damage. Defects in the FA pathway centered around FANCD2 not only lead to genomic instability but also induce tumorigenesis. At present, few studies have investigated FANCD2 in tumors, and no pan-cancer research on FANCD2 has been conducted. We conducted a comprehensive analysis of the role of FANCD2 in cancer using public databases and other published studies. Moreover, we evaluated the role of FANCD2 in the proliferation, migration and invasion of lung adenocarcinoma cells through in vitro and in vivo experiments, and explored the role of FANCD2 in cisplatin chemoresistance. We investigated the regulatory effect of FANCD2 on the cell cycle of lung adenocarcinoma cells by flow cytometry, and verified this effect by western blotting. FANCD2 expression is elevated in most TCGA tumors and shows a strong positive correlation with poor prognosis in tumor patients. In addition, FANCD2 expression shows strong correlations with immune infiltration, immune checkpoints, the tumor mutation burden (TMB), and microsatellite instability (MSI), which are immune-related features, suggesting that it may be a potential target of tumor immunotherapy. We further found that FANCD2 significantly promotes the proliferation, invasion, and migration abilities of lung adenocarcinoma cells and that its ability to promote cancer cell proliferation may be achieved by modulating the cell cycle. The findings indicate that FANCD2 is a potential biomarker and therapeutic target in cancer treatment by analyzing the oncogenic role of FANCD2 in different tumors.
Assuntos
Carcinogênese , Proteína do Grupo de Complementação D2 da Anemia de Fanconi , Neoplasias , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Carcinogênese/genética , Dano ao DNA , Anemia de Fanconi/genética , Anemia de Fanconi/metabolismo , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo , Neoplasias/genética , Neoplasias/patologiaRESUMO
Urothelial carcinoma (UC) with deficient mismatch repair (dMMR) is a specific subtype of UC characterized by the loss of mismatch repair (MMR) proteins and its association with Lynch syndrome (LS). However, comprehensive real-world data on the incidence, clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in the Chinese patients with dMMR UC remains unknown. We analyzed 374 patients with bladder urothelial carcinoma (BUC) and 232 patients with upper tract urothelial carcinoma (UTUC) using tissue microarrays, immunohistochemistry, and targeted next-generation sequencing. Results showed the incidence of dMMR UC was higher in the upper urinary tract than in the bladder. Genomic analysis identified frequent mutations in KMT2D and KMT2C genes and LS was confirmed in 53.8% of dMMR UC cases. dMMR UC cases displayed microsatellite instability-high (MSI-H) (PCR method) in 91.7% and tumor mutational burden-high (TMB-H) in 40% of cases. The density of intratumoral CD8+ T cells correlated with better overall survival in dMMR UC patients. Positive PD-L1 expression was found in 20% cases, but some patients positively responded to immunotherapy despite negative PD-L1 expression. Our findings provide valuable insights into the characteristics of dMMR UC in the Chinese population and highlights the relevance of genetic testing and immunotherapy biomarkers for treatment decisions.
Assuntos
Carcinoma de Células de Transição , Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias da Bexiga Urinária , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/genética , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Receptor de Morte Celular Programada 1/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Reparo de Erro de Pareamento de DNA/genética , População do Leste Asiático , Neoplasias Colorretais Hereditárias sem Polipose/genéticaRESUMO
[This corrects the article DOI: 10.3389/pore.2022.1610638.].
RESUMO
Background: Anoikis is a form of programmed cell death or programmed cell death(PCD) for short. Studies suggest that anoikis involves in the decisive steps of tumor progression and cancer cell metastasis and spread, but what part it plays in bladder cancer remains unclear. We sought to screen for anoikis-correlated long non-coding RNA (lncRNA) so that we can build a risk model to understand its ability to predict bladder cancer prognosis and the immune landscape. Methods: We screened seven anoikis-related lncRNAs (arlncRNAs) from The Cancer Genome Atlas (TCGA) and designed a risk model. It was validated through ROC curves and clinicopathological correlation analysis, and demonstrated to be an independent factor of prognosis prediction by uni- and multi-COX regression. In the meantime, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, immune infiltration, and half-maximal inhibitory concentration prediction (IC50) were implemented with the model. Moreover, we divided bladder cancer patients into three subtypes by consensus clustering analysis to further study the differences in prognosis, immune infiltration level, immune checkpoints, and drug susceptibility. Result: We designed a risk model of seven arlncRNAs, and proved its accuracy using ROC curves. COX regression indicated that the model might be an independent prediction factor of bladder cancer prognosis. KEGG enrichment analysis showed it was enriched in tumors and immune-related pathways among the people at high risk. Immune correlation analysis and drug susceptibility results indicated that it had higher immune infiltration and might have a better immunotherapy efficacy for high-risk groups. Of the three subtypes classified by consensus clustering analysis, cluster 3 revealed a positive prognosis, and cluster 2 showed the highest level of immune infiltration and was sensitive to most chemistries. This is helpful for us to discover more precise immunotherapy for bladder cancer patients. Conclusion: In a nutshell, we found seven arlncRNAs and built a risk model that can identify different bladder cancer subtypes and predict the prognosis of bladder cancer patients. Immune-related and drug sensitivity researches demonstrate it can provide individual therapeutic schedule with greater precision for bladder cancer patients.
Assuntos
RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Humanos , RNA Longo não Codificante/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/terapia , Imunoterapia , Bexiga Urinária , ApoptoseRESUMO
Immune checkpoint inhibitors (ICIs) have shown encouraging outcomes against Lynch syndrome (LS)-associated colorectal cancer (CRC) and endometrial cancer with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H). However, there is as yet no clarity on the safety and efficacy of immunotherapy combined with chemotherapy in LS-associated urothelial carcinoma (UC). Here, we report a patient with recurrent and metastatic LS-associated UC who achieved sustained response to programmed death protein 1 (PD-1) inhibitor combined with chemotherapy over 31 months, during which the side effects of immunotherapy could be controlled and managed. Our findings indicate that the dMMR/MSI status and PD-1 expression in UC may have potential predictive value for the response to PD-1-targeted immunotherapy. Our case supports the inclusion of such combination and/or monotherapy for UC in clinical studies and using dMMR/MSI status and PD-1 expression as potential predictive biomarkers for assessment of the therapeutic response.
Assuntos
Carcinoma de Células de Transição , Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais , Neoplasias da Bexiga Urinária , Feminino , Humanos , Instabilidade de Microssatélites , Receptor de Morte Celular Programada 1 , Reparo de Erro de Pareamento de DNA , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Imunoterapia , Neoplasias Colorretais/patologiaRESUMO
BACKGROUND: Bladder cancer is the second most common urological cancer worldwide, with low early diagnosis and high mortality. The limited progress in diagnostics and treatment greatly impedes the survival of bladder cancer patients. OBJECTIVE: Potential therapeutic biomarkers are urgently needed for future clinical treatment. METHODS: We analyzed the sequencing data and corresponding clinicopathological features and survival information of bladder cancer patients in the TCGA database and identified a new zinc finger protein 485 gene, termed ZNF485, which is highly expressed in the tissues of bladder cancer patients and was verified in cells, animal models and tissue microarrays. RESULTS: We found that inhibition of ZNF485 in the bladder cancer cell lines T24 and 5637 obviously inhibited proliferation and promoted the apoptosis of cancer cells. Furthermore, wound healing and invasion assays showed that downregulation of ZNF485 significantly decreased the mobility and invasion of T24 and 5637 cells. In addition, ZNF485-shRNA transfection obviously inhibited tumor growth in nude mice. Immunohistochemical results of clinical samples showed that the expression level of ZNF485 protein in cancer tissues was higher than that in adjacent tissues. Mechanistic analysis identified possible downstream target genes. CONCLUSIONS: Taken together, the results provide evidence that ZNF485 is involved in bladder cancer proliferation and might be a potential therapeutic biomarker for the treatment of this disease.
RESUMO
OBJECTIVES: Some studies have identified tumour-infiltrating lymphocytes (TILs) in H&E-stained sections of gastric cancer, but the prognostic and clinicopathological significance of this remains unclear. The objective of this study is to evaluate the associations between H&E-based TIL density and prognosis and clinicopathological characteristics of patients with gastric cancer. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Cochrane Library, PubMed and Embase databases were searched through 25 February 2020. ELIGIBILITY CRITERIA: Studies evaluating the correlations between TILs assessed by H&E-stained sections and prognosis and clinicopathological characteristics of gastric cancer were included. DATA EXTRACTION AND SYNTHESIS: Relevant data were extracted and risks of bias were assessed independently by two reviewers. HR and relative risk (RR) with 95% CI were pooled by random-effect models to estimate the associations between TIL density and overall survival (OS) and clinicopathological characteristics, respectively. RESULTS: We enrolled nine studies including 2835 cases for the present meta-analysis. High TILs were associated with superior OS (HR=0.68, 95% CI 0.52 to 0.87, p=0.003) compared with low TILs. High TILs were significantly associated with lower depth of invasion (T3-T4 vs T1-T2) (RR=0.58, 95% CI 0.50 to 0.66, p<0.001), less lymph node involvement (presence vs absence) (RR=0.68, 95% CI 0.56 to 0.81, p<0.001) and earlier TNM (tumour, node, metastasis) stage (III-IV vs I-II) (RR=0.68, 95% CI 0.55 to 0.83, p<0.001). TIL density was not associated with age, gender, Lauren classification or histological grade. The methodology for evaluating TIL and its cut-off value varied across different studies, which might affect the results of our meta-analysis. CONCLUSIONS: Our meta-analysis suggests that H&E-based TIL density is a reliable biomarker to predict the clinical outcomes of patients with gastric cancer. Multicentre, prospective studies are needed to further confirm our findings. PROSPERO REGISTRATION NUMBER: CRD42020169877.
Assuntos
Linfócitos do Interstício Tumoral , Neoplasias Gástricas , Idoso , Feminino , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/imunologiaRESUMO
Tumor mutational burden (TMB), defined as the number of somatic mutations per megabase of interrogated genomic sequence, varies across malignancies. Panel sequencing-based estimates of TMB have largely replaced whole-exome sequencing-derived TMB in the clinic. Retrospective evidence suggests that TMB can predict the efficacy of immune checkpoint inhibitors, and data from KEYNOTE-158 led to the recent FDA approval of pembrolizumab for the TMB-high tumor subgroup. Unmet needs include prospective validation of TMB cutoffs in relationship to tumor type and patient outcomes. Furthermore, standardization and harmonization of TMB measurement across test platforms are important to the successful implementation of TMB in clinical practice. SIGNIFICANCE: Evaluation of TMB as a predictive biomarker creates the need to harmonize panel-based TMB estimation and standardize its reporting. TMB can improve the predictive accuracy for immunotherapy outcomes, and has the potential to expand the candidate pool of patients for treatment with immune checkpoint inhibitors.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias/genética , Carga Tumoral/genética , HumanosRESUMO
OBJECTIVE: To investigate the long-term clinical value of prostate 125I brachytherapy (BT) combined with maximal androgen blockade (MAB) in the treatment of metastatic prostate cancer (mPCa). METHODS: We retrospectively analyzed the clinical data on 173 cases of mPCa treated by MAB (n = 126) or BT+MAB (n = 47) from December 2011 to December 2016 and followed up for 6ï¼76 (44.17 ± 19.73) months. We compared the PSA level, prostate volume, IPSS, progression-free survival, and the rates of 3- and 5-year overall survival between the two groups. RESULTS: After treatment, the minimum PSA level was significantly lower in the BT+MAB than in the MAB group ï¼»3.77 ± 4.14ï¼½ vs ï¼»5.96 ± 7.01ï¼½ ng/ml, P = 0.046) and the time to reach the minimum level was shorter in the former than in the latter (ï¼»5.19 ± 2.83ï¼½ vs ï¼»6.52 ± 3.34ï¼½ mo, P = 0.016). The prostate volume was markedly reduced in both of the groups at 1, 3 and 5 years after treatment as compared with the baseline, even more significantly in the BT+MAB than in the MAB group (P < 0.01), though with no statistically significant difference between the two groups before treatment (P = 0.307). The IPSS was remarkably decreased in both of the groups at 1 and 3 years (P < 0.01) but showed no significant difference at 5 years after treatment as compared with the baseline (P > 0.05) or between the two groups before and after treatment (P > 0.05). The progression-free survival was obviously longer in the BT+MAB than in the MAB group (ï¼»37.29 ± 15.73ï¼½ vs ï¼»29.41 ± 14.37ï¼½ mo, P = 0.011), and the rates of 3- and 5-year overall survival were higher in the former than in the latter (74.60% and 60.70% vs 62.60% and 51.50%, P = 0.227 and P = 0.356). Kaplan-Meier survival curves showed no statistically significant difference in the overall survival between the two groups (P = 0.105). CONCLUSIONS: Both MAB and BT+MAB are effective therapies for mPCa, but the latter can achieve a longer progression-free survival.
Assuntos
Inibidores da Angiogênese , Braquiterapia , Radioisótopos do Iodo , Neoplasias da Próstata , Inibidores da Angiogênese/administração & dosagem , Terapia Combinada/normas , Humanos , Estimativa de Kaplan-Meier , Masculino , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/radioterapia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a rare malignant tumor. The etiology of ICC remains poorly understood. Recently, hepatitis B virus (HBV) infection has been implicated as a potential risk factor for ICC, particularly in HBV-endemic areas. Elevation of serum alpha-fetoprotein (AFP) is seen in approximately 20 % of ICC patients. However, serum AFP levels higher than 10,000 ng/mL have only been reported in a few ICC patients. We report an unusual case of HBV-associated ICC occurring in a male with a markedly elevated serum AFP. CASE PRESENTATION: A 60-year-old East Asian male presented with complaints of epigastric distention and right shoulder pain. Laboratory tests showed HBV infection, HBV deoxyribonucleic acid (DNA) slightly elevated (21 IU/mL) and serum AFP markedly elevated (12,310 ng/mL). Computed tomography (CT) scan found a large and irregular mass in the left lobe of the liver. The patient underwent the left hepatic lobe resection. Histopathological examination showed chronic hepatitis B in the background liver and the immunohistochemical (IHC) findings strongly supported the diagnosis of ICC with aberrant expression of AFP. Serum AFP and HBV DNA declined to normal level postoperatively. The patient received four cycles of gemcitabine plus oxaliplatin and took entecavir to prevent HBV reactivation. The patient kept disease free for 18 months in the latest follow-up. CONCLUSION: ICC patients with HBV infection should be distinguished from other ICC cases, based on distinct clinicopathological features and favorable outcome. Screening for HBV infection should be carried out before initiation of chemotherapy. Antiviral therapy is indicated for prevention of HBV reactivation.
Assuntos
Neoplasias dos Ductos Biliares/complicações , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/complicações , Hepatite B Crônica/complicações , alfa-Fetoproteínas/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antivirais/uso terapêutico , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/metabolismo , Colangiocarcinoma/terapia , DNA Viral/sangue , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Guanina/análogos & derivados , Guanina/uso terapêutico , Hepatectomia , Vírus da Hepatite B/genética , Hepatite B Crônica/sangue , Hepatite B Crônica/patologia , Hepatite B Crônica/prevenção & controle , Humanos , Imuno-Histoquímica , Fígado/diagnóstico por imagem , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Fatores de Risco , Tomografia Computadorizada por Raios X , GencitabinaRESUMO
Diarrhea can be caused by a variety of bacterial, viral and parasitic organisms. Laboratory diagnosis is essential in the pathogen-specific burden assessment. In the pathogen spectrum monitoring in the diarrheal surveillance, culture methods are commonly used for the bacterial pathogens' detection whereas nucleic acid based amplification, the non-cultural methods are used for the viral pathogens. Different methodology may cause the inaccurate pathogen spectrum for the bacterial pathogens because of their different culture abilities with the different media, and for the comparison of bacterial vs. viral pathogens. The application of nucleic acid-based methods in the detection of viral and bacterial pathogens will likely increase the number of confirmed positive diagnoses, and will be comparable since all pathogens will be detected based on the same nucleic acid extracts from the same sample. In this study, bacterial pathogens, including diarrheagenic Escherichia coli (DEC), Salmonella spp., Shigella spp., Vibrio parahaemolyticus and V. cholerae, were detected in 334 diarrheal samples by PCR-based methods using nucleic acid extracted from stool samples and associated enrichment cultures. A protocol was established to facilitate the consistent identification of bacterial pathogens in diarrheal patients. Five common enteric viruses were also detected by RT-PCR, including rotavirus, sapovirus, norovirus (I and II), human astrovirus, and enteric adenovirus. Higher positive rates were found for the bacterial pathogens, showing the lower proportion estimation if only using culture methods. This application will improve the quality of bacterial diarrheagenic pathogen survey, providing more accurate information pertaining to the pathogen spectrum associated with finding of food safety problems and disease burden evaluation.
Assuntos
Infecções por Adenoviridae/virologia , Adenovírus Humanos/classificação , Adenovírus Humanos/isolamento & purificação , Infecções Respiratórias/virologia , Sorogrupo , Infecções por Adenoviridae/epidemiologia , Pré-Escolar , China/epidemiologia , Análise por Conglomerados , DNA Viral/química , DNA Viral/genética , Genótipo , Humanos , Lactente , Epidemiologia Molecular , Dados de Sequência Molecular , Filogenia , Infecções Respiratórias/epidemiologia , Análise de Sequência de DNARESUMO
Our study observed the relationship between transient receptor potential melastatin 7 (TRPM7) expression and the metastatic process of nasopharyngeal carcinoma (NPC). We found that TRPM7 was overexpressed in 102 out of 206 (49.5%) human NPC cases and was significantly associated with clinical stage and lymphatic and distant metastasis. The results suggested that TRPM7 promotes NPC cell migration and invasion in vitro. Further, TRPM7 was correlated with poor clinical outcome and was an independent predictor for 5-year overall survival rate (HR, 1.832; 95% CI, 1.237-4.146 [P = 0.041]). In conclusion, TRPM7 promotes the metastasis of NPC and may serve as a prognostic marker in NPC patients.
Assuntos
Movimento Celular , Neoplasias Nasofaríngeas/secundário , Nasofaringe/metabolismo , Canais de Cátion TRPM/metabolismo , Western Blotting , Carcinoma , Proliferação de Células , Células Cultivadas , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Nasofaringe/patologia , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Proteínas Serina-Treonina Quinases , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Canais de Cátion TRPM/antagonistas & inibidores , Canais de Cátion TRPM/genéticaRESUMO
PURPOSE: A let-7 microRNA-complementary site (LCS6) polymorphism in the 3' untranslated region of the KRAS gene has been shown to disrupt let-7 binding and upregulate KRAS expression. We evaluated the LCS6 genotype and its association with KRAS mutation status, clinicopathologic features, and disease-free survival (DFS) in patients with stage III colon cancer who enrolled in a phase III clinical trial (NCCTG N0147). EXPERIMENTAL DESIGN: The LCS6 genotype was assayed by real-time PCR in DNA extracted from whole blood (n = 2,834) and compared with paired tumor tissue (n = 977). χ(2) and two-sample t tests were used to compare baseline factors and KRAS mutation status between patients defined by LCS6 variant status. Log-rank tests and multivariate Cox models assessed associations between LCS6 status and DFS, respectively. RESULTS: We identified 432 (15.2%) blood samples and 143 (14.6%) tumor samples heterozygous or homozygous for the LCS6 G-allele, and 2,402 of 2,834 (84.8%) blood samples and 834 of 977 (85.4%) tumor samples homozygous for the LCS6 T-allele. Genotype results were highly concordant (99.8%) in cases with paired blood and tumor tissue (n = 977). G-allele carriers were significantly more frequent in Caucasians versus other races (χ(2) test, P < 0.0001). The LCS6 genotype was not associated with KRAS mutation status, clinicopathologic features (all P > 0.2), or DFS (log-rank P = 0.49; HR, 0.929; 95% confidence interval, 0.76-1.14), even after combining LCS6 genotype with KRAS mutation status. CONCLUSIONS: In the largest association study investigating the LCS6 polymorphism in colon cancers, the germline LCS6 genotype was not associated with KRAS mutation status or with clinical outcome in patients with stage III tumors.
Assuntos
Regiões 3' não Traduzidas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/genética , MicroRNAs/genética , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sítios de Ligação , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Proteínas Proto-Oncogênicas p21(ras) , Taxa de Sobrevida , Adulto JovemRESUMO
Abundant epidemiologic evidence indicates that regular and long-term use of aspirin is associated with a significant reduction in the incidence of colorectal cancer. The long duration of aspirin needed to prevent colorectal cancer is believed to be due to inhibition of precursor lesions known as adenomas, the recurrence of which is inhibited by aspirin in randomized trials. Aspirin intake has also been associated with a statistically significant improvement in patient survival after curative resection of colorectal cancer in large observational studies. In these cohorts, the survival benefit of aspirin was shown to depend upon the level of COX-2 expression in the primary colorectal cancer. More recent analysis of patient tumors from these observational cohorts suggests that the benefit of aspirin may be limited to specific molecular subtypes. Aspirin intake following colorectal cancer resection was associated with a significant improvement of survival in patients whose tumors carried mutant, but not wild-type, copies of the phosphoinositide 3-kinase (PI3KCA) gene, especially tumors that overexpressed COX-2. A mechanistic explanation is suggested by the finding that inhibition of COX-mediated prostaglandin E2 synthesis by aspirin attenuates PI3K signaling activity that is known to regulate cancer cell proliferation and survival. Aspirin has also been shown to reduce the incidence of colorectal cancers bearing wild-type, but not mutant alleles of the BRAF(V600E) oncogene. Although provocative, the potential utility of these molecular markers for predicting aspirin efficacy awaits prospective evaluation in clinical trials. If validated, these findings may support a personalized approach to using aspirin for the therapy of colorectal cancer.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Neoplasias Colorretais/prevenção & controle , Inibidores de Ciclo-Oxigenase/administração & dosagem , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Humanos , IncidênciaRESUMO
Standard cytotoxic chemotherapy has limited efficacy in advanced insulinomas, and control of blood glucose concentrations in these patients may be difficult. This article describes an elderly (74-year-old) man with metastatic insulinoma and severe hypoglycemia who was treated with repeated 6-week cycles of oral sunitinib malate (25 mg/day for 4 weeks, followed by 2 weeks off treatment). After treatment for more than 2 years, his condition improved and he continued to have a good quality of life with no evidence of tumor progression based on PET/CT findings. Although sunitinib treatment lowered the patient's blood glucose concentrations further and induced repeated symptomatic hypoglycemic episodes, he was able to tolerate the treatment well after changing the timing of sunitinib dosing and adjusting his diet.
Assuntos
Antineoplásicos/uso terapêutico , Glicemia/metabolismo , Fluordesoxiglucose F18 , Indóis/uso terapêutico , Insulinoma/diagnóstico , Insulinoma/tratamento farmacológico , Tomografia por Emissão de Pósitrons/métodos , Pirróis/uso terapêutico , Tomografia Computadorizada de Emissão/métodos , Idoso , Fluordesoxiglucose F18/farmacocinética , Humanos , Insulinoma/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Masculino , SunitinibeRESUMO
BACKGROUND: The incidence of urinary lithiasis following kidney transplantation is very low, and decision-supporting data are not available. The aim of this study was to review the diagnosis and treatment of urinary lithiasis following kidney transplantation, which is of realistic significance to reduce urinary lithiasis following kidney transplantation, prolong the survival of renal allografts. METHODS: The incidence, diagnosis and treatment of urinary lithiasis in ten patients following kidney transplantation were analyzed retrospectively. Seven out of these patients had stones sized approximately 0.4 - 1.1 cm, and they were treated with low-voltage, low-frequency extracorporeal shock-wave lithotripsy (ESWL). Two patients had stones sized < 0.3 cm and they underwent cystoscopy and ureteroscopy. The ureteral catheter endoscopes were inserted in a retrograde manner to mobilize stones repeatedly. After elimination of obstruction, a ureteral double J stent was indwelt. One patient had a pelvic stone (1.2 cm), which was removed surgically. RESULTS: The major clinical manifestations were hematuria, oliguria or anuria. Some patients were asymptomatic and they were diagnosed through laboratory tests and imaging examinations, e.g., ultrasonography. After elimination of obstruction, subjective symptoms disappeared in all patients, and the function of renal allografts recovered. A six-month follow-up indicated no remnant stones or lithiasis relapse. CONCLUSIONS: The diagnosis and treatment of renal allograft lithiasis are challenging. After prompt and appropriate treatment, the prognosis was satisfactory, and permanent renal functional impairment did not occur in most patients.
Assuntos
Transplante de Rim/efeitos adversos , Litotripsia , Urolitíase/etiologia , Urolitíase/terapia , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
OBJECTIVE: To investigate the method and clinical efficacy of laparoscopic excision of seminal vesicle cyst. METHODS: Laparoscopic excision of seminal vesicle cyst was performed under general anaesthesia in two patients with symptomatic seminal vesicle cyst confirmed by ultrasonography and CT scanning preoperatively. The sizes of the seminal vesicle cysts were 3.3 cm x 3.7 cm x 2.5 cm and 4.1 cm x 4.3 cm x 5.3 cm, respectively. RESULTS: The operations were performed successfully in both the patients, with the operation time of 140 min and 100 min, blood loss of 50 ml and 20 ml, and postoperative stay of 6 days. The patients were followed up for 6 and 7 months, respectively. All the preoperative symptoms disappeared, and no complications and recurrence were found. CONCLUSION: Laparoscopic excision of seminal vesicle cyst, with a good visual field, refined procedure, minimal invasiveness and rapid recovery, is a safe and effective surgical option for patients with seminal vesicle cyst.